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Medicina dello Sport

Sports Medicine Journal

Chief Editors | A. Parisi - G. Santilli

Official Journal of the Italian Federation of Sports Med icine & European Federation of Sports Med icine Associations www.sportsmedicinejournal.com

Supplement to Volume 79 | Number 1 | March 2026

Trimestrale - Poste Italiane SpA - Sped.Abb.Post. - Aut. n° Lo-No/01386/10.2025 - Periodico Roc - Fascicolo singolo € 40,00

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Exercise Prescription in Cardiology Consensus Document Italian Federation of Sports Medicine (FMSI) | Italian Society of Sports Cardiology (SIC Sport) In collaboration with: National Association of Hospital Cardiologists (ANMCO) Italian Society of Cardiology (SIC)

Presentation.......................................................................................III List of abbreviations........................................................................ IV 1

Introduction.............................................................................. 1

1.1

The benefits of physical exercise in cardiology.............................. 3

1.2 Definitions of physical activity, physical exercise, prescription and administration.................................................... 5 1.3

Classification of motor activities................................................... 6

General principles of exercise prescription........................... 7

2.1 Initial assessment and cardiovascular risk stratification.................. 9 2.2 “Cardiorespiratory fitness”: methodology and direct (Cardiopulmonary Exercise Testing) and indirect tests................. 11

3 Exercise prescription in patients with risk factors and/or cardiovascular diseases............... 37 3.1

Dyslipidemia............................................................................... 39

3.2

Arterial hypertension.................................................................. 42

3.3

Diabetes mellitus and metabolic syndrome................................. 45

3.4

Coronary artery disease.............................................................. 48

3.5

Valvular heart disease................................................................. 52

3.6

Cardiomyopathies...................................................................... 56

3.7

Arrhythmias and devices carriers................................................ 61

3.8

Congenital heart disease............................................................ 67

3.9

Heart failure and heart transplantation....................................... 73

2.3 Body composition and neuromuscular functional assessment: methodology and direct and indirect tests.................................. 16

3.10 Arterial disease of the lower limbs.............................................. 77

2.4

3.12 The prescription of physical exercise in post-acute cardiac patients and in patients awaiting cardiac surgery: prehabilitation..... 82

General principles and training programs.................................... 18

2.5 Physical activity and exercise in women and gender differences.............................................................. 24 2.6

Exercise prescription at different ages of life .............................. 27

2.7 Safety in the prescription and administration of structured physical exercise.................................................... 30

3.11 Cardio-oncology........................................................................ 79

Organizational and medical-legal aspects.......................... 85

4.1 Prescription and administration of physical exercise: a multidisciplinary approach....................................................... 87 4.2

Informed consent ...................................................................... 89

4.3

Professional liability.................................................................... 94

Glossary.......................................................................................... 100

Authors Italian Federation of Sports Medicine (FMSI) Maurizio Casasco, Alessandro Biffi, Franco Giada, Marco Scorcu Italian Society of Sports Cardiology (SIC Sport) Giampiero Patrizi, Flavio D’Ascenzi, Silvio Romano, Paolo Zeppilli Reviewers Elena Cavarretta, Stefano Palermi, Marco Vecchiato, Alessandro Zorzi Co-authors / Experts consulted Agostoni Piergiuseppe Ambrosetti Marco Anedda Alberto Bennati Chiara Bianchi Giovanni Bilato Claudio Bonetti Antonio Bonifazi Marco Briante Emiliano Brugin Erica Cammarano Michela Caminiti Giuseppe Canale Maria Laura Castelletti Silvia Cavigli Luna Cecchi Franco Cicero Arrigo Coletti Moia Elena Corigliano Gerardo Corrà Ugo Corrado Domenico Cortesi Matteo

D’Andrea Antonello De Fazio Cristina De Ferrari Francesco Delise Pietro Faggiano Pompilio Fattirolli Francesco Fernando Fredrick Foccardi Giulia Gallina Sabina Garascia Andrea Giallauria Francesco Gianfelici Antonio Iellamo Ferdinando Marzullo Raffaella Mattioli Anna Vittoria Mos Lucio Napoli Raffaele Navazio Alessandro Neunhaeuserer Daniel Paolillo Stefania Pasanisi Giovanni Pavan Daniela Perrone Marco

Perrone Filardi Pasquale Pescatore Valentina Piepoli Massimo Porcelli Simone Porto Italo Riccio Carmine Sarubbi Berardo Savino Gustavo Sciarra Luigi Sinagra Gianfranco Sollazzo Fabrizio Squeo Maria Rosaria Squillante Antonio Strollo Felice Temporelli Pier Luigi Testa Crescenzo Tiberi Monica Tranchita Eliana Turchetta Attilio Verzeletti Andrea Vigorito Carlo Volterrani Maurizio Zanuso Silvano Zovatto Isabella

How to cite: AA. VV. Exercise Prescription in Cardiology. Consensus Document Italian Federation of Sports Medicine (FMSI), Italian Society of Sports Cardiology (SIC Sport). Medicina dello Sport 2026; 79 (Suppl. 1): 1-101

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Presentation Nearly 20 years after the first edition in 2006, the FMSI and SIC Sport, in collaboration with ANMCO and SIC, present the second edition of the document “Prescription of Physical Exercise in Cardiology”, which had met with great success at the time. Indeed, for many years, there had been a clear need to update—based on the latest scientific evidence—that inter-society collaborative effort, modeled after the organizational framework of COCIS, regarding the prescription of structured physical exercise in the presence of cardiovascular risk factors and diseases. Today, no one can question the role of physical exercise as a physiological, cost-effective, and efficient tool for primary, secondary, and tertiary prevention in combating major chronic non-communicable diseases. Promoting physical activity in the general population and reducing sedentary behavior represent, in fact, primary objectives for our healthcare institutions. Yet, despite these premises encouraging a physically active lifestyle, a significant portion of the Italian and European population (approximately 40%) remains sedentary today. While the need for an ever-increasing and constant promotion of physical activity in a general sense remains undisputed, substantial scientific evidence demonstrates the specific benefits of physical exercise when it is correctly prescribed by a specialist physician with targeted expertise, in an individualized manner and at the proper dosage, just like any pharmacological therapy. This carries even greater value when the individual is affected by risk factors or exercise-sensitive conditions, such as cardiovascular diseases, ensuring an increase in life expectancy and an improvement in the patient’s quality of life, with subsequent benefits for the economic sustainability of our healthcare system.

Through a remarkable organizational effort, the sponsoring Scientific Societies—guided by an expert panel that coordinated the project, and with the collaboration of a significant number of researchers in the field and a group of diligent reviewers— have successfully finalized this new document. We are confident that it has integrated all the innovative theoretical and practical insights, as well as the updates from the most recent scientific literature on the subject. The result is a document addressed to healthcare professionals that offers a valuable scientific synthesis, while remaining both comprehensive and user-friendly. After examining the beneficial effects of physical exercise as the primary weapon against sedentary behavior in the general population, the authors systematically describe the rational principles and modalities for prescribing it across various cardiovascular diseases and patient categories, outlining the most appropriate diagnostic pathways while concurrently analyzing potential exercise-related risks and strategies to mitigate them. We hope that this initiative will be well received by experts in the field, trusting that it may serve as a benchmark for future refinements and deeper insights into the topics examined. It is likewise our hope that this work may serve as a guiding policy document for healthcare authorities, so that they may recognize and implement the paramount value of physical exercise as a cornerstone of the population’s physical and mental health. Maurizio Casasco FMSI President

Giampiero Patrizi SIC Sport President

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III

List of abbreviations 1RM = One-repetition maximum AF = Atrial fibrillation APA = Adapted physical activity BIA = Bioelectrical impedance analysis BMI = Body mass index BP = Blood pressure Cardiac CT = Cardiac computed tomography CIED = Cardiac implantable electronic device CPET = Cardiopulmonary exercise testing CRF = Cardiorespiratory fitness CRT = Cardiac resynchronization therapy CVD = Cardiovascular disease DEXA = Dual-energy X-ray absorptiometry ECG = Electrocardiogram EF = Ejection fraction HIIT = High-intensity interval training HR = Heart rate

LT = Lactate threshold LQTS = Long QT syndrome MACEs = Major adverse cardiovascular events MEST = Maximal exercise stress test MET = Metabolic equivalent of task RPE = Rating of perceived exertion SEM = Sports and Exercise Medicine SQTS = Short QT syndrome SPE = Structured physical exercise SV = Stroke volume VE/VCO₂ = Ventilatory equivalent for carbon dioxide VE/VO₂ = Ventilatory equivalent for oxygen VO₂ = Oxygen consumption VO₂max = Maximal oxygen consumption VO₂peak = Peak oxygen consumption VT = Ventilatory threshold

Introduction 1. The benefits of physical exercise in cardiology 2. Definitions of physical activity, physical exercise, prescription and administration 3. Classification of motor activities

| CHAPTER 1.1 |

The benefits of physical exercise in cardiology Alessandro Biffi, Emiliano Briante, Fredrick Fernando, Stefano Palermi, Giampiero Patrizi, Silvio Romano

According to the World Health Organization (WHO), cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the world1. According to ISTAT (Italian Institute of Statistics) 2021 data, in Italy, CVD accounted for 30.8% of all deaths (27.7% in males and 33.7% in females), with ischemic heart disease responsible for 8.4% of all deaths (9.3% in males and 7.5% in females) and cerebrovascular diseases 7.6% (6.3% in males and 8.8% in females)2. To counteract the epidemiological and socioeconomic impact of CVD, there is a need to develop large-scale primary and secondary prevention programmes and effective preventive/therapeutic interventions on the general population. In this context, physical exercise is proposed as an ideal tool because it is physiological, effective, safe and low-cost3. Regular physical activity and a reduction in sedentary lifestyle can induce favorable effects both in primary prevention (dyslipidemia, arterial hypertension, diabetes, metabolic syndrome and obesity) and in secondary prevention of CVD (ischaemic heart disease, valvulopathies, cardiomyopathies, arrhythmias, congenital heart disease, heart failure, heart transplantation, peripheral vasculopathies, aortopathies, cardiac oncology)4,5. The main biological mechanisms underlying these improvements involve not only cardiac tissue, but also metabolism and inflammatory processes4. Exercise is known to positively influence mitochondrial biogenesis and function, fatty acid oxidation and promote blood vessel dilation and neo-capillarization, ensuring better myocardial perfusion6. In addition, it reduces the inflammatory cascade by counteracting the development of atherosclerosis through the release of myokines from skeletal muscle7. The adaptive action of physical exercise on the modulation of autonomic nervous system and on the activity of ion channels and cardiovascular receptors is also relevant. Finally, it optimizes glucose uptake by improving insulin secretion and sensitivity and it plays a significant role in numerous physiological hormonal activities (plasma catecholamines, cortisol, glucagon, etc.)8. WHO guidelines on exercise prescription in apparently healthy adults recommend at least 150 minutes of moderate physical activity per week, or 75 minutes of vigorous activity, supplemented by muscle-strengthening exercises at least twice a week. In addition, it is crucial to limit the time spent in sedentary activities to maintain long-lasting cardiovascular health. Nevertheless, more than a quarter of adults do not comply with these recommendations9. Physical inactivity, in fact, has a negative impact on global health and is an important risk factor for the onset of CVD10. For example, in a study of 116,221 subjects, with a 30-year follow-up, exercise was inversely related to the risk of CVD and all-cause mortality11. A recent meta-analysis showed a direct relationship between an excessive sedentary lifestyle (>10 hours a day) and the incidence of CVD, defining it as dangerous to spend more than 6-8 hours a day sitting (with an increase in cardiovascular risk of about 14%)12. In addition, many studies have shown that physical activity reduces the risk

of high blood pressure, obesity, type 2 diabetes and metabolic syndrome13. Patients with different types of heart disease also benefit from exercise-based rehabilitation programs, showing improvements in quality of life, functional capacity and even mortality14. Current guidelines emphasize an active approach as the foundation of secondary prevention of CVD, with tips for patients similar to the ones for healthy people, although generally prescribed with greater caution. A recent study conducted on 131,558 patients with different types of CVD followed for 6 years, demonstrated an inverse relationship between physical activity and mortality risk15. Another research, with a follow-up of about 5 years, reported a significantly lower risk of mortality (-32%) in patients with CVD participating in cardiac rehabilitation programs compared to sedentary non-participants16. A recent Cochrane review (n = 23,430 patients with different CVD) concluded that exercise-based cardiac rehabilitation documented a reduction in mortality risk and an improvement in quality of life17. In patients with various types of arrhythmias (e.g. atrial fibrillation, AF), exercise not only improves physical capacity, but also reduces symptoms18. Physical activity also appears to be a promising strategy for improving physical capacity even after surgery for aortic stenosis or heart transplantation19,20. Finally, recent evidence shows that structured physical exercise, if correctly prescribed and supervised, is safe and effective, even in patients with cardiomyopathies and congenital heart disease21-23. Although moderate-intensity aerobic training is the most commonly prescribed intervention in cardiac rehabilitation, HIIT (High Intensity Interval Training) has gained popularity in recent years, proving to be safe and effective24. The role of strength training should not be overlooked either, as this modality has been shown to be feasible and effective in most CVD, also as a counteract to sarcopenic degeneration in the elderly14. Beyond the health benefits, promoting exercise as a factor of prevention and therapeutic intervention also offers economic benefits for the health system and society as a whole. First of all, it is possible to estimate the socio-economic impact of low physical activity starting from the number of years lost due to disability or premature death in the various diseases related to sedentary lifestyle (Disability Adjusted Life Years – DALYs), put in relation to the average direct annual health cost (borne by the National Health System or by citizens for visits, diagnostic tests, drug treatment, hospitalizations, rehabilitation, etc.) and indirect (loss of work productivity). In the case of CVD, it is estimated that in Italy a sedentary lifestyle is directly responsible for the loss of more than 130 thousand years of healthy life accumulated every year (224 DALYs per 100,000 inhabitants), for a value equal to more than 10% of the total DALYs lost for this group of diseases25,26. As a result, the economic cost of CVD caused by a sedentary lifestyle, valued using an average expenditure value of approximately €24,500 per year (of which 70% are direct costs)27, is approximately €3.2 billion28. This is a huge amount of resources and a cost that could be largely avoided by reducing the rate of sedentary lifestyle of Italians and therefore reinvested

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EXERC I SE PRESCR IP TION IN C A R DIOLO G Y

in activities of greater value for the health system, such as prevention, research, innovation, etc. Even some cost-effectiveness studies indicate that exercise programs can significantly reduce overall health care costs, making them cheaper than many traditional medical interventions29. It is therefore crucial that health policies actively incentivize active lifestyles to mitigate the impact of CVD, thus improving not only life expectancy, but also the quality of life itself, as well as the economic sustainability of our healthcare system30. In conclusion, physical exercise is an essential and cost-effective tool for the prevention and treatment of CVD. It is therefore necessary for health policies to recognize and implement their fundamental role not only in prevention, but also in the management of these serious diseases, promoting an imperative cultural change that values physical exercise as a medical tool to be prescribed with appropriateness and competence, using all those professional figures dedicated to the purpose, “first and foremost” the doctor specialist in sports medicine and exercise.

References 1.

Mensah GA, Fuster V, Murray CJL, et al. Global Burden of Cardiovascular Diseases and Risks, 1990-2022. J Am Coll Cardiol 2023; 82: 2350-73. 2. Saglietto A, Manfredi R, Elia E, et al. Cardiovascular Disease Burden: Italian and Global Perspectives. Minerva Cardiol Angiol 2021; 69: 231-40. 3. Warburton DER, Nicol CW, Bredin SSD. Health Benefits of Physical Activity: The Evidence. CMAJ 2006; 174: 801. 4. Valenzuela PL, Ruilope LM, Santos-Lozano A, et al. Exercise Benefits in Cardiovascular Diseases: From Mechanisms to Clinical Implementation. Eur Heart J 2023; 44: 1874-89. 5. Isath A, Koziol KJ, Martinez MW, et al. Exercise and Cardiovascular Health: A State-of-the-Art Review. Prog Cardiovasc Dis 2023; 79: 44-52. 6. Ashor AW, Lara J, Siervo M, et al. Exercise Modalities and Endothelial Function: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials. Sports Med 2015; 45: 279-96. 7. Beavers KM, Brinkley TE, Nicklas BJ. Effect of Exercise Training on Chronic Inflammation. Clin Chim Acta 2010; 411: 785-93. 8. Busquets S, Figueras M, Almendro V, et al. Interleukin-15 Increases Glucose Uptake in Skeletal Muscle. An Antidiabetogenic Effect of the Cytokine. Biochim Biophys Acta 2006; 1760: 1613-7. 9. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 Guidelines on Physical Activity and Sedentary Behaviour. Br J Sports Med 2020; 54: 1451-62. 10. Visseren F, Mach F, Smulders YM, et al. 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2021; 42: 3227-337. 11. Lee DH, Rezende LFM, Joh HK, et al. Long-Term Leisure-Time Physical Activity Intensity and All-Cause and Cause-Specific Mortality: A Prospective Cohort of US Adults. Circulation 2022; 146; 523-34. 12. Pandey A, Salahuddin U, Garg S, et al. Continuous Dose-Response Association Between Sedentary Time and Risk for Cardiovascular Disease: A Meta-Analysis. JAMA Cardiol 2016; 1: 575-83. 13. Ciumărnean L, Milaciu MV, Negrean V, et al. Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly. Int J Environ Res Public Health 2021; 19. 14. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease. Eur Heart J 2021; 42: 17- 96.

15. Jeong SW, Kim SH, Kang SH, et al. Mortality Reduction with Physical Activity in Patients with and without Cardiovascular Disease. Eur Heart J 2019; 40: 3547-55. 16. Eijsvogels TMH, Maessen MFH, Bakker EA, et al. Association of Cardiac Rehabilitation With All-Cause Mortality Among Patients With Cardiovascular Disease in the Netherlands. JAMA Netw Open 2020; 3: E2011686; doi:10.1001/JA- MANETWORKOPEN.2020.11686. 17. Dibben G, Faulkner J, Oldridge N, et al. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease. Cochrane Database Syst Rev 2021; 11: doi:10.1002/14651858.CD001800. PUB4. 18. Smart NA, King N, Lambert, J.D., et al. Exercise-Based Cardiac Rehabilitation Improves Exercise Capacity and Health-Related Quality of Life in People with Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomised and Non-Randomised Trials. Open Heart 2018; 5: doi:10.1136/ OPENHRT-2018- 000880. 19. Anayo L, Rogers P, Long L, et al. Exercise-Based Cardiac Rehabilitation for Patients Following Open Surgical Aortic Valve Replacement and Transcatheter Aortic Valve Implant: A Systematic Review and Meta-Analysis. Open Heart 2019; 6: doi:10.1136/OPENHRT-2018-000922. 20. Nytrøen K, Rolid K, Andreassen AK, et al. Effect of High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia. Circulation 2019; 139: 2198-2211. 21. Pelliccia A, Solberg EE, Papadakis M, et al. Recommendations for Participation in Competitive and Leisure Time Sport in Athletes with Cardiomyopathies, Myo- carditis, and Pericarditis: Position Statement of the Sport Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur Heart J 2019; 40: 19-33. 22. Borjesson M, Dellborg M, Niebauer J, et al. Brief Recommendations for Par- ticipation in Leisure Time or Competitive Sports in Athletes-Patients with Coronary Artery Disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur J Prev Cardiol 2020; 27: 770-6. 23. Heidbuchel H, Adami PE, Antz M, et al. Recommendations for Participation in Leisure-Time Physical Activity and Competitive Sports in Patients with Arrhythmias and Potentially Arrhythmogenic Conditions: Part 1: Supraventricular Arrhythmias. A Position Statement of the Section of Sports Cardiology and Exercise from the European Association of Preventive Cardiology (EAPC) and the European Heart Rhythm Association (EHRA), Both Associations of the European Society of Cardiology. Eur J Prev Cardiol 2021; 28: 1539-51. 24. Taylor JL, Holland DJ, Keating SE, et al. Short-Term and Long-Term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation: The FITR Heart Study Randomized Clinical Trial. JAMA Cardiol 2020; 5: 1. 25. Marzolini S, Oh PI, Brooks D. Effect of Combined Aerobic and Resistance Training versus Aerobic Training Alone in Individuals with Coronary Artery Disease: A Meta-Analysis. Eur J Prev Cardiol 2012; 19: 81-94. 26. Global Burden of Disease Study 2019 (GBD 2019) Data Resources | GHDx Available online: https://ghdx.healthdata.org/gbd-2019 27. Gerlier L, Sidelnikov E, Kutikova L, et al. Interim Results of A Multi-Country Survey to Evaluate Productivity Loss and Indirect Costs after Cardiovascular Events in Europe. Value in Health 2017; 20: A404. 28. The European House – Ambrosetti, Osservatorio Valore Sport – Bringing sport and the culture of movement back to the center of the political agenda to Create Value for the country, 2024. 29. Ortolan S, Neunhaeuserer D, Quinto G, et al. Potential Cost Savings for the Healthcare System by Physical Activity in Different Chronic Diseases: A Pilot Study in the Veneto Region of Italy. Int J Environ Res Public Health 2022; 19: 7375; doi:10.3390/IJERPH19127375. 30. Rosenwinkel ET, Bloomfield DM, Arwady MA, et al. Exercise and autonomic function in health and cardiovascular disease. Cardiol Clin 2001; 19: 369-87.

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| CHAPTER 1.2 |

Definitions of physical activity, physical exercise, prescription and administration Franco Giada, Erica Brugin, Marco Scorcu

The purpose of this document, aimed at health professionals, is to describe the rational principles and the correct ways to prescribe and administer physical exercise in cardiology, emphasizing the fundamental role that this plays in the prevention and treatment of the main cardiovascular risk factors and the main CVDs. To this end, it is essential to clarify the terminology that will be used, in order to differentiate the various aspects of the fight against a sedentary lifestyle. There are different types of motor activity that differ in the objectives they pursue, the methods of execution and the level of cardiovascular effort they involve: physical activity, physical exercise and sports activity1-4. • Physical activity is defined as any movement exerted by the musculoskeletal system that results in a higher energy expenditure than in resting conditions. • Physical exercise is a planned, repetitive motor activity designed to improve or maintain physical performance and health. • Sports activity is defined as any form of motor activity based on compliance with rules which, through organized or unorganized participation, has as its main objective the achievement of results and to excel in competitions of any level. • Adapted Physical Activity (APA) refers to physical activity programs, intended for patients with stabilized chronic diseases or physical disabilities, in order to improve well-being and quality of life, reduce disability, prevent recurrences and promote socialization. Osteo-muscular-articular and neurological pathologies are the diseases that most benefit from this type of activity. It is a motor activity generally performed in groups, in non-health places or facilities, such as the “Health Gyms”, with mild cardiovascular effort, such as cardiovascular activation exercises, joint mobilization, muscle strengthening, coordination and balance, conducted free-body or with the aid of small equipment and therefore at low risk of exercise-related adverse cardiovascular events. The prescription of APA, in addition to a careful medical examination, does not necessarily require preventive instrumental investigations (primarily cardiovascular investigations) to reduce this risk. The APA program must be calibrated according to the functional and clinical conditions of the patients and is administered under the supervision of a professional with specific skills, such as the Kinesiologist. • Structured Physical Exercise (SPE) refers to planned and repetitive physical exercise program, intended for patients with stabilized exercise-sensitive chronic diseases or cardiovascular risk factors (such as arterial hypertension, dyslipidemia, diabetes, obesity, etc.), in order to improve well-being and quality of life, prevent recurrences, reduce the risk of morbidity and mortality and promote socialization. Cardiovascular, pneumological, oncological and dysmetabolic diseases are the pathologies that benefit most from these programs, both in primary and secondary prevention. It is a motor activity, performed individually in non-health places or facilities, such as the “Health Gyms”, with moderate/high cardiovascular effort, such as prolonged aerobic exercises (on a cycle ergometer and/or treadmill) and muscle strengthening exercises (with free weights or with specific machines), as well as

• •

•

stretching and cool-down exercises and a mild/moderate risk of exercise-related adverse cardiovascular events. The prescription of SPE, therefore, in addition to a careful medical examination, requires at least in the most complex patients’ preventive instrumental investigations to reduce this risk. The SPE program must be calibrated according to the functional and clinical conditions of the patients and is administered under the supervision of a professional with specific skills, such as the Kinesiologist. Heath Gym refers to public or private non-health facilities, where SPE and APA programs are carried out. The fight against a sedentary lifestyle involves different intervention strategies: the promotion of physical activity, the prescription and administration of APA and SPE1-4. The promotion of physical activity is a population strategy and is carried out through health information and education campaigns on the importance of practicing physical activity, aimed at the general population or homogeneous groups of healthy subjects, or with simple diseases. Promotion of physical activity is a prerogative of the Health Institutions and all health professionals. The prescription of APA and SPE, on the other hand, is an individual intervention strategy aimed at the single patient. Like the prescription of a drug, it is a real medical act based on an in-depth clinical evaluation aimed at the correct management and prevention of a specific disease. It provides for a careful evaluation of indications and possible contraindications and a training program built on the clinical and social characteristics of the individual patient. The prescription of APA and SPE is the prerogative of any doctor with adequate expertise in the field, from the general practitioner and pediatrician to the specialist, while for more complex patients the prescription should be made by the specialist competent for the patient’s specific pathology. For the prescription of SPE in the cardiovascular field, which is the subject of this document, the doctors most prepared and dedicated to this task are specialists in Sports and Exercise Medicine and in Cardiology. The administration of APA and SPE, continuing the parallelism with drug therapy, consists in the provision to patients of the training program prescribed by the doctor, by professionals, with specific skills and adequately prepared for this purpose, i.e. Kinesiologist.

References 1.

2. 3. 4.

Legislative Decree no. 36 of 28 February 2021, updated with the provisions of Legislative Decree no. 120 of 29 August 2023 (containing “Supplementary and corrective provisions of legislative decrees nos. 36, 37, 38, 39 and 40 of 28 February 2021”), published in the Official Gazette, General Series, no. 206 of 4 September 2023. WHO Guidelines on Physical Activity and Sedentary Behaviour. Geneva: World Health Organization; 2020. PMID: 33369898. Giada F, Biffi A, Agostoni P, et al. La prescrizione dell’esercizio fisico in ambito cardiologico. Documento di Consenso della Task Force Multisocietaria. G Ital Cardiol 2007; 8: 681-731. Ministry of Health. Guidelines On Physical Activity. Revision of recommendations for different age groups and physiological situations and new recommendations for specific pathologies. Approved by the State-Regions Conference, 3 November 2021.

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| CHAPTER 1.3 |

Classification of motor activities Antonio Gianfelici, Marco Bonifazi, Matteo Cortesi, Simone Porcelli

In the practice of motor activities, the cardiovascular effort can be constant, as in long-term aerobic activities (e.g., walking, marathon, cycling), or intermittent, as in individual (tennis, squash) or team (football, basketball) ball games1-3. The intensity of the effort is directly proportional to the metabolic demands of the muscles involved, representing a key parameter for the classification of motor activities4. A simple and effective measure of metabolic intensity is the MET (metabolic equivalent of physical activity): 1 MET corresponds to the Oxygen uptake (VO2) by an individual at rest, estimated at about 3.5 ml of O2 per kg of body weight per minute (ml/kg/min)1-3,5. The hemodynamic response to exercise is strongly influenced by the type of activity carried out. Aerobic activities are characterized by cyclical technical gestures (walking, running, cycling) and a moderate use of muscle strength. From a cardiovascular point of view, they determine an increase in heart rate (HR) proportional to the intensity of the effort, accompanied by a prevalent peripheral vasodilation and a modest or no increase in blood pressure (BP). These activities are particularly indicated in the primary and secondary prevention of CVD, thanks to the possibility of a precise prescription based on simple and reliable parameters, such as HR2,3. Aerobic activities are clearly distinguished from strength activities. In these lastly, the cardiovascular response is characterized by a significant increase in mean BP, caused by greater peripheric vascular resistance6. As regards the risk of cardiovascular complications, aerobic sports activities (both constant and intermittent effort) and strength sports do not show substantial differences. Epidemiological studies on unplanned death in sport indicate that the main determinant of risk is the intensity of exercise6. This risk threshold varies with age and with the presence of pre-existing cardiovascular diseases, making it necessary to accurately assess the intensity of the activity to ensure benefits without increasing the risk of complications. Intermittent activity is more difficult to monitor, since metabolic expenditure and cardiovascular effort depend on external variables, such as the opponent and the level of competition. In addition, these activities, characterized by movements with an abrupt start and end, have a higher risk of cardiac arrhythmias than those of the constant type, which have a more gradual start and end6. Another aspect to be considered in the classification of motor activities is the so-called “intrinsic risk”, specific to certain disciplines (underwater sports, mountaineering, motor sports, etc.)1. On the basis of these concepts, for the purpose of prescribing physical exercise, motor activities can be divided into three large groups: • GROUP 1 - Predominantly aerobic activities with constant cardiovascular effort.

• GROUP 2 - Predominantly aerobic activities with intermittent cardiocirculatory engagement. • GROUP 3 - Mainly strength or balance/stability activities. By way of example, while considering that the prescription of physical exercise must be personalized, some sports activities that can be used in specific contexts (for example, in children with congenital heart disease) are reported in table 1. Table 1. Classification of motor activities for the purpose of exercise prescription. Group 1

Group 2

Group 3

Walking

Boules

Sport climbing

Canoeing

Football

Horse riding

Cycling

Cricket

Fencing

Running

Crossfit

Alpine skiing

Swimming

Dance

Weightlifting

Skating

Golf

Tai Chi

Skiing

Basketball

Windsurfing

Triathlon

Volleyball

Yoga

Softball Squash Tennis Table tennis The classification is illustrative and not exhaustive. The exercise prescription must always be individualized according to the clinical conditions.

References 1.

4. 5. 6.

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Zeppilli P, Biffi A, Cammarano M, et al. Italian Cardiological Guidelines (COCIS) for Competitive Sport Eligibility in Athletes with Heart Disease: update 2024. Minerva Med 2024; 115: 533-64. Giada F, Biffi A, Agostoni P, et al. La prescrizione dell’esercizio fisico in ambito cardiologico. Documento di Consenso della Task Force Multisocietaria. G Ital Cardiol 2007; 8: 681-731. Pelliccia A, Sharma S, Gati S, et al. ESC Scientific Document Group. 2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Di- sease. Eur Heart J 2021; 42: 17-96; doi: 10.1093/eurheartj/ ehaa605. Erra- tum in: Eur Heart J 2021; 42: 548-9. Mitchell JH, Haskell W, Snell P, et al. Task Force 8: Classification of Sports. J Am Coll Cardiol 2005; 45: 1364-7. Byrne NM, Hills AP, Hunter GR, et al. Metabolic Equivalent: One Size Does Not Fit All. J Appl Physiol (1985) 2005; 99: 1112-9. Palermi S, Cavarretta E, D’Ascenzi F, et al. Athlete’s Heart: A Cardiovascular Step-By-Step Multimodality Approach. Rev Cardiovasc Med 2023; 24: 151.

2 General principles of exercise prescription 1. Initial assessment and cardiovascular risk stratification 2. “Cardiorespiratory fitness”: methodology and direct (Cardiopulmonary Exercise Testing) and indirect tests 3. Body composition and neuromuscular functional assessment: methodology and direct and indirect tests 4. General principles and training programs 5. Physical activity and exercise in women and gender differences 6. Exercise prescription at different ages of life 7. Safety in the prescription and administration of Structured Physical Exercise

| CHAPTER 2.1 |

Initial assessment and cardiovascular risk stratification Paolo Zeppilli, Fabrizio Sollazzo

Before starting an SPE program, especially when high intensity exercise is planned, patients should undergo a pre-exercise medical evaluation aimed at identifying those at risk of major adverse cardiovascular events (MACEs), particularly sudden cardiac death and acute coronary syndromes. Cardiovascular risk stratification is essential to maximize the benefits of physical exercise while minimizing the risks for the patient. Despite the substantial health benefits of physical activity, there is ample evidence that high-intensity exercise may trigger MACEs in individuals with an underlying cardiac substrate1. Such events are largely caused by ventricular tachyarrhythmias leading to cardiac arrest. In younger individuals (approximately <40 years in men and <50 years in women), the main underlying substrates are structural and electrical heart diseases, such as cardiomyopathies and channelopathies. In older individuals, exercise-related adverse events are more commonly associated with atherosclerotic coronary artery disease2,3. For this reason, many international scientific and sports organizations have emphasized the importance of preventing these events and have endorsed cardiovascular screening, although substantial controversy remains regarding how screening should be performed4,5. A fundamental premise is that the initial assessment of an individual entering a SPE prescription pathway should not be limited to cardiovascular risk stratification. It should also provide the objective and measurable parameters needed to design an individualized training programme, particularly with regard to exercise intensity. According to current international recommendations, the most appropriate approach to estimate training intensity is cardiopulmonary exercise testing (CPET) with the identification of the two ventilatory thresholds (first and second Ventilatory Threshold - VT1 and VT2), rather than the use of indirect or subjective parameters derived from other maximal tests, such as HR, workload or rate of perceived exertion, RPE6,7. CPET is a valuable risk stratification tool, providing clinically relevant information on cardiorespiratory fitness (CRF) and on the cardiovascular and respiratory response to exercise8,9. Because of its combined functional and clinical value, CPET has a central role in the definition of SPE protocols. However, it should not be considered a mandatory routine investigation in the general population with a low probability of MACEs, in whom cost-effectiveness may not justify systematic execution. In general, cardiovascular risk stratification for the probability of MACEs can be broadly divided into two scenarios. The first includes subjects with no known cardiovascular disease, in whom risk stratification is primarily aimed at preventive screening, The second encompasses individuals with established heart disease, in whom assessment is specifically aimed at identifying those at higher risk of MACEs. In individuals without known heart disease, screening approaches differ considerably across different medical traditions. In the American approach, as reflected in the American College of Sport Medicine guidelines, cardiovascular risk stratification

relies on a simple history-based screening that may also be performed by non-physician personnel. This screening aims to identify habitual physical activity levels, signs or symptoms suggestive of cardiovascular, metabolic or renal disease, as well as individuals with known cardiovascular, metabolic or renal disease. On the basis of this initial screening, individuals may or may not be referred for targeted medical evaluation10. By contrast, the European, and especially Italian, strategy for sport medicine cardiovascular screening, emphasizes that a history-based assessment alone is insufficient to identify most individuals at risk of sudden cardiac death. In this setting, adding a resting ECG, especially when interpreted by an experienced clinician, appears to improve diagnostic yield with limited additional cost11,12. In younger individuals without known heart disease (<40 years in men, <50 years in women) a basic evaluation including an adequate medical history, physical examination and resting ECG combined with an indirect assessment of CRF for exercise prescription purposes may be considered acceptable. In older individuals without known heart disease (>40 years in men, >50 years in women) the higher prevalence of coronary heart disease, which confers an increased risk of MACEs, suggests a targeted assessment of cardiovascular risk factors. At a minimum, this should include estimation of the likelihood of previously unrecognized coronary artery disease using the most recent risk algorithms for European populations, namely SCORE2 and SCORE2-OP13. The decision to perform a Maximal Exercise Testing (MET) or a CPET should then be guided by individual clinical judgment, but should take at least the following factors into account: 1) High or very high SCORE2/SCORE2-OP estimated cardiovascular risk. 2) Symptoms suggestive of cardiovascular disease. 3) Family history of sudden death at young age and/or familial hypercholesterolemia. If at least one of these criteria is present, a MET should be regarded as the minimum assessment required to guide the diagnostic and therapeutic approach, as well as to reduce the risk of exercise-related adverse events14. A negative MET (absence of significant ST-segment changes, normal chronotropic and blood pressure response, normal exercise capacity/workload achieved, and the absence of frequent and/or complex exercise-induced ventricular arrhythmias) significantly reduces the likelihood of obstructive coronary artery disease. In such cases, high intensity activities may be considered without further diagnostic investigations, provided that cardiovascular risk factors are appropriately managed. By contrast, an equivocal, uninterpretable, or clearly positive MET should prompt further targeted investigations, (upsloping ST segment depression >2 mm, horizontal or downsloping ST depression between 0.5 and 1 mm, pacemaker rhythm, pre-existing left bundle branch block) or a frankly positive MET (exercise induced symptoms of cardiovascular origin such as angina, dyspnea or heart palpitations, frequent and/or complex ventric-

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ular arrhythmias induced by exercise, horizontal or downsloping ST depression>1 mm, appearance of frequency-dependent left bundle branch block) should prompt further targeted investigations, including coronary CT angiography or functional imaging. According to current guidelines, coronary CT angiography is generally preferred in patients with a lower pre-test probability of obstructive coronary artery disease, whereas functional imaging is more appropriate in those with a higher pre-test probability15. In the presence of significant symptoms and a high clinical likelihood of coronary artery disease, together with a positive exercise test, direct referral for invasive coronary angiography may also be appropriate. Pending completion of the diagnostic work-up, prescription of SPE at light intensity, or participation in adapted physical activity (APA), may be considered appropriate and potentially beneficial. This approach helps balance the need for appropriate screening with the equally important goal of initiating cardiovascular prevention without delay. In patients with established cardiovascular disease, decisions regarding SPE prescription should be based on the individual level of risk of MACEs. This requires a targeted cardiological assessment tailored to the underlying condition and including not only the evaluations discussed above, but also the additional disease-specific investigations addressed in the relevant chapters of the paper. In this group of patients, CPET represents the gold standard for stress tests both for diagnostic purposes and for individualized prescription of SPE. In summary, in most patients with heart disease, appropriate risk stratification allows participation in at least moderate-intensity physical activity in those at low-risk, whereas progression to high-intensity exercise should be reserved for carefully selected clinical settings. On the contrary, light-intensity SPE should be prescribed for patients classified as high risk after diagnostic evaluation and for those in whom risk stratification is still incomplete. Even in these individuals, the benefits of low-intensity physical activity are now considered to outweigh the potential risks associated with this type of exercise.

References 1.

Franklin BA, Thompson PD, Al-Zaiti SS, et al. Exercise-Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following LongTerm Exercise Training: Placing the Risks into Perspective-An Update: A Scientific Statement from the American Heart Association. Circulation. 31 march 2020; 141: e705-36.

Harmon KG, Asif IM, Maleszewski JJ, et al. Incidence, Cause, and Comparative Frequency of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A Decade in Review. Circulation 2015; 132: 10-9. 3. Finocchiaro G, Papadakis M, Robertus JL, et al. Etiology of Sudden Death in Sports: Insights from a United Kingdom Regional Registry. J Am Coll Cardiol 2016; 67: 2108-15. 4. Corrado D, Pelliccia A, Bjørnstad HH, et al. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005; 26: 516-24. 5. Drezner J.A., O’Connor F.G., Harmon K.G., et al. AMSSM Position Statement on Cardiovascular Preparticipation Screening in Athletes: Current evidence, knowledge gaps, recommendations and future directions. Br J Sports Med 2017; 51: 153-67. 6. D’Ascenzi F, Cavigli L, Pagliaro A, et al. Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. Br J Sports Med 2022; bjsports-2021-105261. 7. Hansen D, Abreu A, Ambrosetti M, et al. Exercise intensity assessment and prescription in cardiovascular rehabilitation and beyond: why and how: a position statement from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2022; 29: 230-45. 8. Ross R, Blair SN, Arena R, et al. Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement from the American Heart Association. Circulation 2016; 134 9. Cauwenberghs N, Sente J, Van Criekinge H, et al. Integrative Interpretation of Cardiopulmonary Exercise Tests for Cardiovascular Outcome Prediction: A Machine Learning Approach. Diagnostics (Basel) 2023; 13: 2051. 10. Liguori G, Feito Y, Fountaine C, et al. American College of Sports Medicine’s guidelines for exercise testing and prescription. 6th ed. Philadelphia: Wolters Kluwer; 2021. 11. Williams EA, Pelto HF, Toresdahl BG, et al. Performance of the American Heart Association (AHA) 14-Point Evaluation Versus Electrocardiography for the Cardiovascular Screening of High School Athletes: A Prospective Study. J Am Heart Assoc 2019; 8: e012235. 12. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96. 13. SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J 2021; 42: 2439-54. 14. Borjesson M, Dellborg M, Niebauer J, et al. Brief recommendations for participation in leisure time or competitive sports in athletes-patients with coronary artery disease: Summary of a Position Statement from the Sports Cardiology Section of the European Association of Preventive Cardiology (EAPC). Eur J Prev Cardiol 2020; 27: 770-6. 15. Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J 2024; 45: 3415-537.

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| CHAPTER 2.2 |

“Cardiorespiratory Fitness”: methodology and direct (Cardiopulmonary Exercise Testing) and indirect tests Paolo Zeppilli, Piergiuseppe Agostoni, Flavio D’Ascenzi, Fabrizio Sollazzo

Cardiorespiratory fitness (CRF) reflects the integrated response of all the body systems involved in physical activity, including the respiratory, cardiovascular, neurological and muscular systems. This response depends on several factors, including the body’s ability to use oxygen, which is why it is also referred to as “maximal aerobic power”. Oxygen uptake (VO2) increases progressively during exercise, both when energy production (ATP) is entirely aerobic and when aerobic and anaerobic metabolism coexist. The parameter used to quantify CRF is maximal oxygen uptake (VO2max), expressed in milliliters of oxygen per unit of time (ml O2/min) or normalized to body weight (ml O2/kg/min), in order to standardize values across individuals with different body size and composition. The importance of CRF in prevention, rehabilitation and exercise prescription lies in the fact that it represents a meaningful health target. Numerous studies have shown a strong inverse association between CRF and both cardiovascular and all-cause mortality: low CRF is a stronger predictor of mortality and morbidity than many traditional risk factors. In addition, CRF is positively associated with habitual physical activity levels and can be improved through regular exercise training. CRF can be assessed either by tests that directly measure (VO2max), or by test that estimate it indirectly1.

Direct measurement of maximal oxygen uptake: Cardiopulmonary Exercise Testing Cardiopulmonary Exercise Testing (CPET) is the gold standard for the assessment of CRF, as it is specifically designed to analyze the gas (oxygen and carbon dioxide) exchange in response to a known exercise workload and, consequently, to measure (VO2max). During the test, ECG, HR, blood pressure (BP), inspired and exhaled gases, ventilatory volumes and airflow are collected simultaneously. CPET therefore offers a comprehensive analysis of cardiovascular, respiratory and metabolic responses to exercise. In addition to providing information, it can also provide valuable insight into the pathophysiological mechanisms underlying exercise limitations or exertional symptoms. For this reason, CPET is used both in athletes and in a wide range of clinical settings, including diagnosis, prognostic stratification, therapeutic monitoring, rehabilitation programs and exercise prescription in numerous diseases2,3. Strictly speaking, VO2max should only be defined when a plateau of VO2 is demonstrated despite a continuous increase in external workload. This plateau is generally defined as an increase of less than 2 ml/kg/min (or <50% of the expected increase) over the last 30 seconds. Because this criterion is often difficult to demonstrate in clinical practice, the highest VO2 achieved during the test is more commonly reported as VO2peak. In addition, CRF resulting from CPET is influenced by both methodological factors, that is, how the test was performed, and physiological factors, also called

determinants, which are instead intrinsic of the individual. The main methodological factors include the following: 1) Correct calibration of the flowmeter and gas analyser4. 2) Type of ergometer: treadmill testing involves a larger active muscle mass and generally yields higher VO2 values, typically by about 10-15%)5. However, cycle ergometer is often preferred because it allows better ECG and BP monitoring, reduces the risk of falls and enables more direct interpretation of the relationship between VO2 and external workload (VO2/ work-rate slope). On the other hand, treadmill testing may be preferable in specific patient groups, such as children, older adults, and patients with pacemakers, and the choice remains individual, based on the subject, the habit of the center where the test is performed and the type of physical activity for which exercise is being prescribed. 3) Type of protocol: a distinction should first be made between constant load and incremental protocols. Constant load protocols maintain a fixed workload for the entire duration of the test: they are mainly used in patients with low functional capacity and they do not directly measure CRF. Incremental protocols progressively increase workload in order to achieve VO2peak: these may be step protocols, in which workload increases are applied at intervals longer than one minute, or ramp protocols, in which very small workload increments are applied at short time intervals6. Ramp protocols are the most commonly used in CPET because they allow better modulation and customization of workload, and a more accurate relationship between workload and gas exchange. They also provide more precise estimates of VO2peak and derived variables such as VE/VCO2 slope and the VO2/work rate slope. Appropriate workload increments also help achieve the ideal test duration (between 8 and 12 minutes): in healthy individuals, workload increments per minute may be selected using appropriate equations7, whereas in patients and athletes this choice depends to a large extent on operator experience. 4) Procedural validity of the test: this includes, in particular, checking for gas leakage due to incorrect positioning of the face mask (“mask leakage”), which may lead to underestimation of VO2. 5) Adequate filtering of breath by breath data, which are inherently subject to biological variability. Taken together, these considerations show that performing CPET requires technical expertise, familiarity with equipment and procedures, and the ability to recognize and manage potential problems in order to ensure high-quality results. As for the physiological factors, or determining factors, the most relevant are listed below: a. individual factors: gender, age, genetics, training status, height, body weight; b. central hemodynamic factors: HR and stroke volume (SV);

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c. peripheral hemodynamic factors: oxyhemoglobin concentration and affinity, blood flow redistribution capacity, skeletal muscle mass and efficiency, which are influenced by blood pH, partial pressure of oxygen and temperature; d. pulmonary factors: ventilatory response and breathing pattern, bronchial reactivity, alveolar-capillar oxygen diffusion, ventilation/perfusion matching; e. neuro-hormonal factors: autonomic nervous system response to exercise, β-adrenergic sensitivity, balance between vasoconstrictor and vasodilator factors. Optimal integration of all these factors, as in endurance athletes, is associated with an excellent CRF. Conversely, impairment in one or more of these determinants, may reduce CRF and should therefore be quantified objectively. One possible approach is to use Weber8 functional classes, which are based on weight-normalized VO2peak. However, these classes were developed in patients with chronic heart failure and do not even take age or sex into account. Alternatively, CPET results can be compared with reference values, although this approach is as useful as it is potentially problematic. In fact, the choice of an inappropriate reference for the population under study may compromise the ability to identify and grade the reduction in exercise tolerance. Ideally, reference values should be derived from pop-

ulations from the same geographical area, with similar age and of the same sex, and evaluated using comparable ergometers, exercise protocols, gas sampling methods and gas exchange analysis procedures in studies of high methodological quality9. In this respect, the classic reference values proposed by Hansen and Wasserman, despite their historical value, do not fully meet these requirements10. For this reason, the use of more effective prediction equations is encouraged (e.g. those derived from the SHIP11, FRIEND12, LowLands Fitness Registry13 for adults, Griffith et al.14, Burstein et al.15 for children). Once appropriate reference values are available, exercise tolerance can be graded using cutoffs that classify any impairment in exercise tolerance as mild, moderate, or severe16. Beyond the evaluation of the CRF alone, CPET also provides several additional parameters of major value for the clinical characterization of the patient and, above all, for a more individualized prescription of physical exercise. Interpretation of these parameters is greatly facilitated by graphic display formats that summarize the main relationships among the parameters of interest. The most widely used is the Wasserman’s 9-panel plot, which will be referred to in the following sections, particularly in the version modified in the fifth edition of the book.

Figure 1. The graphical representation of the analysis of gas exchange using the Wasserman’s 9 panels plot.

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First and second ventilatory threshold Identification of the two ventilatory thresholds during CPET (VT1 and VT2) allows the definition of the exercise intensity domains. Because several different classifications have been proposed17, an intuitive and physiologically grounded framework is presented here: a. Exercise below VT1 is classified as mild intensity. This is substantially aerobic exercise, characterized by a linear increase in VO2, VCO2 and ventilation, with negligible lactates accumulation. VT1 represents the point at which this linearity begins to change, reflecting the progressive accumulation of hydrogen ions [H+] associated to the increasing contribution of anaerobic metabolism (and, consequently, of lactates). The rise in [H+] is buffered by the bicarbonate system, which produces additional CO2, that must be eliminated by an increase of ventilation. b. Exercise performed above VT1 but below VT2 is classified as moderate intensity. This exercise domain is characterized by the presence of metabolic acidosis buffered by bicarbonates. VT2 marks the point at which this compensatory mechanism is no longer sufficient: the production of [H+] will no longer be able to be fully buffered by [HCOs -], this leads to unbuffered acidosis, which leads to a disproportionate increase in ventilation compared to the CO2 output. More precisely, the transition from moderate to high intensity domain corresponds to the upper limit of prolonged heavy aerobic work, more appropriately described by concepts such as Critical Power (CP) or maximal lactate stationary work (MLSS). Although these three parameters (VT2, CP, MLSS) are not entirely superimposable from a physiological standpoint18, they may be used as broadly interchangeable reference points for exercise prescription19. c. Exercise performed above VT2 is classified as high intensity. Its essential feature is the inability to achieve a metabolic steady

Blood lactate (mmol/L)

First ventilatory threshold (VT1)

Light

<2 mmol/l

Second ventilatory threshold (VT2)

Moderate

6 4

state due to marked [H+] accumulation and disproportionate hyperventilation, ultimately driving the individual toward VO2peak and leading to exhaustion in a short period of time. VT1 may be identified using three main criteria, derived from the Wassermann 9-panel plot7: a. A change in the slope of the relationship between VCO2 (y-axis) and VO2 (x-axis), the so-called “V-slope” method, shown in panel 3. A “modified V-slope” approach could also be used, based on the assumption that the slope of the curve is <1 before VT1 and >1 after VT1. In practical terms, a line with slope 1 is drawn on the graph, and the tangency point is identified as VT1, moving from right to left. b. Lowest point (nadir) of the VE/VO2 curve in panel 4, which displays VE/VCO2 and VE/VO2 over time and describes the point of greatest ventilatory efficiency for oxygen. c. Lowest point (nadir) of the PETO2 curve in panel 7, describing the PETO2 and PETCO2 over time, and identifies the point of lowest end-tidal oxygen pressure corresponding to maximal ventilatory efficiency for oxygen. VT2 is likewise identified by the simultaneous presence of three main criteria on the Wassermann 9-panel plot: a. A clear increase in the slope of ventilation in panel 5, which relates ventilation to workload. b. Lowest point (nadir) of the VE/VCO2 curve in panel 4, which highlights the point of maximal ventilatory efficiency for carbon dioxide, beyond which the increase in ventilation becomes excessive in respect to CO2 elimination. c. Highest point (zenit) of the PETCO2 curve in panel 7, followed by its decline, which reflects the onset of excessive ventilatory compensation. Identification of ventilatory thresholds can be complex in individuals who are unaccustomed to intense exercise and in specific clinical settings, such as advanced age, heart failure, chronic obstructive pulmonary disease, erratic and oscillatory breathing. By

2-3 mmol/l

3-4 mmol/l

Hight

>5 mmol/l

Exercise intensity Figure 2. The intensity domains of exercise – modified by Faggian S, Centanini A, Quinto G., et al. The many faces of exercise intensity17.

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contrast, the prescription of physical exercise based on fixed percentages of VO2peak or peak HR requires truly maximal testing, which is not always achievable, and may lead to misclassification of intensity domains. This, in turn, may make the prescribed training ineffective or, in some cases, less safe, as may occur for example in patients receiving beta-blocker therapy20,21.

VO2/workload relationship a. From panel 1, which displays VO2, VCO2 and workload over time, it is possible to derive the relationship between VO2 and workload. This relationship is physiologically linear, with a normal slope of approximately 9-11 ml/min/watt and is closely related to cardiovascular performance. Three main abnormalities may be observed: Position: in individuals with obesity this relationship is shifted upwards due to the increased metabolic cost of exercise (increased masses lead to a greater VO2 at a given workload). b. Slope (VO2/work-rate slope): this may be reduced when oxygen transportation is impaired, as occurs in some cardiovascular disease (heart failure, pulmonary hypertension). c. Linearity: a clear change in the slope of the curve (the socalled “double slope” pattern) is typically of cardiac origin and suggests exercise-induced myocardial ischemia or mitral regurgitation.

Oxygen pulse Oxygen pulse is defined as the ratio of VO2 to HR and therefore reflects the amount of oxygen used per heartbeat. According to Fick’s principle, it is directly proportional to the product of SV and arteriovenous oxygen difference. Considering that, under normal conditions, the arteriovenous difference of O2 increases progressively during exercise, oxygen pulse may be considered an indirect index of SV during exercise (this is not true in the case of exercise-induced desaturation). Physiologically, this curve shows an approximately hyperbolic pattern, with an increase up to high workloads, followed by a gradual flattening. The main abnormalities include: a. reduced slope and reduced peak value: suggestive of impaired oxygen transport and utilization (heart disease, myopathies, peripheral arterial disease and anaemia); b. steeper slope: suggestive of chronotropic incompetence, typically in patients receiving β-blockers and/or with heart failure; c. abnormal curve pattern, including an early and persistent plateau (flattening of the curve before 65% of the exercise duration) or an actual decline (reversal of the upward slope)22, which is a typical sign of stress-induced contractile dysfunction, typical of exercise-induced myocardial ischemia, systolic or diastolic disfunction and significant mitral and/or tricuspid valve regurgitation23. When interpreting the oxygen pulse, possible confounding and limiting factors include anaemia, hypoxia, marked physical deconditioning, all of which may alter the normal arteriovenous oxygen difference.

VE/VCO2 slope This relationship, illustrated in panel 6, is mainly determined by the dead space/tidal volume ratio (VD/VT) and arterial CO2 tension (PaCO2). An increase in the VE/VCO2 slope therefore reflects either an increase in VD/VT or a reduction in PaCO2 and provides useful information on both ventilation/perfusion matching and gas-exchange efficiency. Because the relationship between ven-

tilation and CO2 output loses linearity above VT2, the VE/VCO2 slope should ideally be calculated excluding the portion of exercise above VT2, as well as the very early phase of the test, which may be affected by hyperventilation. Although a mild increase in this slope may sometimes be nonspecific or related to primary hyperventilation, elevated values are also found in a range of pulmonary and cardiovascular disorders, including heart failure, hypertrophic cardiomyopathy, primary and secondary pulmonary hypertension, chronic obstructive pulmonary disease, and interstitial lung disease. In these conditions, VE/VCO2 slope often correlates with both disease severity and prognosis. In addition, VE/ VCO2 values tend to increase physiologically with age. Interpretation of the VE/VCO2 slope should also include calculation of the y-axis intercept, that is, the theoretical ventilation at VCO2 = 0. This value is usually between 2 and 4 L/min. Higher values suggest increased fixed anatomical dead space, whereas lower values may indicate the development of dead space during exercise.

Respiratory Exchange Ratio (RER) The RER represents the ratio of VCO2 to VO2 and provides information on the predominant metabolic substrate being used: at rest normal RER values are typically around 0.7-0.8, since metabolism is almost entirely based on fatty acid oxidation. At high exercise intensities, carbohydrates become the main energy substrate, and RER rises toward 1.0 and then exceeds it. RER therefore helps identify possible anticipatory hyperventilation, assess whether the test was adequately performed and truly maximal, and estimate the extent of metabolic stress reached during exercise. An RER >1.10 is generally considered consistent with maximal or near-maximal effort.

Ventilatory parameters The ventilatory assessment performed during CPET includes analysis of the relationship between ventilation and time (panel 5), allowing evaluation of the ratio between peak ventilation (peak VE) and maximal voluntary ventilation measured at rest (MVV). A VE/MVV ratio >0.85-0.9 indicates marked use of ventilatory reserve during exercise and may therefore suggest a ventilatory limitation, particularly in patients complaining of exertional dyspnoea. Reduced values may also be observed in patients with obesity, because of both the increased metabolic cost of exercise and the restrictive effect of increased abdominal pressure on ventilatory volumes. By contrast, in highly trained endurance athletes, an isolated reduction in ventilatory reserve may be a physiological finding. The relationship between tidal volume and ventilation is also evaluated in panel 9. This plot reflects the interaction between tidal volume and respiratory rate during exercise, since respiratory rate can be derived as VE divided by tidal volume. Under normal conditions, the curve initially shows a steep increase in tidal volume; later, further increases in ventilation are driven mainly by an increase in respiratory rate, giving the plot an “inverted-L” appearance. In obstructive ventilatory disorders, the main limitation is related to respiratory rate, and the curve tends to shift to the left. In restrictive ventilatory disorders, the main limitation is reduced tidal volume, and the curve shifts downward, often with a compensatory increase in respiratory rate.

Circulatory Power (CP) Cardiac power, defined as the product of cardiac output (CO) and mean arterial blood pressure, is a fundamental index of

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systolic cardiac performance, but it can only be measured invasively and not during exercise testing. Circulatory Power (CP) is a non-invasive surrogate for cardiac power derived from CPET and is calculated as the product of VO2 and systolic blood pressure. It provides useful information on both disease severity and the prognosis in patients with heart failure. More specific information on cardiac output may also be obtained using modern non-invasive techniques, such as thoracic bioimpedance or inert-gas rebreathing methods. CPET can be complemented by additional measurements such as arterial blood gas analysis, flow/volume loops and Near Infrared Spectroscopy (NIRS)24.

Indirect methods of CRF assessment There are two main reasons why direct measurement of CRF may not be feasible: either the necessary equipment or time required for individual instrumental assessment of VO2peak is not available, or patient safety considerations make maximal testing inadvisable. To address these limitations, several tests have been developed to provide an indirect estimate of CRF. In the first situation, maximal exercise tests are performed and predictive equations are applied, usually incorporating variables such as age, sex, and anthropometric characteristics, together with easily obtainable indicators such as power output during cycle ergometer testing or treadmill speed and grade. In addition, several field tests have been developed to estimate CRF simply from distance covered over a defined time or distance, such as the Cooper test, the 1.5-mile test, or the Yo-Yo test. When maximal testing cannot be performed, HR response is commonly used as a surrogate marker. Examples include the heart rate achieved during a constant-load test of predefined duration, such as the Astrand cycle ergometer test; the comparison of heart-rate responses at different submaximal workloads, as in the Maritz test; or the assessment of heart-rate recovery after a step test of standardized height, as in the YMCA step test. One of the simplest submaximal tests for which predictive equations are available is the 6-minute walk test. In this test, heart rate, blood pressure, and above all the distance covered provide useful information for estimating CRF25. Finally, it should be noted that non-exercise algorithms have also been developed to estimate CRF without any physical testing. Their use should, however, be restricted to clinical settings in which it is genuinely not possible to subject the patient to physical exertion26.

References 1.

Ross R, Blair SN, Arena R, et al. Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement from the American Heart Association. Circulation 2016; 134: e653-99. Anselmi F, Cavigli L, Pagliaro A, et al. Cardiopulmonary exercise testing: an essential tool for a tailored exercise prescription in patients with cardiac disease. G Ital Cardiol (Rome) 2021; 22: 716-26.

D’Ascenzi F, Cavigli L, Pagliaro A, et al. Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. Br J Sports Med 2022; 56: 1180-7. 4. Balady GJ, Arena R, Sietsema K, et al. Clinician’s Guide to Cardiopulmonary Exercise Testing in Adults: A Scientific Statement from the American Heart Association. Circulation 2010; 122: 191-225. 5. Mezzani A. Cardiopulmonary Exercise Testing: Basics of Methodology and Measurements. Ann Am Thorac Soc 2017; 14 (Suppl 1): S3-11. 6. Myers J, Bellin D. Ramp exercise protocols for clinical and cardiopulmonary exercise testing. Sports Med 2000; 30: 23-9. 7. Sietsema K, Sue D, Stringer W, et al. Wasserman & Whipp’s Principles of Exercise Testing and Interpretation. 6th ed. Philadelphia: Wolters Kluwer; 2021. 8. Weber KT, Janicki JS. Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am J Cardiol 1985; 55: 22A-31A. 9. Takken T, Mylius CF, Paap D, et al. Reference values for cardiopulmonary exercise testing in healthy subjects: an updated systematic review. Expert Rev Cardiovasc Ther 2019; 17: 413-26. 10. Hansen JE, Sue DY, Wasserman K. Predicted values for clinical exercise testing. Am Rev Respir Dis 1984; 129: S49-55. 11. Koch B, Schäper C, Ittermann T, et al. Reference values for cardiopulmonary exercise testing in healthy volunteers: the SHIP study. Eur Respir J 2009; 33: 389-97. 12. Kaminsky LA, Arena R, Myers J. Reference Standards for Cardiorespiratory Fitness Measured with Cardiopulmonary Exercise Testing: Data from the Fitness Registry and the Importance of Exercise National Database. Mayo Clin Proc 2015; 90: 1515-23. 13. Mylius CF, Krijnen WP, van der Schans CP, et al. Peak oxygen uptake reference values for cycle ergometry for the healthy Dutch population: data from the LowLands Fitness Registry. ERJ Open Res 2019; 5: 00056-2019. 14. Griffith GJ, Wang AP, Liem RI, et al. Reference Values for Cardiorespiratory Fitness in Patients Aged 6 to 18 Years. J Pediatr 2024; 264: 113770. 15. Burstein DS, McBride MG, Min J, et al. Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents. J Pediatr 2021; 229: 61-69.e5. 16. Guazzi M, Arena R, Halle M, et al. 2016 Focused Update: Clinical Recommendations for Cardiopulmonary Exercise Testing Data Assessment in Specific Patient Populations. Circulation 2016; 133: e694-711. 17. Faggian S, Centanini A, Quinto G, et al. The many faces of exercise intensity: a call to agree on definitions and provide standardized prescriptions. Eur J Prev Cardiol 2024; 31: e89-91. 18. Galán-Rioja MÁ, González-Mohíno F, Poole DC, et al. Relative Proximity of Critical Power and Metabolic/Ventilatory Thresholds: Systematic Review and Meta-Analysis. Sports Med 2020; 50: 1771-83. 19. Keir DA, Pogliaghi S, Murias JM. The Respiratory Compensation Point and the Deoxygenation Break Point Are Valid Surrogates for Critical Power and Maximum Lactate Steady State. Med Sci Sports Exerc 2018; 50: 2375-8. 20. Hansen D, Abreu A, Ambrosetti M, et al. Exercise intensity assessment and prescription in cardiovascular rehabilitation and beyond: why and how: a position statement from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2022; 29: 230-45. 21. Anselmi F, Cavigli L, Pagliaro A, et al. The importance of ventilatory thresholds to define aerobic exercise intensity in cardiac patients and healthy subjects. Scand J Med Sci Sports 2021; 31: 1796-808. 22. Mapelli M, Romani S, Magrì D, et al. Exercise oxygen pulse kinetics in patients with hypertrophic cardiomyopathy. Heart 2022; 108: 1629-36. 23. Adachi H. Cardiopulmonary Exercise Test. Int Heart J 2017; 58: 654-65. 24. Mattavelli I, Vignati C, Farina S, et al. Beyond VO2: the complex cardiopulmonary exercise test. Eur J Prev Cardiol 2023; 30(Suppl 2): ii34-9. 25. Liguori G, Feito Y, Fountaine C, et al. American College of Sports Medicine’s Guidelines for Exercise Testing and Prescription. 11th ed. Philadelphia: Wolters Kluwer; 2021. 26. Artero EG, Jackson AS, Sui X, et al. Longitudinal algorithms to estimate cardiorespiratory fitness: associations with nonfatal cardiovascular disease and disease-specific mortality. J Am Coll Cardiol 2014; 63: 2289-96.

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| CHAPTER 2.3 |

Body composition and neuromuscular functional assessment: methodology and direct and indirect tests Simone Porcelli, Giovanni Bianchi, Marco Bonifazi, Erica Brugin, Matteo Cortesi, Giulia Foccardi, Ferdinando Iellamo, Antonio Squillante

Body composition and health The human body, although considered a relatively stable system, is actually highly dynamic and responds to numerous external (diet, climate, stress) and internal stimuli (metabolic changes, hormonal, pathologies)1-4. Assessing body composition plays a crucial role in exercise prescription, especially in clinical settings such as obesity and associated diseases, including cardiovascular disease and hypertension. However, body fat does not uniformly affect cardio-metabolic risk, as adipose tissue distribution varies the incidence of cardiovascular events1-3. As a result, an accurate analysis of nutritional status requires the evaluation of different components of body mass4. The main methods used to measure fat mass include: • Anthropometric measurements: Waist circumference and waist to hip ratio (WHR) are tools used to assess fat distribution and identify individuals with visceral fat gain2. A high WHR value is associated with an increased risk of hypertension, type 2 diabetes mellitus, dyslipidemia and CVD. Waistto-height ratio (WHR >0.5) is also a significant predictor of CVD and poor prognosis in heart failure. • Measurement of skin folds: this technique involves measuring the thickness of subcutaneous adipose tissue at specific sites (triceps, subscapularis, abdominal, iliac crest, thigh) using a skin fold caliper5, 6. The percentage of fat mass is estimated using specific formulas, such as the Jackson-Pollock equation. However, the accuracy of this method depends on the experience of the operator and the type of equipment used. In addition, in subjects with severe obesity, the measurement may be less accurate. • Bioimpedance analysis (BIA)6,7: it uses the passage of an alternating electric current to estimate the percentage of fat mass. It is a valid tool for monitoring body composition and hydration status. However, the reliability of the results can be influenced by the subject’s hydration.

• Dual Energy X-ray Absorptiometry (DEXA)6,7: Accurately quantifies fat mass and lean body mass and is the standard clinical tool for assessing osteoporosis. Despite its high accuracy, it has high costs and limited availability, as well as the use of ionizing radiation. • Musculoskeletal ultrasound and nuclear magnetic resonance imaging (MRI)5-7: ultrasound is useful for assessing the thickness of subcutaneous adipose tissue and skeletal muscle, while MRI is indicated for monitoring changes in muscle volume in pathological conditions. Both techniques are highly accurate, but MRI is more expensive and less accessible. None of these techniques can assess all body components in a single measurement4-7. For example, visceral fat and ectopic adipose tissue (epicardic, perivascular) have a greater impact on cardiovascular risk than subcutaneous fat. However, while advanced techniques such as DEXA are more precise, simpler and more accessible methods, such as BIA and skinfold measurement, remain more viable in daily clinical practice6.

Neuromuscular function and fatigue For a comprehensive assessment of skeletal muscle, in addition to structural characteristics, it is essential to consider its function, defined as “neuromuscular function”8,9. Measurements of muscle strength and physical performance are rarely integrated into clinical practice, despite the fact that reduced strength is a predictor of negative outcomes such as dependency on caregiving, falls, and fractures9. For this reason, the prescription of strength training in cardiology should be based on an appropriate assessment of individual strength. The single maximum repetition (1RM) test is considered the “gold standard” for assessing muscle strength10. It consists of identifying the maximum weight that a subject can lift for a single repetition with correct technique11. It is a safe and well-tolerated method in cardiac rehabilitation patients but requires specific equipment and expert supervision.

Table 1. Cut-off values for the diagnosis of sarcopenia defined by the European Working Group on Sarcopenia in Older People (EWGSOP2) (Cruz-Jentoft et al, 201915). Testing Handgrip test

Men’s cut-off

Women’s cut-off

<27 kg

<16 kg

Chair raise test

>15 s for five lifts

Timed-get-up-and-go

>20 s

Walking speed 4 m

<0,8 m/s

400 m walk

>6 minutes

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In cases where the 1RM test is excessively demanding, maximal strength can be estimated using predictive tests based on fewer repetitions (5RM or 3RM)12,13. However, these estimates can be subject to inherent errors when applying general equations at the individual level. A practical alternative is muscle power tests, which measure the time it takes to complete a set number of repetitions or the maximum number of repetitions that can be performed in a defined time10. These tests are easily implemented in most cardiac rehabilitation settings and require minimal equipment. Among the simplest and cheapest tools for assessing muscle strength, the Handgrip test is particularly useful, as it is related to the general muscle strength of the upper and lower limbs. This test is widely used for the diagnosis of sarcopenia and offers advantages in terms of portability and ease of administration14-18. Finally, to ensure safety in strength and power assessments, patients should be instructed to avoid breath retention during strength exercise, understand that muscle tension is a normal sensation and that post-exercise muscle soreness is common in the first few days but tends to progressively reduce19-24.

References 1. 2. 3.

4. 5. 6. 7.

Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: age- and sex-specific prediction formulas. Br J Nutr 1991; 65: 105-14. Huxley R, Mendis S, Zheleznyakov E, et al. Body mass index, waist circumference and waist-to-hip ratio as predictors of cardiovascular risk: a review of the literature. Eur J Clin Nutr 2010; 64: 16-22. Heitmann BL, Erikson H, Ellsinger BM, et al. Mortality associated with body fat, fat-free mass and body mass index among 60-year-old Swedish men: a 22-year follow-up. The Study of Men Born in 1913. Int J Obes 2000; 24: 33-37. McArdle WD, Katch FI, Katch VL. Exercise Physiology: Nutrition, Energy, and Human Performance. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2015. Machann J, Horstmann A, Born M, et al. Diagnostic imaging in obesity. Best Pract Res Clin Endocrinol Metab 2013; 27: 261-77. Wang H, Chen YE, Eitzman DT. Imaging body fat: techniques and cardiometabolic implications. Arterioscler Thromb Vasc Biol 2014; 34: 2217-23. Heyward VH. Evaluation of body composition: current issues. Sports Med 1996; 22: 146-56.

Gandevia SC, Enoka RM, McComas AJ, et al. Neurobiology of muscle fatigue: advances and issues. Adv Exp Med Biol 1995; 384: 515-25. 9. Vøllestad NK. Measurement of human muscle fatigue. J Neurosci Methods 1997; 74: 219-27. 10. Heyward VH. Advanced Fitness Assessment and Exercise Prescription. Champaign, IL: Human Kinetics; 1992. 11. Kraemer WJ, Fry AC. Strength testing: development and evaluation of methodology. In: Maud PJ, Foster C, editors. Physiological Assessment of Human Fitness. Champaign, IL: Human Kinetics; 1995. p. 115-38. 12. Brzycki M. Strength Testing—Predicting a One-Rep Max from Reps-to-Fatigue. J Phys Educ Recreat Dance 1993; 64: 88-90. 13. DiStasio TJ. Validation of the Brzycki and Epley Equations for the 1 Repetition Maximum Back Squat Test in Division I College Football Players. Master’s Thesis; 2014. 14. Lauretani F, Russo CR, Bandinelli S, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 2003; 95: 1851-60. 15. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019; 48: 16-31. 16. Hardy R, Cooper R, Shah I, et al. Is chair rise performance a useful measure of leg power? Aging Clin Exp Res 2010; 22: 412-18. 17. Liebermann DG, Katz L. On the assessment of lower-limb muscular power capability. Isokinet Exerc Sci 2003; 11: 87-94. 18. Caserotti P, Aagaard P, Puggaard L. Changes in power and force generation during coupled eccentric-concentric versus concentric muscle contraction with training and aging. Eur J Appl Physiol 2008; 103: 151-61. 19. Beaudart C, Rolland Y, Cruz-Jentoft AJ, et al. Assessment of muscle function and physical performance in daily clinical practice: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Calcif Tissue Int 2019; 105: 1-14. 20. Dodds RM, Syddall HE, Cooper R, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One 2014; 9: e113637. 21. Beaudart C, McCloskey E, Bruyère O, et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr 2016; 16: 170. 22. Bruyère O, Beaudart C, Reginster JY, et al. Assessment of muscle mass, muscle strength and physical performance in clinical practice: an international survey. Eur Geriatr Med 2016; 7: 243-46. 23. Hansen D, Abreu A, Ambrosetti M, et al. Exercise intensity assessment and prescription in cardiovascular rehabilitation and beyond: why and how: a position statement from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2022; 29: 230-45. 24. Verdicchio C, Freene N, Hollings M, et al. A clinical guide for assessment and prescription of exercise and physical activity in cardiac rehabilitation: a CSANZ position statement. Heart Lung Circ 2023; 32: 1035-48.

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| CHAPTER 2.4 |

General principles and training programs Marco Bonifazi, Matteo Cortesi, Antonio Gianfelici, Ferdinando Iellamo, Simone Porcelli, Maria Rosaria Squeo

Fundamentals principles of training: introduction The theory of sports training emerged in the middle of the last century. At the time, scientific understanding of the effects of physical preparation on athletes was limited, and theoretical models were based on scarce objective evidence. Nevertheless, the foundational principles of training theory have persisted and have progressively been refined in light of accumulating scientific knowledge. These principles represent an essential framework both for elite athletes and for individuals seeking to structure physical activity appropriately for health promotion, prevention, and overall well-being. General principles of training theory They are based on the concept of “periodization”. Exercise methodologists use this criterion to define the different phases of training so that goals are clearly defined and distinct in each phase. As a consequence of this approach, the general principles of training theory are1: 1) The interaction between training load and recovery. The principle of overload is a fundamental pillar of training. It provides that, in order to improve physical condition and performance, the body must be exposed to progressively increasing workloads. This continuous stimulus leads to physiological adaptation, which results in improvements in strength, endurance, speed, and other physical abilities. It is essential to properly balance overload with adequate recovery periods to avoid the risk of injury and ensure maximum benefit from training. Adequate recovery (i.e. rest, active or passive), therefore, is an integral part of the training process. Without recovery, the adaptations stimulated by training would not occur, compromising the improvement of performance or the effects on health.

2) The cyclical structure of training. It is linked to the need to alternate training load and active recovery by organizing specific stimuli during defined periods of time. For exercise therapy, the cyclical structure should be considered according to the person’s work and leisure needs. 3) The hierarchical structure of training cycles. There are training cycles of different durations. A distinction is usually made between macrocycles (lasting a few months), mesocycles (lasting a few weeks) and microcycles (lasting a few days). The objectives of the various are linked to a medium-long term objective, so the individual exercise session should be planned last, after defining the overall plan.

Fundamental criteria for exercise prescription The fundamental parameters of the prescription of exercise sessions are usually described through the acronym FITT (Frequency, Intensity, Time and Type), later modified to FITT-VP to also include parameters derived from the former such as volume (V) or progression (P, which reflects how FITT parameters are modulated during training) as reported in the Table 12,3. Of primary importance is the type of exercise, of which the intensity and duration, and therefore the volume, must be clearly defined in relation to the objectives and the subject’s ability to work. The frequency of training (understood as the number of training sessions per unit of time, generally weekly) – on which the correct alternation between load and recovery depends – must be evaluated in relation to the needs of each person.

Aerobic exercises The various forms of human locomotion are the main way to do aerobic activity (walking, running, cycling, swimming, rowing,

Table 1. Exercise prescription according acronym FITT-VP.

Frequency

Number of training sessions per week

Intensity

Aerobic training • Objective parameters related to metabolic and cardiorespiratory effort: ventilatory thresholds, blood lactate, % HR max, % HR reserve, % VO2peak • Subjective parameters: Rate of perceived exertion (RPE), feeling of “shortness of breath” • Strength training • Objective parameters relating to the amount of load to be lifted: % of 1RM Subjective parameters: RPE

Time

Duration of the single session or weekly total (minutes)

Type

Aerobic: walking, running, cycling, swimming, cross-country skiing, etc. Strength: overloaded or bodyweight Flexibility Balance

Volume

Total amount of exercise per session (intensity x duration) or weekly (intensity x duration x frequency) The volume of aerobic exercises is also indicated by the energy expended for this purpose in kcal or kJ per week or in METs/hour/week The volume of strength exercises is indicated by the number of repetitions and sets for each exercise or by the total amount of load lifted (in kg)

Progression

Modulation of FITT parameters over time

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etc.). For training, the intensity of aerobic exercise can be divided into zones that have different impacts on metabolism and subjective perceptions. In literature, the number of zones usually varies from three to six. For aerobic exercise, public health exercise guidelines typically refer to two or three intensity levels: light (not always), moderate, and vigorous (or high), while duration is usually defined in minutes per week of exercise (Time, table 2)4,5. In the scientific literature, the benefits are usually correlated with the energy expended with exercise (Volume, table 2)2. What does aerobic mean? The term aerobic defines a condition in which the total energy for muscle metabolism is provided prevalently from the aerobic system. Under such conditions, during prolonged exercise (several minutes) at a constant intensity, lactate in the blood remains stable over time. The highest intensity at which this condition is met is called the anaerobic threshold. The aerobic threshold, on the other hand, corresponds to the intensity of exercise below which the muscle fibers involved (or most of them) are aerobic and therefore the actual production of lactate is very low6. Measurement of metabolic thresholds as a parameter to define intensity. In the scientific literature, several methods are reported to measure the thresholds with objective parameters using the relationship between exercise intensity and blood lactate or respiratory parameters (ventilation, VO2 and VCO2) during incremental tests7-9. In the first case, blood lactate collects at the end of each of the steps at increasing intensity, programmed to have an adequate duration (at least three minutes), by means of a capillary blood sample. In the second case, “ramp” protocols are usually used for CPET (Cardiopulmonary Exercise Testing) with a continuous increase in the workload (usually represented by the watts required). To avoid underestimating VO2peak, the optimal test should last 8 to 12 minutes. It is modulated through the amount of the increase in watts over time (and therefore the slope of the “ramp”) according to the individual fitness level. Through the study of the variation of respiratory parameters or lactate as a function of the increase in exercise intensity, two thresholds are identified: the first ventilatory threshold (VT1) or lactate (LT1, Lactate Threshold) and the second ventilatory thresh-

Lactate

LT1

LT2

Exercise intensity

old (VT2) or lactate (LT2) as shown in Figure 1. Conventionally, LT1 and LT2 are considered to correspond to a blood lactate concentration of 2 and 4 mmol/l, respectively6. However, the value of lactate at the first and second thresholds is widely variable on an individual basis. Whatever method is applied to determine the thresholds, it is essential to always use the same one to reliably compare the results of the tests over time. Moderate intensity is considered to be around or slightly above that corresponding to the first threshold; on the other hand, the vigorous or high one is placed around or slightly before the second threshold. In the absence of CPET or lactate testing, the intensity can be derived through maximal exercise testing7. In this case, the exercise intensity is derived from the percentage calculation of the max HR or the % of the reserve HR, although this method does not appear to be very precise in determining the correct intensity7. It is essential that the exercise test is truly maximal: a submaximal test, in fact, would not allow the intensity of physical exercise to be adequately defined. For the definition of aerobic exercise intensity using subjective and objective methods, see chapter 2.2 and table 2. Subjective parameters of intensity. For the evaluation of thresholds, in addition to assessing objective parameters, those who need to practice exercise for preventive or therapeutic purposes can be taught to consider subjective references for intensity control (see chapter 2.2). A first parameter is represented by a numerical scale known as the Borg Scale (CR 0-10 or 6-20), which corresponds to the perceived effort during exercise. According to this parameter, moderate intensity is usually 3-4 on the CR-10 Borg scale and 10-11 on the 6-20 scale, while high intensity corresponds to values of 5-6 and 12-13 on the two Borg scales, respectively2,3,9. A second reference that can be used is the so-called talk test, based on the fact that the increase in pulmonary ventilation during exertion interferes with the ability to speak comfortably2,3,9. Moderate intensity is when the person can speak quite easily during exercise despite the increased demand for ventilation making the breathing slightly labored. Vigorous or high activity, on the other hand, corresponds to an intensity that makes it very difficult to speak due to the increase

VT1

VT2

Exercise intensity

Figure 1. Schematic representation of the relationship between lactate (left) and pulmonary ventilation (right) and exercise intensity. The values of both parameters tend to increase markedly at the first and second thresholds (modified by Binder et al., 20086).

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Table 2. Classification of exercise intensity based on the test adopted. CPET* (Cardiopulmonary Exercise Testing)

Maximal exercise testing**

Corresponding Lactate level

Corresponding RPE

Light

HR < of HR at VT1 % VO2peak < 40

%HR max < 55 %HR Reserve < 40

< 2 mmol/l

RPE (CR-10): 1-2 RPE (Borg 6-20): ≤ 11

Moderate

VT1 < HR < VT2 % VO2peak: 40-70

%HR max: 55-75 %HR Reserve: 40-70

2-4 mmol/l

RPE (CR-10): 3-4 RPE (Borg 6-20): 12-13

High

HR > of HR at VT2 % VO2peak > 70

%HR max > 75 %HR Reserve > 70

> 4 mmol/l

RPE (CR-10): ≥ 5 RPE (Borg 6-20): ≥ 14

Intensity

* The method using HR identification in relation to ventilatory thresholds (VT1 and VT2) is preferable to % VO2peak for determining intensity ** %HR max is not applicable if the patient is on β-blockers therapy.

in the frequency and depth of breathing (the so-called “heavy breathing”). Both parameters, RPE and talk test, are interesting to use for prescribing and self-monitoring the intensity of the exercise once the practitioner has become familiar with the evaluation methods. Numerous evidences support the use of subjective parameters (mainly the RPE scale) for the prescription of exercise for preventive purposes2,3,9. It is believed, in fact, that subjective measures of exercise intensity are less influenced by alterations induced by medical therapy (e.g. β-blockers); moreover, they do not require periodic recalibration, as a result of improving the level of fitness as the training progresses. Finally, objective measures of exercise intensity have limited applicability for laboratory without access to ad hoc stress testing facilities. High-intensity interval training. This mode of aerobic training, defined in scientific literature by the acronym HIIT (High Intensity Interval Training), is widely practiced in many variations for the training of athletes’ aerobic power. In the context of exercise for prevention, HIIT is mainly described as aerobic training in which a few minutes of vigorous-high intensity work alternate with a few minutes at a mild-moderate intensity several times. In the structure of HIIT, the multiplicity of parameters that can be combined allows for numerous protocols that can be adapted to specific purposes or needs. It is usually offered after an introductory period of continuous training mainly at moderate intensity. HIIT is described as safe even for patients in cardiac rehabilitation, more motivating and able to guarantee greater increases in VO2peak in the short term (4 weeks) compared to continuous training at moderate intensity. However, in the long term (12 months) no higher effects are reported of HIIT compared to other forms of training. In addition, factors such as its sustainability over time, especially in the most fragile patient populations, require consideration10. Knowing the energy cost of locomotion is useful for prescribing aerobic exercise. Scientific studies have also been aimed at identifying whether there are minimum parameters of volume and/or intensity of exercise to be exceeded to obtain the expected benefits (see Table 3). The most widely measure used for this purpose is the amount of energy expended in a certain period of time (for example, kcal or kJ per week) for physical activity. In this case, estimating the energy cost is crucial to understand if the amount of exercise is suitable for a certain purpose. The energy cost is the amount of energy that people need to cover a certain distance. The energy cost is expressed in kcal or in kJ consumed for each km covered in relation to body mass in kg. The two units of measurement are interchangeable: one kcal corresponds to about 4.2 kJ. In the main forms of locomotion, the energy cost

is as follows14: • Walking. The net energy cost (i.e. beyond the basal metabolic rate) of walking on level ground for a healthy and normal-weight adult is about 0.5 kcal per kg of body mass per km covered (about 2 kJ/kg/km). A 70 kg person walking 4 km (just one hour) consumes about 140 kcal. It is minimal at cruising speed (about 4.5 km/h) and increases by 20-30% at lower and higher speeds. In addition, it doubles uphill with a gradient of 6%, while it halves in a descent of 10%. On sand, the energy cost is almost double that on firm surface due to the lower recovery of elastic energy. It also increases with age (by about 20% at age 70). • Run. The energy cost of running in trained people is about 0.9 kcal per kg of body mass for each km covered (about 3.6 kJ/ kg/km). A 70 kg person running 10 km consumes about 630 kcal. However, there are individual differences: good marathon runners consume about 10-20% less than untrained runners. Even in running, the energy cost is influenced by the terrain: it increases by about 20% on grass and about 50% on sand, on which the recovery of elastic energy is lower. Uphill on a 5% gradient, it increases by about 40%. In addition, it is important to remember that the cost of energy increases, in an extremely variable way, in the presence of pathologies that alter the coordination and technique of locomotion and with it its efficiency. For running, the aerodynamic cost is practically negligible below 20 km/h and this means that the energy cost is substantially independent of the speed within that limit. In cycling,

Table 3. Minimum dose of exercise for prevention. In a good number of cases, the recommended aerobic activity will consist of walking (for most sedentary people, especially if they are overweight and not young) and running (for those who are able to do so). Since, according to the current scientific literature, a weekly “minimum threshold” of energy expended must be reached in order to obtain the beneficial effects of exercise, being able to estimate the energy commitment in the two most common forms of locomotion allows us to prescribe exercise more accurately.

Minimum weekly exercise dose for prevention • To obtain metabolic effects useful for diabetes, dyslipidemia, obesity: 900-1200 kcal or 10-15 METs/hour (equal to 200-300 minutes of walking per week at moderate intensity)11 • For the reduction of all-cause mortality by more than 20%: 300-400 kcal or 4-5 METs/hour (equal to 70-100 minutes of walking per week at moderate intensity)12,13. However, remember that the beneficial effects are directly proportional to the amount of exercise.

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due to the higher speeds, and in swimming, due to the greater density of water compared to air, the aerodynamic-hydrodynamic cost becomes fundamental and increases exponentially by increasing speed, being also significantly conditioned by technical efficiency. The practical consequence is that there is no simple formula for these activities that allows you to reliably estimate, without measuring metabolic parameters, the amount of energy consumed per distance covered as it can be done for walking and running. METs can define the intensity and volume of exercise. We can also use METs to measure the intensity of exercise: a MET corresponds to VO2 at rest in a sitting position and is approximated to 3.5 ml/kg/min2. For example, an intensity of 6 METs corresponds to a VO2 of 21 ml/kg/min. METs are also sometimes used to quantify the volume of exercise: for example, doing 10 METs/hour/week means that the person has done a volume of exercise in one week corresponding to an amount of energy equal to 10 METs for one hour. For an 80 kg person it means 10 (METs) x 3.5 (ml/kg/min) x 80 (kg) x 60 (minutes), i.e. 168 liters of O2 equal to about 840 kcal per week.

Strength exercises They are used to counteract sarcopenia and reduce the risk of falls. The weight of force (or weight) is the measure of the force of gravity exerted on an object with mass. Muscle strength corresponds to the tension exerted by muscle contraction to counteract or overcome the weight of the object. It depends on the type of contraction itself: • Isometric contraction. During isometric contraction, muscle strength corresponds to the tension developed by the muscle to keep an object stationary by counteracting the force of gravity. • Concentric contraction. During concentric contraction, muscle strength corresponds to the tension developed by the muscle to lift an object. In this case, the tension developed by the muscle is equal to the force of gravity of the object plus the force necessary to accelerate it during movement. • Eccentric contraction. During eccentric contraction, muscle force corresponds to the tension developed by the muscle to slow down the descent of an object. In eccentric contraction, the tension developed by the muscle is equal to the force of gravity of the object minus the force for acceleration during movement (to which gravitational attraction contributes). For strength exercises with overloads, the training volume is determined by the number of repetitions (and sets) for each exercise, while the intensity is determined by the amount of load (in kg) to be lifted. Usually the load is expressed in % of 1RM. How to establish 1RM. 1RM represents the mass (in kg) that, for a given exercise, can be lifted with a concentric contraction only once. It defines, only for that exercise, the maximum muscle strength and is normally used as a reference (100%) to determine the training intensity according to the objectives. Attempting 1RM in some exercises could lead to a risk of injury, especially in people who are not skilled, deconditioned or vulnerable. It may be convenient to identify the number of repetitions (usually less than 10) that can be performed with a sub-maximal load and the value of 1RM can be estimated with the following formula: 1RM = m * (36/(37-n)), where m is the load used and n the number of maximum repetitions15.

For example, if you can perform 5 repetitions of a given exercise with a load of 40 kg (5RM load), the estimated value of 1RM will be 1RM = 40 * [36/(37-5)] = 45 kg Subjective parameters of intensity. The determination of 1 or even 5 RMs may be unfeasible for people who have no experience of training with overloads. For them, the RPE CR-10 scale of the Borg scale can also be applied for the determination of the correct intensity, which must not exceed the value of 5-6 during the execution of the exercise16.

Key points for exercise with overloads for primary and secondary prevention17 n Start with 3-4 basic multi-joint exercises for the major muscles, progressively introducing the mono-joint exercises into the program (and in the training session) after the multi-joint ones. n Alternate exercises for the upper and lower body and for agonist and antagonist muscles. n The stimulus for protein synthesis depends more on the volume of work rather than on the intensity. This is important for therapeutic and preventive exercise for which high intensity (the weight to be lifted) is normally more difficult to sustain than high volume (the number of repetitions). n The intensity should be between 50 and 70% of 1RM, but as mentioned it is difficult to establish 1RM for a beginner or a patient. Alternatively, you could opt to stay within the value of 5-6 on the Borg scale during the series. n Start with a set for each basic exercise to be performed for 8-12 repetitions, using a load such that the last repetition is done with an effort that does not recommend trying to do subsequent repetitions (or if the value of 6 on the Borg scale is exceeded). Increase progressively, if possible, up to three sets per exercise. n The speed of execution of the movement should be low and consistent with the however, such as to always guarantee adequate control of the gesture: about 1-2 seconds for the load lifting phase (concentric contraction) and 2-3 seconds for the eccentric phase for a total of about 40 seconds for a series. This method should be the most effective for stimulating muscle trophism. n The rest interval between sets should be at least 1-2 minutes or in any case such as to allow the correct execution of the movements and the predetermined number of repetitions to be maintained. n Start with one training session per week to increase to two when the person is ready. It can take several weeks or months, but in the meantime, the training will still be effective. n All these indications must be applied progressively according to the conditions, skills and response to the exercise of each one. A periodic medical evaluation is used to verify that the program is beneficial and not counterproductive or even dangerous.

Flexibility exercises They are used to reduce the risk of osteo-musculoskeletal complications/injuries during training sessions. They improve the amplitude of all movements allowed by a joint, facilitating daily gestures. Flexibility is specific to each person and also to each joint and depends largely on the ability of muscles and tendons to stretch. Flexibility exercises (stretching) act by increasing muscle flexibility by maintaining positions that determine a slight stretching of the muscles (which must be felt but not painful) for a few seconds to be repeated several times.

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Balance training They are used to reduce the risk of falls. It concerns static and dynamic exercises to improve a person’s ability to better cope with the risk of falling resulting from postural oscillations, voluntary movement, or external factors. These exercises, which improve responses to proprioceptive stimuli, must be personalized and adapted in their difficulty to the person’s ability. They should therefore be prescribed and followed over time by expert personnel. Proprioception is the type of sensitivity that concerns the stability of the joints, the control of balance, the sense of position and the sense of movement.

Practical recommendations regarding physical exercise Previous experience. Experience and fitness level are essential elements for safe physical activity: less fit adults are more at risk when performing a certain amount of activity, compared to fitter adults3. The increase in intensity must always be understood as relative (intensity of activity compared to the person’s physical fitness) and measured through evaluation and monitoring indicator described above. The level of physical activity should be gradually increased over time5,18. Proper progression of activities safely requires increasing the duration (as minutes per session) or frequency (as days per week) earlier than increasing the intensity19. Nutrition. To optimize the effects of exercise, introducing adequate energy is essential. In particular, consuming adequate food and fluids before, during, and after exercise maintains euglycemia, maximizes performance, and improves recovery time20. Two hours before exercising it would be ideal to hydrate with water, eat healthy carbohydrates such as whole grains, whole meal toast, low-fat yogurt, whole meal pasta, brown rice, fruits and vegetables and avoid slowly digestible foods (saturated fats and lots of healthy proteins). If there is no time before exercise (10 minutes), feed on a fruit such as apple or banana. It is not necessary to feed during an exercise lasting less than an hour. From 20 minutes to 4-6 hours after physical activity, carbohydrate intake optimizes the restoration of muscle glycogen, while protein intake optimizes muscle regeneration. All these intakes can generally be met by food sources. You need to be well hydrated before exercise and drink fluids during (small, frequent sips) and after exercise to balance out losses. The goal of fluid intake during exercise is to cope with sweat losses that occur to promote thermoregulation. Furthermore, in some pathological contexts, such as in patients with hypertrophic cardiomyopathy,

Table 4. Determination, monitoring and verification of aerobic work intensities. Step 1

Preliminary determination of the first and second thresholds • VT1 and VT2 via CPET or • LT1 and LT2 by lactate measurement during incremental testing extrapolating HR and external load parameters (e.g. watts or speed) in both cases

Step 2

Check intensity during the training session of prescribed exercise intensity • Objectively: by VTs and/or lactate and/or HR • Subjectively: by RPE and/or Talk Test

Both steps can be repeated to assess improvements and step 2 in particular to check and possibly adjust the intensity of aerobic exercise.

adequate hydration is essential to avoid the establishment of a significant dynamic gradient to the outflow or its worsening. An adequate integration of mineral salts is also essential, in case of significant sweating and physical activity in hot environments20. Organization of the training session. Each activity session of physical activity should include a preliminary warm-up, approximately 10 minutes for moderate activities, preceding a central conditioning phase (prescribed activity) lasting 20-60 minutes, and a subsequent phase of cool-down of about 5-8 minutes. In general, warm-up and cool-down involve performing a session at a slower speed or at a lower intensity than the prescribed conditioning exercise21. Preliminary warm-up facilitates the transition from rest to training, stretching postural muscles and increasing blood flow. Such a preliminary phase can also reduce the risk of exercise-related cardiovascular complications. Warmup allows a gradual increase in cardiorespiratory, metabolic and neuromuscular commitment in preparation for conditioning19. To prepare for moderate activity, the warm-up session should include light aerobic activity (such as brisk walking) or bodyweight and flexibility exercises. Preparation for a muscle-strengthening activity should generally include an initial phase of general warmup and/or the execution of exercises with lighter weights21. Determination and verification of the correct intensity of the exercise. During the middle phase of the session, it is useful to determine whether the intensity of the exercise coincides with that expected according to the procedures summarized in table 4. The importance of cool-down. Cooling down after the conditioning activity allows a gradual decrease in HR at the end of the session. Cool-down allows correct circulatory regulation and return to values close to resting values; improves venous return by reducing possible dizziness after exercise; facilitates the dissipation of body heat; promotes faster elimination of lactic acid than rest recovery19,21. Failure to cool down in the immediate aftermath of exercise may result in a transient decrease in venous return, possibly reducing coronary blood flow. The consequences can be cardiovascular disorders21.

References 1.

Issurin VB. New horizons for the methodology and physiology of training periodization. Sports Med 2010; 40: 189-206. 2. Garber CE, Blissmer B, Deschenes MR, et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43: 1334-59. 3. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96. 4. World Health Organization. Global Recommendations on Physical Activity for Health. Geneva: World Health Organization; 2010. 5. U.S. Department of Health and Human Services. Physical Activity Guidelines for Americans. 2nd ed. Washington, DC: U.S. Department of Health and Human Services; 2018. 6. Binder RK, Wonisch M, Corra U, et al. Methodological approach to the first and second lactate threshold in incremental cardiopulmonary exercise testing. Eur J Cardiovasc Prev Rehabil 2008; 15: 726-34. 7. Anselmi F, Cavigli L, Pagliaro A, et al. The importance of ventilatory thresholds to define aerobic exercise intensity in cardiac patients and healthy subjects. Scand J Med Sci Sports 2021; 31: 1796-808. 8. Faggian S, Centanini A, Quinto G, et al. The many faces of exercise intensity: a call to agree on definitions and provide standardized prescriptions. Eur J Prev Cardiol 2024; 31: e89-91. 9. D’Ascenzi F, Cavigli L, Pagliaro A, et al. Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. Br J Sports Med 2022; 56: 1180-87. 10. Taylor JL, Holland DJ, Keating SE, et al. Short-term and Long-term Feasi-

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bility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation: The FITR Heart Study Randomized Clinical Trial. JAMA Cardiol 2020; 5: 1382-89. 11. Wasfy MM, Baggish AL. Exercise Dose in Clinical Practice. Circulation 2016; 133: 2297-313. 12. Wen CP, Wai JP, Tsai MK, et al. Minimal amount of exercise to prolong life: to walk, to run, or just mix it up? J Am Coll Cardiol 2014; 64: 482-84. 13. Garcia L, Pearce M, Abbas A, et al. Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies. Br J Sports Med 2023; 57: 979-89. 14. Di Prampero PE. Human Locomotion on Land, in Water, in the Air: Facts and Theories. Milan: Edi-Ermes; 2015. 15. Brzycki M. A Practical Approach to Strength Training. New York: McGraw-Hill; 1998. 16. Gomes RL, Lixandrão ME, Ugrinowitsch C, et al. Session Rating of Per-

ceived Exertion as an Efficient Tool for Individualized Resistance Training Progression. J Strength Cond Res 2022; 36: 971-76. 17. Kraemer WJ, Ratamess NA. Fundamentals of resistance training: progression and exercise prescription. Med Sci Sports Exerc 2004; 36: 674-88. 18. Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA 2018; 320: 2020-28. 19. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020; 54: 1451-62. 20. Thomas DT, Erdman KA, Burke LM. Nutrition and Athletic Performance. Med Sci Sports Exerc 2016; 48: 543-68. 21. Franklin BA, Eijsvogels TMH, Pandey A, et al. Physical activity, cardiorespiratory fitness, and cardiovascular health: A clinical practice statement of the American Society for Preventive Cardiology. Part II: Physical activity, cardiorespiratory fitness, minimum and goal intensities for exercise training, prescriptive methods, and special patient populations. Am J Prev Cardiol 2022; 12: 100425.

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| CHAPTER 2.5 |

Physical activity and exercise in women and gender differences Sabina Gallina, Anna Vittoria Mattioli, Daniela Pavan

Introduction CVDs are the leading cause of morbidity and mortality in women1. According to the latest WHO data, the incidence of Physical Inactivity is more frequent and severe in the female population, for all age groups, with a global average of 31.7% for women compared to 23.4% for men2. The protective role of physical activity and exercise in primary and secondary prevention has been widely described in the literature, even in women, with an average reduction in cardiovascular risk more significant in women than in men3. Women benefit more than men in terms of reducing all-cause mortality, and exercise appears to be equally effective for the prevention of CVD regardless of global cardiovascular risk levels4. Together with the reduction of the time spent in a sedentary lifestyle, it represents a protective factor in the etiology of many risk factors, not only the traditional or emerging ones but also the specific and unique ones related, in the various stages of life, to the hormonal state, including polycystic ovaries, cardio-metabolic gestational disorders, autoimmune diseases, breast cancer.

Childhood and adolescence The gender gap in physical activity begins early in life, as early as childhood and adolescence, and can have short- and long-term negative effects on health outcomes. Lack of adequate exercise is more frequently associated with sedentary behaviors, especially in terms of screen time spent recreationally. Exposure to cardiovascular risk factors early in life affects mental and physical health and well-being, causing structural and functional vascular changes, such as increased intima-media thickness and pulse wave velocity, which are related to early atherosclerosis5. In addition, this seems to be associated with the increase in numerous harmful habits in adulthood, especially in women6.

Childbearing age and pregnancy Recently, the American Heart Association has drawn up a document on women’s cardiovascular health and its influence on pregnancy complications7. According to the latest statistics, less than 1% of women of reproductive age have optimal cardiovascular health and almost 1 in 5 pregnancies have complications with a substantial increase in cases in the last ten years, especially regarding hypertensive states8. These complications, strongly correlated with the risk of subsequent short- and long-term CVD, would be related to the presence of risk factors in pre-pregnancy, such as obesity, high blood pressure values, insulin resistance9. Among the cardiovascular health parameters mentioned above, physical activity and exercise can counteract risk factors before, during and after pregnancy and the improvement of maternal cardio-metabolic health is reflected in the cardio-metabolic health of the fetus and future offspring10. There are numerous benefits of SPE for maternal cardio-metabolic health, including

positive vascular remodeling and neo angiogenesis, improved endothelial function and arterial stiffness, and reduced oxidative stress and decreased levels of inflammatory cytokines and cortisol11. Women who exercise during pregnancy have a 30% lower risk of developing hypertensive disorders and experience a reduced cardiovascular risk profile in perimenopause11. SPE has also been associated with a significant reduction in weight gain during and post-pregnancy, both of which correlate with a higher risk of short- and long-term cardiovascular events, especially in women with a history of gestational diabetes and hypertensive disorders. SPE significantly improves maternal quality of life, with a positive effect on prenatal anxiety and depression states, related to an increased risk of new CVDs within 24 months after delivery12. In addition, SPE improves fertility and assisted reproductive therapy outcomes, as well as the metabolic profile in polycystic ovary syndrome, recognized as the leading cause of anovulatory infertility and an important cardiovascular risk factor. The WHO 2020 guidelines on physical activity and sedentary behavior recommend that all pregnant women, without contraindications, carry out at least 150 minutes of moderate or moderate-high intensity aerobic exercise per week in relation to the activity carried out before weighting, to which muscle strengthening exercises should be associated13. The indication and type of physical exercise to be prescribed in women with gestational diabetes and preeclampsia are still being studied. Although more than two-thirds of pregnant women participate in some type of recreational physical activity, the percentage of women who exercises at the recommended level is still low, ranging from 15 to 27.3%.

Menopause and old age The prescription of SPE is a fundamental tool to counteract, during menopause and after menopause, the deficiency of ovarian hormone concentrations and the secondary negative consequences on the cardio-metabolic profile and on the inflammatory state, the common denominator of pathologies of the female world14. An adequate fitness program and a high level of adherence can improve the immuno-neuroendocrine profile and angiogenic properties during the menopausal transition15,16. As far as aerobic exercise is concerned, both continuous aerobic and high-intensity interval training have a positive effect on both the lipid and glycemic metabolic profile and aerobic capacity. Perimenopausal women may also benefit from regular strength training, which can help improve bone density, reduce body fat, and build skeletal muscle mass, while maintaining adequate physical performance17. Unfortunately, after menopause, women are generally more sedentary and less active than men. In this population, physical inactivity has been correlated with metabolic disorders, CVD, cancer, mortality, and psychological distress, as well as adverse changes in coagulation homeostasis18,19.

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The 2020 WHO guidelines on physical activity and sedentary behavior recommend similar exercise and intensity in both genders. However, recent research conducted on the subject has shown a positive effect in women even with mild and moderate physical exercise. Recent work has found that the benefit in women for allcause mortality is also achieved at a lower intensity of exercise, both endurance and muscle strength, than that for men, especially in the age group between 40 and 59 years. In fact, while men needed 300 minutes per week of moderate to vigorous physical activity to achieve the greatest reduction in risk of death, women had the same benefit with 140 minutes per week, and their risk continued to decrease as they reached 300 minutes per week20. Such data could lead to future guidelines to “personalize” the prescription of SPE according to gender, regarding modality, intensity, duration, series and repetitions.

Exercise and secondary prevention With regard to secondary prevention, maintaining at least 7.5 METs/hour/week of SPE before and after myocardial infarction is associated with a lower risk of all-cause mortality, including cardiovascular mortality. Negative lifestyle adjustment, poor adherence to SPE after an acute coronary syndrome (ACS) event are associated with a worse long-term prognosis, reduced cardiorespiratory capacity, and increased risk of heart failure in postmenopausal women21. The latest guidelines on cardiovascular prevention in clinical practice, approved by the European Society of Cardiology, suggest that every patient with atherosclerotic events or with a history of heart failure should participate in a structured, exercise-based cardiac rehabilitation program, prescribed by the physician and started as soon as possible after the initial event. The program should be tailored to each patient and include both aerobic and resistance exercises22. Unfortunately, women are less likely to join rehabilitation programs than men, and if they do, they very often do not end their journey.

Proposal for intervention Every woman needs to find a pleasant activity that adapts to her daily lifestyle23 and that allows her to overcome the practical and personal barriers represented by the lack of awareness of her state of health, low self-esteem and perception of her body, socio-cultural expectations and the role of the female gender in working life and in the responsibilities of the family unity24. In order to improve women’s adherence to fitness programs, strategies must be implemented that can be adapted to the specific demands and needs of the female population of all ages, starting from already known facilitators, such as adaptation of SPE programs for each level of physical activity that the woman is able to perform, gratifications that can improve self-esteem, and create non-competitive but inclusive contexts, together with adequate family support. In this regard, it is important to provide suitable infrastructures to facilitate access with timetables and services compatible with the world of work and other family and social commitments. Thanks to the advent of technology, remote training with an online instructor and specific interventions aimed at the use of an interactive accelerometer equipped with cloud-based services to store and monitor habitual online activity have been suggested, in order to create a profile of the patient’s habitual activity, which can be supervised for long periods of time. Health

education messages delivered to mobile devices, promoting WHO guidelines and explaining the positive effects of SPE through engaging visual content can be an effective tool to improve knowledge and adherence even in the youngest population25,26. In cases of secondary prevention, home telemonitoring and telemedicine interventions can be valid supports to increase the percentage of participation in the SPE program.

Conclusion The lack of physical activity that remains throughout a woman’s life can be attributed to gender problems of both an economic and socio-cultural nature and to the lack of awareness and knowledge on the part of the woman herself of her cardiovascular risk and the advantages related to SPE. On the other hand, work on the subject must address issues that highlight the gender-specific correlation of the benefits of SPE in order to understand and define the modalities of “administration” of exercise in both genders.

References 1.

Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and Stroke Statistics 2023 Update: A Report from the American Heart Association. Circulation 2023; 147: e93-e621. 2. World Health Organization. Global Action Plan on Physical Activity 2018– 2030: More Active People for a Healthier World. Geneva: World Health Organization; 2018. 3. Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation 2010; 122: 743-52. 4. Chomistek AK, Cook NR, Rimm EB, et al. Physical Activity and Incident Cardiovascular Disease in Women: Is the Relation Modified by Level of Global Cardiovascular Risk? J Am Heart Assoc 2018; 7: e008234. 5. Raitakari OT, Juonala M, Kähönen M, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: The Cardiovascular Risk in Young Finns Study. JAMA 2003; 290: 2277-83. 6. Lounassalo I, Hirvensalo M, Palomäki S, et al. Life-course leisure-time physical activity trajectories in relation to health-related behaviors in adulthood: The Cardiovascular Risk in Young Finns Study. BMC Public Health 2021; 21: 533. 7. Khan SS, Brewer LC, Canobbio MM, et al. Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring: A Scientific Statement from the American Heart Association. Circulation 2023; 147: e76-e91. 8. Freaney PM, Harrington K, Molsberry R, et al. Temporal Trends in Adverse Pregnancy Outcomes in Birthing Individuals Aged 15 to 44 Years in the United States, 2007 to 2019. J Am Heart Assoc 2022; 11: e025050. 9. Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005; 330: 565. 10. Nagpal ST, Mottola MF. Physical activity throughout pregnancy is key to preventing chronic disease. Reproduction 2020; 160: R111-R118. 11. Witvrouwen I, Mannaerts D, Van Berendoncks AM, et al. The Effect of Exercise Training During Pregnancy to Improve Maternal Vascular Health: Focus on Gestational Hypertensive Disorders. Front Physiol 2020; 11: 450. 12. Ackerman-Banks CM, Lipkind HS, Palmsten K, et al. Association of Prenatal Depression with New Cardiovascular Disease Within 24 Months Postpartum. J Am Heart Assoc 2023; 12: e028133. 13. Bull FC, Al-Ansari SS, Biddle S, et al. World Health Organization 2020 Guidelines on Physical Activity and Sedentary Behaviour. Br J Sports Med 2020; 54: 1451-62. 14. Mattioli AV, Moscucci F, Sciomer S, et al. Cardiovascular Prevention in Women: An Update by the Italian Society of Cardiology Working Group on Prevention, Hypertension and Peripheral Disease. J Cardiovasc Med (Hagerstown) 2023; 24 (Suppl 2): e147-e155. 15. Bucciarelli V, Bianco F, Mucedola F, et al. Effect of Adherence to Physical Exercise on Cardiometabolic Profile in Postmenopausal Women. Int J Environ Res Public Health 2021; 18: 656. 16. Izzicupo P, Ghinassi B, D’Amico MA, et al. Effects of ACE I/D Polymorphism and Aerobic Training on the Immune-Endocrine Network and Car-

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diovascular Parameters of Postmenopausal Women. J Clin Endocrinol Metab 2013; 98: 4187-94. 17. Juppi HK, Sipilä S, Cronin NJ, et al. Role of Menopausal Transition and Physical Activity in Loss of Lean and Muscle Mass: A Follow-Up Study in Middle-Aged Finnish Women. J Clin Med 2020; 9: 1588. 18. Bellettiere J, LaMonte MJ, Evenson KR, et al. Sedentary Behavior and Cardiovascular Disease in Older Women: The Objective Physical Activity and Cardiovascular Health (OPACH) Study. Circulation 2019; 139: 1036-46. 19. Mattioli AV, Selleri V, Zanini G, et al. Physical Activity and Diet in Older Women: A Narrative Review. J Clin Med 2022; 12: 81. 20. Ji H, Gulati M, Huang TY, et al. Sex differences in association of physical activity with all-cause and cardiovascular mortality. J Am Coll Cardiol 2024; 83: 783-93. 21. LaMonte MJ, Larson JC, Manson JE, et al. Association of Sedentary Time and Incident Heart Failure Hospitalization in Postmenopausal Women. Circ Heart Fail 2020; 13: e007508. 22. Abreu A, Frederix I, Dendale P, et al. Standardization and quality improve-

ment of secondary prevention through cardiovascular rehabilitation programmes in Europe: the avenue towards EAPC accreditation programme: a position statement of the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2021; 28: 496-509. 23. Cugusi L, Manca A, Serpe R, et al. Effects of a mini-trampoline rebounding exercise program on functional parameters, body composition and quality of life in overweight women. J Sports Med Phys Fitness 2018; 58: 287-94. 24. Peng B, Ng JYY, Ha AS. Barriers and facilitators to physical activity for young adult women: a systematic review and thematic synthesis of qualitative literature. Int J Behav Nutr Phys Act 2023; 20: 23. 25. Hamilton SJ, Mills B, Birch EM. Smartphones in the secondary prevention of cardiovascular disease: a systematic review. BMC Cardiovasc Disord 2018; 18: 25. 26. Galati A, Piccoli M, Tourkmani N, et al. Cardiac rehabilitation in women: state of the art and strategies to overcome the current barriers. J Cardiovasc Med (Hagerstown) 2018; 19: 689-97.

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| CHAPTER 2.6 |

Exercise prescription at different ages of life Francesco Giallauria, Pompilio Faggiano, Raffaele Napoli, Marco Perrone, Crescenzo Testa, Carlo Vigorito

The prescription of physical exercise varies according to age, in consideration of the different needs and functional capacity of individuals.

Recommendations from leading international health organizations offer clear, evidence-based guidance for promoting physical activity safely and effectively in all ages (table 1).

Table 1. Recommendations from leading international organisations on minimum levels of physical activity to be achieved. Child and Adolescent

Adult

Elderly (Seniors)

WHO (2020)¹

For children and adolescents from 5 to 17 years old, the WHO advises at least 60 minutes of moderate or vigorous intensity physical activity per day.

For adults aged between 18 and 64 years, the WHO recommends at least 150 minutes of moderate-intensity aerobic physical activity during the week, or at least 75 minutes of high-intensity physical activity.

For the elderly (65 years and over), the WHO suggests the same amount of recommended physical assets for older adults and young people, provided that their abilities allow it.

ACSM (2021)²

At least 60 minutes of moderate or high-intensity physical activity every day. Resistance exercises for the muscles and bone strengthening at least three days a week.

At least 150 minutes of moderate-intensity aerobic physical activity during the week, or at least 75 minutes of high-intensity physical activity. Strengthening muscle exercises for all main muscular groups at least two days a week.

Seniors should follow the same recommendations of adults, provided that their physical abilities allow. It is important to include exercises that improve balance and flexibility.

AHA (2019)³

At least 60 minutes of moderate or highintensity aerobic physical activity every day. Resistance exercises for muscle and bone at least three days per week.

At least 150 minutes of moderate-intensity aerobic physical activity during the week, or at least 75 minutes of high-intensity physical activity. Resistance exercises for all main muscle groups at least two days a week.

Seniors should follow the same recommendations of adults, provided that their physical abilities allow it. It is also recommended to include exercises to improve balance and flexibility.

NICE (2014)⁴

NICE recommends that children and young people (under 18 years of age) carry out at least 60 minutes of moderate or vigorous physical activity every day. Activities should include exercises that strengthen muscles and bones at least three times per week.

Adults should try to do at least 150 minutes of moderate-intensity aerobic physical activity every week, or 75 minutes of high-intensity aerobic activity. We recommend that you deploy physical activity during the week in sessions of at least 10 minutes each.

Continue or start physical activity also in old age, by adapting the intensity and the type of activity to the individual capabilities.

CDC (2018)⁵

Physical activity of moderate intensity for at least 3 hours a day. Strengthening physical activity for muscle and bone at least three days a week.

At least 150 minutes of moderateintensity aerobic physical activity during the week, or 75 minutes of high-intensity aerobic physical activity, or an equivalent combination. Strengthening exercises involving all major muscle groups two or more days a week.

Seniors should follow the same recommendations of adults, provided that their physical abilities allow. Exercises that improve aerobic and balance are particularly important to reduce the risk of falls.

CSEP (2011)⁶

Preschool (0-4 years) The children of Preschool should be active for at least 180 minutes (3 hours) at At least 150 minutes of moderate-intensity different levels of intensity during the day. aerobic physical activity per week, or 75 minutes of high physical activity, or a combination equivalent. Strengthening Children and adolescents (5-17 years) muscle physical activity involving main At least 60 minutes of moderate to groups at least two days a week. vigorous physical activity every day. At least three days a week of strengthening physical activity for muscles and bones.

Seniors should follow the same recommendations of the most young people, provided that their capabilities allow. It is also recommended to include activities that improve balance and flexibility.

AGDH (2021)⁷

Preschoolers (0-5 years) The children of Preschool should be active At least 150-300 minutes of moderatefor at least three hours a day, including intensity aerobic physical activity during periods of moderate or high activity. the week, or 75-150 minutes of high aerobic physical activity, or an equivalent Children and Adolescents (5-17 years) combination. Muscle activity involving all At least 60 minutes of moderate and major muscular groups at least two days vigorous physical activity every day. a week. Strengthen muscles and bones at least three days a week.

Seniors should follow the same recommendations of the most young people, provided that their physical abilities allow. We recommend also including activities that improve balance and flexibility.

Legenda - WHO: World Health Organization; ACSM: American College of Sports Medicine; AHA: American Heart Association; NICE: National Institute for Health and Care Excellence; CDC: Centers for Disease Control and Prevention; CSEP: Canadian Society for Exercise Physiology; AGDH: Australian Government Department of Health. SPORTS MEDICINE JOURNAL | SUPPL. 1 - VOL 79 N 1 | MARCH 2026

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A personalized and flexible approach is essential to ensure that everyone can get the maximum benefits from physical activity, thereby improving overall health and well-being.

Children and adolescents (5-17 years) Physical activity in children and adolescents is crucial for physical and mental development. It allows an improvement in general fitness, cardiovascular health and muscle strength. Proper physical activity also promotes the establishment of correct healthy habits that can be maintained even in adulthood. Children and adolescents should engage in at least 60 minutes of moderate or high-intensity physical activity each day. Activities should include exercises that strengthen muscles and bones at least three times a week. Activities should be fun and age-appropriate to promote adhesion and socialization. Examples of exercises for children and adolescents include: • Aerobic Exercises: Activities such as running, cycling, and active play that increase HR. • Muscle Strengthening: Exercises such as climbing and gymnastics twice a week. • Flexibility: Activities such as yoga to improve mobility and prevent injuries. Incorporating a variety of physical activities is crucial for maintaining long-term interest and adherence. In addition, regular physical activity can improve mood and concentration, thus contributing to academic success and psychological well-being. Another important aspect is the integration of physical activity into daily routines, such as walking or cycling to school, which can promote an active lifestyle from a young age8,9.

Adults (18-64 years) In adults, regular physical activity helps maintain a healthy body weight, reduce the risk of CVD, type II diabetes mellitus and some cancers. In addition, it improves psychological well-being and sleep homeostasis. Adults should get at least 150 to 300 minutes of moderate-intensity aerobic physical activity or 75 to 150 minutes of high-intensity activity each week. It is recommended to include muscle-strengthening exercises two or more days a week, especially over the age of 5010. Examples of exercises for adults include: • Aerobic Exercises: Brisk walking, swimming, running. • Muscle Strengthening: Weight lifting, resistance band exercises. • Flexibility and Balance: Yoga and Pilates to improve posture and prevent falls. Regular physical activity plays a crucial role in the prevention of chronic diseases, reducing the risk of high blood pressure, hyperlipidemia and other pathological conditions related to sedentary lifestyle. In addition, it can play an important role in stress management and in the prevention of mental disorders such as depressive states and anxiety. To maximize the benefits, adults should try to include a combination of aerobic, strength, flexibility, and balance exercises in their weekly routine.

Seniors (65+ years) For seniors, physical activity is crucial for maintaining autonomy, improving quality of life, and preventing falls. Proper physical activity improves cardiovascular and respiratory health and has been shown to reduce the risk of dementia. Older adults should follow the same recommendations as adults, with an emphasis on including activities that improve balance at least three times a week to reduce the risk of falls. The National Institute for Health and Care Excellence (NICE) suggests continuing or starting physical activity even in old age, adapting the intensity and type of activity to individual abilities. Examples of exercises for seniors include: • Aerobic exercises: Walking, stationary cycling, swimming. Muscle Strengthening: Exercises with light weights or resistance bands. Balance: Exercises such as Tai Chi to prevent falls. Physical activity in older adults helps preserve muscle mass and bone density, reducing the risk of osteoporosis and fractures. It can also improve mood and cognitive abilities, promoting greater social participation and a better quality of life. It is important for seniors to choose activities that they find pleasant and sustainable in the long term, to ensure the continuity of the operation. Group activities can also be very useful to encourage socialization and mutual support among peers.

Conclusion Physical activity is a crucial element for health and well-being at all ages of life. The prescription of physical exercise must be personalized and adapted to the specific needs and abilities of each individual. Supplementing aerobics, muscle-strengthening, flexibility, and balance exercises can maximize health benefits. Educating people about the importance of physical activity and providing ongoing support are key elements in maintaining adherence to exercise programs. Regular monitoring and reshaping exercise programs based on individual progress are essential to optimize outcomes and improve quality of life11,12. Ultimately, physical activity should not be seen as an obligation, but as a pleasurable and integral component of daily life. In young people, adults and the elderly, physical activity offers countless benefits that go far beyond just preventing disease. Promoting an active approach to life from a young age can help create healthy habits that will benefit the health of the individual until later in life. Public policies and community initiatives should support access to exercise opportunities for all age groups, recognizing the value of physical activity as a fundamental right for the health and well-being of all individuals.

References 1.

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World Health Organization (2020). WHO Guidelines on Physical Activity and Se- dentary Behaviour. Available on: https://www.who.int/publications/i/item/97 89240015128. American College of Sports Medicine (ACSM). ACSM’s Guidelines for Exercise Testing and Prescription. Available on: https://www.acsm.org/ education- resources/books/guidelines-exercise-testing-prescription. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140: e596-e646. National Institute for Health and Care Excellence (NICE). Physical Activ-

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6. 7.

ity Guidelines: General Adults. Available on: https://www.nice.org.uk/ guidance/ph44/chapter/Recommendations. Centers for Disease Control and Prevention (CDC). Physical Activity Guidelines for Americans. Available on: https://health.gov/sites/default/ files/2019- 09/Physical_Activity_Guidelines_2nd_edition.pdf. Tremblay MS, Warburton DE, Janssen I, et al. New Canadian physical activity guidelines. Appl Physiol Nutr Metab 2011; 36: 36-46; 47-58. Guidelines for Physical Activity of Australian Government Department of Health. Available on: https://www.health.gov.au/topics/physical-activity-and-exercise/ physical-activity-and-exercise-guidelines-for-all-Australians. Jebeile H, Kelly AS, O’Malley G, et al. Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol 2022; 10: 351-65. van Sluijs EMF, Ekelund U, Crochemore-Silva I, et al. Physical activity be-

haviours in adolescence: current evidence and opportunities for intervention. Lancet 2021; 398 (10298): 429-442. 10. European Society of Cardiology (ESC). ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Diseases. Available on: https://academic.oup.com/eurheartj/article/42/1/17/5898937. 11. Stathi A, Greaves CJ, Thompson JL, et al. Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults:the REACT (Retirement in Action) randomised controlled trial. Lancet Public Health 2022; 7: e316-e326. 12. Huang X, Zhao X, Li B, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: A systematic review and network meta-analysis. J Sport Health Sci 2022; 11: 212-23.

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| CHAPTER 2.7 |

Safety in the prescription and administration of structured physical exercise Franco Giada, Marco Ambrosetti, Giuseppe Caminiti, Daniel Neunhaeuserer, Stefano Palermi, Giovanni Pasanisi, Gustavo Savino, Marco Vecchiato, Silvano Zanuso

Foreword As is well known, the benefits of SPE, even in patients with heart diseases, far outweigh the risks of adverse cardiovascular exercise-related events, including sudden death and acute myocardial infarction. However, to ensure the best risk/benefit ratio, the prescription and administration of SPE must be individualized as much as possible in the individual patient. For this reason, it is essential to consider: the possible interactions between SPE and cardiovascular and non-cardiovascular drug therapy the patient usually takes; the setting in which the prescribed SPE is to be administered; some general and specific precautions for individual pathologies; the effects of environmental conditions; the monitoring of the SPE carried out.

Interactions with patient therapy When prescribing an SPE program to patients with CVD, it is necessary to consider the interactions between the hemodynamic effects produced by exercise with those of the drugs they take, with potential negative effects on performance and some risks to their health. It is therefore necessary, during the process of prescribing and administering SPE, to acquire the complete list of drugs taken by the patient and the times of taking them1. In this section we will deal with the interactions between physical exercise and the main cardiovascular drugs and those with some centrally acting drugs, often used in cardiology. Interactions with other categories of drugs used in heart patients, such as lipid-lowering and antidiabetic drugs, will instead be dealt inside the specific chapters of this document. Cardiovascular drugs. Patients with arterial hypertension, ischemic heart disease, and heart failure are taking one or more of the following classes of drugs: beta-blockers, mineralocorticoid receptor antagonists, ACE inhibitors, angiotensin receptor inhibitors, sacubitril/valsartan, nitrates, calcium channel blockers, thiazide diuretics, or loop diuretics2, 3. All these drugs reduce pressure through vasodilation, bradycardia, or volume depletion. Since exercise also causes protracted vasodilation, which is the basis of post-exercise hypotension, it is possible that excessive reductions in blood pressure may be generated soon after training, with the appearance of symptoms such as asthenia, dizziness and, in rare cases, syncope. Therefore, it is essential that patients taking these categories of drugs perform a gradual cool-down phase, lasting 5-10 minutes, after all exercise sessions, in order to prevent the accumulation of blood in the muscles, improve venous return and limit the drop in blood pressure in the immediate post-exercise period. It is also necessary to monitor blood pressure during training and possibly modify the dose(s) of the drug(s) to prevent blood pressure drop or excessive hypertensive peaks during exertion. Patients taking beta-blockers, non-dihydropyridine calcium channel blockers (verapamil and diltiazem) or antiarrhythmics

(amiodarone, flecainide, propafenone, sotalol) may have an attenuated heart rate response to exercise; this effect, which is variable in relation to the dose of the drug and the time of its intake, can cause a decrease in physical performance and make difficult to use heart rate-based methods to plan the intensity of training. In patients receiving diuretics, proper hydration should be suggested in order to prevent excessive volume depletion and electrolyte imbalances. Most patients with cardiovascular diseases also take anti-platelet and/or anticoagulant drugs. These drugs increase the risk of significant bleeding in case of trauma occurring during training sessions (table 1). Centrally acting drugs. Patients with cardiovascular diseases, especially those over 65 years of age, often have multiple comorbidities and need to take other medications to manage these conditions. Some of these drug acts on the central nervous system and can interfere with SPE4. Hypnotic sedatives, such as high-dose benzodiazepines, can impair physical performance and concentration, slow reflexes, and increase the risk of falls and trauma. Opioid analgesics, drugs used for neuropathic pain, and antidepressants can cause cognitive impairment, sedation, and increase the risk of falls and trauma (table 2).

The setting for the administration of SPE In cardiopathic patients, it is essential from a safety point of view to choose the correct setting in which to administer the SPE. In patients with a recent acute cardiovascular event (first weeks after hospital discharge), such as acute coronary syndrome, percutaneous or surgical revascularization, valve replacement or valve plastic, heart failure and in patients with severe heart disease and/or comorbidities, it is indicated to refer the patient, at least for the first training sessions, to the Medical Gym of a Cardiovascular Rehabilitation Center and only then to a Health Gym. On the other hand, in the case of chronic, stabilized, asymptomatic heart patients without particular comorbidities, or in subjects with only risk factors, it is possible to refer the subject directly to a Health Gym. Finally, some patients, for the most varied reasons, prefer to train individually and generally outdoors. However, in order for this individual training mode to be sufficiently safe, the patient must be able to: correctly perform the prescribed exercise program, and evaluate the intensity of the exercise performed; know the precautions to be taken based on the pathology of which he is a carrier; be aware of the effects of environmental conditions; recognize cardiovascular alarm symptoms. In this chapter we will deal with the structural, instrumental and organizational requirements recommended in order to ensure the safety of training in Medical Gyms and Health Gyms.

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Table 1. Main cardiovascular drugs and their interaction with physical exercise. CARDIOVASCULAR DRUGS

Hemodynamic effects

Potentials side effects

BETA-BLOCKERS

↓ Inotropism ↓↓ HR (R and E) ↓ BP (R and E)

Asthenia Fast fatigue during exercise

↓

ACE INHIBITORS RECEPTOR BLOCKERS ANGIOTENSIN

↓BP (R and E)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

SACUBITRIL/ VALSARTAN

↓ BP (R and E)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

–

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

–

CALCIUM CHANNEL BLOCKERS Dihydropyridines Non-dihydropyridine

- /↑ HR (R and E) ↓ BP (R and E) ↓ Inotropism ↓ BP (R and E) ↓ HR(R and E)

ALPHA-LITHIC

Effect on functional capacity

↓

↓BP (R and E)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

–

NITRATES

↑ HR (R) ↓ BP (R)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

DIURETICS RECEPTOR ANTAGONISTS MINERAL CORTICOIDS

↓ Volemia ↓ BP (R and E)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope

–

THIAZIDE DIURETICS LOOP DIURETICS

↓ Volemia ↓ BP (R and E)

Asthenia Dizziness Orthostatic hypotension Post-exercise syncope Arrhythmias

–

ANTIARRHYTHMICS Amiodarone Sotalolo

↓ HR (R and E) ↓ Inotropism ↓ HR (R )

Asthenia Arrhythmias Asthenia

Propafenone Flecainide

↓↓ Inotropism

Arrhythmias

ANTI-PLATELET AGENTS

–

↑ Risk of post-trauma bleeding

ANTI-COAGULANTS

–

↑ Risk of post-trauma bleeding –

– /↓ – /↓

–

BP= Blood pressure; HR= heart rate; R = rest; E = exercise; ↑= increase; ↓= reduction; – = no change.

Safety in Medical Gyms The Medical Centers in which SPE is prescribed, administered and supervised must meet the usual requirements of the environments where health care is provided (together with measures for the protection of the health and safety of workers) and specific structural and organizational metrics. The fulfilment of these requirements is aimed at achieving the objectives of increasing cardiorespiratory fitness and muscle strength, minimizing at the same time the risks associated with physical exercise in a subject with heart disease, whether they are

cardiovascular (cardiac arrest, myocardial ischemia, threatening arrhythmias, syncope, hypertensive crises, malfunction of implanted cardiac devices) or non-cardiovascular (trauma, muscle injuries, and so on). The requirements can be derived from the current accreditation criteria for Cardiovascular Rehabilitation activities and from the recommendations of the sector guidelines5,6. From an epidemiological point of view, it should be considered that – under such conditions of environmental protection and active supervision – a rate of major cardiovascular events between 1/50,000 and 1/120,000 hours of training and about 1 death per 750,000 hours of training is estimated7,

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Table 2. Main centrally acting drugs and their interaction with physical exercise. MEDICATIONS

Effects on the cognitive sphere Potentials Side effects

Benzodiazepine

Drowsiness ↓ Coordination ↓ Reflections

Asthenia ↑ Risk of falls and traumas

Effect on functional capacity ↓

Neuroleptics

Drowsiness Extrapyramidal symptoms Cognitive disorders

Asthenia ↑ Risk of falls and traumas

↓

Dopaminergic agonists

Cognitive disorders

Asthenia Orthostatic hypotension ↑ Risk of falls and traumas

↓

Antidepressants

↓ Motor coordination ↓ Reflections

↑ Risk of falls and traumas

↓

Opiates

↓ Coordination ↓ Reflections

↑ Risk of falls and traumas

↓

Anticholinergics

Cognitive disorders Visual disturbances ↓ Motor coordination

↑ Risk of falls and traumas

↓

↑= increase; ↓= reduction

with a significant difference if the training program was preceded by an ergometric/cardiopulmonary test (zero events in over 270,000 hours/patient analyzed in England by the National Audit of Cardiac Rehabilitation 2022) or not (two events per 105,000 patient-hours)8. The execution of an incremental stress test tending to the maximum is therefore the main determinant of reducing the risk associated with training, which must be followed by a precise determination of the training program to be followed according to the FITT-VP scheme. Table 3 shows the structural standards of the Medical Gyms assigned to this activity.

ECG telemetry

As far as telemetric monitoring of the ECG during physical exercise is concerned, a strategy to maintain this device in all patients (regardless of the risk assessment) and for all sessions – solely for the purpose of early warning for major adverse events – is currently controversial. For this reason, the authors, after a critical review of the available guidelines referring to the modern era of cardiological therapies and interventional strategies9, unequivocally contemplate the following conditions as indications for carrying out physical training with telemetry monitoring: • left ventricular dysfunction with left ventricular ejection fraction (EF) • <30% • unstabilized heart failure • complex ventricular arrhythmias at rest or under exertion • hypotensive response on exertion (increased systolic blood pressure • <20 mmHg) • low-intensity exercise-induced myocardial ischemia (<5 METs) • previous cardiac arrest. Obviously with the recommendation to extend telemetry monitoring as much as possible to each gym activity as much as logistically possible.

Emergency trolley (defibrillator, SatO2 monitoring, ventilation unit, first aid drugs) with location known to all staff and ad hoc signage

Safety in Health Gyms

Table 3. Structural and organizational requirements for the administration of SPE at the Medical Gym. Room of adequate size for individual and group physical activities Equipment with various types of ergometers (exercise bike, treadmill, armoergometer), strength exercise machines, mats and other gym equipment (height-adjustable parallel bars, exercise ladders, dumbbells, set of graduated resistance elastic bands, oscillating boards, wedges and padded cylinders, gym mirror)

Dressing box for wounds and minor traumas Availability of infirmary room with bed, stethoscope, sphygmomanometer, electrocardiograph, pulse oximeter, scale Alarm system that allows, regardless of telephone lines, the reporting of events that require the immediate presence in the gym of medical staff Adjacent to all equipment: use and maintenance manuals, safety instructions, calibration instruments and protocols, documents certifying the competence of the personnel in charge in the management of the equipment. Availability of structured paths (internal or external to the Medical Center) to access specific instrumental evaluations (echocardiogram, stress test, blood chemistry tests, and so on)

In order to optimize the health benefits of SPE and reduce its cardiovascular and non-cardiovascular risks (both traumatic and due to osteo-musculo-skeletal overload), it is desirable that cardiac patients, especially if fragile, even if stabilized and asymptomatic, practice the prescribed training program in safe local facilities, called “Health Gyms”. The Health Gyms, according to current Italian legislation9-13, are public or private non-health facilities, where APA and SPE programs take place. In some Italian regions, the Health Gyms have been activated and are certified by the local health authorities. To obtain this certification, they must comply with regulations relating to safety, accessibility and hygiene, meet the organizational requirements relating to respect for privacy and specific instrumental requirements13,14 (table 4).

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At the Health Gyms, the administration of SPE must be provided by a Kinesiologist in possession of a specific training course for the management of patients with stabilized non-communicable exercise-sensitive chronic diseases and the BLS-D13,14.

Precautions and environmental conditions In order to reduce the risk of exercise-related adverse events, it is essential to adopt some general and/or disease-specific precautions when prescribing/administering SPE and to take into account the environmental conditions during training sessions. General precautions. Before starting an SPE program, the patient’s therapy should be optimized in terms of dosage and mode of intake. It will be essential to adapt the workload gradually, first increasing the weekly frequency of training sessions, then the duration of the single session and finally the intensity of exercise. In addition, it is important to record the physical exercise performed and monitor perceived fatigue and/or dyspnoea (through the Borg Scale and/or the Dyspnoea Scale) and saturation, comparing these values with heart rate and workload: any discrepancies between the recorded values and those expected could suggest a worsening of the patient’s clinical status. Regular follow-up should be scheduled, even in patients with a good response to the SPE program, because adaptations and advances may unmask other functional limitations not previously evident. In addition, the re-evaluation makes it possible to reshape the prescription by considering new types of exercise and training intensities, or to identify any non-responders who require pharmacological and/or surgical interventions. Specific precautions. Bronchodilator drugs and oxygen should be available for patients with ventilatory limitations. Particular attention should be paid to the prevention of exacerbations of respiratory diseases, especially in winter, paying attention to hygiene and avoiding overcrowded gyms. In subjects with cardiogenic limitations, the recommended intensities below the arrhythmic and/or ischemic thresholds should be respected, avoiding hypertensive peaks and Valsalva maneuvers during sub-maximal strength exercises. It is therefore always useful to recommend good control of breathing during effort and correct

Table 4. Instrumental requirements for Health Gyms. Security tools: • Automated external defibrillator, with the requirement that kinesiologists be in possession of the Basic Life Support and Defibrillation (BLS-D) patent • Personal scale • Automatic sphygmomanometer for blood pressure measurement • Heart rate monitors • Oximeters • First aid kit for wound and minor trauma dressings • Availability of an infirmary room with a bed Aerobic training tools: • Treadmill, Cyclette, Arm ergometer Muscle strength training tools: • Strength Exercise Machines • Dumbbells & Free Weights • Mats, height-adjustable parallel bars, exercise ladders • Graduated resistance elastic bands

execution of technical gestures. Post-exercise cool-down should be slow and prolonged to avoid sudden drops in blood pressure. In the case of patients with hypertension or diabetes (especially if insulin-treated), blood pressure and blood glucose should be monitored first, during and after training, at least in the first training sessions. For patients with peripheral limitations, the risks associated with mechanical damage to the extremities should be considered, appropriate footwear should be recommended, and the soles of the feet should be checked frequently. In the case of sensory-motor neuropathies, the risk of falling should be examined (for example through the Tinetti Scale), adapting the prescription and proposing specific exercises. Finally, in patients also suffering from pathological conditions of the musculoskeletal system, especially if bone metastases or advanced osteoporosis are present, slow progression must be expected, limiting high intensities and avoiding joint overload and trauma. During any exacerbations of osteoarticular pathologies, high-intensity exercise is contraindicated, but low-intensity maintenance or mobility exercises may be proposed. Environmental conditions. Altitude, temperature, humidity and pollution must be considered in the prescription/administration of the SPE, especially for outdoor training sessions1-5, to avoid possible adverse events induced by risky environmental conditions. Table 5 provides general advice and practical precautions that can be easily adapted to environmental conditions15-18.

Exercise monitoring with wearable devices The quantification of the physical exercise performed by the patient through the use of devices provides very useful indications to the physician regarding safety issues. In fact, although monitoring with devices does not generally take place live but requires a post evaluation of the exercise carried out, thus allowing both control of the trend of workloads and modulation. All this is based on real data on volume and intensity carried out. If in the recent past quantification was done simply through anamnesis or by using special questionnaires, in recent years there has been the development of a series of technologies and devices, both wearable and non-wearable, which allow exercise monitoring by measuring internal and external metabolic and muscle load, i.e. the work done20-23. The internal load consists of: 1. heart rate: the HR measurement allows you to have a measure of the intensity of the exercise 2. calories expended: generally derived from the percentage of HR and body weight 3. single-lead electrocardiogram: single-lead ECG can give indications of atrial fibrillation 4. intensity of exercise (METS or VO2): derived from estimates made by devices or exercise equipment with specific estimation equations. The external load consists of: 1. number of steps: used to assess the volume of activity accumulated over the course of a day. They do not provide measures related to exercise intensity 2. calories expended: derived from work done and body weight 3. watts produced: deriving from exercise equipment such as exercise bikes, ellipticals, climbers, steppers

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Table 5. Tips and precautions for the practice of SPE according to various environmental conditions. Altitude

Patients who want to exercise at high altitudes (>2500 meters) should be evaluated on the basis of the severity of the disease, symptoms and scheduled altitude of programmed exercise. The clinical stability of the disease, the asymptomatic nature of the patient and good therapeutic control are necessary conditions. Progressive (pre)acclimatization and slow ascent above 2500 m (300-500 m per day) are recommended. In the first 24-48 hours, prudence and regular progression in the execution of technically/ physically demanding exercises, to allow cardiovascular and neuromotor adaptations, are mandatory Prepare a backpack with a weight of less than 1015% of body weight. Schedule regular breaks to facilitate recovery. Hiking poles can reduce the impact on the lower limbs, improve balance, and reduce the risk of falling. Sunscreen and sunglasses are essential. Never go to the mountains alone. Carry emergency call devices and continuously detect landmarks along the way. In remote areas, plan in advance for exit routes and rescue possibilities. Plan your outing in the mountains well based on your physical/technical abilities, the characteristics of the route, weather and daylight hours.

Temperature/ Schedule the exercise session in the daily schedule humidity adapted according to the season, avoiding temperatures that are too high or low. Carefully choose the technical clothing suitable for the expected temperature, possibly also bringing a change in case of long rides. Hydration will have to be adapted according to the temperature/humidity, the physical exercise practiced and any pathological conditions. The risk of heatstroke increases with temperature, humidity and the duration of exercise: take all precautions to prevent it. Prevent frostbite, with particular attention to the most exposed areas (fingers and toes). Pollution

In highly polluted outdoor environments, practice SPE indoors, in gyms or facilities with purifiers or air filters. Perform the SPE at a distance of more than 400 meters from the busiest roads. Evaluate the use of certified masks and respirators in case of high risk of exposure to pollutants. Programming SPE in green spaces and nature.

4. kilograms lifted: total weight and percentage of the ceiling. It represents numerous limitations and is not a substitute for subjective and better objective methods for determining intensity. All the parameters listed above, in order to be viewable by the doctor, once measured and/or calculated, must be saved on

a web-based platform. The most common device/tool and platform combination to date is shown in Table 6. It should be noted, however, that most wearable devices currently on the market provide data that do not have adequate accuracy to replace the classic medical evaluation in presence. In fact, only a small part of commercial wearable devices has currently received approval from the Food and Drugs Administration (FDA) as health-related devices and only for certain parameters, such as HR and ECG. For this reason, to date, wearable devices can only be used as a corollary to a medical assessment to ensure the safety of SPE. Real-Time Monitoring and Feedback. One of the main advantages of wearable devices is the ability to monitor various physiological and exercise parameters in real time (24). The collection of this data allows patients to receive immediate feedback on their physical performance, increasing awareness and commitment to the training program and consequently improving their results. In fact, the use of wearable devices has proven effective in increasing the level of SPE carried out in different age groups and clinical conditions, with clinically significant benefits maintained overtime (24-27). In addition, these features allow you to monitor progress during follow-up and assess adherence to SPE prescription (27). Examples are having satisfied the number of daily steps or the amount of time of moderate-vigorous intensity exercise28. Customization and adaptation of the prescribed SPE. Most wearable devices can be integrated with online digital health platforms, where the data collected is stored and analyzed. These platforms allow clinicians to easily access patient data, monitor progress, and tailor treatment plans as needed. For example, by analyzing heart rate data, you can adjust the intensity of your exercises to optimize benefits and minimize risks29. In addition, continuous monitoring helps identify any adherence issues, or a failure to achieve set goals, allowing timely interventions to motivate and support patients30. In fact, the integration of gamification functions, i.e. typical elements of games in non-ludic contexts, can significantly improve motivation and adherence to exercise programs. Features such as exercise reminders, challenges with other users, and recognition for achieving daily goals can turn training into a more engaging and fun activity, increasing patient adherence31. Ultimately, continuous monitoring of the patient’s clinical data and the actual volume and intensity of the exercise performed can help adjust the intensity of the prescribed exercise according to the patient’s physical condition, thereby minimizing the risks and maximizing the benefits (Table 7). Current limitations and future challenges. The use of wearable devices in healthcare settings is set to increase as technology advances; health systems and healthcare professionals will need to implement their management to maximize their potential and ensure that the benefits reach as many patients as possible. Several challenges still hinder the widespread adoption of wearable devices in clinical practice, including strong device heterogeneity in data collection accuracy, cost and battery life, and the issue of privacy32. The new challenge for the future will be the integration of artificial intelligence into the prescription of physical exercise33. Artificial intelligence algorithms can analyze large amounts of collected data, identify patterns, and predict risks, improving the personalization of training programs. In addition, artificial intelligence can provide real-time feedback and suggest adjustments based on the patient’s current health status and past performance, increasing the efficacy and safety of SPE. However, it should be underlined that these technologies are not yet able to replace the personalized and specific prescriptions for each clinical condition provided by health professionals34.

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Table 6. Combination of common wearables/tools and web-based platform. HR

CAL

ECG

VO2

STEPS.

WATT

MOST COMMON WEARABLES + PLATFORM Smartwatch with ECG* Sporty Smartwatch*

Sensor Bracelet*

Sensor Ring *

Wrist accelerometer

ECOSYSTEM Connected tools + Platform

Table 7. Benefits of wearable devices in the prescription of SPE. For the doctor

For the patient

Customize the prescription/administration of SPE based on the patient’s condition, using the data collected, improving their safety.

Provide immediate feedback on performance, improving safety and execution during exercise.

Monitor patient progress during follow-up.

Improve self-awareness and commitment toward the therapeutic pathway.

Detection of adherence problems of patient to the prescribed schedule.

Increase motivation and adherence to exercise programs through playful elements (gamification).

Provide easy access to data of patient training.

Identify the goals to be reached clearly and progressively.

References 1.

American College of Sports Medicine. Guidelines for Exercise Testing and Prescription. Tenth Edition. Wolters Kluwer Health 2018. 2. Giada F, Biffi A, Agostoni P, et al. Exercise prescription for the prevention and treatment of cardiovascular diseases: part I. J Cardiovasc Med 2008; 9: 1-16. 3. Clarke CL, Witham MD. The Effects of Medication on Activity and Rehabilitation of Older People. Opportunities and Risks. Rehabilitation Process and Outcome 2017; 6: 1-8. 4. Taylor JL, Myers J, Bonikowske AR. Practical guidelines for exercise prescription in patients with chronic heart failure. Heart Fail Rev 2023; 28: 1285-96. 5. Abreu A, Frederix I, Dendale P, et al. Standardization and quality improvement of secondary prevention through cardiovascular rehabilitation programmes in Europe: The avenue towards EAPC accreditation programme. Eur J Prev Cardiol 2021; 28: 496-509. 6. Griffo R, Ambrosetti M, Furgi G, et al. Requirements and indicators in rehabilitation cardiology: consensus document of the ICRC/IACPR. Monaldi Arch Chest Dis 2012; 78: 166-92. 7. Iliou MC, Pavy B, Martinez J, et al. Exercise training is safe after coronary stenting: a prospective multicentre study. Eur J Prev Cardiol 2015; 22: 27-34. 8. American Heart Association Scientific Statement. Update to practice standards for electrocardiographic monitoring in hospital settings. Circulation 2017; 136: e273-344. 9. Legislative Decree no. 36 of 28 February 2021. Implementation of Article 5 of Law No. 86 of 8 August 2019. Gazzetta Ufficiale 2021. 10. State-Regions Conference 3 November 2021. Guidelines on physical activity. Revision of recommendations for different age groups. Ministero della Salute 2021. 11. Legislative Decree no. 163 of 5 October 2022. Supplementary and corrective provisions of Legislative Decree no. 36 of 28 February 2021. Gazzetta Ufficiale 2022. 12. Resolution of the Veneto Regional Council no. 549 / DGR of 09/05/2023.

Update of the D.G.R. n.925 and n.280 relating to the “Health Gyms”. Bollettino Ufficiale Regione Veneto 2023. 13. Resolution of the Regional Council of Emilia Romagna: D.G.R. no. 2127 of 5 December 2016. Bollettino Ufficiale Regione Emilia-Romagna 2016. 14. Cornwell WK 3rd, Baggish AL, Bhatta YKD, et al. Clinical Implications for Exercise at Altitude Among Individuals with Cardiovascular Disease: A Scientific Statement from the American Heart Association. J Am Heart Assoc 2021; 10: e023225. 15. Andrew ML, Peter HH. Medical Conditions and High-Altitude Travel. N Engl J Med 2022; 386: 364-73. 16. Parati G, Agostoni P, Basnyat B, et al. Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions. Eur Heart J 2018; 39: 1546-54. 17. Rajagopalan S, Brauer M, Bhatnagar A, et al. Personal-Level Protective Actions Against Particulate Matter Air Pollution Exposure: A Scientific Statement From the American Heart Association. Circulation 2020; 142: e411-431. 18. Alnasser S, Alkalthem D, Alenazi S, et al. The Reliability of the Apple Watch’s Electrocardiogram. Cureus 2023; 15: e49786. 19. Fuller D, Colwell E, Low J, et al. Reliability and Validity of Commercially Available Wearable Devices for Measuring Steps, Energy Expenditure, and Heart Rate: Systematic Review. JMIR Mhealth Uhealth 2020; 8: e18694. 20. Miller DJ, Sargent C, Roach GD. A Validation of Six Wearable Devices for Estimating Sleep, Heart Rate and Heart Rate Variability in Healthy Adults. Sensors (Basel) 2022; 22: 6317. 21. Hajj-Boutros G, Landry-Duval MA, Comtois AS, et al. Wrist-worn devices for the measurement of heart rate and energy expenditure: A validation study for the Apple Watch 6, Polar Vantage V and Fitbit Sense. Eur J Sport Sci 2023; 23: 165-77. 22. Ferguson T, Olds T, Curtis R, et al. Effectiveness of wearable activity trackers to increase physical activity and improve health: a systematic review of systematic reviews and meta-analyses. Lancet Digit Health 2022; 4: e615-626. 23. Hannan AL, Harders MP, Hing W, et al. Impact of wearable physical activity monitoring devices with exercise prescription or advice in the mainte-

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nance phase of cardiac rehabilitation: systematic review and meta-analysis. BMC Sports Sci Med Rehabil 2019; 11: 14. 24. Vecchiato M, Battista F, Duregon F, et al. Tailored exercise with telehealth monitoring improves adherence and global health in kidney transplant recipients. Front Sports Act Living 2024; 6: 1-10. 25. Shei RJ, Holder IG, Oumsang AS, et al. Wearable activity trackers-advanced technology or advanced marketing? Eur J Appl Physiol 2022; 122: 1975-90. 26. Stamatakis E, Ahmadi MN, Gill JMR, et al. Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality. Nat Med 2022; 28: 2521-9. 27. Lunde P, Bye A, Bergland A, et al. Long-term follow-up with a smartphone application improves exercise capacity post cardiac rehabilitation: A randomized controlled trial. Eur J Prev Cardiol 2020; 27: 1782-92.

28. Finkelstein EA, Haaland BA, Bilger M, et al. Effectiveness of activity trackers with and without incentives to increase physical activity (TRIPPA): a randomised controlled trial. Lancet Diabetes Endocrinol 2016; 4: 983-95. 29. Bayoumy K, Gaber M, Elshafeey A, et al. Smart wearable devices in cardiovascular care: where we are and how to move forward. Nat Rev Cardiol 2021; 18: 581-99. 30. Palermi S, Vecchiato M, Saglietto A, et al. Unlocking the potential of artificial intelligence in sports cardiology: does it have a role in evaluating athlete’s heart? Eur J Prev Cardiol 2024; 31: 470-82. 31. Dergaa I, Saad HB, El Omri A, et al. Using artificial intelligence for exercise prescription in personalised health promotion: A critical evaluation of OpenAI’s GPT-4 model. Biol Sport 2024; 41: 221-41.

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3 Exercise prescription in patients with risk factors and/or cardiovascular disease 1. Dyslipidemia 2. Arterial hypertension 3. Diabetes mellitus and metabolic syndrome 4. Coronary artery disease 5. Valvular heart disease 6. Cardiomyopathies 7. Arrhythmias and devices carriers 8. Congenital heart disease 9. Heart failure and heart transplantation 10. Arterial disease of the lower limbs 11. Cardio-oncology 12. The prescription of physical exercise in post-acute cardiac patients and in patients awaiting cardiac surgery: prehabilitation

| CHAPTER 3.1 |

Dyslipidemia Giampiero Patrizi, Claudio Bilato, Arrigo Cicero, Franco Giada, Pasquale Perrone Filardi

The concept that exercise produces favorable effects both in established cardiac patients and in subjects with cardiovascular risk factors is now universally accepted1,2. One of the mechanisms involved in these effects is certainly represented by the action of physical activity on the different components of the lipid profile at different levels of lipid metabolism, on the reduction of triglycerides and, to a lesser extent, also of total and LDL cholesterol. In addition, perhaps the most significant beneficial effect is the increase of HDL cholesterol,3. Recent data show that non-HDL cholesterol is a better predictor of cardiovascular disease than traditional LDL cholesterol and exercise has confirmed its beneficial effect on this fraction of the lipid profile, too. Therefore, the practice of physical activity on a regular and continuous basis is able to act and favorably modify the totality of circulating plasma lipoproteins, both in normolipemic subjects and in dyslipidemic patients, as summarized in table 14,5. Table 1. Exercise-induced changes in lipid profile (modified from Lavie 20194 and Vanhees 20125). NORMOLIPEMIC

DYSLIPIDEMIC

Total cholesterol

-5%

-8%

Triglycerides

-15%

-20%

HDL-C

+6%

+11%

LDL-C

-2%

-10%

Several studies have shown how other elements can influence, from a merely numerical and quantitative point of view, the extent of these changes. First, the basal levels of the various lipid components; the higher the initial lipid values, the greater the expected benefit6. A further multiplier of the beneficial effect of exercise is represented by the simultaneous observance of a virtuous diet. Genetic factors can also influence the extent of the reductions expected from the application of physical exercise on dyslipidemic subjects. Finally, the type and intensity of exercise practiced have profound influences on variations in the lipid profile. The beneficial effects of purely aerobic exercise have been known for a long time ago, while it is a more recent acquisition that also isometric or strength exercise has similar efficacy, also rewarded by the need of shorter exercise sessions6-8. Moreover, the correlation between the age of the dyslipidemic patient and the extent of changes in the lipid structure is another important issue9,10. The application of regular physical activity is quantitatively more effective on the reduction of lipid parameters in the intermediate-high age group (between 40 and 70-75 years), while the effect seems to be attenuated in frankly advanced age when a physiological decrease in cholesterolemia values takes place. This observation reiterates the importance of engaging in SPE programs as early as possible and maintaining the habit of physical activity throughout life, even considering that the lipid

cardiovascular risk is function of the time of exposure to high cholesterol levels, more than cholesterol lever “per se”11. Different observations have highlighted the discrepancy between the significant reduction in mortality obtained by the practice of regular physical exercise and its limited effect on LDL cholesterolemia, even independently from the reduction in body weight or body mass index (BMI). This apparent inconsistency can be explained by the qualitative variations induced by the exercise on the different components of the lipid profile: in particular, the reduction of particularly atherogenic LDL subfractions, such as small and dense LDL (sdLDL) or even intermediate density lipoproteins (IDL) or very low density lipoproteins (VLDL). This favorable modification of the lipoprotein pattern is independent from the decrease in body weight, suggesting the advantage of a regular SPE program per se. Other studies show that structured physical activity results in a reduction in circulating levels of oxidized LDL and this is particularly relevant as this subfraction is associated with an increased atherogenic risk12,13. A more recent lipid component of great scientific interest and pharmacological research is lipoprotein (a) or Lp(a), which is an important cardiovascular risk factor and whose levels are genetically determined Only intense physical activity can reduce, even if only very partially, Lp(a) levels and then without obtaining a significant reduction in global cardiovascular risk14-17. In case of marked dyslipidemia or high basal cardiovascular risk, in addition to the practice of physical exercise (central core of this document), pharmacological treatment becomes necessary. The intensity of the intervention to be undertaken must consider various elements such as the primary or secondary prevention condition, the global cardiovascular risk profile of the patient to be treated, the presence/absence of vascular atheromasia and, obviously, plasma lipid values. In case of hypertriglyceridemia (in a non-diabetic subject) the initial intervention is dietary/nutritional, very often effective and conclusive in these patients, differently from what happens in hypercholesterolemia, followed by the use of polyunsaturated fatty acids (omega-3) such as alpha-linolenic acid (ALA), eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) and finally by a pharmacological therapy with fibrates (gemfibrozil or preferably fenofibrate) in cases of greater severity. In case of concomitant use of statins, combination with fibrates is recommended only for fenofibrate. In athletes, in primary prevention and with a mild/moderate cardiovascular risk profile, but with LDL cholesterol levels above the recommended targets, the initial treatment can be represented by the use of nutraceuticals, especially if the distance from the target LDL cholesterol value is small. As LDL cholesterol values and/or the CV risk profile increase, treatment with statins + ezetimibe becomes mandatory18-21. These are extremely effective and safe drugs, only minimally penalized by the possible appearance of myalgias, a side effect

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that is generally not severe, but particularly undesired by those who practice physical activity. The association of myalgias with statin therapy is certainly known and probably reported to a greater extent than what actually happens (“nocebo effect”). The incidence of this disturbing adverse effect is not higher than 10% of subjects treated, but there is great evidence that myalgias moderately increase in those who regularly exercise22. More uncommon is the occurrence of true statin-induced myositis, expressed by the significant rise (x 5 times above upper normal values) of muscle enzymes such as creatine kinase (CK). However, the phenomenon is usually reversible when treatment is stopped. On the other hand, the doubt that statin therapy can cause the worsening of muscle and athletic performance has been repeatedly rejected23. The strategies suggested to manage this side effect are different: • change of the molecule • preference for hydrophilic statins over lipophilic ones • use of combination therapy with ezetimibe reducing statin dose • use on alternate days and • replacement with bempedoic acid particularly indicated among those who practice physical exercise. Figure 1 shows the differences in pharmacodynamic potency of the individual statin molecules on LDL cholesterolemia. Bempedoic acid is characterized by an excellent tolerability profile without inducing the onset of myalgias and, either in combination with or as an alternative to statins, it still obtains

significant reductions in LDL cholesterolemia capable of targeting the vast majority of patients. If oral cholesterol-lowering therapies are not sufficient, parenteral administration of PCSK9 inhibitor drugs (alirocumab and evolocumab monoclonal antibodies and inclisiran siRNA), characterized by high cholesterol-lowering efficacy and excellent tolerability, can be used. However, the indications for their use and the criteria for reimbursement by the NHS make the prescription infrequent in the population covered by this document. The table 2, taken from the 2019 Guidelines of the European Society of Cardiology on the treatment of dyslipidemia, is shown below, concerning the percentage reductions expected from the use of the main cholesterol-lowering treatments, alone or in combination with two or more products11. Table 2. Intensity of lipid-lowering treatment. TREATMENT

% LDL Reduction

Nutraceuticals

10-20%

Moderate-intensity statins

approx 30%

High-intensity statins

approx 50%

High Intensity Statins + Ezetimibe

approx 65%

Inhibitors PCSK9

approx 60%

PCSK9 Inhibitors + High Intensity Statins

approx 75%

PCSK9 Inhibitors + High Intensity Statins + Ezetimibe

approx 85%

70 60 LDV ↓ %

50 40 30 20 10 0

A10 A20 A40 A20 F20 F40 F80 L10 L20 L40 L80 P10 P20 P40 S10 S20 S40 S80 R6 R10 R20 R40 P1 P2 P4 ATOR FLUVA LOVA PRAVA SIMVA ROSU PITA

Figure 1. Therapeutic equivalence of the various statins on LDL24 cholesterolemia values. ATOR: atorvastatin; FLUVA: fluvavastatin; LOVA: lovavastatin; PRAVA: pravavastatin; SIMVA: simvastatin: ROSU: rosuvastatin; PITA: pitavastatin.

Table 3. Indications for exercise prescribing in patients with dyslipidemia.

Aerobic

Frequency

Intensity

Time

Type

2-5 times/week

Moderate-high

30-60 min

Aerobic at constant intensity

2-5 times/week

High

10-15 min

HIIT

Strength

2-3 times/week

Moderate-high

2-4 sets, 8-12 reps

Isometric / Power

Complementary

2-3 times/week

Moderate

10-30 sec, 2-4 reps

Flexibility

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In conclusion, the practice of physical exercise, especially when correctly prescribed according to the FITT methodology (table 3), has a very favorable effect on the lipid profile, generating benefits not only in terms of laboratory parameters, but also, and above all, on significant clinical end-points.

References 1.

U.S. Department of Health and Human Services. Physical Activity Guidelines for Americans: 2nd Edition. www.health.gov 2018. 2. Romano S, Minardi S, Patrizi G, et al. Sport in ischemic heart disease: Focus on primary and secondary prevention. Clin Cardiol 2023; 46: 1021-7. 3. Mendoza MF, Lavie CJ. Clinical associations between exercise and lipoproteins. Curr Opin Lipidol 2022; 33: 364-73. 4. Lavie CJ, Kachur S, Sui X. Impact of fitness and changes in fitness on lipids and survival. Prog Cardiovasc Dis 2019; 62: 431-5. 5. Vanhees L, Gelads N, Hansen D, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular risk factors: recommendations from the EACPR (Part II). Eur J Prev Cardiol 2012; 19: 1005-33. 6. Sulague RM, Suan NNM, Mendoza MF, et al. The associations between exercise and lipid biomarkers. Prog Cardiovasc Dis 2022; 75: 59-68. 7. Doewes RI, Gharibian G, Zadeh FA, et al. An Updated Systematic Review on the Effects of Aerobic Exercise on Human Blood Lipid Profile. Curr Probl Cardiol 2023; 48: 101108. 8. Madan K, Sawhney JPS. Exercise and lipids. Indian Heart J 2024; 76 Suppl 1: S73-S74. 9. Barbosa AO, Silva JMDPF, Silva DJ, et al. Longitudinal association between moderate to vigorous physical activity and lipid profile indicators in adolescents. Eur J Sport Sci 2023; 23: 1405-1414. 10. Yun H, Su W, Zhao H, et al. Effects of different exercise modalities on lipid profile in the elderly population: A meta-analysis. Medicine (Baltimore) 2023; 102: e33854. 11. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41: 111-88.

12. Bachi ALL, Barros MP, Vieira RP, et al. Combined Exercise Training Performed by Elderly Women Reduces Redox Indexes and Proinflammatory Cytokines Related to Atherogenesis. Oxid Med Cell Longev 2019; 2019: 6469213. 13. Afşin A, Bozyılan E, Asoğlu R, et al. Effects of regular exercise on inflammatory biomarkers and lipid parameters in soccer players. J Immunoassay Immunochem 2021; 42: 467-77. 14. Fogacci F, Di Micoli V, Sabouret P, et al. Lifestyle and Lipoprotein(a) Levels: Does a Specific Counseling Make Sense? J Clin Med 2024; 13: 751. 15. Mosteoru S, Gaiţă L, Gaiţă D. Sport as Medicine for Dyslipidemia (and Other Risk Factors). Curr Atheroscler Rep 2023; 25: 613-17. 16. Föger B, Jennings C, Pirillo A, et al. Hypercholesterolemia and cardiovascular disease: What to do before initiating pharmacological therapy. Atheroscler Suppl 2020; 42: e25-e29. 17. Barone Gibbs B, Hivert MF, Jerome GJ, et al. Physical Activity as a Critical Component of First-Line Treatment for Elevated Blood Pressure or Cholesterol: Who, What, and How? A Scientific Statement from the American Heart Association. Hypertension 2021; 78: e26-e37. 18. Katsiki N, Mikhailidis DP, Bajraktari G, et al. Statin therapy in athletes and patients performing regular intense exercise - Position paper from the International Lipid Expert Panel (ILEP). Pharmacol Res 2020; 155: 104719. 19. Gavilán-Carrera B, Soriano-Maldonado A, Mediavilla-García JD, et al. Prescribing statin therapy in physically (in)active individuals vs prescribing physical activity in statin-treated patients: A four-scenario practical approach. Pharmacol Res 2023; 197: 106962. 20. Alvarez-Jimenez L, Moreno-Cabañas A, Ramirez-Jimenez M, et al. Effectiveness of statins vs. exercise on reducing postprandial hypertriglyceridemia in dyslipidemic population: A systematic review and network meta-analysis. J Sport Health Sci 2022; 11: 567-77. 21. Petridou A, Mougios V. Exercise to Lower Postprandial Lipemia: Why, When, What and How. Int J Sports Med 2022; 43: 1013-22. 22. Noyes AM, Thompson PD. The effects of statins on exercise and physical activity. J Clin Lipidol 2017; 11: 1134-44. 23. Morville T, et al. Aerobic Exercise Performance and Muscle Strength in Statin Users – The Lifestat Study. Med Sci Sports Exerc 2019; 51: 1429-37. 24. Mukhtar RY, et al. Pitavastatin. Int J Clin Pract 2005; 59: 239-52.

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| CHAPTER 3.2 |

Arterial hypertension Lucio Mos, Francesco Fattiroli, Stefania Paolillo, Silvio Romano

Physical exercise exerts favorable effects in the patient suffering from arterial hypertension, and several training programs can be safely recommended in most hypertensive patients. An inverse relationship exists between exercise and blood pressure levels. The effect was observed for all exercise modalities, in a different way, but in a consistent direction in demonstrating a significant reduction in BP1,2. The extent of the pressure drop that is obtained with aerobic physical training is equal to 3-4 mmHg, both for systolic and diastolic blood pressure, an effect that is more marked during the day, modest during sleep. This drop in blood pressure does not seem to be proportional to the intensity and frequency of training. Recent studies3 have, in fact, shown that the greatest effects of reducing BP, for aerobic exercises, occur for a training frequency equal to three times a week, without a gain for training carried out at higher weekly frequencies. Similarly, exercise intensity is related to lowering blood pressure with a J-curve: the greatest benefits are obtained with moderate-intensity exercise (45-65% of the predicted VO2max). With regard to the mechanisms underlying this relationship, the reduction of sympathetic tone is one of the main ones and tends to reduce the activity of the renin-angiotensin-aldosterone system as well. In addition, the persistence of increased muscle blood flow after training has been demonstrated, which in turn is linked to increased nitric oxide production and activation of histamine metabolic pathways. Finally, induced long-term vasodilation aerobic exercise is attributed to changes in skeletal muscle, such as the enrichment of slow muscle fibers (oxidative, red), accompanied by capillarization, angiogenesis, and metabolic changes4. The physiological reduction in sympathetic tone operated by aerobic training is also able to modify in a favorable way numerous other risk factors for atherosclerosis, namely tachycardia, dyslipidemia, reduced glucose tolerance, increased plasma renin activity, alterations in membrane ion transports5. Starting from these premises, an activity program based on moderate-intensity workloads appears sufficient in the hypertensive patient. The most suitable activities are aerobic ones, combined with dynamic and isometric strength training sessions. In order to establish the optimal intensity of the effort, a MEST should be performed, which allows you to know the maximum HR achievable by the subject, or a CPET, capable of identifying the functional capacity of the subject by measuring the peak oxygen consumption (VO2peak), the values of the ventilatory thresholds, the cardiorespiratory response to exercise, useful parameters to better calibrate training programs and verify their the effects on cardiovascular performance and, of course, on BP6,7. The first step is to evaluate the CV risk profile and any indications to the clinical-instrumental evaluation. A number of assessment systems are available, based on country-specific cohort data. In the European context, the guidelines suggest the adoption of the SCORE2 system (SCORE2-OP for subjects over 70 years of age), as well as the SCORE2-diabetes system for diabetic subjects (see chapter 2.1 on risk stratification). There are additional elements, such as the presence of atherosclerotic plaques in the carotid or femoral arteries, that can refine the classification of individual cardiovascular risk. People with documented car-

diovascular disease, diabetes mellitus, familial hypercholesterolemia or chronic kidney disease should be considered at high or very high cardiovascular risk. In order to streamline the identification of the individual risk profile and the indication of the most suitable method in the evaluation of the subject with arterial hypertension in the prescription of physical exercise, the following scheme is proposed (table 1).

Drug therapy8 ACE inhibitors have been shown to be effective in controlling BP during both dynamic and isometric exercise without affecting VO2peak, maximum tolerated workload, and overall exercise duration. Sartans have been shown to be as effective in reducing BP during dynamic exercise as ACE inhibitors, and some studies have shown even a slight improvement in performance4. In subjects in whom the use of compounds belonging to the aforementioned classes is not sufficient or contraindicated, the choice should fall on dihydropyridine calcium channel blockers, which reduce BP during dynamic exercise without affecting physical performance. Diltiazem, a non-dihydropyridine calcium channel blocker, also seems not to cause changes in VO2peak, while verapamil seems to reduce performance. It is necessary to remember that, in women of childbearing age, the first choice is always calcium channel blockers due to the possible teratogenic effect of sartans and ACE inhibitors. Alpha-blockers are no longer included among the drugs of first choice, but in the case of subjects who have intolerance to the antihypertensive drugs mentioned above, doxazosin can be used, a drug without negative effects on performance, but with the possibility of facilitating post-exercise orthostatic hypotension (causing presyncope or syncope). Centrally acting antiadrenergics (alphamethyldopa, clonidine) are not recommended, because they reduce myocardial contractility and easily cause annoying side effects. Beta blockers alter the metabolic response during exercise, reduce exercise tolerance. If the use of these drugs is appropriate, for example in subjects with marked adrenergic activation and hypertensive response to effort, it is preferable to use nebivolol (with very high cardioselectivity) in order to minimize the negative effects on performance. Diuretics should always be used carefully as they can induce hemodynamic and electrolyte alterations that can promote arrhythmia and reduce performance. In subjects with low cardiovascular risk and mild hypertension, the initial approach may be monotherapy; if, on the other hand, the cardio-vascular risk is moderate or high or the BP values are higher, it will be necessary to set up a combination therapy immediately and in this case calcium channel blockers associated with ACE inhibitors or sartans should be preferred. Beta blockers may be associated in individuals with a strong adrenergic component and hypertensive response to exertion. For other general considerations on drug therapy, see also the chapter on safety in the prescription and administration of SPE.

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Table 1. Cardiovascular evaluation of the patient with arterial hypertension. Cardiovascular risk classes

Low-moderate

High

Very high AH >160/100 mmHg or with cardiovascular risk factors or with mild-moderate organ damage.

Hypercholesterolemia col LDL >190 mg/dl) Arterial hypertension (AH) not well controlled (>140/90 mmHg) at rest. Asymptomatic with controlled hypertension and pre-hypertension, in the absence of known risk factors.

Definition

Type 1 diabetes with age <35 years.

Type 2 diabetes with age <50 years, present for less than 10 years, controlled and without other known risk factors.

Diabetes with organ damage (microalbuminuria, retinopathy, neuropathy).

Renal insufficiency (creatinine 1.3-1.5 mg/dl in men, 1.2-1.4 mg/dl in women)

Left ventricular hypertrophy.

Carotid atherosclerotic plaque.

Documented cardio-cerebrovascular disease (see chapter on ischemic heart disease). Clinical-instrumental evaluation

Clinical evaluation, therapy optimization, possible Stress test or CPET.

Adequate blood pressure (BP) control is sufficient, no further evaluation is necessary.

Practical indications in the prescription of exercise in hypertensive subjects It is essential to choose exercises that improve cardiovascular health by avoiding an excessive pressure load on the cardiovascular system9,10. For people with high blood pressure, it’s generally important to choose exercises that help reduce blood pressure without reaching very high values during exercise9,11.

Clinical evaluation, therapy optimization, echocardiogram, Stress testing/CPET.

For people with low-risk high blood pressure, a medical evaluation is not considered necessary before starting the activity. The higher the cardiovascular risk, the greater the indication to consult the Sports Physician regularly to assess progress and make any changes to the exercise program. In addition to general recommendations, such as an adequate warm-up period, we report in table 2 some examples of prescription of SPE for subjects with arterial hypertension.

Table 2. Indications for exercise prescribing in patients with arterial hypertension.

Aerobic

Strength

Complementary

Frequency

Intensity

Time

Type

5-7 times/week

Moderate

30-60 min

Aerobic - walking

3-5 times/week

Moderate

20-40 min

Aerobic - light running/jogging

3-5 times/week

Moderate

30-60 min

Aerobic - cycling

3-5 times/week

Moderate

30-60 min

Aerobic - swimming

2-3 times/week

Mild-moderate

20-30 min (1-2 sets, 10-15 rep)

Light weight lifting

2-3 times/week

Mild-moderate

20-30 min (large muscle groups)

Exercises with elastic bands

2-3 times/week

Mild-moderate

30-60 min

Yoga dolce (Hatha Yoga)

2-3 times/week

Mild-moderate

30-60 min (breathing techniques)

Pilates

2-3 times/week

Mild-moderate

30-60 min (slow and controlled movements)

Tai Chi

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References 1. 2.

3. 4. 5.

American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and Prescription; Eleventh edition, 2021. Wolters Kluwer Health. Cornelissen VA, Fagard RH, Coeckelberghs E, et al. Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension 2011; 58: 950. Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and meta-analysis. J Am Heart Assoc 2013; 2: e004473. Hayes P., Ferrara A., Keating A, et al. Physical Activity and Hypertension. Rev. Cardiovasc Med 2022; 23: 302. Juhlin-Dannfelt A, Frisk-Holmberg M, Karlsson J, et al. Central and peripheral circulation in relation to muscle-fibre composition in normo- and hyper-tensive man. Clin Sci (Lond) 1979; 56: 335. Lee SH, Chae YR. Characteristics of Aerobic Exercise as Determinants of

Blood Pressure Control in Hypertensive Patients: a Systematic Review and Meta- Analysis. J Korean Acad Nurs 2020; 50: 740. 7. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023; 41: 1874. 8. Mos L, Degano C, Plett G, et al. Antihypertensive therapy in Athletes. Austin Sport Med 2020; 5: 1042. 9. Niebauer J, Börjesson M, Carre F, et al. Recommendations for participation in competitive sports of athletes with arterial hypertension: a position statement from the sports cardiology section of the European Association of Preventive Car- diology (EAPC). Eur Heart J 2018; 39: 3664. 10. Palatini P. Blood pressure behaviour during physical activity. Sports Med 1988; 5: 35. 11. Palatini P. Cardiovascular effects of exercise in young hypertensives. Int J Sports Med 2012; 33: 683.

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| CHAPTER 3.3 |

Diabetes mellitus and metabolic syndrome Antonio Bonetti, Alberto Anedda, Gerardo Corigliano, Cristina De Fazio, Felice Strollo

Diabetes mellitus (DM) is both a chronic progressive disease and one of the main cardiovascular risk factors. It is in eighth place as the cause of death and disability in the world, in rapid and continuous expansion, so much so that it is considered the epidemic of the third millennium (96% DM type 2), with prevalence that has doubled in the last 30 years and will have tripled (1.3 billion people) in the projections by 20501,2. Physical inactivity is a major cause of type 2 DM and metabolic syndrome (MS). Conversely, regular physical activity is a primary prevention factor for cardiometabolic diseases and also plays a fundamental therapeutic role. Through induced adjustments and adaptations, glucose uptake by peripheral tissues improves (mainly due to the increased insulin sensitivity). The muscle represents 90% of insulin-sensitive tissues: glucose, in order to be captured, must first be made available for the trans-membrane transport of muscle fibrocells by the increased secondary flow to exercise-induced vasodilation (acute effect) and training-induced capillarization (chronic effect). Physical exercise also induces the transmigration of glucose transporters (GLUT4) to the cellular surface (acute effect), while training increases the generalized synthesis of proteins (chronic effect). At the same time, the increased expression of PGC1 increases the mitochondrial ability to oxidize glucose (epigenetic modifications). Therefore, increased insulin sensitivity is bigger in trained people than in sedentary people. Additional effects are described in table 1. Table 1. Exercise-induced metabolic adaptations in diabetes. INCREASE

REDUCTION

Receptors insulin

Fat Mass, Plasma and muscle myostatin

Bulk Muscular

Pro-inflammatory cytokines (TNF-α, IL-1-β, IL-6, CRP), interfibrillar fat

DNA Mitochondrial Biogenesis, Endothelial metabolic dysfunction Enzymatic Activities and Atherosclerosis Glycolytic Capacity

The major effects are observed with aerobic or HIIT exercise and with a lasting longer than 24 weeks (3 sessions/week and >60’/session) program3. Type 2 diabetes. This is probably the area in which SPE acts as a real drug since it reaches various levels of prevention. In primary prevention, it is “cost-effective” and “cost-saving” and is also more effective than metformin, universally used drug both to treat clinically manifest DM2 and to slow down its progressive transition from the prediabetic condition4. SPE can maintain a good metabolic balance without the need of drug therapy for years of DM2 caught at onset5, before it becomes highly dangerous for cardiovascular damage (secondary prevention). In addition, DM2 is often associated with comorbidities (obesity, hypertension, dyslipidemia, etc.) on which SPE, due to its pleiotropic effects, exerts an equally important action.

Type 1 diabetes. The role of SPE is, in this case, different because, to date, the autoimmune genesis does not provide for any preventive action (apart from trying primary prevention in autoantibody-positive children with the monoclonal antibody Teplizumab, a procedure still considered experimental to date) and the cure is represented exclusively by insulin replacement therapy. However, SPE remains fundamental, as in DM2, for diminishing of cardiovascular risk factors and for the increase in insulin sensitivity, which lasts even more than 24 hours in relation to the volume of work performed (acute effect), and over time reduces the exogenous insulin requirement in the trained person (chronic effect), while requiring the variation of insulin dosage and carbohydrate intake in relation to the type, intensity, duration, frequency and timing of the sessions carried out. Metabolic syndrome (MS). In addition to the elements that define it (at least three among abdominal obesity, hypertriglyceridemia, low HDL cholesterol values, “dysglycemia”, hypertension), MS often exponentially increases its cardiovascular risk through other factors. Its prevalence is about 25% in the general population and increases with age to almost 50% in the over 50s. This makes pharmacological treatment unfeasible for any National Health Service due to the high cost (polypharmacy required and related iatrogenic risks from interactions), but also due to the impracticability of screening and treatment of a quarter of the population, without certainty that tangible results will be obtained on a disease not recognized by everyone as such. SPE, on the other hand, is an effective and low-cost treatment of MS, because, if combined with dietary restriction, in the obese person if it induces weight loss (5-10%), reduces insulin resistance by 30-60%, with clear beneficial effects on all related risk factors and with the possibility that the parameters of MS themselves (de facto recovery) will disappear. Depending on the clusters present, the prescription of SPE (type, intensity, duration, frequency) will be inter- and intra-individual6-8. Therapy. Given that sulphalinureas and glinides should be avoided in 2024 due to high hypoglycemic risk, which becomes higher in those who practice SPE, the safest therapies include: metformin, acarbose, DPP4 inhibitors. The recent introduction on the market of innovative drugs (inhibitors of the sodium-glucose co-transporter type 2 [SGLT2i], analogues of glu-cagonlike-peptide-1 [GLP1ra] has revolutionized the therapy of DM2. Benefits include the reduction of: • glycated hemoglobin-HbA1c, similar to insulin therapy without, however, hypoglycemic risks; • hunger and body weight; • progression of renal disease (45%) and MACE (14%) for SGLT2i9, including Dapaglifozin that improve exercise capacity in heart failure with preserved EF10. More evidence in the prevention of acute cardiovascular events (26%) has been demonstrated with some GLP1-ra, so much so that the prescription of GLP1-ra in case of previous events is mandatory, even from a forensic medicine point of view11-13.

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In individuals with DM, who practice SPE, the greatest risk is insulin-induced hypoglycemia due to increased glucose uptake, improved insulin sensitivity and reduced/absent compensatory activation of hepatic gluconeogenesis due to lack of physiological reduction in portal insulinization. The complex adjustments required are now possible thanks to therapeutic education and available technologies (insulin pumps-CSII, integrated in-closedloop sensors and apps for “carbohydrate calculation”). In particular, the pumps are equipped with a “physical exercise” function and therefore designed for the reduction and/or suspension of continuous insulin delivery in response to sensors with a “predictive alarm” function. The integration of these devices with specific apps allows those who have DM1 to also practice sports at a professional level without cardio-metabolic risks. For a correct and safe prescription of the SPE and the practice of recreational-motor sports activities in the cardiometabolic field and of the relationship “functional capacity-health-related quality of life”, both in DM1 and DM2 it is recommended to follow a four-phase protocol, as illustrated in the flow-chart (figure 1)14. The indicated flow-chart represents the ideal method of prescription, even if at the moment it is not reasonably applicable throughout the national territory. The protocol provides for:

1) clinical assessment and risk stratification (see dedicated chapter); 2) motor-motivational counseling to assess the attitude to change and related assessment of physical fitness; 3) planning and structuring of an SPE program; 4) check and follow-up (3-6 months) for the monitoring of clinical-anthropometric results. A moderate-intensity SPE is most likely to popularly change cardiometabolic biomarkers of chronic inflammation and is therefore particularly indicated in people with MS and/or DM2. Both aerobic and SPE appear to be effective in improving insulin sensitivity and glucose tolerance: the best results derive from the association of the two types of work, whose frequency and duration (at least 150 minutes/week distributed over at least 5 days) affect the reduction of glycated hemoglobin (HbA1c) more than intensity15, 16. A high-intensity SPE may be prescribed without additional risk, in selected and conditioned people with DM2 and/ or MS with moderate cardiovascular risk for a total of at least 75 minutes/week over multiple daily sessions. In DM1 frequency, intensity and duration vary in relation to the degree of performance required. Given that moderate-intensity aerobic SPE is better suited for prevention of hypoglycemia and the reduction of insulin requirements, in addition to improving CRF, HIIT can also be performed, but it requires high

Diabetes Care Team Diabetologist

Sports Medicine Specialist

Cardiologist

Cardiorespiratory Evaluation

Metabolic Evaluation

Kinesiologist

Diabetologist

Sports Medicine Specialist

Kinesiologist

Motivational Interviewing for Physical Activity

Metabolic Evaluation

Sports Medical Examination for Fitness

Fitness Evaluation

Motor Activity Prescription

Fitness Evaluation

SPE Prescription SPE Program Planning and Organization 3-6 months Follow-up

SPE

Motor Activity

1. Improvement of clinical and metabolic parameters 2. Daily routine changes 3. Improvement in perceived health and quality of life

1. performance optimization 2. Injury prevention 3. Health promotion

Motor Activity Program Planning and Organization

3-6 months Follow-up

Figure 1. Role of the Diabetes Team, in an integrated and shared approach, in ensuring that every aspect of the health and/or fitness of the person with DM is carefully considered and managed, as well as personalized and monitored.

Table 2. Exercise Management in Diabetes Complications. COMPLICATIONS

INDICATIONS

Coronary artery disease

See chapter on ischemic heart disease

Retinopathy

Avoid high-intensity strength exercises

NOTES Risk of vitreous haemorrhages, retinal detachment

Peripheral neuropathy

Light training

Breathable footwear with a unique, flexible upper, seamless

Autonomicneuropathy

Pay attention to the water intake (heat dissipation)

Risk of dehydration and thromboembolism

Hypoglycemia unawareness syndrome: low-intensity SPE Always wear sensors with low predictive alarms

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awareness and therapeutic education, good metabolic control, absence of complications and the use of technologies (sensors with hypopredictive alarms, insulin pumps with “physical exercise” functions, better if integrated)18,19. The prescription of SPE cannot be separated from a correct clinical framework: absence/presence, level and relative-absolute contraindications of chronic complications as indicated below (table 2). For the parameters and criteria to be used for the intensity levels, please refer to the chapters of the first part of the book. In table 3 is shown an accurate description of a possible decalogue for the person with DM who wants to practice SPE or recreational sports activities in safety 3.

Table 3. Recommendations for SPE in diabetic patients. I

Plan an SPE and an adequate nutrition. If on insulin therapy, administer rapid/ultrarapid insulin avoiding insulin peak during SPE and do not inject into areas affected by movement.

Measure blood glucose before SPE: If <100 mg/dl, take fast-absorbing carbohydrates and check again before starting. If >300 mg/dl, procrastinate SPE and correct with an extra dose of insulin (2-3 IU) until come back in limits.

III

For 50–60-minute activities, increase the pre-activity carbohydrate dose; for 1-2 h activities, take carbohydrates even during SPE.

For long-term activities (cross-country skiing, cycling, etc.), take carbohydrates at regular intervals and, if on insulin therapy, reduce the insulin dose by 30-50% compared to your usual needs.

In case of high-intensity SPE during the day, reduce the dose of slow insulin in the evening to prevent nocturnal hypoglycemia (Post-Exercise Late-Onset Hypoglycemia).

Do no stop abruptly SPE to avoid post-exercise hypotension, especially in the presence of autonomic neuropathy.

VII

Always keep a sachet of sugar or a sweet drink with you to correct any hypoglycemia and make sure that coaches/ teammates know how to attend in case of serious crisis.

VIII

Use proper equipment, check socks and footwear, and selfinspect your feet after each SPE session.

Be sure to maintain adequate hydration during prolonged SPE in a hot-humid environment.

Consider the use of diuretics and SGLT2i (promote dehydration) and β-blockers (mask symptoms of hypoglycemia and reduce aerobic capacity).

References 1.

GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Borden of Disease Study 2021. Lancet 2023; 402: 203-34.

Lang JJ, Prince SA, Merucci K, et al. Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies. Br J Sports Med 2024; bjsports-2023-107849. 3. Garcia-Hermoso A, Ramírez-Vélez R, Díez J, et al. Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients: a systematic review and meta-analysis of randomized controlled trials. J Sport Health Sci 2023; 12: 147-57. 4. Li R, Qu S, Zhang P, et al. Economic Evaluation of Combined Diet and Physical Activity Promotion Programs to Prevent Type 2 Diabetes Among Persons at Increased Risk: A Systematic Review for the Community Preventive Services Task Force. Ann Intern Med 2015; 163: 452-60. 5. Tian X, Tang Y, Hu R, et al. Practice effects of personalized interventions with interdisciplinary teamwork in type 2 diabetes remission: a retrospective study. Front Endocrinol (Lausanne) 2024; 15: 1341531. 6. Morales-Palomo F, Moreno-Cabañas A, Alvare-Jimenes L, et al. Effect of yearly exercise on benefit-cost ratio in individuals with metabolic syndrome: a randomized clinical trial. Med Sci Sports Exerc 2023; 55: 158-66. 7. Atashak S, Stannard SR, Daraei A, et al. High-intensity interval training improves lipocalin-2 and omentin-1 levels in men with obesity. Int J Sports Med 2022; 43: 328-35. 8. Wood G, Taylor E, Ng V, et al. Determining the effect size of aerobic exercise training on the standard lipid profile in sedentary adults with three or more metabolic syndrome factors: a systematic review and meta-analysis of randomized controlled trials. Br J Sports Med 2021; bjsports-2021-103999. 9. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Eng J Med 2015; 373: 2117-28. 10. Lim GB. Dapagliflozin improves exercise capacity in HFpEF. Nat Rev Cardiol 2022;19: 6. 11. Nauck MA., Quast D.R. Cardiovascular safety and benefits of semaglutide in patients with type 2 diabetes: findings from SUSTAIN 6 and PIONEER 6. Front Endocrinol (Lausanne) 2021; 12: 645566. 12. Simms-Williams N, Treves N, Yin H, et al. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ 2024; 385: e078242. 13. Subramanian S, Khan F, Hirsch IB. New advances in type 1 diabetes. BMJ 2024; 384: e075681. 14. Strollo F, Corigliano G, De Fazio C, et al. Exercise related care pathways for people with diabetes: Literature review and expert consensus. Diabetes Metab Syndr 2019; 13: 2755-2762. 15. Kanaley JA, Colberg SR, Corcoran MH. Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from American College of Sports Medicine. Med Sci Sports Exerc 2022; 54: 353-8. 16. Houburg Petersen M, Stridsen JV, Eisemann de Almeida M, et al. High- intensity interval training combining rowing and cycling improves but does not restore beta-cell function in type 2 diabetes. Endocr Connect 2024; 13: e230558. 17. De Fazio C, Strollo F, Corigliano G. Treatment of hypoglycemia from sports activity in type 1 diabetics by the use of a liquid supplement containing glucose, thiamine and manganese. The Journal of AMD 2016, Vol. 19, n. 3. 18. Palermi S, Iacono O, Sirico F, et al. The complex relationship between physical activity and diabetes: an overview. J Basic Clin Physiol Pharmacol 2021; 33: 535-47. 19. Vecchiato M, Zanardo E, Battista F, et al. The Effect of Exercise Training on Irisin Secretion in Patients with Type 2 Diabetes: A Systematic Review. J Clin Med 2022; 12: 62.

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| CHAPTER 3.4 |

Coronary artery disease Silvio Romano, Marco Ambrosetti, Franco Giada, Italo Porto, Pier Luigi Temporelli

Introduction Coronary artery disease (CAD) is the cardiological condition in which SPE programs are most frequently recommended both immediately after an ACS or interventional procedure, and in chronic coronary syndromes (CCS)1-3. In the first case, exercise prescription, aimed above all at resuming a normal social life, should be carried out in a rehabilitation setting, where, through experience and professional skills, the resumption of physical activity can be graduated and quantified in safe conditions. In CCS, SPE, aimed at secondary prevention, can instead be administered, after careful evaluation, also in the so-called Health Gyms, or independently.

Beneficial effects of exercise in CAD With regard to major endpoints, observational epidemiological studies have long reported lower total and cardiovascular morbidity and mortality in physically active individuals, both healthy and cardiopathic, compared to sedentary ones, and an inverse relationship between functional capacity and risk of total and cardiovascular morbidity and mortality1-3. Furthermore, randomized controlled trials (RCTs) have shown a reduction in total and cardiovascular morbidity and mortality in sedentary and CAD patients who practice SPE4,5. In the pre-fibrinolytic era, a meta-analysis of Oldrige4 and one of O’Connor5 reported a reduction in total mortality of 24% and 20% and cardiovascular mortality of 25% and 22%, respectively, in CAD patients who practiced physical exercise compared to sedentary people. More recent studies, conducted in the fibrinolytic or primary angioplasty era, have provided comparable results. In fact, a meta-analysis by Taylor2, one by Clark6 and one by Cochrane3, also conducted on RCTs, reported a reduction in total mortality of 20%, 47% and 27%, and in cardiovascular mortality of 26%, 17% and 13% respectively. Even after coronary artery bypass, a Cochrane meta-analysis reported a significant reduction in cardiovascular events in patients randomized to SPE3,7. On the other hand, with regard to minor endpoints, an adequate SPE program in CAD patients increases functional capacity, reduces hospitalizations and disease symptoms, raising the angina and/or dyspnoea threshold, and increasing exercise tolerance8,9. Due to these favorable effects on top of the best pharmacological therapy, all national and international guidelines consider the prescription of SPE in CAD as a class I indication with level of evidence A10,11.

Pathophysiology of the beneficial effects of physical exercise in CAD SPE exerts favorable effects on total and cardiovascular morbidity and mortality, both by acting directly on the cardiovascular system and by improving modifiable risk factors. Cardiovascular adaptations to exercise induce direct positive effects on the cardiovascular system. The reduction of HR and BP at rest and during exercise results in a lower O2 myocardial consumption for the same workload, increasing exercise tolerance and contributing, together with increased O2 myocardial

extraction, hemorheological effects and those on the endothelium, to raise the ischemic threshold. Improved sympathovagal balance, together with a reduction in circulating catecholamines, reduce the arrhythmic risk. SPE also exerts positive effects by contributing to the reduction of cardiovascular risk factors, through its favorable effects on lipid and carbohydrate metabolism, BP values, weight and body fat distribution, inflammation indices, psychological outcomes and blood coagulation status. SPE appears to counteract the progression of atherosclerotic CAD by reducing the volume of atheroma in residual coronary plaques after angioplasty12. Finally, SPE improves quality of life and contributes to global lifestyle changes, with a reduction in smoking habits and the adoption of a healthy diet in patients who exercise regularly.

Management of patients after acute coronary syndrome Patients in the immediate post-ACS period, approximately in the first month after discharge from an acute care facility, represent a distinct group within the context of CAD. A class IA recommendation exists for these patients to begin a Cardiac Rehabilitation program which, together with a comprehensive secondary prevention intervention, usually includes an individualized and adequately supervised SPE program, both in inpatient and outpatient setting10. The failure to start this path should therefore be linked to clearly impeding reasons, particularly patient’s refusal or insufficient territorial offers of rehabilitation programs. In Italy, referral to Cardiac Rehabilitation after ACS, as recently documented by AGENAS13, unfortunately appears to be rare, with a national average of 6% and peaks in some regions of just over 10%. The reasons behind this scenario, common to many other Western countries, are beyond the scope of this document. The authors wanted to pragmatically identify some guidelines for the prescription of SPE for those who, after the index event, directly relate to the territory and to the management of General Medicine, based on the information typically contained in a clinical discharge report. The first operational step is to identify high-priority patients for inpatient admission to Cardiac Rehabilitation14 and, more generally, those for whom an SPE not managed by Cardiac Rehabilitation would pose a greater risk than no SPE. This population, according to the criteria summarized in table 1, must necessarily be referred for a specialized SPE prescription and cannot be the subject of a standard program. In the absence of impeding conditions, the Authors therefore propose to adopt the prescriptive approach codified for CCS reported below, unchanged for the frequency, type and time domains, but with the application of the “minimum” setting (table 2) for the intensity of aerobic and strength work in the absence (or pending) of a direct functional assessment test. Subsequently, especially with regard to aerobic training, the execution of an ergometric or CPET test may eventually lead to the prescription of an “optimum” or “selected” setting, after evaluation by a suitable specialist.

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Table 1. Risk conditions after ACS in which the prescription of physical exercise must necessarily take place in structured settings of Cardiac Rehabilitation Cardiology or Cardiology/Sports Medicine with high expertise. Condition

Notes

Patients with uncontrolled arterial hypertension Patients with arrhythmias

Example: paroxysms of AF, SVB runs, single PVCs in increase with stress, PVC run

Patients at high risk of heart failure or unfavorable left ventricular remodeling

• LVEF <40% • LVEF between 40% and 45% but with an associated predictor of unfavorable remodeling (mild mitral regurgitation, restrictive diastolic filling, high asynergy score and non-dilated ventricle)

Patients with very high thrombotic risk

• Recurrent cardiovascular events (history of angina or previous heart attack, other vascular event) • Advanced renal failure • Absent or incomplete revascularization • Complex revascularization (long lesions, bifurcations, left main coronary artery, small stents, previous restenosis or stent thrombosis)

Patients at high bleeding risk Patients with comorbidities Frail/sarcopenic patients AF: atrial fibrillation; SVB: supraventricular beats; PVC: premature ventricular complex; LVEF: left ventricular ejection fraction.

Table 2. Indications for exercise prescribing in patients with chronic coronary syndrome. Frequency 3 times/week (minimum) Aerobic 6-7 times/week (optimum)

2 times/week (minimum) Strength 3 times/week (optimum)

Intensitya Mild-moderate (minimum) Moderate (optimum) High (selected) Mild (minimum) Moderate (optimum) High (selected)

Time

Type Indoor/outdoorb

20 min (minimum)

Exercise: Cycling, Running, Nordic walking, Rowingc, Other

30-45 min (optimum)

Tool: Cyclette, Treadmill, Pedal Set, Rowing Machine, Other Mode: Continuous, Intervald

5-10 reps, 1-3 sets (minimum) e 24 sessions (minimum) At least three muscular groups in Potential Circuit : Deltoid, Biceps, Triceps, Quadriceps, Flexor hip, Abductor hip, Adductor hip 10-15 reps, 1-3 sets Device: Weights, Machine 36 sessions (optimum) 8-10 reps (selected)

* Minimum: 3 times/week Mild

Complementary

Route completion

* Optimum: 6-7 times/week

Exercise: Balance, Coordination, Flexibilityf, Respiratory training. Device: Equipment, Inspiratory training device

See table 2 in Chapter 2.4. When exercising outdoors, avoid practicing alone and areas not covered by the telephone network/emergency services. Ensure permanent tracking through apps or other devices and retrieval of clinical information related to chronic coronary syndrome in clothing. Avoid cardiovascular drift due to excessive temperatures and dehydration. c After evaluation for possible trauma to any implantable cardiac device. d Individualized schedule. Standard proposal for a single 45-minute session: 10-min warm-up at 60-70% HRpeak; 4 bouts × 4 min at 85-95% HRpeak alternating with 3 min of work at 60-70% HRpeak; 5-10-min cool-down at 60-70% HRpeak. e Activate groups bilaterally, activate agonists and antagonists. f Standard complementary circuit proposal: step forward and arm raised; widen foot and arm; walk sideways; hand on opposite knee; draw circles with one foot; walk in a straight line; stand on one leg; stand with feet aligned; stand on tiptoes; raise leg sideways. a

Management of patients with chronic coronary syndrome The prescription of physical exercise in patients with CCS must respond to multiple objectives15,16, all of which must be taken into account when drafting the SPE program, namely: 1) increase in global functional capacity, 2) favorable effect on modifiable car-

diovascular risk factors, 3) reduction of long-term cardiovascular events and 4) integration of the continuous training practice into the individual lifestyle. On this basis, more specific objectives can then be established, such as the reduction of exertional angina episodes (if present) by raising the threshold and the control of risk factors. Furthermore, the main clinical variables (the degree of initial deconditioning, comorbidities, concomitant therapies, the possible

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presence of cardiac devices), personal factors (preferences, logistics and living conditions, financial availability) and the necessary safety requirements for the training to be ensured should not be overlooked. Therefore, the “standard” proposal in this Document (table 2) must necessarily undergo a careful critical re-assessment by the prescribing physician. As a general rule, the SPE program must always include the combination of aerobic and strength exercises, possibly considering complementary treatments (balance, flexibility, coordination, breathing exercises) in special cases. The standard proposal developed by the panel includes a “minimum” setting, with training volumes essential to achieve the main objectives of functional and prognostic improvement, and an “optimal” setting, based on the main evidence in the literature, to optimize these benefits. In the aerobic and strength domain, a “selected” setting is also identified, based on high-intensity workloads (HIIT), which focuses on improving maximal performance over cardiovascular prognosis; this approach is therefore applicable in highly selected subjects and with adequate supervision and safety. The authors decided not to consider the possibility of moderate intensity interval training (MIIT), due to limited evidence in the literature and to offer the most immediate options to the non-expert prescriber. Many of the criteria for patients’ selection and the prescription/administration of the SPE program are borrowed from the guidelines of the Rehabilitation Cardiology discipline, i.e. the setting with the greatest know-how and the main structural and organizational capabilities for the management of physical exercise in cardiac patients17. The patients with CCS targeted by the recommendations are those covered by the ESC 202411 guidelines, with particular reference to the following clinical scenarios modified from the original wording: 1) patients between one month and one year after ACS and/or coronary revascularization, asymptomatic or with stabilized symptoms, for whom mild-moderate intensity SPE is usually indicated 2) asymptomatic and symptomatic patients more than one year after the index event, for whom moderate and elevated intensity SPE can also be prescribed. Most of the general recommendations can also be extended to asymptomatic patients with evidence of CAD at screening examinations, falling into the group of CCS according to ESC guidelines, while patients with only suspected CAD were obviously excluded. Due to their pathophysiological and clinical peculiarities, patients with 1) documented effort ischemic threshold, 2) left ventricular dysfunction and 3) MINOCA and INOCA have been treated as

special groups in the CCS setting, as well as elderly subjects, due to the need for fine tuning in the SPE prescription, (table 3). Regarding subjects practicing competitive sports (master athletes) in whom, according to the COCIS indications18, the suitability for competitive activity is not confirmed due to an intercurrent diagnosis of CAD, the panel emphasizes the importance of prescribing SPE according to the methods indicated in table 2, avoiding high/very high intensity activities and making it clear to the patient that the “right dose” of physical exercise is aimed at improving the prognosis of the disease and quality of life and not at achieving performance similar to those of competitive sport activity. As regards the functional assessment tests preparatory to the SPE prescription, the authors reiterate the gold standard value of CPET19 and secondly of the ergometric test (without gas analysis, with a ramp protocol preferably on an exercise bike) aimed at obtaining HR thresholds for aerobic exercise, or the lactate test with the identification of work thresholds (also with the fast method by finger/ear lobe puncture), together with the detection of 1RM for the strength exercise on each muscle group activated in the training circuit by means of a suitable dynamometer (see table 3 in chapter 2.4). In particular, for aerobic training, the panel reiterates the superiority of the direct calculation of the intensity derived from the ventilator thresholds at the CPET or, alternatively, at the lactate test (“Threshold-based” training) compared to the derivation of intensity domains as percentages of HR at the peak of effort or chronotropic reserve (“Range-based” training). Recognizing the possible logistical challenges in implementing such tests (in particular cardiopulmonary and ergometric testing, whose training prescription purpose in the absence of other assessments, e.g. inducible ischemia, makes their availability even more limited) the authors consider the use of other methods acceptable pending the execution of an incremental load test tending toward maximal load. These alternative indirect parameters for aerobic training consist of – the subjective Rate of Perceived Exertion (RPE) score using the Borg scale 6-21 or even better (for greater ease of use and in accordance with Italian tradition) the CR-10 scale – the theoretical calculation of maximal HR (corrected for the intake of negative chronotropic therapy), while for strength training they consist of – the <10-RM test – the subjective load perception score using the OMNI-RES scale (Omnibus Resistance Exercise Scale).

Table 3. Prescribing adaptations of physical training in subpopulations with Chronic Coronary Artery Syndrome.

Ischemic threshold

• Maintain aerobic and strength training intensity at 75% of the ischemic threshold effort in terms of HR and/or Watts • Provide appropriate patient education to maintain prescribed exercise intensity and self-diagnose ischemic symptoms

Left ventricular dysfunction (see specific chapter if EF <40%)

• Exercise of mild to moderate intensity (“minimum”) left ventricular • Ensure arrhythmic monitoring with ECG telemetry, (at least in the initial stages

MINOCA/INOCA

• Exercise of mild to moderate intensity (“minimum”) in case of coronary dissection etiology

Elderly

• Age alone is not sufficient to adjust (reduce) the programme: use the criteria in table 2 for prescription • Training prescription tailored to activities of daily living • In the presence of sarcopenia increase the amount of strength exercise

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In the absence of conclusive evidence on patients with CCS, the authors do not recommend the 6-minute walk test and similar tests, mostly validated in healthy subjects (20-m shuttle test, incremental shuttle test, 2 km walking test, etc.) as an alternative test for the theoretical evaluation of HR and VO2peak.

References 1. 2. 3. 4. 5. 6. 7. 8.

Taylor RS, Brown A, Shah E, et al. Exercise-Based Rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Medicine 2004; 116: 682-92. Anderson L, Oldridge N, Thompson DR, et al. Exercise-Based Cardiac Rehabi- litation for Coronary Heart Disease: Cochrane Systematic Review and Meta- Analysis. J Am Coll Cardiol 2016; 67: 1-12. Dibben G, Faulkner J, Oldridge N, et al. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database Syst Rev 2021; 11. Art. No.: CD001800. DOI: 10.1002/14651858.CD001800.pub4. Oldridge NB, Guyatt GH, Fischer ME, et al. Cardiac rehabilitation after myocardial infarction. Combined experience of randomized clinical trials. JAMA 1988; 260: 945-50. O’Connor GT, Buring JE, Yusuf S, et al. An overview of randomized trials of rehabilitation with exercise after myocardial infarction: Circulation 1989; 80: 234-44. Clark AM, Hartling L, Vandermeer B, et al. Meta-analysis: secondary prevention programs for coronary artery disease. Ann Intern Med 2005; 143: 659-72. Mendes M. Is There a Role for Cardiac Rehabilitation After Coronary Artery Bypass Grafting? Circulation 2016; 133: 253. Li T, Jiang H, Ding J. The role of exercise-based cardiac rehabilitation after percutaneous coronary intervention in patients with coronary artery disease: a meta- analysis of randomised controlled trials. Acta Cardiol 2024; 79: 127-35. Ingle L, Powell R, Begg B, et al. Effects of Exercise Training Response on Quality of Life and Cardiovascular Risk Factor Profiles in People with Coronary Artery Disease: Insights from the HIIT or MISS UK Trial. Arch Phys Med Rehabil 2024; S0003-9993(24)00883-9.

10. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J 2023; 44: 3720-3826, 11. Vrints C, Andreotti F, Koskinas KC, et al. ESC Guidelines for the management of chronic coronary syndromes: Developed by the task force for the management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J 2024; 45: 3415-3537. 12. Vesterbekkmo EK, Aksetøy IA, Follestad T, et al. High-intensity interval training induces beneficial effects on coronary atheromatous plaques: a randomized trial. Eur J Prev Cardiol 2023; 30: 384-92. 13. National Agency for Regional Health Services, Technical Group for the development of proposals for the implementation and evolution of the cardiology network for emergencies. Final Report. https:// www.agenas.gov. it/images/agenas/RETI/cardio/rete_car- dio_relazione_finale.pdf. 14. Greco C, Bovenzi FM, Berti S, et al. Document ANMCO/GICR-IACPR/GISE. The organization of care in the post-acute phase of coronary syndromes. G Ital Cardiol 2014; 15 (Suppl 1): 3S-27S. 15. Pelliccia A, Sharma S, Gati S, et al. ESC Scientific Document Group. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96. Erratum in: Eur Heart J. 2021 Feb 1; 42(5):548-549. PMID: 32860412. 16. Hansen D, Beckers P, Neunhäuserer D, et al. Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group. Sports Med 2023; 53: 2013- 37. 17. Ambrosetti M, Abreu A, Corrà U, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: from knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2021; 28: 460-95. 18. COCIS. Cardiological protocols for the judgment of fitness for competitive sport 2023 (VI edition). Roma: CESI Edizioni; 2023. 19. Anselmi F, Cavigli L, Pagliaro A, et al. The cardiopulmonary exercise test: a fundamental tool for a personalized prescription of physical exercise in patients with cardiovascular disease. G Ital Cardiol 2021; 22: 716-26.

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| CHAPTER 3.5 |

Valvular heart disease Maurizio Volterrani, Elena Cavarretta, Antonello D’Andrea, Paolo Zeppilli

Patients with untreated valvular heart disease Valvular heart disease (VHD) is common in the general population and its prevalence increases with age, ranging from 0.7% in young people (18-44 years) to 13.3% in people aged ≥75 years. Given the benefits of physical activity on cardiovascular health and overall well-being, individuals with VHD should be encouraged to engage in regular physical activity, the frequency, intensity, duration and type of which should be tailored to the individuals’ characteristics as well as type and severity of the valvular dysfunction (table 1).

Aortic Stenosis In most cases aortic valve stenosis (AS) is due to a degenerative, age-dependent process that causes progressive thickening, calcification and reduced mobility of the valve cusps, with an increase

in the transvalvular pressure gradient and left ventricular (LV) workload and consequent hypertrophy, fibrosis and increased myocardial oxygen demand. Ejection fraction (EF) is usually preserved, at least in an early stage of natural history, while diastolic function begins to be impaired early2. Mild AS (mean gradient <20 mmHg; aortic valve area (AVA) >1.5 cm2) in subjects in sinus rhythm who are asymptomatic at rest and exertion, evaluated with a Cardiopulmonary Exercise Test (CPET) or even just an Ergometric Test (ET) to evaluate the cardiovascular fitness and functional capacity, the normal increase in systolic BP and the absence of arrhythmias and ST/T segment alterations and the absence of left ventricular hypertrophy and normal systolic and diastolic ventricular function on echocardiography. These individuals can exercise at a high intensity level at least 1-3 times per week. Moderate AS (mean gradient between 20 and 40 mmHg; AVA between 1.5 and 1 cm2) in asymptomatic/paucisymptomatic

Table 1. Indications for exercise prescription in patients with untreated valvular heart disease. AS Mild in subjects with sinus rhythm and asymptomatic

• Moderate-intensity, up to high-intensity exercise, 1–3 times a week

Moderate in asymptomatic/ paucisymptomatic subjects

• Exercise at a mild intensity, 1–3 times a week

Severe and symptomatic subjects (candidates for surgery)

• No physical exercise, but an active lifestyle attitude (>4000 steps per day, postural and flexibility exercises)

AR Mild/moderate

• Moderate-intensity exercise up to high intensity, 1–3 times a week

Moderate-severe/severe

• Possible physical exercise at a mild intensity and an active lifestyle attitude (>4000 steps per day, postural and flexibility exercises)

BAV Uncomplicated

• Moderate to high intensity exercise, 1–3 times a week

Complicated

• No physical exercise, but an active lifestyle (>4000 steps per day, postural and flexibility exercises)

MS Mild/mild-moderate in subjects with • Moderate-intensity exercise, 1–3 times a week sinus rhythm and asymptomatic Moderate/moderate-severe/severe in sinus rhythm, asymptomatic/ paucisymptomatic

• Exercise at a mild intensity, 1–3 times a week

Severe and symptomatic subjects (candidates for surgery)

• No physical exercise, but an active lifestyle (>4000 steps per day, postural and flexibility exercises)

MR Mild/moderate

• Moderate or high intensity exercise, 1–3 times a week

Moderate-severe/severe

• Exercise at a mild intensity, 1–3 times a week

MVP Barlow’s syndrome

• Moderate or high intensity exercise, 1–3 times a week

Arrhythmogenic

• Mild intensity exercise and an active lifestyle (>4000 steps per day, postural and flexibility exercises), 1–3 times a week

AS: Aortic Stenosis; AR: Aortic Regurgitation; BAV: Bicuspid Aortic Valve; MS: Mitral Stenosis; MR: Mitral Regurgitation; MVP: Mitral Valve Prolapse.

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subjects. To determine the actual absence of symptoms during efforts, subjects must undergo a CPET/ET to assess functional capacity, normal increase of systolic BP. In the absence of arrhythmias, ST/T segment alteration, and an abnormal pattern of systolic BP at peak exercise, these individuals may exercise at up to moderate intensity. A progressive fall in systolic BP with exercise, or failure to increase it by at least 20 mmHg, associated or not with ST-segment elevation on ECG, identifies individuals at higher risk for whom exercise intensity should be mild. Exercise-induced ventricular arrhythmias should similarly be considered as a criterion for exercise restrictions. Severe AS and symptomatic subjects who are candidates for surgery (mean gradient >40mmHg; AVA <1 cm2): any physical exercise of greater than mild intensity is not recommended, but the maintenance of a lifestyle, sufficient to counteract sedentary lifestyle and frailty (>4000 steps per day, postural and flexibility exercises with a frequency of 1-3 times a week) must always be encouraged, also in view of surgery.

Aortic regurgitation Aortic valve regurgitation (AR) can be caused by a congenitally altered valve (aortic bicuspid valve, BAV), degeneration of a tricuspid valve, or loss of coaptation due to dilation of the aortic root. Exercise prescription parameters to consider are: the degree of regurgitation, atrial fibrillation (AF) and the size of the aorta4. Mild/mild-moderate IA (vena contracta <5 mm; PHT >300 msec; AOR <0.2 cm²): AI is well tolerated from a hemodynamic point of view and affected subjects (even moderate regurgitation) can exercise even at high intensity or moderate intensity identified at CPET or even just at ET with a frequency of at least 1-3 times a week. The annual echocardiogram check with quantification of the degree of AI, the size/volumes of the 4 cardiac chambers, the EF and the PAPs is useful. Moderate-severe/severe AR (vena contracta >5mm; PHT <300msec; AOR >0.2cm2): these subjects may be asymptomatic or apparently asymptomatic and want to practice physical exercise, but in order to prescribe it is necessary to accurately quantify the degree of AR using resting echocardiography, the dimensions and volumes of the 4 cardiac chambers, the EF and the PAPs (<40 mmHg), with six-monthly follow-up. It is useful to complete with physical stress echocardiography to exclude the worsening of the degree of AR at the peak of exertion, the contractile reserve of LV and the actual absence of exercise-related symptoms by evaluation of the course of PAPs. These patients should be encouraged to maintain a lifestyle sufficient to counteract a sedentary lifestyle and frailty (>4000 steps a day, postural and flexibility activity at least 1-3 times a week) with clinical-instrumental control, also in view of surgery. It is also necessary to identify the correct timing of surgery, before the appearance of excessive dilation of the LV, the left atrium and the right ventricle (in this order of appearance), or of any reduction in the systolic performance of the LV (LVEF <50%, which in the presence of severe AR already represents a moderate dysfunction).

Bicuspid aortic valve Bicuspid aortic valve (BAV) is the most frequent congenital anomaly (0.5-2% of live births). Uncomplicated BAV is defined as one that does not cause significant obstruction to outflow, does not cause significant AR (absent/minimal regurgitation) and is associated with normal size of the bulb and ascending aorta. The

most common complications are valvular dysfunction, infective endocarditis and aortic dilatation. In general, people with uncomplicated BAV can exercise even at high intensity. In cases of complicated BAV, the considerations expressed for AS and AR apply depending on the prevailing defect. Dilation of the ascending aorta, when present, is an element to be considered in the prescription of exercise. Exercise has no worsening effects on valve function and aorta size. High-intensity isometric (strength) activities should generally be discouraged due to the tendency to high pressure peaks during isometric effort at high intensity.

Mitral stenosis Risk stratification in mitral stenosis (MS) is largely based on data provided by the echocardiogram with particular attention to severity of the stenosis, PAPs and the presence or absence of AF. When planning the physical activity of these patients, the assessment should include a CPET/ET to identify functional capacity and symptoms not present at rest, but possibly identifiable by exertion. In case of discrepancy between the symptoms reported by exertion, or to evaluate the trend of PAPs due to exertion, supplementation with physical stress echo may be indicated. Mild/mild-moderate MS (mean gradient <6 mmHg, mitral valve area (MVA) >1.5 cm2) in subjects with sinus rhythm and asymptomatic both at rest and during exertion (assessed with CPET/ET), who have good functional capacity, with resting PAPs values <40 mmHg, can practice physical exercise with an intensity level up to moderate at CPET, or alternatively to ET with a frequency of at least 1-3 times per week1. Moderate/moderate-severe/severe MS in sinus rhythm, asymptomatic/paucisymptomatic (mean gradient <10 mmHg, MVA <1.5 but >1.0 cm2): to determine the actual absence of exertional symptoms and the excessive increase in the mean gradient at the peak of exertion, subjects should ideally undergo an echo stress test (first choice from physical stress) and CPET to assess functional capacity, the increase in the mean stress gradient (the stenosis becomes severe if the same is >15mmHg during physical stress or >18mmHg during do-butamine) and the trend of PAPs. If there is a rapid increase in PAPs >90% of baseline at the second step or if the PAPs >60 mmHg at the peak, dyspnoea during exercise is highly likely. In the absence of worsening of the degree of MS with exertion, the subject can practice physical exercise at a mild intensity identified at CPET with a frequency of 1-3 times a week. Severe MS and symptomatic subjects’ candidates for surgery (average gradient >10 mmHg, MVA <1.0 cm2): any physical exercise is not discouraged, however, a lifestyle sufficient to counteract sedentary lifestyle and fragility should be encouraged (>4000 steps per day, postural and flexibility activity with a frequency of 1-3 times a week) with clinical-instrumental control, also in view of surgery.

Mitral regurgitation Mitral regurgitation (MR) is in most cases a primary condition, linked to the degeneration of the valve leaflets. The factors that affect the prescription of physical exercise are: the presence of symptoms, the severity of MR, the function of the LV, the PAPs and the presence or absence of arrhythmias during exercise. For secondary MI, it is advisable to refer to the chapter dedicated to ischemic and/or dilated heart disease.

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Mild to moderate primary MR (vena contracta <6 mm, regurgitant orifice area <30 mm2): Primary MR is well tolerated from a hemodynamic point of view and subjects with up to moderate regurgitation can practice physical exercise without particular limitations, even high-intensity activities identified at CPET/ET and at moderate intensity with a frequency of at least 1-3 times per week, under annual echocardiographic control with quantification of the degree of MR, the size/volumes of the 4 cardiac chambers and the PAPs. Moderate-severe/severe MR (>6mm vena contracta, regurgitating orifice area >30 mm2): these subjects may be asymptomatic or apparently asymptomatic and want to practice physical activity, but in order to prescribe it, it is necessary to correctly quantify with semi-quantitative and quantitative parameters the degree of MR at resting echocardiogram, the size and volumes of the 4 cardiac chambers and the PAPs (<40 mmHg), with six-monthly follow-up. Stress echocardiogram is useful for assessing functional capacity, worsening of the MR during effort and the actual absence of exertional symptoms during exercise by assessing the trend of PAPs (if there is a rapid increase in PAPs >90% of baseline at the second step or if the PAPs >60 mmHg at peak it is highly probable the appearance of dyspnoea on exertion during exercise)7. These subjects must be directed to activities of mild intensity identified at CPET with a frequency of 1-3 times a week and it is necessary to identify the correct timing of surgery, before the appearance of excessive dilation of the LV, the left atrium and the right ventricle (in this order of appearance), the presence of AF or any reduction in the systolic performance of the LV (LVEF <60%, which in severe MI already represents a moderate dysfunction)8. Also in these patients, a lifestyle sufficient to counteract sedentary lifestyle and frailty (>4000 steps a day, postural and flexibility activity at least 1-3 times a week) should be encouraged with clinical-instrumental control, also in view of surgery.

Degenerative mitral prolapse True mitral valve prolapse (MVP) is characterized by fibromyxomatous degeneration of the valve leaflets and has a prevalence of 1-2.4% of the general population. Although it is considered a benign condition, PVM can evolve in 5-10% of cases into severe MR which, in turn, can lead to heart failure and pulmonary hypertension. In people with “true” MVP, symptoms such as heart palpitations, anxiety syndrome, and atypical chest pain (Barlow’s syndrome) may be present, regardless of the degree of MR and whether or not clinically detectable arrhythmias are present. In such subjects, a prescription of aerobic adapted exercise, of moderate or high intensity identified at CPET with a frequency of 1-3 times a week, may be useful10. Depending on the degree of MR, the indications for prescribing adapted exercise do not differ from those for primary MI, but the presence of ventricular arrhythmias at CPET/ET should be excluded. Arrhythmogenic MPV, with proven complex ventricular arrhythmias due to exertion, regardless of the degree of MR, is compatible only with physical activity of mild intensity, with a frequency of 1-3 times a week and even daily activity aimed at counteracting a sedentary lifestyle (>4000 steps per day, postural and flexibility activity aimed at counteracting frailty)12.

Patients with treated valvular heart disease All patients undergoing surgery for VHD, including those after minimally invasive cardiothoracic surgery or transcatheter aortic valve replacement, are recommended to undergo rehabilitation programs, which have been shown to improve short-term functional capacity by positively influencing the return to work. Physical activity can be started early in the hospital. Patients are also advised to follow inpatient and/or outpatient training programs immediately after discharge from the acute care unit.

Patients undergoing valve surgery Cardiac rehabilitation programmes facilitate a gradual return to physical activity and exercise for patients. In the immediate post-surgery period, factors such as bed rest, anemia, the onset of arrhythmias such as atrial fibrillation (AF) and the impairment of respiratory mechanics following pleural effusion and sternotomy, contribute to a marked reduction in the functional capacity and muscle mass of patients. Early physiotherapy consisting of mobilization, resumption of ambulation, balance-coordination exercises and training of the inspiratory muscles, helps to reduce peri-operative morbidity13. This physiotherapy should be performed 1-2 times a day, should be started during the stay in intensive care, and should be continued in the rehabilitation ward. Recently, it has been shown that the early addition of aerobic exercises with the lower limbs, such as pedaling for 15-20 minutes a day on a pedal board, is able to achieve a faster recovery of functional capacity and muscle strength than mobilization alone14. The rate of progression of exercise loads varies in relation to the individual characteristics of the patient, the complexity of the procedure and the hemodynamic and rhythm sequelae. It is therefore advisable to plan physical activity on the basis of a CPET/ET and an echocardiogram, the latter to assess the degree of residual valve stenosis and/or insufficiency. In the different studies, post-operative rehabilitation lasts from 4 to 12 weeks and includes 2-3 sessions/week, each session lasting between 20 and 60 minutes. The most commonly used exercise is continuous moderate-intensity aerobic exercise15. Upper body training can start when the chest is stable, i.e. after about six weeks. With regard to long-term physical activity, it should be considered that prosthetic valves and repaired native valves present a certain degree of obstruction to blood flow. Therefore, current European guidelines recommend that asymptomatic subjects with mitral and/or aortic valve prosthesis and/or repair receive the same adapted exercise prescriptions as subjects with moderate native valve disease, provided that ventricular function is preserved and PAPs is within normal limits1. Patients taking anticoagulants should take special precautions given the increased risk of significant bleeding occurring during training sessions.

Patients with percutaneous transcatheter aortic valve prosthesis implantation (TAVI) The percutaneous transcatheter aortic valve prosthesis implantation (TAVI) procedure is intended to treat severe AS in patients who have a high or intermediate cardiac surgeon risk. It is therefore reserved for elderly patients with high comorbidities. The studies carried out so far indicate that in patients undergoing TAVI, supervised physical activity in the context of cardiac rehabilitation significantly improves functional capacity, expressed as distance covered on the 6-minute walk test, and self-perception of quality of life. The training frequency reported by studies rang-

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es from 1 to 3 sessions per week for outpatients, up to 4-6 times/ week for hospitalized patients. Most studies used short sessions (≤30 minutes) of continuous aerobic exercise, carried out on a stationary bike or treadmill. Training intensity was moderate and training duration ranged from 2 to 12 weeks16.

Mitra Clip The Mitra-clip is a percutaneous mitral valve repair procedure that results from the edge-to-edge surgical technique. It is a “clip” that is hooked onto the leaflets of the mitral valve and serves to significantly reduce mitral regurgitation. Data on adapted exercise in patients undergoing miter clips are still very preliminary. In a recent retrospective study, exercise started 2 weeks after the miter clip and continued for 3 weeks was well tolerated by 85% of patients and resulted in a significant increase in distance covered at the 6-minute walk test and muscle strength17.

References 1. 2. 3.

4. 5.

Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96. Lee G, Chikwe J, Milojevic M, et al. ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis. Eur Heart J 2023; 44: 1-10. van Buuren F, Gati S, Sharma S, et al. Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol 2021; 28: 1569-78. Monda E, Verrillo F, Rubino M, et al. Thoracic Aortic Dilation: Implications for Physical Activity and Sport Participation. Diagnostics (Basel) 2022; 12: 1392. D’Ascenzi F, Valentini F, Anselmi F, et al. Bicuspid aortic valve and sports: From the echocardiographic evaluation to the eligibility for sports competition. Scand J Med Sci Sports 2021; 31: 510-20.

D’Andrea A, Della Corte A, Padalino R, et al. The Role of Multimodality Cardiac Imaging for the Assessment of Sports Eligibility in Patients with Bicuspid Aortic Valve. J Cardiovasc Echogr 2015; 25: 9-18. 7. Lancellotti P, Pellikka PA, Budts W, et al. The Clinical Use of Stress Echocardiography in Non-Ischaemic Heart Disease: Recommendations from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr 2017; 30: 101-38. 8. Perone F, Peruzzi M, Conte E, et al. An Overview of Sport Participation and Exercise Prescription in Mitral Valve Disease. J Cardiovasc Dev Dis 2023; 10: 304. 9. Caselli S, Mango F, Clark J, et al. Prevalence and Clinical Outcome of Athletes with Mitral Valve Prolapse. Circulation 2018; 137: 2080-2. 10. Scordo KA. Effects of aerobic exercise training on symptomatic women with mitral valve prolapse. Am J Cardiol 1991; 67: 863-8. 11. Perazzolo Marra M, Cecere A, Cipriani A, et al. Determinants of Ventricular Arrhythmias in Mitral Valve Prolapse. JACC Clin Electrophysiol 2024; 10: 670-81. 12. Cavarretta E, Peruzzi M, Versaci F, et al. How to manage an athlete with mitral valve prolapse. Eur J Prev Cardiol 2021; 28: 1110-7. 13. Chen B, Xie G, Lin Y, et al. A systematic review and meta-analysis of the effects of early mobilization therapy in patients after cardiac surgery. Medicine (Baltimore) 2021; 100: e25314. 14. Doyle MP, Indraratna P, Tardo DT, et al. Safety and efficacy of aerobic exercise commenced early after cardiac surgery: A systematic review and meta-analysis. Eur J Prev Cardiol 2019; 26: 36-45. 15. Abraham LN, Sibilitz KL, Berg SK, et al. Exercise-based cardiac rehabilitation for adults after heart valve surgery. Cochrane Database Syst Rev 2021; 5: CD010876. 16. Hosseinpour A, Azami P, Hosseinpour H, et al. Efficacy of exercise training-based cardiac rehabilitation programmes after transcatheter aortic valve implantation: A systematic review and meta-analysis. Int J Cardiol Cardiovasc Risk Prev 2024; 20: 200238. 17. Schmidt T, Kowalski M, Bjarnason-Wehrens B, et al. Feasibility of inpatient cardiac rehabilitation after percutaneous mitral valve reconstruction using clipping procedures: a retrospective analysis. BMC Sports Sci Med Rehabil 2022; 14: 120.

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| CHAPTER 3.6 |

Cardiomyopathies Flavio D’Ascenzi, Luna Cavigli, Franco Cecchi, Domenico Corrado, Gianfranco Sinagra, Alessandro Zorzi

Introduction The benefits of physical activity are also documented in patients with cardiomyopathies, in whom, on the other hand, a sedentary lifestyle is a risk factor for overweight, obesity, diabetes, atherosclerosis, major cardiovascular events, cancer, chronic conditions that add to the natural progression of cardiomyopathy itself1. In these patients, the relationship between a sedentary lifestyle and cardiovascular events can be even worse and a personalized exercise prescription becomes essential, aimed at promoting or maintaining cardiovascular well-being, improving quality of life, reducing the risk of adverse events and pathology-specific events2. Especially in the context of cardiomyopathies, the exercise prescription needs to be individualized according to the specific characteristics of the patient, the clinical history and possibly personal sports, the specific type of cardiomyopathy, home therapy, response to physical activity, therapeutic goals and the different clinical pictures to be improved2. Monitoring of exercise activities, patient education, and periodic reassessment are crucial to tailoring the program to individual needs in individuals with cardiomyopathies2. This chapter provides an overview of the personalized prescription of SPE for individuals with cardiomyopathies, taking into account the different types of cardiomyopathies and the importance of carefully considering the individual needs of each patient when prescribing physical activity.

Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) is defined as the presence of left ventricular hypertrophy not explained by abnormal loading conditions3,4. It has been recognized as one of the leading causes of sudden cardiac death among athletes, as evidence suggests an increased arrhythmic risk related to sporting activity. However, more recent research has indicated that the risk of sudden cardiac death during physical activity would be lower than initial estimates, making it possible to prescribe an SPE1. Currently, most patients with HCM are in a grey area, with limited or non-existent information on physical activities to maintain an active lifestyle, and exercise is the exception rather than rule1. As a result, patients with HCM are often overweight, which is even more important in this context, given that obesity is independently related to adverse cardiac remodeling, increased left ventricular mass, increased likelihood of dynamic ventricular outflow tract obstruction, and congestive symptoms5. Therefore, it is crucial to find the right balance through SPE1. In fact, moderate-intensity aerobic physical activity has been shown to lead to improved functional capacity, VO2, and symptoms, in the absence of significant adverse events6,7. In RESET-HCM, the first randomized trial of moderate-intensity exercise8 in HCM, patients with HCM were assigned to a 16-week moderate-intensity aerobic training program based on back-up HR. Patients started with an intensity of 60% of the HR reserve, for a minimum of three sessions per week, each lasting at least 20 minutes, progressively increasing to 70% of the HR reserve6. The type of exercise included cycling, walking, and running protocols. In another study, patients with

HCM were placed in a supervised cardiac rehabilitation program. The training program starts with a minimum of two one-hour sessions per week, starting with an intensity of 50-60% of the reserve HR and gradually reaching 65-85%. Patients were monitored using wireless telemetry systems and under medical supervision, completing an average of about 40 hours of aerobic training without adverse symptoms or sustained arrhythmias7. Although principles related to SPE are common, HCM patients may exhibit certain features that constitute contraindications to physical activity, including a history of syncope/hypotension during exertion, clinically relevant arrhythmias (particularly during exertion), hemodynamically significant left ventricular outflow tract obstruction at rest or during exertion, recent history of heart failure, and hospitalizations, severe symptoms, extended late gadolinium enhancement (LGE) to cardiac magnetic resonance imaging (CMRI)1. In some of these patients, however, a prescription for SPE may still be made after implementation of medical therapy, e.g. optimization of the gradient to the efflux tract with medical and/or invasive therapy. Indeed, inclusion in an SPE pathway can also improve clinical surveillance and lead to further optimization of therapy. CPET in HCM plays a key role, as it allows determination, in addition to the presence of hypotension and/or exertional arrhythmias, of functional capacity, VO2peak, ventilatory efficiency (VE/VCO2 slope), and ventilatory thresholds to determine the appropriate exercise intensity. In addition, the test can be combined with the stress echocardiogram to simultaneously assess, during exercise, the left ventricular response and the possible presence of mitral valve disease, and the trend of the dynamic gradient to the outflow tract of the left ventricle, the correct identification of which is essential for prognostic, therapeutic and structuring purposes of an SPE program. Maintaining good peak VO2 and functional capacity values has prognostic implications in HCM. In fact, the risk of death or transplantation in HCM patients is reduced by 21% for every 1 mL/kg/min increase in VO2peak9. In addition, among patients with obstructive HCM and mild or no symptoms, low exercise capacity is associated with an increased risk of death and subsequent development of severe symptoms10. In addition, the VE/VCO2 slope has a prognostic role in predicting adverse cardiovascular events such as death or transplantation in patients with HCM9.

Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and dysfunction not explained by abnormal loading conditions or coronary artery disease4,11. Exercise is recommended by the European guidelines on heart failure in patients with heart failure to improve functional capacity, quality of life and reduce hospitalizations12. However, the studies were mainly conducted on patients with reduced EF heart failure and not specifically on patients with DCM12. A systematic review of the literature13 evaluated prospective studies regarding the effect

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of exercise programs on DCM, demonstrating an improvement in quality of life, symptoms, functional capacity, VO2peak and left ventricular EF13-17. In these studies, the frequency of physical activity was 3-5 times per week, in line with recommendations for healthy adults, combining aerobic exercise with counter-resistance exercise in some of them13. The latter consisted of 2-3 sets of 10-15 repetitions for 2-3 sessions per week13,17. The intensity of aerobic exercise prescribed for patients with DCM was similar to that recommended in previous studies in patients with other forms of heart failure, initially prescribing moderate exercise intensity and progressing to high intensity whenever possible13. In these studies, intensity was determined using one of the equations based on the percentage of HR, reserve HR, or reserve VO213. The duration of aerobic physical activity ranged from 20 to 60 minutes per session, depending on the patients’ health status, previous levels of physical activity and functional capacity13. In fact, for the purposes of SPE in patients with DCM , it is important to take into account the symptoms, the degree of biventricular dysfunction, the presence of significant arrhythmias, in particular from exertion, the presence of valvulopathies, extensive areas of LGE on magnetic resonance imaging (MRI), high-risk pathogenic mutations for disease progression and ventricular arrhythmias, current medical therapy, hemodynamic response to exercise, exercise capacity, exercise history, and patient preferences2. In the context of DCM, CPET is critical for objectively determining exercise capacity and VO2 values, establishing causes of dyspnoea, stratifying transplant candidates, assessing aerobic work efficiency, ventilatory efficiency, performing an appropriate SPE by determining exercise intensity via ventilatory thresholds, and monitoring the progress and effectiveness of exercise programs2,18,19. An improvement in exercise capacity not only results in a better quality of life and independence in daily activity but is also a strong predictor of all-cause mortality. Even a slight improvement in VO2peak correlates with a reduction in all-cause mortality, cardiovascular mortality, and hospitalizations20. The mechanism by which an increase in VO2peak affects clinical outcomes, including mortality and morbidity, involves several factors. In fact, the determinants of VO2peak include central components (HR, stroke volume, cardiac output) and peripheral components (muscle oxygen extraction)20. Each of these factors tends to respond positively to training for most individuals with chronic heart failure and DCM, resulting in favorable outcomes20. In addition, patients with idiopathic DCM tend to have a better response to exercise and a lower risk of complications than patients with ischemic disease origin21. Finally, patients with DCM show an increased incidence of loss of muscle mass and function compared to healthy people, due to structural, metabolic and functional abnormalities in skeletal muscle that can only be counteracted through physical training and strength exercises22,23.

Arrhythmogenic cardiomyopathy Arrhythmogenic cardiomyopathy (ACM) is a disease of the heart muscle, whose most distinctive phenotypic feature is myocardial scarring (fibrous or fibroadipose replacement of the myocardium) that underlies global and/or regional ventricular dysfunction and predisposes to potentially lethal ventricular arrhythmias, regardless of the severity of systolic ventricular dysfunction24.

ACM is one of the main causes of athlete’s sudden cardiac death (SCD), particularly during sporting activity. In patients with ACM, sport is associated with an increased risk of SCD, ventricular arrhythmias and heart failure25. In experimental models, exercise appears to play a key role in the pathogenesis of ACM, demonstrating that abnormalities in desmosomal protein expression leads to pathological responses to exercise26. Mouse models of ACMs with abnormal expression of three different desmosomal proteins have demonstrated earlier disease onset and more severe structural abnormalities when exposed to intense physical training26. In individuals carrying mutations, strenuous physical activity is associated with early disease onset, increased likelihood of diagnosis, development of sustained ventricular arrhythmias, and ventricular dysfunction26,27. It should be noted that evidence on the adverse role of exercise in ACM has mainly been obtained in patients with the classic form (“right domino”) of ACM, while solid evidence on the predominantly interesting forms of the left ventricle is not currently available. In ACM, therefore, on the one hand, intense physical activity is associated with an increased risk of SCD and seems to have a negative effect on the progression of the disease, even in genotype-positive and phenotype-negative subjects; on the other hand, a sedentary lifestyle leads to an increase in mortality and comorbidities, especially cardiovascular. For this reason, it has been hypothesized that low-to-moderate-intensity SPE may have beneficial effects, reducing cardiovascular risk without accelerating disease progression26. It has been shown that carriers of mutations who exercised at an intensity below the upper limit of the minimum recommended threshold (i.e., aerobic physical activity at a mild to moderate intensity for a minimum of 30 minutes for five days a week)25 were significantly less likely to develop a diagnosis of ACM and significant arrhythmias, as opposed to those who had exceeded this threshold, suggesting that this limit may be associated with adverse remodelling in these patients26. In a registry of patients with a definitive or borderline diagnosis of ACM, participation in recreational physical activities was not associated with earlier disease development or increased risk of ventricular arrhythmias/SCD compared to the sedentary counterpart, although the absolute risk of ventricular arrhythmias/SCD was high in both groups28. A further study evaluated the effects of exercise in terms of intensity and duration in patients with ACM29. High-intensity exercise was a strong and independent predictor of ventricular arrhythmias, regardless of exercise duration. In fact, the combination of high-intensity exercise and prolonged duration was associated with adverse events, similar to short-duration high-intensity exercise and contrary to what was observed for long-duration low-intensity exercise29. In addition, mild intensity exercise has been associated with ventricular function and size within the normal range, even when practiced for long durations29. However, one-fifth of patients who practiced mild-intensity exercise had experienced ventricular arrhythmias, reflecting the high prevalence of ventricular arrhythmias in ACM, regardless of exercise29. Therefore, taking into account the current evidence, albeit not strong, mild intensity exercise, even for long durations, has not been associated with unfavorable outcomes and may be an acceptable alternative for ACM patients who wish to maintain an active lifestyle29. Large-scale studies are certainly needed to verify the long-term efficacy and safety of mild-to-moderate intensity aerobic exercise in individuals with ACM. In addition, it is of paramount importance to individually evaluate each patient for the purpose of prescribing an exercise program, taking into account

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factors such as symptoms, degree of biventricular dysfunction, arrhythmic profile, LGE pattern on MRI, hemodynamic response to exercise, exercise capacity, exercise history, and patient preferences. Also in the context of ACM, CPET plays an important role in the objective assessment of functional capacity, exertional arrhythmias, the fundamental correct determination of thresholds to define exercise intensity ranges, and in prognostic stratification; in fact, for example, the VE/VCO2 slope allows prognostic stratification even in the case of submaximal testing and provides important information on transplant-free survival30.

Myocarditis Myocarditis is an inflammatory disease of the heart muscle, generally caused by infectious agents, autoimmune disorders or toxins of pharmacological and environmental origin31. Most patients with acute myocarditis have mild and transient cardiac involvement, with a generally favorable clinical course with full recovery31. Clinical presentations of acute heart failure and SCD are less frequent. Post-inflammatory myocardial sequelae consist of subepicardial and intramural myocardial fibrosis, which develops as a result of the repair process of a previous acute myocardial trauma31 and which can constitute a substrate for life-threatening ventricular arrhythmias particularly in young people and athletes31. Subjects with an uncomplicated course of acute myocarditis and a complete recovery, including normal left ventricular function without evidence of LGE, have an excellent prognosis32. Before resuming exercise, after a 3-6-month suspension of physical activity, a thorough cardiological evaluation, including clinical evaluation, blood tests, ECG, echocardiogram, ambulatory ECG monitoring, CPET, and CMRI is required. In individuals who wish to participate in competitive sport and who are considered suitable according to current recommendations, it would be advisable to resume moderate-intensity physical activity for 4-6 weeks before resuming high-intensity exercise32. In subjects with persistently reduced left ventricular EF beyond six months, despite optimal medical therapy for heart failure, it is not possible to grant fitness for competition32. However, moderate-intensity exercise can be resumed, according to recommendations based on studies in patients with heart failure32. As part of the SPE prescribing program, the CPET provides information about the maximum exercise capacity and, in particular, about individual exercise intensity thresholds. In addition, the performance of the exercise test plays a crucial role in the evaluation of exercise-induced arrhythmias, representing a fundamental step in risk stratification and in the planning of therapeutic interventions. In patients with previous myocarditis, the test allows the identification of arrhythmic events induced by physical activity, providing indispensable indications for the optimization of antiarrhythmic therapy before the start of SPE programs. In some cases, the high arrhythmic risk may also be a temporary contraindication to SPE, highlighting the need for careful individual assessment. It is crucial to adopt a personalized approach in the evaluation of each patient with previous myocarditis, integrating a multiplicity of clinical and diagnostic factors. Among these, it is essential to consider: the presence and severity of the reported symptoms, the extent of ventricular dysfunction, the arrhythmic profile, the highlighted picture of LGE on MRI, the hemodynamic response during physical exercise, the global functional capacity, the previous history of physical activity and the patient’s person-

al preferences, which may affect the feasibility and adherence to the exercise program. A multi-dimensional approach of this type makes it possible to optimize the safety and efficacy of the therapeutic intervention, maximizing the benefits for the patient and minimizing the risks. In subjects considered suitable for SPE, especially if sedentary at the start, Initially, the sessions should be limited to mild to moderate intensity, which will then be gradually increased in duration and, if well tolerated, in intensity. During this phase, strength exercises can also be included32. In fact, moderate-intensity aerobic physical activity and strength exercises have been shown to lead to improved exercise and functional capacity, myocardial perfusion, diastolic and systolic function with an increase in left ventricular EF33.

Recommendations In subjects with cardiomyopathies excluded from competition or in sedentary subjects, SPE represents a therapy that should not be denied but, on the contrary, be favored, with the necessary precautions and with an approach that enhances and takes into account the specific characteristics of the individual. Therefore: • the SPE must take into account the clinical, individual, and pharmacological characteristics of the patient with cardiomyopathy, as well as the presence of contraindications to exercise itself. Some patients may be temporarily excluded from the SPE pathway and re-evaluated after implementation of therapy (e.g. optimization of the gradient to the outflow tract with medical and/or invasive therapy in patients with HCM); • some genetic subgroups of DCMs (see lamin, filamine, desmin, desmosomes, phospholamban, RBM 20, desmosomes) and ACMs in general, even when not genetically determined, require personalized programs also on the basis of phenotype and risk factors. Therefore, prudent personalization of physical exercise is absolutely necessary in some settings at greater risk; • once the SPE program has been prescribed, the patient must be followed over time and re-evaluated, in order to check the safety and efficacy of the same, as well as in order to remodulate the training program, based for example on the variation of the thresholds induced by the training program, on the variation of the therapy in progress (especially on the variation of beta-blocker therapy, given the significant impact that this has on the modification of ventilatory thresholds and functional capacity) and the clinical status of the patient; • an informed decision shared with the patient is crucial, also taking into account that SPE does not confer immunity from SCD to our patients and accurate self-monitoring of symptoms before, during and after exercise sessions is essential; • SPE should take place, especially in individuals at risk of arrhythmic events and in those who are not defibrillator wearers, in appropriate settings, where a Semi-Automatic External Defibrillator is present (AEDs) and personnel specialized in the administration of physical exercise and the customization of SPE programs in the gym. In all patients, and especially in patients with HCM, it is also essential to recommend an adequate state of hydration and attention to avoid an involuntary Valsalva maneuver during exercises; • particular care should be taken during pre-adolescence and adolescence, when cardiomyopathy is often first discovered

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Table 1. Recommendations for SPE in the HCM, DCM and ACM. FITT-VP

HCM (Hypertrophic Cardiomyopathy)

DCM (Dilated Cardiomyopathy)

ACM (Arrhythmogenic Cardiomyopathy)

Frequency

3-5 sessions/week. Strength exercises (unless contraindicated) and flexibility (e.g., stretching) about twice a week.

3-5 sessions/week. Strength exercises and flexibility (e.g., stretching) about twice a week.

3-5 sessions/week. Strength exercises and flexibility (stretching) about twice a week.

Intensity

Aerobic exercise: Moderate intensity, corresponding to the range between VT1 and VT2, closer to VT1. Strength activities: Intensity at 40%70% of 1RM, to be adapted on an individual basis.

Aerobic exercise: Performed at a mild-moderate intensity, corresponding to ≤VT1. Strength activities: Intensity at 40%60% of 1RM, to be adapted on an individual basis.

Time

150-300 minutes/week of aerobic exercise at a moderate intensity. 75-150 minutes/week at a higher intensity (selected cases).

150-300 minutes/week of aerobic exercise to a mild-moderate intensity.

Type

Endurance exercises: (e.g., running, cycling, swimming, walking) with constant and controlled HR. Strength exercises: (When not contraindicated, avoiding the Valsalva maneuver).Recommend adequate hydration.

Progression

In sedentary subjects, start with 2 sessions/week and introduce the third session when appropriate for the patient. In untrained and intermediate-to-high risk patients, start with 20-30 minutes of aerobic exercise and increase by 10 minutes each week to reach optimal weekly volume in 3-4 weeks. For strength activities, the patient should start gradually with 1-3 sets of 8-10 repetitions (or 10-15 repetitions with light weights in untrained and frail patients), increasing the volume and possibly the intensity every week according to the response to the training program.

HCM: Hypertrophic Cardiomyopathy; DCM: Dilated Cardiomyopathy; ACM: Arrhythmogenic Cardiomyopathy.

and discontinuation of physical activity may be useful in reaching a definitive diagnosis and in avoiding potential effects of exercise on cardiac remodeling at a dynamic stage of phenotype development. In young patients with cardiomyopathy with early and aggressive development, SPE can sometimes be postponed, waiting for greater disease stability and to obtain more information on the clinical picture based on a longer follow-up; • CPET should be performed before the start of the program to quantify hemodynamic, metabolic, and ventilatory parameters and to identify the appropriate intensity of the training program. Its repetition makes it possible to evaluate the response and effectiveness of the program and re-identify the exact ventilatory thresholds to prescribe the appropriate intensity of training; • in subjects with cardiomyopathy, it is essential to correctly establish the intensity of exercise: prescribing a higher intensity of exercise than expected involves an increased risk of adverse events (e.g. threatening arrhythmias); moreover, when exercise is set around VT1, there are the greatest metabolic benefits related to the consumption of lipids at this intensity instead of sugars as is the case at higher intensities2,18. The gold standard for identifying the correct exercise intensity is represented by the determination of the ventilatory thresholds (VT1 and VT2) through the CPET17. In fact, determining intensity using other subjective or objective parameters may not correctly classify exercise intensity, particularly in patients with cardiomyopathy, especially if they are taking beta-blocker therapy2,34. Consequently, prescribing the intensity of physical exercise on the basis of the percentages derived rather than

on the basis of the individually defined ventilatory thresholds, could lead to an over- or underestimation of exercise intensities, leading the patient to train at a different level of exercise intensity from that for which a clear clinical benefit has been demonstrated34. Although CPET is unfortunately not widely used, its use for the prescription of physical exercise in patients with cardiomyopathy represents an essential evaluation, fundamental for the purposes of an SPE program but also a unique moment in which to provide prognostic parameters useful for the clinical management of the patient. Table 1 presents the recommendations for SPE in HCM, DCM and ACM.

References 1.

4. 5.

Cavigli L, Olivotto I, Fattirolli F, et al. Prescribing, dosing and titrating exercise in patients with hypertrophic cardiomyopathy for prevention of comorbidities: Ready for prime time. Eur J Prev Cardiol 2020; 2047487320928654. D’Ascenzi F, Cavigli L, Pagliaro A, et al. Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. Br J Sports Med 2022; 56: 1-10. Wilson M, O’Hanlon R, Prasad S, et al. Diverse patterns of myocardial fibrosis in lifelong, veteran endurance athletes. J Appl Physiol (1985) 2011; 110: 1622-6. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023; 44: 1-12. Fumagalli C, Maurizi N, Day SM, et al. Association of Obesity with Adverse Long-term Outcomes in Hypertrophic Cardiomyopathy. JAMA Cardiol 2020; 5: 65-72. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients with Hyper-

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trophic Cardiomyopathy: A Randomized Clinical Trial. JAMA 2017; 317: 1349-57. 7. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise training in symptomatic patients with hypertrophic cardiomyopathy: results of a structured exercise training program in a cardiac rehabilitation center. Eur J Prev Cardiol 2015; 22: 13-9. 8. Cavigli L, Ragazzoni GL, Vannuccini F, et al. Cardiopulmonary Fitness and Personalized Exercise Prescription in Patients with Hypertrophic Cardiomyopathy. J Am Heart Assoc 2024; 13: 1-8. 9. Coats CJ, Rantell K, Bartnik A, et al. Cardiopulmonary Exercise Testing and Prognosis in Hypertrophic Cardiomyopathy. Circ Heart Fail 2015; 8: 1022-31. 10. Sorajja P, Allison T, Hayes C, et al. Prognostic utility of metabolic exercise testing in minimally symptomatic patients with obstructive hypertrophic cardiomyopathy. Am J Cardiol 2012; 109: 1494-8. 11. Sinagra G, Elliott PM, Merlo M. Dilated cardiomyopathy: so many cardiomyopathies! Eur Heart J 2020; 41: 3784-6. 12. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail 2022; 24: 4-131. 13. Seo YG, Jang MJ, Lee GY, et al. What Is the Optimal Exercise Prescription for Patients with Dilated Cardiomyopathy in Cardiac Rehabilitation? A Systematic Review. J Cardiopulm Rehabil Prev 2019; 39: 235-40. 14. Holloway CJ, Dass S, Suttie JJ, et al. Exercise training in dilated cardiomyopathy improves rest and stress cardiac function without changes in cardiac high energy phosphate metabolism. Heart 2012; 98: 1083-90. 15. Beer M, Wagner D, Myers J, et al. Effects of exercise training on myocardial energy metabolism and ventricular function assessed by quantitative phosphorus-31 magnetic resonance spectroscopy and magnetic resonance imaging in dilated cardiomyopathy. J Am Coll Cardiol 2008; 51: 1883-91. 16. Mehani SH. Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy. J Adv Res 2013; 4: 189-200. 17. Stolen KQ, Kemppainen J, Ukkonen H, et al. Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy. J Am Coll Cardiol 2003; 41: 460-7. 18. Anselmi F, Cavigli L, Pagliaro A, et al. Cardiopulmonary exercise testing: an essential tool for a tailored exercise prescription in patients with cardiac disease. G Ital Cardiol 2021; 22: 716-26. 19. Sinagra G, Carriere C, Clemenza F, et al. Risk stratification in cardiomyopathy. Eur J Prev Cardiol 2020; 27: 52-8. 20. Swank AM, Horton J, Fleg JL, et al. Modest increase in VO2peak is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail 2012; 5: 579-85.

21. Webb-Peploe KM, Chua TP, Harrington D, et al. Different response of patients with idiopathic and ischaemic dilated cardiomyopathy to exercise training. Int J Cardiol 2000; 74: 215-24. 22. Song T, Manoharan P, Millay DP, et al. Dilated cardiomyopathy-mediated heart failure induces a unique skeletal muscle myopathy with inflammation. Skelet Muscle 2019; 9: 4. 23. Skriver SV, Krett B, Poulsen NS, et al. Skeletal Muscle Involvement in Patients with Truncations of Titin and Familial Dilated Cardiomyopathy. JACC Heart Fail 2024; 12: 740-53. 24. Corrado D, Perazzolo Marra M, Zorzi A, et al. Diagnosis of arrhythmogenic cardiomyopathy: The Padua criteria. Int J Cardiol 2020; 319: 106-14. 25. Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96. 26. Sawant AC, Te Riele AS, Tichnell C, et al. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers. Heart Rhythm 2016; 13: 199-207. 27. James CA, Bhonsale A, Tichnell C, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol 2013; 62: 1290-7. 28. Ruwald AC, Marcus F, Estes NA, et al. Association of competitive and recreational sport participation with cardiac events in patients with arrhythmogenic right ventricular cardiomyopathy: results from the North American multidisciplinary study of arrhythmogenic right ventricular cardiomyopathy. Eur Heart J 2015; 36: 1735-43. 29. Lie OH, Dejgaard LA, Saberniak J, et al. Harmful Effects of Exercise Intensity and Exercise Duration in Patients with Arrhythmogenic Cardiomyopathy. JACC Clin Electrophysiol 2018; 4: 744-53. 30. Scheel PJ, Florido R, Hsu S, et al. Safety and Utility of Cardiopulmonary Exercise Testing in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia. J Am Heart Assoc 2020; 9: e013695. 31. Vio R, Zorzi A, Corrado D. Myocarditis in the Athlete: Arrhythmogenic Substrates, Clinical Manifestations, Management, and Eligibility Decisions. J Cardiovasc Transl Res 2020; 13: 284-95. 32. Halle M, Binzenhofer L, Mahrholdt H, et al. Myocarditis in athletes: A clinical perspective. Eur J Prev Cardiol 2021; 28: 1050-7. 33. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation. Eur J Heart Fail 2011; 13: 347-57. 34. Anselmi F, Cavigli L, Pagliaro A, et al. The importance of ventilatory thresholds to define aerobic exercise intensity in cardiac patients and healthy subjects. Scand J Med Sci Sports 2021; 31: 1-10.

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| CHAPTER 3.7 |

Arrhythmic patients and device carriers Alessandro Biffi, Silvia Castelletti, Pietro Delise, Fredrick Fernando, Franco Giada, Stefano Palermi, Luigi Sciarra, Alessandro Zorzi

In providing guidance on the prescription of SPE in arrhythmic subjects, some main aspects should be considered1: a) Many physical activities, including recreational activities, involve a high cardiovascular involvement and sudden sympathetic stimulations, so much so that they can be equated with competitive activities. In these conditions, various arrhythmias, both benign and malignant, can be favoured. b) Some physical activities can take place in harsh environmental conditions, such as to lead to negative hemodynamic consequences, dehydration and electrolyte imbalances. c) In arrhythmias and potentially arrhythmogenic syndromes associated with syncope or pre-syncope, physical activities in which loss of consciousness can cause traumatic death or drowning should be discouraged. In such cases, so-called “intrinsic risk” activities, such as mountaineering, swimming, diving, windsurfing, motor sports and others, should be prohibited. The following recommendations are for individual arrhythmias, and suggestions are often distinguished based on the presence or absence of symptoms and heart disease. It is understood that, in the presence of heart disease, the recommendations expressed in the specific chapters apply.

Atrial fibrillation AF is prevalent in middle-aged individuals who participate in high-intensity endurance sports2,3. Characterization of the substrate underlying AF is crucial for the prescription of SPE. In endurance athletes, a reduction in high-volume physical activity may decrease the incidence of AF2,3. In contrast, in the general population, AF is often associated with overweight, sedentary lifestyle, high blood pressure, and obstructive sleep apnoea4. Structured programs for the mitigation of various cardiovascular risk factors and including SPE, have demonstrated significant benefits in reducing the burden of AF. Even after treatment with catheter ablation, exercise promotes the maintenance of sinus rhythm5-8. Another key element for the prescription of SPE is the characterization of the type of AF. In patients with paroxysmal AF and mild underlying heart disease (a typical example is the overweight subject with hypertensive heart disease and normal EF), who spend most of their time in sinus rhythm, SPE programs are mainly aimed at reducing cardiovascular risk and weight loss, without particular limitations on exertion. On the contrary, in patients with persistent or permanent AF, the SPE program must take into account the hemodynamic alterations induced by the arrhythmia and the consequent reduction in exercise tolerance. A further element to take into consideration is the drug therapy taken by patients. In fact, anticoagulant therapy increases the risk of bleeding following trauma and therefore it is essential to consider this aspect when prescribing physical activity (for example, running could be safer than cycling). In addition, therapy for the control of CF (beta blockers or calcium channel blockers) may affect maximum HR and VO2max during exercise in patients with paroxysmal AF. While in patients with persistent AF it could lead

to a reduced ventricular response at rest, without being able to adequately reduce AF during exertion. Antiarrhythmic drugs, in particular those of the IC class (flecainide and propafenon), could cause frequency-dependent bundle branch blocks9. Finally, the so-called triggering factors must be considered: in most patients with paroxysmal AF, arrhythmia arises in conditions of increased vagal stimulation (at night or in the post-prandial period), but in a minority of cases it can be favoured by exercise. In all of them, hypovolemia due to sweating and loss of mineral salts are recognized as pro-arrhythmic factors10.

Atrial fibrillation and physical activity It is evident that the prescription of SPE in patients with AF cannot be subject to general rules, but must be personalized, taking into account some fundamental elements: • type and severity of the underlying substrate; • characteristics of AF and response to exercise (to be assessed by MEST/CPET in therapy and Holter ECG); • drug therapy. In most patients with persistent or permanent AF it is appropriate to stimulate the increase in the volume and intensity of physical exercise, to reach at least the levels recommended by the guidelines for the general population, to reduce cardiovascular risk and promote weight loss. In subjects with “lone” AF, who practice endurance sports at high intensity it should be proposed, on the contrary, a reduction in the load. In the general population, it has been shown that exercise corresponding to 360-720 MET-minutes/week, which is equivalent to approximately 60-120 minutes of moderate-to-vigorous intensity exercise, may already be sufficient to improve AF-specific outcomes, quality of life, and possibly prevent major adverse cardiovascular events in the long term10. Even mild to moderate intensity exercises, such as yoga, have shown promising benefits on the quality of life of patients with AF and could therefore be considered in a personalized rehabilitation program, especially in elderly subjects and/or with more severe heart disease11. It is also recommended to include strength exercises two or more days a week, using light weights or resistance bands, to improve muscle strength and endurance. The combination of aerobic and strength exercise has been shown to be effective in improving functional capacity and quality of life in patients with AF. Finally, it is important for patients with AF to perform an adequate warm-up before physical activity and a cool-down afterwards to reduce the risk of arrhythmias. Regular monitoring of HR during exercise, through portable devices such as smartwatches, can be useful to avoid overexertion and to detect any recurrence of AF, although it should be taken into account that devices based on plethysmography, such as sports watches, become inaccurate if the frequencies are high and the rhythm is irregular, so the use of the chest strap12 is better recommended.

Brugada syndrome Brugada syndrome, first described in 1992 by brothers Pedro and Joseph Brugada, is linked in 20-30% of cases to a genetic disease of ion channels, the most common of which is a mutation in

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the SCN5A gene. Brugada ECG patterns can be recorded in one or more of the V1-V3 leads and are of three types, but Type 1 is the only diagnostic one. It is characterized by a point J elevation and ST point elevation ≥2 mm, convex (coved), which has a descending trend, followed by negative T; it generally occurs in middle-aged men. In subjects with a spontaneous Brugada type 1 pattern, according to some authors, the risk would increase in the following conditions13: a) presence of fragmented QRS; b) associated conduction disorders (first-degree AV block, left anterior or posterior hemiblock); c) elevation ST increase/appearance in the recovery phase of the exercise test; d) coexistence of Brugada type 1 pattern and early ventricular repolarization. In Brugada syndrome, malignant arrhythmias, such as torsade de pointes or ventricular fibrillation, generally occur at rest during phases of vagal prevalence (e.g. at night) or in the case of febrile states1. These arrhythmias may be preceded by syncope, linked to rapid, self-resolving ventricular tachycardias. The most fearsome event in subjects with Brugada type 1 ECG pattern is sudden death. However, it should be emphasized that the type 1 pattern is found in about 1 per thousand of the population, while severe arrhythmias are observed in a very limited number of cases14. This shows that in the majority of cases the Brugada type 1 pattern has a benign prognosis, especially in the case of a negative electrophysiological study. In any case, the effect of physical training on sympatho-vagal balance in relation to a possible arrhythmogenicity is still unknown.

Brugada syndrome and physical activity In asymptomatic and low-risk subjects (even with inducible ECG pattern) it is reasonable to prescribe physical activity with stable cardiac activity, even at moderate intensity, avoiding repeated phases of acceleration/deceleration1. In these subjects, it is advisable to take preventive measures to reduce the risk of major arrhythmic events, such as avoiding certain drugs (see www. brugadadrugs.org), treating electrolyte imbalances, aggressively treating any feverish states and avoiding the increase in body temperature above 39°C (avoiding sports in hot conditions, such as long endurance events, but also extreme cold and at high altitudes). In subjects with spontaneous type 1 ECG pattern, it may be useful to perform an electrophysiological study, as well as for competitive athletes. In symptomatic subjects, it is possible to prescribe an SPE of moderate intensity (such as the one described above), at least 3 months after ICD implantation, trying to avoid contact activities1.

Wolff-Parkinson-White The Wolff-Parkinson-White (WPW) syndrome is determined by a congenital anomaly of the conduction system characterized by the presence of an abnormal atrio-ventricular pathway that bypasses the normal node-hissian system15. WPW can be complicated by various types of arrhythmias and in particular: a) orthodromic atrioventricular re-entry tachycardia; b) the rare antidromic atrioventricular re-entry tachycardia; c) AF, which can be partially or totally pre-excited and decisively affects the prognosis, given the risk of degeneration into ventricular fibrillation.

Physical exertion can facilitate all the arrhythmias listed above and in the case of AF can cause dangerous ventricular rates1.

WPW and physical activity From the baseline ECG it is not possible to establish the presence and/or degree of risk for physical exercise. Exceptions are asymptomatic individuals without heart disease, in whom WPW is intermittent at rest and remains intermittent or disappears during stress testing1. In such subjects, it can be reasonably safe to prescribe physical activities even at medium to high intensity, without increasing the clinical risk. Particular caution should be applied, however, in the presence of heart disease. In WPW, the real arrhythmic risk can be assessed only by transoesophageal or endocavity electrophysiologic study at rest and during exercise or after catecholamine infusion. With this examination, the induction of pre-excited AF with minimum R-R <250 ms baseline and during exertion and the inducibility of A-V re-entry tachycardia are considered risk criteria. In asymptomatic subjects with these electrophysiological parameters at risk and in symptomatic subjects, high-intensity, moderate or intrinsic risk physical activities should be discouraged1.

Long QT Syndrome Long QT syndrome (LQTS) is an inherited channelopathy characterized by prolongation of the QT interval on surface ECG and the occurrence of syncopal episodes that may result in cardiac arrest and sudden death16. Some genes are responsible for the LQT1, LQT2 and LQT3 forms, respectively, which are associated with particular correlations with disease expression (genotype-phenotype correlation)17. The disorder may be suspected in the presence of a prolonged QT interval on surface ECG (>460 ms for women after puberty and >440 ms for men). However, in sportsmen these values have been raised to 480 ms in women and 470 ms in men18. The syndrome is diagnosed in the presence of a disease-causing mutation and using the Schwartz score in the presence of a score of at least 3.5. In some cases, clinical screening of family members is useful. Obviously, secondary causes of QTc prolongation must be excluded: hypokalaemia and hypocalcaemia, intake of drugs capable of altering repolarization18.

Long QT syndrome and physical activity In long QT syndrome, arrhythmias mostly occur during situations of physical and emotional stress. In LQT1, sport and swimming in particular are considered the main arrhythmic trigger. In LQT2, arrhythmic events are triggered by strong emotions and sudden noises, while in LQT3, arrhythmic events occur mostly during sleep and rest19. Genotypic characterization is therefore important for the prescription of SPE. However, the risk of arrhythmic events also depends on the length of the QT interval, gender, age, the gene involved, as well as the type of mutation. It is essential that patients follow general precautions: avoid dysionias, dehydration and taking drugs that can prolong QTc. In this regard, it should be remembered that patients with LQT2 tend more easily to hypokalaemia. The association of arrhythmic events with exercise physical activity, especially in patients with LQT1, has led to the contraindication of competitive physical activity in affected patients. Considering all these elements, it is evident that the prescription of SPE in patients with long QT syndrome can hardly be generalized and several elements must be considered:

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1. personal history: history of syncope, cardiac arrest, recorded arrhythmias, dietary regimen, tendency to hypokalaemia; 2. gender and age; 3. QT interval ≥500 ms; 4. genetic substrate (LQT1, LQT2, LQT3) and type of mutation; 5. adherence to beta-blocker therapy; 6. the behaviour of QTc and HR during MEST and 24-hour Holter ECG. It is also essential to educate the patient on the adherence to the therapy and general precautions to maintain a low arrhythmic risk. It is also important to check blood chemistry tests, particularly the dosage of plasma electrolytes, suggesting that potassium should be supplemented before executing physical activity. Furthermore, since the intake of energy drinks has been shown to increase the risk of arrhythmia, it is important to advise on their abuse19.

Short QT syndrome Short QT syndrome is an inherited channelopathy characterized by a short QT on surface ECG and increased risk of life-threatening arrhythmias20. It is an autosomal dominant disease whose genetic substrate is partially in common with long QT syndrome1: the genes mainly involved are in fact KCNQ1, KCNH2, KCNJ2. Diagnosis is generally made for persistently short QTc between 330-340 ms; between 340 and 360 ms additional criteria are required: presence of a mutation, family history of short QT syndrome and/or sudden death under the age of 40 or personal history of ventricular fibrillation or ventricular tachycardia. Athletes have shorter QT intervals than non-athletes21; however, the athletic status does not predict a short QT interval22. For diagnostic purposes, reversible causes of short QTc, such as hypercalcaemia, hyperkalaemia, digitalis toxicity, metabolic acidosis, hyperthermia, androgen use should be excluded. The only medical therapies that could play a role are hydroquinidine and sotalol. Defibrillator implantation remains the choice for the prevention of sudden death in all patients with a history of cardiac arrest or sustained ventricular tachycardia1.

Short QT and physical activity There are no data on prescribing schedules of SPE in patients with short QT syndrome and the only ones available have shown that trained subjects have a shorter interval than sedentary subjects, but that their arrhythmic risk is not increased22 during increasing sympathetic tone, such as strong emotions or physical activity23. Several genes have been associated with the disease, but the main ones are two: RyR2 and CASQ2 which are responsible for the dominant and recessive forms of the disease, respectively24. The arrhythmic episodes generally occur in children or adolescents, more rarely in adulthood25. Diagnosis is mainly based on MEST, which can trigger arrhythmias. These arrhythmias initially present as single ventricular ectopic beats for HR >100-110 bpm; complexity and frequency increase progressively with the increase in HR, with phases of bigeminism, trigeminism, couplets, triplets up to TVNS and VT, typically polymorphic and/ or bidirectional. The therapy is based on beta-blockers (nadolol and propranolol are the most effective). In asymptomatic patients, with no family history, on therapy (and compliant with therapy), who do not show arrhythmias during ergometric testing and with potassium levels monitored, physical activity with low cardio-vascular engagement may be considered. In all other cases, physical exercise should be discouraged.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease characterized by a normal baseline ECG, but with bidirectional or polymorphic VTs induced by increased adrenergic tone, such as strong emotions or physical activity23. Several genes have been associated with the pathology, but the main two are RyR2 and CASQ2, which are responsible for the dominant and recessive forms of the condition, respectively24. Arrhythmic episodes generally manifest in children or adolescents, and more rarely in adulthood25. Diagnosis is mainly based on the EST (Exercise Stress Test), which is capable of triggering the arrhythmias. These initially present as isolated ventricular ectopic beats at HR >100-110 bpm; complexity and frequency progressively increase as the HR rises, with phases of bigeminy, trigeminy, couplets, triplets, up to NSVTs and VT, typically polymorphic and/or bidirectional. Therapy is based on beta-blockers (nadolol and propranolol are the most effective). In asymptomatic patients, with no family history, on therapy (and compliant with therapy), who do not show arrhythmias during the ergometric test, and with monitored potassium levels, low-cardiovascular-demand physical activity may be considered. In all other cases, physical exercise should be discouraged.

Post-ablation period and physical activity Catheter ablation is a well-established technique in the treatment of cardiac arrhythmias. The procedure consists of creating lesions at the level of the atrial and ventricular myocardium to eliminate the substrates causing the various arrhythmias26, through the insertion of diagnostic or scaled catheters into the heart. Leads are introduced through vascular accesses that are generally venous and, less frequently, arterial. Exercise is known to extend its multiple beneficial effects to patients with arrhythmias1. Therefore, there are few limitations and attentions to be followed in the prescription of SPE in the subject undergoing catheter ablation. Since ablative therapy is a potentially definitive cure, the main attention regarding the prescription of SPE must be oriented towards any underlying heart disease1. If, in fact, the arrhythmia is the expression of a larger structural cardiac disease, ablation could be considered “cosmetic” and aimed at containing symptoms: the pathological substrate, that is, would not be affected. These considerations should always be considered when scheduling an SPE to the patient, as limitations related to the underlying heart disease. Many arrhythmic forms, such as most paroxysmal supraventricular re-entry tachycardias, arise in structurally healthy hearts: if the previous limitation to exercise prescription resulted from symptoms related to tachycardia, in most cases the subject after ablation can be defined as clinically cured, allowing ample zones for prescription of SPE. In the immediate post-procedural period, however, it is necessary to pay particular attention to the state of vascular access to avoid complications, however rare; greater caution should be applied in the case of femoral arterial access. In any case, there are no differences in the effectiveness and safety of the procedure between active and sedentary subjects, regardless of the type of physical activity, duration and intensity of training. Generally, there is no evidence to attribute major arrhythmogenic effects to ablation, and limitations depend mainly on the

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arrhythmia treated. It follows that, after an effective ablation intervention, the subject can perform physical activities compatible with his or her state of health in a relatively short time, even after two weeks for most arrhythmias, apart from AF26. However, it is necessary to pay particular importance to symptomatic or electrocardiographic recurrences, in order to detect them promptly. The electrophysiological control study in asymptomatic subjects is not necessary, except in special cases. In patients undergoing ablation for AF, early arrhythmic recurrences can often occur, even asymptomatic. In these patients, it is important to provide adequate observation periods before resuming physical exercise, which must in any case be modulated according to the case. In subjects undergoing AF ablation, post-procedural anticoagulant therapy is maintained, generally for at least three months, even in cases with low embolic risk. Although in the absence of underlying heart disease it is possible to undertake early SPE programmes after AF ablation, it is preferable to advise against traumatic risk activities for the duration of concomitant anticoagulant treatment.

Pacemakers and implantable defibrillators Implantable cardioverter defibrillator (ICDs), pacemakers (PMKs) and cardiac resynchronization therapy (CRT) devices are widely used in a large spectrum of heart diseases: from arrhythmias in morphologically healthy hearts, to advanced forms of heart disease, with severe hemodynamic impairment. Patients with ICDs or PMKs are safely returning to physical activity, following the current recommendations of scientific societies27, 28. A multinational registry on the safety of ICDs in athletes has shown that, after a follow-up of 44 months, there were no deaths or physical problems related to arrhythmia or shock, inappropriate or not, in athletes who continued competitive sports after the implantation procedure29. On the other hand, the prescription of SPE in patients with devices, who are unable to return to a competitive sport as before, has proven to be safe and effective in improving numerous clinical outcomes. A meta-analysis evaluating the efficacy of SPE in patients with ICD and CRT30 was recently published for this purpose. In total, 16 studies were included in the review, for a total of 2,547

patients, which varied significantly in characteristics, duration of interventions (from 23 to 168 days) and follow-up (from 23 days to 48 months). In addition to a significant improvement in CRF, the results showed that patients who had exercised had a lower incidence of shock (15.6%), compared to patients who had not exercised (23%). Similar results, both in terms of cardiorespiratory improvement and shock reduction, were reported from the reviews by Pandey et al and Isaksen et al.27,31. In general, however, there are few studies on the prescription of SPE in patients with device1,28,29 and there are no specific indications on which type of exercise can be indicated a priori, without considering the underlying disease32. The consensus statement of the Sports Cardiology Section of the European Society of Cardiology33 has provided some guidance for patients with cardiomyopathy, including those implanted with an ICD. This document stresses that it is necessary to correctly identify the intensity, frequency and duration of physical exercise to be prescribed, taking due account of the patient’s clinical status and the evolution of the underlying heart disease. A recent Italian article34 documented the efficacy on physical performance and safety of an exercise prescription program carried out on 30 patients with devices (25 with PMK and 5 with ICD). These patients, with different heart conditions (such as AF, post-ischemic CMD, sinus node syndrome, complete AV block, hypertrophic cardiomyopathy and others), underwent three training sessions per week (90 minutes), including mixed aerobic, strength and flexibility training. As for the aerobic part (treadmill and/or cycle ergometer), patients were assigned an initial HR goal of 60% of the HR reserve, which was then progressively adjusted to 80%, with an absolute maximum limit of exercise intensity equal to 10 beats below the ICD intervention threshold. Strength training (lateral raises, unilateral biceps and triceps curls, leg presses and leg extensions), for a total of four sets with 8-10 repetitions each, started at about 40% of the 1RM for the upper limb exercises and 50-60% of the 1RM for the lower limbs. Finally, flexibility training consisted of stretching the hip flexors, pectorals, upper limb muscles and quadriceps, with holds lasting one minute, repeated three times. As far as ICDs are concerned, the literature agrees that the device must be constantly programmed and adapted, so that the intervention zones are high enough to allow adequate HR

Table 1. General recommendations for a correct prescription of physical exercise in patients with devices (PMK, ICD, CRT).

Post-implantation Waiting Time

Wait at least six weeks after the implantation procedure before initiating structured exercise programs. Consider any outcomes of the surgical implantation procedure (e.g., wound healing).

Post-procedure Evaluation

It is essential to perform a maximal exercise test or CPET (Cardiopulmonary Exercise Testing) to rule out residual complications and to guide exercise prescription. Consider any outcomes of the implantation surgical procedure (e.g., wound).

Prescription Guidelines

Optimize device programming (sensing, pacing, mode of intervention) and consider the underlying pathology in prescribing the frequency, intensity, duration, and type of exercise according to the FITT model.

Monitoring during Exercise

In ICD wearers: It is essential to monitor HR during training, always keeping it 10–20 beats below the first discharge (shock) threshold. In PMK and CRT wearers: Use the RPE or Borg scale to measure intensity, as the chronotropic response may be altered. Important Note: Remember that electrocardiographic changes related to myocardial distress (e.g., ST elevation) may not be visible on the ECG trace due to the function of the device.

Precautions

Avoid exercises that involve repetitive movements of the upper limbs in the first 3-4 weeks (e.g., swimming, elliptical, canoeing, weightlifting). Avoid physical exercises with traumatic risk and activities where a potential loss of consciousness could be dangerous (e.g., diving, climbing). Consider the risk of electromagnetic interference in environments where electronic equipment is present.

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to the desired levels of exercise35. A document of the Section of Secondary Prevention and Rehabilitation of the European Society of Cardiology36 has highlighted that, generally, it is necessary to wait at least six weeks after ICD implantation before embarking on an SPE program, to allow adequate healing of the surgical wound and the fixation of catheters. It is essential to carry out a post-procedure MEST (preferably with the use of the device programmer), which excludes residual problems and guides the prescription of physical exercise37. In detail, it must be ascertained: a) an adequate increase in HR in response to exertion (if the rate-adaptive function is activated); b) adequate adaptation of the exertional AV interval (if paced ventricular rhythm); c) adequate ventricular pacing in response to sinus rhythm up to peak exertion (adequate upper tracking rate, if paced ventricular rhythm); d) persistent biventricular capture (if CRT); e) absence of oversensing during exertion, especially important for ICD and subcutaneous ICD. It should also be remembered that sinus tachycardia, such as that physiologically associated with physical exertion, can cause an inappropriate discharge of the ICD. The device, in fact, can interpret sinus tachycardia, when it reaches the planned intervention HR, as a ventricular tachycardia and intervene with shock. Therefore, to avoid inappropriate shocks, it is good that the discrimination algorithms are active, that the ICD intervention HR is high, possibly higher than the patient’s maximal HR (or that beta-blocker drugs are possibly used)37. The patient should be informed of this problem, to carefully monitor the HR during exercise. In fact, the impact of any shocks, especially inappropriate ones, on the psychological balance of the subject is an aspect that should not be underestimated (30-40% of athletes who experienced a shock stopped participating in the SPE program, at least temporarily, for fear of repeated shocks1,37.

Implantable devices and physical activity In the early post-implantation periods, for all devices, activities that may increase the risk of electrode dislocation and malfunction should be avoided, such as abrupt movements of the upper limbs, ipsilateral to the implantation of the device28,29,35. It is also recommended to avoid physical exercises at risk of trauma due to the possibility of direct damage to the device (e.g. boxing)1,37,38. Electromagnetic interference is unlikely with modern devices, but should always be suspected and carefully evaluated in environments where potentially interfering electronic equipment is present (e.g. fencing). Before prescribing exercise in these patients, it is necessary to consider the type of heart disease that was the reason for the implant, in which exercise could have favoured the progression of the disease (as for arrhythmogenic cardiomyopathy39. Finally, intrinsically risky physical exercises should be avoided in which loss of consciousness (due to ICD intervention or PMK malfunctions) could cause harm to oneself or others40. Therefore, when prescribing physical exercise in patients implanted with a device, it is important to consider some crucial aspects (table 1):

References 1.

Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on Sports Cardiology and exercise in patients with cardiovascular disease. Eur Heart J 2021; 42: 17-96.

Valenzuela PL, Santos-Lozano A, Morales JS, et al. Physical Activity, Sports and Risk of Atrial Fibrillation: Umbrella Review of Meta-Analyses. Eur J Prev Cardiol 2021; 28: e11-16. 3. Tatangelo M, Rebecchi M, Sgueglia M, et al. The Complex but Fascinating Relationship between Sport and Atrial Fibrillation: from Pathophysiology to the Clinical Scenario. J Cardiovasc Dev Dis 2023; 10: 255. 4. Chung MK, Eckhardt LL, Chen LY, et al. Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement from the American Heart Association. Circulation 2020; 141: e750-772. 5. Elliott AD, Verdicchio CV, Mahajan R, et al. An Exercise and Physical Activity Program in Patients With Atrial Fibrillation: the ACTIVE-AF Randomized Controlled Trial. JACC Clin Electrophysiol 2023; 9: 455-65. 6. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive Risk Factor Reduction Study for Atrial Fibrillation and Implications for the Outcome of Ablation: the ARREST-AF Cohort Study. J Am Coll Cardiol 2014; 64: 2222-31. 7. Yang L, Chung MK. Lifestyle Changes in Atrial Fibrillation Management and Intervention. J Cardiovasc Electrophysiol 2023; 34: 2163-78. 8. Buckley BJR, Risom SS, Boidin M, et al. Atrial Fibrillation Specific Exercise Rehabilitation: Are We There Yet? J Pers Med 2022; 12: 610. 9. Zorzi A, Cipriani A, Corrado D. Anti-Arrhythmic Therapy in Athletes. Pharmacol Res 2019; 144: 306-14. 10. Marcus GM, Modrow MF, Schmid CH, et al. Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial. JAMA Cardiol 2022; 7: 167-74. 11. Lakkireddy D, Atkins D, Pillarisetti J, et al. Effect of Yoga on Arrhythmia Burden, Anxiety, Depression, and Quality of Life in Paroxysmal Atrial Fibrillation: The YOGA My Heart Study. J Am Coll Cardiol 2013; 61: 1177-82. 12. Quinn R, Leader N, Lebovic G, et al. Accuracy of Wearable Heart Rate Monitors During Exercise in Sinus Rhythm and Atrial Fibrillation. J Am Coll Cardiol 2024; 83: 1177-9. 13. Brugada J, Katritsis DG, Arbelo E, et al. 2019 ESC Guidelines for the Management of Patients with Supraventricular Tachycardia. Eur Heart J 2020; 41: 655-720. 14. Mascia G, Arbelo E, Ojeda JH, et al. Brugada Syndrome and Exercise Practice: Current Knowledge, Shortcomings and Open Questions. Int J Sports Med 2017; 38: 573-81. 15. Rao AL, Salerno JC, Asif IM, et al. Evaluation and Management of Wolff-Parkinson-White in Athletes. Sports Health 2014; 6: 326. 16. Zeppenfeld K, Tfelt-Hansen J, De Riva M, et al. 2022 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Eur Heart J 2022; 43: 3997-4126. 17. Wilde AAM, Semsarian C, Márquez MF, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases. EP Europace 2022; 24: 1307-67. 18. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-Phenotype Correlation in the Long-QT Syndrome: Gene-Specific Triggers for Life-Threatening Arrhythmias. Circulation 2001; 103: 89-95. 19. Martinez KA, Bains S, Neves R, et al. Sudden Cardiac Arrest Occurring in Temporal Proximity to Consumption of Energy Drinks. Heart Rhythm 2024; 21: 1083-8. 20. Giustetto C, Schimpf R, Mazzanti A, et al. Long-Term Follow-up of Patients with Short QT Syndrome. J Am Coll Cardiol 2011; 58: 587-95. 21. Gollob MH, Redpath CJ, Roberts JDR. The Short QT Syndrome: Proposed Diagnostic Criteria. J Am Coll Cardiol 2011; 57: 802-12. 22. Dhutia H, Malhotra A, Parpia S, et al. The Prevalence and Significance of a Short QT Interval in 18,825 Low-Risk Individuals Including Athletes. Br J Sports Med 2016; 50: 124-9. 23. Leenhardt A, Lucet V, Denjoy I, et al. Catecholaminergic Polymorphic Ventricular Tachycardia in Children. A 7-Year Follow-up of 21 Patients. Circulation 1995; 91: 1512-9. 24. Peltenburg PJ, Pultoo SNJ, Tobert KE, et al. Repeatability of Ventricular Arrhythmia Characteristics on the Exercise-Stress Test in RYR2-Mediated Catecholaminergic Polymorphic Ventricular Tachycardia. EP Europace 2023; 25: 619-26. 25. Hayashi M, Denjoy I, Extramiana F, et al. Incidence and Risk Factors of Arrhythmic Events in Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation 2009; 119: 2426-34. 26. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation. Europace 2009; 11: 132. 27. Isaksen K, Morken IM, Munk PS, et al. Exercise Training and Cardiac Rehabilitation in Patients with Implantable Cardioverter Defibrillators. Eur J Prev Cardiol 2012; 19: 804-12. 28. Heidbuchel H, Arbelo E, D’Ascenzi F, et al. Recommendations for Partici-

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pation in Leisure-Time Physical Activity and Competitive Sports of Patients with Arrhythmias and Potentially Arrhythmogenic Conditions. Part 2: Ventricular Arrhythmias, Channelopathies, and Implantable Defibrillators. Europace 2021; 23: 147-8. 29. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of Sports for Athletes with Implantable Cardioverter-Defibrillators: Long-Term Results of a Prospective Multinational Registry. Circulation 2017; 135: 2310-2. 30. Steinhaus DA, Lubitz SA, Noseworthy PA, et al. Exercise Interventions in Patients with Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy: A Systematic Review and Meta-Analysis. J Cardiopulm Rehabil Prev 2019; 39: 308. 31. Pandey A, Parashar A, Moore C, et al. Safety and Efficacy of Exercise Training in Patients with an Implantable Cardioverter-Defibrillator: A Meta-Analysis. JACC Clin Electrophysiol 2017; 3: 117-26. 32. Sciarra L, Salustri E, Petroni R, et al. Sport Activity in Patients with Cardiac Implantable Electronic Devices: Evidence and Perspectives. J Cardiovasc Med (Hagerstown) 2021; 22: 335-43. 33. Pelliccia A, Solberg EE, Papadakis M, et al. Recommendations for Participation in Competitive and Leisure Time Sport in Athletes with Cardiomyopathies, Myocarditis, and Pericarditis. Eur Heart J 2019; 40: 19-33. 34. Squeo MR, Di Giacinto B, Perrone MA, et al. Efficacy and Safety of a Com-

bined Aerobic, Strength and Flexibility Exercise Training Program in Patients with Implantable Cardiac Devices. J Cardiovasc Dev Dis 2022; 9: 182. 35. Hansen D, Abreu A, Ambrosetti M, et al. Exercise Intensity Assessment and Prescription in Cardiovascular Rehabilitation and beyond: Why and How. Eur J Prev Cardiol 2022; 29: 230-45. 36. Ambrosetti M, Abreu A, Corrà U, et al. Secondary Prevention through Comprehensive Cardiovascular Rehabilitation: from Knowledge to Implementation. 2020 Update. Eur J Prev Cardiol 2021; 28: 460-95. 37. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of Sports for Athletes with Implantable Cardioverter-Defibrillators: Results of a Prospective, Multinational Registry. Circulation 2013; 127: 2021-30. 38. Nesti M, Russo V, Palamà Z, et al. The Subcutaneous Implantable Cardioverter-Defibrillator: A Patient Perspective. J Clin Med 2023; 12: 6675. 39. Maron BJ, Zipes DP, Kovacs RJ. Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular Abnormalities: Preamble, Principles, and General Considerations. Circulation 2015; 132: e256-261. 40. Palermi S, Cavarretta E, D’Ascenzi F, et al. Athlete’s Heart: A Cardiovascular Step-By-Step Multimodality Approach. Rev Cardiovasc Med 2023; 24: 151.

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| CHAPTER 3.8 |

Congenital heart disease Paolo Zeppilli, Michela Cammarano, Raffaella Marzullo, Berardo Sarubbi, Attilio Turchetta

Introduction Despite the demonstration that regular physical exercise is able to improve their prognosis and quality of life, the participation in physical activity of patients with congenital heart disease in children and adults is still limited today. Partly because of the distorted perception of the health condition by the young patient, his parents and sometimes even by overly “protective” treating doctors, partly because of the objective difficulty of identifying an SPE program, due to the anatomical and pathophysiological heterogeneity of congenital heart defects, the different surgical approach and result. In addition, there are extracardiac conditions, such as limitations of respiratory capacity related to cardiac pathology or surgical procedures, musculoskeletal limitations, the discomfort created by exposing scars or skeletal deformities and sometimes even psychomotor limitations in “syndromic” subjects (on a genetic basis) that make the prescription of physical activity more complex. We will not deal here with competitive certification, which has been extensively analysed in recent publications on the subject1.

The benefits of exercise in congenital heart disease Mechanisms that make regular exercise useful in congenital heart patients, whether operated or not, include2,5: – a “healthy” cardiac remodelling, due to the production of growth factors and cytokines that promote angiogenesis and increase the production of type III collagen, improving perfusion and elasticity of myocardial tissue and preventing fibrosis; – Improved functional capacity: exercise increases myocardial mass and contractility, optimizes autonomic nervous system function, reducing resting HR, increasing stroke volume and venous return, improving exercise tolerance and reducing fatigue. The capillarization in skeletal and cardiac muscles, the increase in mitochondrial density and the improved efficiency of energy metabolism, induce better tissue oxygenation, with elevation of ventilatory thresholds and reduction of lactic acid accumulation in muscles; – the improvement of lung capacity: exercise improves ventilation and pulmonary perfusion, increases the capacity of respiratory muscles and the functionality of lung tissue, thus improving the efficiency of gas exchange; – the reduction of oxidative stress: exercise increases the release of endothelial nitric oxide which exerts a positive effect on vascular structure and activity, reducing vasoconstriction and oxidative damage both at the systemic and pulmonary level; – the improvement of insulin sensitivity and mobilization of fatty acids and glucose (increased uptake and use at the peripheral level) with a reduction in the risk of cardiometabolic diseases;

– Modulation of synaptic transmission and cerebral blood flow: exercise improves cerebral regional blood flow. It enhances the functionality of the anterior cingulate and prefrontal cortex, areas involved in executive functions, and promotes the release of neurotransmitters involved in the regulation of mood and cognitive functions. These benefits play a greater role in complex congenital heart diseases, in which there is a chronic maladaptation as a result of the anatomical malformation and volume and/or pressure overload pre-existing or subsequent to surgery, as well as a “chronic” condition of reduced functional capacity (sedentary lifestyle). It is precisely these patients, habitually excluded from competitive sporting activity, who benefit most from an appropriate SPE program for therapeutic purposes.

Prescription of physical activity The prescription of physical activity in patients with congenital heart disease must be formulated with the criteria amply illustrated in the first chapters (identification of the type of SPE, personalization, monitoring, etc.). The prescription, however, varies according to age, as the strategies to be adopted in a child before the age of 6, before puberty (from 6-7 to 12-13 years), are obviously different than in a young adult. It must be taken into account that, in younger children, the use of sports and sports games of a playful nature, they are essential for adherence to the program. The prescription, as in other cases, must be structured taking into account age, heart disease, psychomotor skills, the presence of comorbidities and the patient’s preferences6,11. Before doing so, it is essential to proceed with an accurate risk stratification, based on the evaluation of oxygen saturation, ventricular function, pulmonary pressure, arrhythmic “burden” and structural/ functional abnormalities of the heart valves and aorta. It often requires the integration of several diagnostic methods. CPET is indicated to study the cardiac, ventilatory, neurohormonal, and metabolic response to exercise and to document any “maladapted” responses to exercise and/or inducible ischemia. In addition to morpho-functional evaluation (cardiac volumes, flow abnormalities, etc.), Cardiac MRI allows myocardial tissue characterization, which is essential in subjects with sometimes significant scarring outcomes. The main elements to consider when prescribing a training program have been covered in the specific chapters to which we refer. Currently, in congenital heart disease, there is no evidence in favour of prescribing exercises with a static component (power, strength) or dynamic. Patients with uncontrolled arrhythmias, ventricular dysfunction, severe outflow obstruction, and aortic dilatation should avoid activities with power engagement (pressure overload). Subjects initiated into the practice of SPE and/or a recreational sports activity must be regularly monitored taking into account the type of defect and the results of surgical and/or interventional procedures. Careful follow-up allows therapeutic goals to be

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assessed and gradually modified and to increase motivation and adherence to the exercise program.

Prescription of physical exercise under specific conditions Pulmonary hypertension The increase in afterload associated with pulmonary hypertension conditions a compensatory hypertrophy of the right ventricle which over time becomes insufficient causing progressive dilation/dysfunction. In non-cyanotic patients, variation in ventriculoarterial coupling is the main cause of reduced physical performance. In cyanotic patients or patients with Eisenmenger’s physiology, on the other hand, the physical limitation is conditioned by the desaturation of oxygen on exertion. In these patients, compression of the left coronary artery by the dilated pulmonary trunk may occur during physical activity, resulting in angina. Recent evidence shows that mild, aerobic physical activity (walking for limited time and in comfortable environments or yoga practice) can have positive effects on muscle strengthening and respiratory function. When prescribing SPE or recreational sports, the risks of exposure to extreme temperatures, high altitudes and dehydration must always be considered, always recommending practice in a “protected” environment.

Cyanosis Patients with right-to-left shunts and univentricular heart have an increase in exertional cyanosis. In the case of >90% exertional saturation, the intensity and duration of exercise should be symptom limited.

Heart rhythm abnormalities Patients with congenital heart disease, whether natural history or corrected, have an increased risk of supraventricular and ventricular arrhythmias, although total restriction of physical activity does not appear to significantly reduce their incidence. Sinus bradycardia and chronotropic incompetence are found in 30-60% of patients. They often have a multifactorial aetiology: autonomic dysfunction, negative chronotropic effect of specific drugs, post-surgical impairment of the sinus and atrio-ventricular node and/or vascularization of the coronary branches assigned to them. The reduction in maximal HR can also be a consequence of reduced preload. In patients with uncontrolled arrhythmias, ablative therapy should be proposed before prescribing exercise.

Myocardial ischemia Myocardial ischemia in congenital heart disease is mainly attributable to: – congenital coronary artery anomalies; – occlusive pathology of the coronary ostium following coronary artery reimplantation (switch, Ross surgery, correction of coronary abnormality, aortic root replacement, etc.); – mismatch between oxygen demand and demand, such as in the presence of a hypo-represented coronary circulation (systemic right ventricle) and/or cyanosis or pulmonary hypertension; – In adults, the incidence of coronary artery disease-ischemia is related to traditional cardiovascular risk factors.

SPE can change the risk profile and reduce the incidence of events. In prescribing it, the evaluation of myocardial ischemia and the mechanism that supports it is of considerable importance. For this purpose, patients should undergo a functional evaluation with CPET, physical stress echocardiogram and other tests to assess the status of the coronary arteries, primarily Coronary CT.

Musculoskeletal abnormalities Patients with complex congenital heart disease have varying degrees of sarcopenia and musculoskeletal abnormalities (especially those who have undergone surgery). Sarcopenia is frequently associated with muscle dysfunction that contributes to the onset of fatigue and dyspnoea on exertion. Personalized training programs have been shown to be effective in increasing muscle mass, improving oxygen consumption, controlling pain and correcting incorrect postural attitudes in patients with scoliosis and/ or kyphosis.

Respiratory function Physical exercise is essential for the recovery of functional respiratory capacity in patients undergoing cardiac surgery, both in the case of a sternotomy and thoracotomy procedure. In patients with Fontan type hemodynamics (see below) the finding of a restrictive ventilatory deficit (reduction of lung volume and limitation in alveolar diffusion) is common. Training the inspiratory muscles can increase their strength, improving breathing performance.

Psychosocial aspects Patients with congenital heart disease have an increased risk of anxiety, depression, attention deficit hyperactivity disorder, which can lead to a negative lifestyle with social isolation and physical inactivity. In children and adolescents, physical activity promotes social interaction, increases the sense of accomplishment and acceptance of one’s state. In adults, regular physical activity makes it possible to prevent neuro-cognitive decline, the incidence of which has increased in recent years not only due to the increase in average age, but also due to the late effects of incorrect brain protection during cardiac surgery carried out in pioneering times.

Indications for pathology Simple shunts In this group we can include atrial septal defects (DIA), interventricular defects (DIV), and patent ductus arteriosus of Botallo (PDA). In subjects with a natural history with hemodynamically insignificant shunt (ratio of pulmonary flow rate to systemic flow rate, Qp/Qs <1.5), normal dimensions of the ventricular chambers and absence of pulmonary arterial hypertension, the prescription of any SPE and also of recreational sports is possible. In subjects with a significant shunt (Qp/Qs >1.5), it is possible to prescribe SPE with mild-moderate cardiovascular effort, with a predominantly dynamic component, in order to maintain and/ or improve ventilatory thresholds until the correction of heart disease. After surgical and/or percutaneous correction, in the absence of sequelae (significant shunt, pulmonary hypertension, atrial/ventricular arrhythmias and ventricular dysfunction) it is

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possible to prescribe an early rehabilitation program in order to achieve a prompt functional recovery and, after 3-6 months, it is possible to prescribe SPE or sport more extensively. In subjects with pulmonary hypertension and/or ventricular dysfunction, it is possible to prescribe mild intensity SPE with a prevalent dynamic component, as part of rehabilitation programs or personalized training.

Left ventricular outflow obstruction Obstruction to left ventricular outflow may be subvalvular (fibrous membrane or hypertrophic muscle tissue), valvular or supravalvular (hourglass deformation, fibrous membrane, diffuse hypoplasia). The most frequent form is stenosis on VAB. Frequently, VAB is associated with progressive dilation of the bulb and ascending aorta, with an increased risk of dissection (see chapter 3.5 VAB in adults). Left outflow obstruction may occur in isolation or in association with other intracardiac defects. In supravalvular forms, arterial abnormalities (coronary artery and supra-aortic trunks) are frequently found, while in subvalvular forms there may be “damage” to the aortic valve. Obstruction to left outflow subjects the ventricle to chronic pressure overload (increased afterload) resulting in adaptive myocardial hypertrophy, initially concentric, which can evolve into eccentric in natural history forms. Patients with significant obstruction have reduced exercise tolerance and increased risk of sudden cardiac death. Treatment is surgical, except in neonatal-onset and early childhood valvular forms in which percutaneous valvuloplasty may be evaluated. Given the potential progression of obstructions, the prescription of SPE or recreational sports will have to be re-evaluated every six months (or not based on the starting condition). The criteria that can be used in the different degrees of obstruction to the outflow are those indicated in the chapter on valvular pathologies. In subjects undergoing correction by surgery or interventional valvuloplasty, it is possible to prescribe a rehabilitation program in order to obtain early functional recovery. Resumption of more extensive physical activity is possible at least 6 months after correction. Type and intensity of activity should be chosen based on ventricular function, arrhythmic risk and the presence of sequelae based on the same criteria described above for native obstructions. In subjects undergoing Ross surgery (aortic valve replacement with pulmonary autograft and placement of pulmonary homograft) an early rehabilitation program allows rapid functional recovery, while the resumption of physical activity and any recreational sports is possible at least 6 months after correction surgery. Type and intensity of the same should be prescribed in relation to ventricular function, right ventricle-pulmonary artery peak gradient, residual arrhythmic risk and presence of sequelae. Subjects with a good surgical result who have a normal exercise tolerance, with achievement at CPET of 80% of theoretical VO2max, may be eligible for the subsequent prescription of moderate-intensity activities. In cases of doubt, performing a physical stress echocardiogram may be useful.

Aortic coarctation Aortic coarctation (CoAo) is defined by narrowing at the isthmic level associated with varying degrees of hypoplasia of an aortic segment. Surgical repair, with various techniques, is reserved for neonatal and early childhood forms. In the case of re-coarctation

at a distance from surgery and in forms with a late diagnosis, percutaneous treatment with angioplasty and stenting is possible. Despite the optimal results of modern surgical and percutaneous techniques, arterial hypertension persists in about 30% of those operated, sometimes associated with reduced functional capacity, coarctation or vascular aneurysms, aspects that must be sought at the time of prescription. In subjects with hemodynamically and clinically non-significant and/or successfully corrected native CoAo (upper limb/ lower limb gradient <20 mmHg at rest, no diastolic run-off on echo-Doppler evaluation, absence of arterial hypertension at rest/exertion, left ventricular hypertrophy, ascending aortic dilatation, aneurysms, kinking, and/or other sequelae at the repair site) prescription of any SPE or recreational sports at mild-moderate cardiovascular engagement with a predominantly dynamic component (and with low risk of chest impact). In subjects with hemodynamically and clinically significant native CoAo or re-coarctation (especially if with significant dilation of the ascending aorta), the prescription of mild intensity SPE, with an exclusively dynamic component, is possible. In subjects undergoing surgical/percutaneous correction, an early rehabilitation program can be prescribed. The resumption of physical activity and any recreational sports in a more extensive way (with the exclusion of activities with high static/strength and contact intensity) can take place at least 3/6 months after correction, after careful evaluation of the pressure response to exertion and after excluding aneurysms at the repair site or other sequelae.

Right outflow obstruction Right ventricular outflow obstruction can be valved, subvalvular (infundibular or midventricular) and/or supravalvular. The increase in right ventricular pressure leads to the initial development of compensatory hypertrophy of the ventricle and, over time, its deferral and fibrosis. The severity of the obstruction affects the reduction of exercise capacity and an increase in arrhythmic risk. Treatment of valve obstruction can be percutaneous or surgical; for the other forms it is in most cases surgical. Sometimes, treatment results in lung failure, which can become an additional factor limiting functional capacity. In subjects with mild right ventricular outflow obstruction (peak Doppler gradient <30 mmHg) with good functional capacity, absence of right ventricular hypertrophy and/or sustained arrhythmias, an unrestricted prescription is possible. In asymptomatic subjects with moderate right ventricular outflow obstruction (peak gradient 30-50 mmHg) with good functional capacity, mild pulmonary insufficiency, mild right ventricular hypertrophy and without sustained arrhythmias, it is possible to prescribe SPE and play sports at mild-moderate intensity, with a prevalent dynamic component. Asymptomatic subjects with severe right ventricular outflow obstruction (peak gradient >50mmHg) with hypertrophy, dilation and/or dysfunction of the right ventricle and/or non-sustained arrhythmias, it is only possible to prescribe physical activity of mild intensity with a dynamic component, as part of rehabilitation programs or personalized training, until correction. In subjects undergoing surgical correction or interventional valvuloplasty, an early rehabilitation program can be prescribed in order to achieve rapid functional recovery. Resumption of SPE programs or recreational sports is possible at least 3-6 months after correction. In the case of implantation of a percutaneous valve prosthesis or surgical application of a prosthetic duct, it

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is recommended to avoid contact sports. Type and intensity of physical activity should be prescribed based on the criteria described above for native obstructions.

Tetralogy of Fallot Tetralogy of Fallot (ToF) is a complex congenital heart disease characterized by a large interventricular defect (IVD) due to malalignment, right outflow obstruction, straddling of the aorta on the interventricular septum and right ventricular hypertrophy. The most severe spectrum of heart disease is represented by the form with pulmonary valve atresia. Corrective surgery tends to correct defects (DIV closure, right outflow enlargement, etc.) with possible onset of pulmonary insufficiency in patch-corrected subjects and progressive reduction of functional capacity and right ventricular dysfunction. These individuals are predisposed to major arrhythmic events. The integration of imaging methods (echocardiography, MRI) with functional data (CPET) allow optimal management of the sequelae of the intervention and the stratification of arrhythmic risk12. In asymptomatic subjects who do not have significant complications (residual shunts, ventricular dysfunction, lung failure and/ or obstruction, arrhythmias, ischemia, dilation of the ascending aorta) and have no risk factors for sudden death, it is possible to prescribe SPE at even medium-high intensity with a prevalent dynamic component. In asymptomatic subjects with moderate-to-severe pulmonary insufficiency and/or with significant right obstruction, associated with mild-moderate right ventricular dilatation, it is possible to prescribe SPE with mild, dynamic cardiovascular effort, provided that biventricular function is preserved and no spontaneous and/ or inducible arrhythmias are documented. In symptomatic subjects with moderate-severe pulmonary insufficiency and/or with significant right obstruction, ventricular dysfunction and/or dilation, poorly controlled atrial/ventricular arrhythmias, who are not eligible for treatment, it is possible to prescribe SPE with mild intensity cardiovascular engagement as part of rehabilitation or personalized training programs. In the case of atrial/ventricular arrhythmias, an electrophysiological evaluation (with possible ablation) is indicated before prescribing sports activity (see chapter arrhythmias).

Ebstein’s disease It is a heart disease characterized by varying degrees of congenital dysplasia of the tricuspid valve and right ventricle. The variability of anatomical pictures corresponds to clinical variability: from severe to mild forms, well tolerated or pauci-symptomatic until adulthood. Atrial tachyarrhythmias, sometimes associated with multiple accessory pathways, are frequently found in these patients. There are several surgical repair techniques. The functional capacity of patients in natural history and operated on correlates with the volume of the functional right ventricle and is inversely proportional to the severity of tricuspid insufficiency (constant in severe forms). In asymptomatic natural history subjects with optimal cardiac conditions (normal oxygen saturation during exercise, normal-represented right ventricle, mild tricuspid insufficiency, normal left ventricular systolic function, absence of supraventricular/ventricular arrhythmias) it is possible to prescribe SPE even at moderate intensity with prevalent dynamic component and some sports of a recreational nature. In subjects who show desaturation during exertion with tricuspid insufficiency and/or su-

praventricular arrhythmias despite medical treatment, prescription of mild intensity SPE may be possible as part of rehabilitation or personalized training programs. In surgically corrected asymptomatic patients who present a normal saturation both at rest and during exertion, in the absence of significant hemodynamic and/or arrhythmic sequelae, an early rehabilitation program can be prescribed in order to achieve functional recovery. A wider resumption of physical activity and recreational sports is possible after 3/6 months from correction, with regular “personalized” monitoring of the patient.

Transposition of the large vessels Transposition of the great vessels (TGA) is characterized by ventriculo-arterial discordance: the morphologically right ventricle is connected to the aorta while the morphologically left ventricle is connected to the pulmonary artery. Currently, the surgical treatment of choice is arterial switching performed in the neonatal period with restoration of the connection between the native root of the pulmonary artery (“neo-aorta”) with the ascending aorta and between the native root of the aorta with the pulmonary bifurcation. At the same time, the coronary arteries are reimplanted on the neo-aorta. Long-term post-operative complications include: neo-aortic valvular insufficiency, pulmonary branch stenosis, arrhythmias and more rarely ventricular dysfunction. In the absence of late sequelae, patients have almost normal functional capacity. Although rare, coronary artery reimplantation can affect the deformation and/or obstruction of the ostia with the appearance of inducible myocardial ischemia. In subjects undergoing arterial switch with good functional capacity, preserved biventricular function, ascertained patency of the coronary circulation (assessed with Coronary CT), absence of major arrhythmias and/or ischemia uninducible to physical echo stress or myocardial scintigraphy, it is possible to prescribe SPE and recreational sports without restrictions. In subjects with normal capacity functional dysfunction, mild neo-aorta insufficiency/stenosis, non-significant gradient to pulmonary outflow, isolated supraventricular and/or ventricular extrasystole, it is possible to prescribe SPE or recreational sports at mild to moderate intensity. Subjects with ventricular dysfunction (left and/or right), more than moderate neo-aorta insufficiency/stenosis, invasive gradient to pulmonary outflow >30 mmHg organized atrial and/or ventricular tachyarrhythmias (exercise ECG and Holter) only mild intensity SPE with a predominantly dynamic component can be prescribed. In case of direct/indirect evidence of inducible ischemia and/or obstacle stenosis at the level of the reimplanted coronary arteries, abstention from any activity is recommended.

Univentricular heart (Palliation according to Glenn and Fontan) Univentricular heart disease is a heterogeneous group of malformations united by the presence of a single functioning ventricle and/or the impossibility of performing a biventricular correction. Surgical palliation of univentricular heart disease includes two main possibilities: 1) anastomosis between the superior vena cava and pulmonary arteries (Glenn surgery); 2) the connection of the inferior vena cava to the pulmonary circulation (Fontan’s surgery). The ultimate goal of the surgical pathway is to create a “neo-portal” circulation directly connect-

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Table 1. Indications for the prescription of physical exercise in patients with congenital heart disease. Congenital Heart Disease

Prescription of Physical Activity

Simple Shunts Hemodynamically non-significant – Absence of complications

Optionally, by subjecting patients to periodic re-evaluations.

Hemodynamically significant – Pending correction

2–3 weekly sessions (max 20 min) of SPE at mild intensity or recreational sports: swimming, water exercises, flat terrain cycling, cross-country skiing (flat, light), dance, fencing, tennis (technique with master), horse riding, golf, etc.

* Complicated by ventricular dysfunction, pulmonary hypertension, or arrhythmias awaiting electrophysiological evaluation.

2 weekly sessions (max 15–20 min) of SPE, or alternatively yoga, gymnastics, and stretching.

Left Ventricular Outflow Obstruction Mild – Good functional capacity – Absence of associated complications

Patient’s choice: SPE or recreational sport (see sports listed above).

Moderate – Asymptomatic

2-3 weekly sessions (max 20 min) of SPE or recreational sport while maintaining a light intensity.

Severe – Associated complications

2 weekly sessions (max 15–20 min) of SPE or recreational sport while maintaining a light intensity.

CoA Hemodynamically and clinically not significant

Patient’s choice: SPE or recreational sport (see above), excluding activities at risk of chest impact.

Hemodynamically significant

2-3 sessions per week (max 20 min) of SPE or recreational sport while maintaining a light intensity.

Right Outflow Obstruction Mild – Preserved functional capacity

Patient’s choice: SPE or recreational sport (see above).

Moderate – Asymptomatic – Preserved functional capacity – Unsustained arrhythmias

Patient’s choice: SPE or recreational sport (see above).

Severe – Asymptomatic – Unsustained arrhythmias

2 sessions per week (max 10–15 min) of SPE or recreational sport while maintaining a light intensity.

Tetralogy of Fallot Absence of hemodynamic sequelae – Absence of hyperkinetic arrhythmias, inducible ischemia, and ascending aortic dilatation – Absence of risk factors for sudden cardiac death

Patient’s choice: SPE or play/recreational sport (see above).

Asymptomatic Significant Right Obstruction / Grade moderate-severe 2-3 sessions per week (max 20 min) of SPE or recreational sport, pulmonary insufficiency – Asymptomatic – Biventricular function preserved keeping the intensity light. – Absence of spontaneous and/or inducible arrhythmias Symptomatic severe right obstruction / Moderate-to-severe pulmonary insufficiency 2 sessions per week (max 10-15 min) of SPE or recreational sport, – Symptomatic – Ventricular dysfunction and/or dilation – Atrial/ventricular keeping the intensity light. arrhythmias Ebstein’s Disease Asymptomatic – Good SpO2 even under stress – Good right ventricular (RV) performance – Mild tricuspid regurgitation (TR) – No arrhythmias

2-3 weekly sessions (max 30 min) of SPE or recreational sport, maintaining a light intensity.

Asymptomatic – Good SpO2 even under stress – Good right ventricular (RV) performance – Mild tricuspid regurgitation (TR) – Well managed supraventricular arrhythmias

2-3 sessions per week (max 20 min) of SPE or recreational sport, maintaining a mild intensity.

Desaturation under stress – Moderate-to-severe tricuspid regurgitation (TR) – Little-controlled supraventricular arrhythmias

2 weekly sessions (max 10-15 min) of SPE with yoga exercises, stretching, checking if possible oxygen saturation.

Transposition of the Great Arteries (Arterial Switch) Absence of surgical sequelae – Good functional ability – No arrhythmias – Absence of coronary artery problems

Patient’s choice: SPE or recreational sport (see above).

Good functional capacity – Mild neo-aortic stenosis/insufficiency – Absence of obstruction to pulmonary outflow – Isolated supraventricular or ventricular ectopy

2-3 sessions per week (max duration 30 min) of SPE or recreational sport, maintaining a mild intensity.

Ventricular dysfunction – Moderate-to-severe neo-aortic stenosis/ insufficiency – Pulmonary outflow obstruction – Major arrhythmias

2 sessions per week (max duration 10–15 min) of SPE or recreational sport, maintaining a mild intensity.

Univentricular Heart Glenn Palliation: SpO2>80% at rest and >70% during exertion – Good single ventricle contractile function – Absence of cardiac decompensation or arrhythmias

2-3 sessions per week (max 20 min) of SPE or recreational sport, keeping the intensity light.

Fontan Palliation: SpO2>90% during exertion – Good ventricular contractile function – Absence of heart failure or arrhythmias

2-3 sessions per week (max 15 min) of SPE or recreational sport, keeping the intensity light.

*Assess the traumatic risk associated with physical activity.

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ed to the pulmonary circulation in which the subpulmonary ventricle is bypassed. Although survival of these patients has improved, long-term complications remain a major problem. They are related to the characteristics of univentricular palliation, which causes chronic reduction of ventricular preload and elevation of central venous pressure. Among the most frequent: arrhythmias, thromboembolisms, protein-losing enteropathy, cardiac cirrhosis, ventricular dysfunction and plastic bronchitis. Patients with univentricular circulation have reduced functional capacity, the main mechanism of which seems to be the reduction of muscle mass. In this sense, physical activity would play an important therapeutic role aimed at supporting the propulsive effect of the muscles on the return and the maintenance of physical performance, but its prescription in these patients is very delicate and should be reserved for Centres and Health Personnel with specific experience13-17. In subjects undergoing palliation according to Glenn with oxygen saturation >80% at rest and >70% during exertion, without symptoms and/or signs of heart failure and/or arrhythmias, it is possible to prescribe SPE at mild intensity with a predominantly dynamic component. In subjects undergoing Fontan surgery with systemic saturation at rest and exercise >90%, good contractile function of the single ventricle, in the absence of symptoms and/or signs of decompensation and/or arrhythmias, it is possible to prescribe mild-moderate intensity SPE with a mixed component (dynamic and static). In these patients, if saturation is >90% during exercise, single ventricular contractile function is good and there are no arrhythmias, prescription of mild-to-moderate intensity SPE is possible.

Conclusion Physical activity, whether as part of an active lifestyle or an SPE program, promotes the physical, psychological, and social well-being of patients with congenital heart disease in natural history and surgery. The benefits outweigh the potential risks, even in complex heart disease, if the patient undergoes careful preventive evaluation. The prescription must be made by competent personnel able to provide an SPE program identified on the basis of the type of heart disease, the patient’s abilities and preferences and must be adapted over time to the patient’s functional responses (table 1). Thanks for their contribution to the text: Antonio Orlando and Massimiliana Abbate.

References 1.

COCIS. Cardiological protocols for the judgment of fitness for competitive sport 2023 (VI edition). Roma: CESI Edizioni; 2023. 2. Amedro P, Gavotto A, Guillaumont S, et al. Cardiopulmonary fitness in children with congenital heart diseases versus healthy children. Heart 2018; 104: 1026-36. 3. Tran D, Maiorana A, Ayer J, et al. Recommendations for exercise in adolescents and adults with congenital heart disease. Prog Cardiovasc Dis 2020; 63: 350-66. 4. Williams CA, Wadey C, Pieles G, et al. Physical activity interventions for people with congenital heart disease. Cochrane Database Syst Rev 2020; 10: CD013400. 5. Selamet Tierney ES. The benefit of exercise in children with congenital heart disease. Curr Opin Pediatr 2020; 32: 626-32. 6. Marzullo R, Balducci A, Cafiero G, et al. Physical activity in subjects with congenital heart disease in natural history is operated. Task Force on physical activity in congenital heart patients of the Italian Society of Paediatric Cardiology and Congenital Heart Disease. G Ital Cardiol (Rome) 2021; 22: 756-66. 7. Amir NH, Dorobantu DM, Wadey CA, et al. Exercise training in paediatric congenital heart disease: fit for purpose? Arch Dis Child 2022; 107: 525-34. 8. Anderson CAJ, Suna JM, Keating SE, et al. Safety and efficacy of exercise training in children and adolescents with congenital heart disease: A systematic review and descriptive analysis. Am Heart J 2022; 253: 1-19. 9. Hansen K, Tierney S. Every child with congenital heart disease should be exercising. Curr Opin Cardiol 2022; 37: 91-8. 10. Leone D, Buber J, Shafer K. Exercise as Medicine: Evaluation and Prescription for Adults with Congenital Heart Disease. Curr Cardiol Rep 2023; 25: 1909- 19. 11. Stuart G, Forsythe L. Exercise prescription in young children with congenital heart disease: time for a change in culture. Open Heart 2021; 8: e001669. 12. Sarubbi B, Pacileo G, Pisacane C, et al. Exercise capacity in young patients after total repair of tetralogy of Fallot. Pediatric Cardiology 2000; 21: 211-5. 13. Scheffers LE, Berg L, Ismailova G, et al. Physical exercise training in patients with a Fontan circulation: a systematic review. Eur J Prev Cardiol 2021; 28:1269- 78. 14. Terol Espinosa de Los Monteros C, Harteveld LM, Kuipers IM, et al. Prognostic value of maximal and submaximal exercise performance in Fontan patients < 15 years of age. Am J Cardiol 2021; 154: 92-8. 15. Egbe AC, Driscoll DJ, Khan AR, et al. Cardiopulmonary exercise test in adults with prior Fontan operation: the prognostic value of serial testing. Int J Cardiol 2017; 235: 6-10. 16. Hedlund ER, Lundell B, Soderstrom L, et al. Can endurance training improve physical capacity and quality of life in young Fontan patients? Cardiol Young 2018; 28: 438-46. 17. Khoury M, Cordina R. Exercise Training for People Living With Fontan Circulation: An underutilized intervention. Can J Cardiol 2022; 38: 1012- 23.

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| CHAPTER 3.9 |

Heart failure and heart transplant Massimo Piepoli, Piergiuseppe Agostoni, Ugo Corrà, Andrea Garascia, Alessandro Navazio, Maurizio Volterrani

Introduction Guidelines recommend the prescription of physical exercise in patients with heart failure (HF), stabilized by optimal medical therapy1. The recommendations are based on the results of meta-analyses documenting significant improvements in exercise tolerance and quality of life associated with reductions in hospitalizations for both all-cause and HF. A modest effect on allcause mortality and HF mortality was also observed2,3. The benefits of exercise in patients with HF impact on a number of prognostic indicators: exercise capacity, ventilatory response and autonomic control. – Exercise capacity. Already in the early stages of an exercise prescription program, an improvement in exercise tolerance is observed, not only as the duration of the exercise itself, but also as an increase in VO2peak. – Ventilatory response. In patients with HF, symptoms during exercise are determined by early increase in serum lactate, reduction in VO2 and disproportionate increase in ventilation from the sub-maximal phases of exertion. Increased metabolic demands, reflex activation of ventilation, and increased dead space result in the appearance of frequent and superficial breathing and therefore not very effective. Numerous studies have demonstrated the favourable effects of exercise on ventilatory response in decompensated patients. At the basis of a reduced ventilatory response following exercise there is a decrease in the accumulation of lactate in the circulation, as well as a better ventilation/perfusion ratio in the lung and a decrease in the activation of the reflexes that regulate ventilation. – Autonomic control. Data from the literature have shown an increase in vagal tone with a decrease in sympathetic activation and circulating catecholamines associated with an increase in nitric oxide and a decrease in the production of

pro-inflammatory cytokines and the expression of inducible nitric oxide synthase (iNOS) as well as an increase in insulin-like growth factor (IGF). These changes in turn are reflected in an improvement in autonomic control of exercise with a consequent greater tolerance to physical exertion.

Risk stratification and preliminary assessment Exercise training can only be initiated in a clinically stable patient. The key components before starting are: 1. exclusion of contraindications (table 1); 2. thorough cardiological evaluation including comorbidity and severity of HF (e.g., by evaluation of blood natriuretic peptides and echocardiography). Maximal exercise testing (preferably cardiopulmonary exercise test, CPET) is used to assess functional capacity, ascertain potential complications during exercise, and prescribe exercise intensity, based on VO2peak or HR at rest and during exercise4; 3. optimization of medical therapy: All patients with HF should be treated according to current guidelines including implantation of devices when necessary. The training session should be individually adapted over several weeks, according to objective measures and symptoms; the intensity, on the other hand, should be adapted according to the symptoms, the HR response and the power generated (Watts). In the presence of AF, the intensity of exercise can be monitored only by power or on the basis of the Borg scale as in the fibrillating patient the response to HR exercise, although modulated by therapy, is characterized by rapid increase and values on average higher than those observed in those in sinus rhythm. High-risk patients should be monitored more frequently during the early stages, when exercise should be supervised.

Table 1. Summary of contraindications to exercise in subjects with heart failure (modified from Piepoli et al.7). Contraindications

Details

Cardiovascular

• SBP <90 mmHg or >160 mmHg. During exercise, a decline in systolic blood pressure (>20 mmHg) or below the or a disproportionate increase, i.e. a systolic blood pressure >200 mmHg • Resting HR: <40 bpm or >100 bpm (>120 bpm in permanent AF) • Clinical worsening of exercise tolerance or dyspnoea at rest within the previous 3-5 days • Myocardial ischemia; if treatment is ineffective, exercise should be limited to the threshold • Hemodynamic or arrhythmic instability (e.g., ACS or recent, myocarditis, pericarditis) (e.g., new onset of AF/atrial flutter, ventricular arrhythmias) • Severe or symptomatic valvular disease • Severe or symptomatic obstructive hypertrophic cardiomyopathy • Intracardiac thrombosis or recent pulmonary embolism and recent deep venous thrombosis

Respiratory

• Oxygen desaturation, i.e. <88% or cyanosis • Unstable respiratory rate: <5 or >40 breaths/minute • Uncontrolled asthma or severe illness chronic obstructive airways

• Clinical instability (e.g. active bleeding, fever, comorbidities that limit exercise capacity), frailty • Excessive muscle soreness or fatigue (Borg’s RPE >15/20) remaining from the last exercise or activity session.

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Only after the execution of sessions carried out without complications, non-supervised home sessions can be gradually added5. Following the above guidance shows the overall risk of exercise is low, even during high-intensity exercise and in the most severely severe patients6. Follow-up for re-evaluations of exercise training programs should be scheduled regularly, at least every 3-6 months. The intervals between controls depend on the patient’s clinical condition, the severity of the disease, the comorbidities, the type of sessions set up (supervised or at home), the age and adherence of the patient.

Prescription of exercise in heart failure with reduced ejection fraction Exercise programs must be prescribed and adapted individually7. After control of risk factors and optimization of therapy, the patient should be encouraged to start personalized programs, under close clinical supervision even if performed at home (table 2). Recreational activities of low to moderate intensity may be considered in parallel with participation in structured training programs8.

In addition, HIIT programs have been shown to be less feasible than those with moderate constant intensity. In the largest study in this field6, 51% of patients in the HIIT group did not meet the target intensity, while 80% of patients in the constant moderate intensity group trained above the target.

Strength exercise Strength training can complement, but not replace, aerobic exercise training because it reverses skeletal muscle loss and deconditioning without putting undue stress on the heart11. The intensity of the training can preferably be set in such a way that the patient can perform 10-15 repetitions at 40-60% of 1RM. In patients with impaired musculoskeletal function and muscle atrophy, Physical training should initially focus on increasing muscle mass using strength programs. A meta-analysis showed that strength exercise as a single intervention has the ability to increase muscle strength, aerobic capacity, and quality of life in subjects with HF who are unable to participate in an aerobic exercise program12. In addition, in patients with advanced HF or in patients with reduced exercise tolerance, strength exercises can be safely applied if small muscle groups are trained at each session.

Aerobic exercise Aerobic exercise is recommended for stable patients (NYHA class I-III), due to its proven efficacy and safety. Recommendations on the optimal dose of exercise have been previously described in the ESC guidelines8. The most evaluated exercise modality is continuous moderate exercise. In the most symptomatic patients and NYHA advanced functional class III, exercise intensity should remain during the first 1-2 weeks at a level below <50% of VO2peak, based on perceived symptoms and clinical status. The primary goal is a gradual increase in intensity. It is recommended to start early with moderate-intensity interval exercise even after acute HF and in parallel with drug titration9. High intensity interval training (HIIT) programs have been considered as an alternative exercise modality for low-risk patients10. A meta-analysis showed that HIIT is superior to continuous moderate-intensity exercise in improving VO2peak in patients with short-term reduced EF (HFrEF)9. However, this superiority has disappeared in the analysis of subgroups for isocaloric protocols.

Breathing exercises Inspiratory muscle training improves VO2peak, dyspnoea, and muscle strength13, and typically involves several sessions per week with an intensity of 30% to 60% of maximum inspiratory pressure, lasting 15 to 30 minutes, for an average of 10 to 12 weeks. This training modality could be recommended as an initial modality to more severely deconditioned patients, who can then switch to conventional physical training, to optimize cardiopulmonary benefits.

Water exercises Aquatic exercise was not recommended in the past, due to fears that the increase in central blood volume and cardiac preload as a result of hydrostatic pressure might not be tolerated. However, a more recent meta-analysis has shown that aquatic training, as long as it is not at depth, can be safe and clinically effective14.

Table 2. Indications for exercise prescribing in patients with HF with reduced EF.

Frequency

Intensity

Time

Type

Aerobic

3 times/week Up to 5/week

<50% VO2 max in the first 2 weeks and then moderate level intensity

From 20 to 60 min.

Strength

1-2 non-consecutive days/ week

40%-50% of 1RM With slow progression (over weeks up to 70% of 1RM)

1-2 sets of 10-15 reps, with Isometric against resistance, with elastic bands, or a focus on major muscle dumbbells groups

Complementary

2 times/week up to daily

Stretching up to appreciate tension or mild annoyance

Hold 10-30 sec for static stretches; 2-4 reps of each exercise

Both static and dynamic; for proprioceptive sensitization

For 10-12 weeks

30%–60% of the maximal inspiratory pressure

15-30 min.

Respiratory exercises

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Continuous moderate exercise

E XE RC I SE PRE S C RI PT ION I N C ARDIOLO GY

Heart failure with preserved ejection fraction Exercise promotion represents a milestone in the prevention and holistic management of HF with preserved EF (table 3)1. Exercise intervention for 12-24 weeks increases maximal exercise capacity and quality of life, with no impact on diastolic dysfunction. Its effects seem to be mediated by the improvement of muscle oxidative metabolism and vascular function15. In obese patients, weight reduction has been shown to have similar effects compared to exercise alone16. Higher exercise intensities such as HIIT (4 reps x 4 minutes at 85-90% of peak HR, with 3 minutes of active recovery) have revealed positive effects on myocardial function. HIIT performed over 4 weeks significantly improved VO2peak and left ventricular diastolic function. High-intensity exercise should be limited to stable patients and could be introduced gradually after 4 weeks of moderate, constant-intensity aerobic exercise. Training sessions should begin with short 10-minute phases of strength exercises, gradually extended over time. The ultimate goal should be to achieve a frequency ≥3 days a week for at least 30-45 minutes, as for the general population. Depending on the symptomatic status and capacity of the patient, intervals of greater intensity may be introduced. The duration of the intervention seems to be related to the induction of functional and structural changes. In fact, training for more than 2 years in healthy subjects has led to the regression of the first signs of diastolic dysfunction17.

Patients after heart transplant Heart transplant patients have a maximal exercise capacity corresponding to 40-50% of that of healthy subjects comparable in age and sex, due to multiple factors (table 4)18. These factors may be present in the early post-transplant stages and reduce/ attenuate over the years (e.g. denervation and sympathetic activation) or characterize transplant patients for several years (e.g. diastolic dysfunction or myocardial ischemia due to coronary artery disease). Physical exercise allows the increase of performance to reach levels comparable to age-matched controls. Heart transplant recipients, who participate in exercise-based cardiac rehabilitation programs, show an improvement in both hospitalizations and long-term survival19. Improvements in exercise capacity depend primarily on the volume of exercise, which induces peripheral muscle and vascular adaptations or neural reinnervation in cardiac allograft. The combination of strength and aerobic exercises is considered the preferred training program. The average intensity of resistance exercise should begin with moderate activity, up to 60% VO2peak, which can subsequently be increased, as applied in most exercise intervention studies in heart transplant recipients20. In uncomplicated cases, the intensity can also be high.

Strength exercises should focus on large muscle groups, using exercises with your own body weight or exercises on machines with the possibility of loading. Upper body resistance exercises should begin at least 3 months after surgery and the intensity should gradually increase from mild to moderate, but a sub-maximal intensity can also be reached in the case of uncomplicated disease. The most common number of recommended sessions and duration of strength exercise per session is reported as being up to five 30-minute exercise sessions per week, although previous studies show great variability (between 30 minutes and 90 minutes 2-5 times per week)21. Among the limitations of the force exercise, the reduced chronotropic response due to the denervation of the allograft stands out. However, when prescribing and conducting an exercise program in cardiac transplant patients, all present pathophysiological changes should be considered (table 4), such as, for example, any exercise-induced myocardial ischemia due to coronary artery disease due to cardiac allograft disease, particularly when performing high-intensity exercise.

Patients with ventricular assist devices In patients with ventricular assist devices (VADs), there is increasing evidence that exercise is feasible and can improve work capacity and quality of life22. The primary mode of intervention is the prescription of moderate aerobic exercise at a constant intensity, accompanied by dynamic resistance training. Exercise can begin as early as 2 weeks after surgery, and in fact, most intervention studies are initiated within the first 6 weeks after ventricular assist device

Table 4. Cardiopulmonary limitations of exercise in heart transplant patients, who have reduced exercise capacity (VO2peak) and reduced cardiac output Denervation of cardiac allograft Diastolic dysfunction of the transplanted left ventricle 20% reduction in end-diastolic peak and stroke volume during exercise Increased ratio of pulmonary capillary wedge pressure/end-diastolic volume index during maximal ergometry in the upright position Myocardial ischemia due to cardiac allograft vasculopathy impaired Peripheral vascular endothelial function 50% increase in systemic vascular resistance Decreased skeletal muscle oxidative fibers, mitochondrial volume, enzyme activity, and capillary density 25% reduction of arteriovenous oxygen difference High sympathetic activation

Table 3. Indications for exercise prescribing in patients with HF with preserved.

Frequency

Intensity

Time

Aerobic

At least 3 days a week for 4 weeks

30-45 min

Strength

For 4 weeks

10 minutes

Type Interval exercise

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implantation. Clinical beneficial effects were observed when patients exercised 3-5 times per week with a perceived exercise intensity (RPE) of 12-14 on the Borg scale or 60-80% of HRR with sessions lasting 30-45 minutes. Increasing the pump speed during sustained, mild-intensity activity can also further adapt the exercise cardiac output. This procedure is feasible and safe and allows you to extend the duration of the exercise if and when managed by trained personnel. During the first few weeks after surgery, patients should be monitored and exercised in appropriate settings, such as in cardiac rehabilitation units, but they may, once stabilised, carry out the physical activity programme at home. Supervisors should be familiar with the physiology of the exercise, the different modes and intensities of training, but at the same time with the operation of the device, the adaptation of the speed and the management of potential complications. Detailed rules for physical training are outlined in Table 5 and in more detail in a dedicated document of the Heart Failure Association of the ESC22.

Table 5. Exercise guidance in patients with ventricular assist devices. Thoroughly train exercise instructors on physiology and potential complications during exercise Perform thorough cardiopulmonary diagnostics including CPET before starting an exercise program Prescribe exercise individually, based on diagnostic tests regarding modality, frequency, intensity, and duration Closely monitor the patient’s symptoms, including blood pressure during exertion and the recovery phase Start exercise only under supervision Include gradual warm-up and cool-down phases Start with moderate continuous exercise at low intensity (Borg scale <5/10) Advise the patient to continue exercise, e.g. cycling without resistance, during the active recovery phase Observe the patient for at least 15 minutes or until complete recovery after exercise

References 1. 2. 3.

McDonald T, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021; 42: 1-12. Long L, Mordi IR, Bridges C, et al. Exercise-based cardiac rehabilitation for adults with heart failure. Cochrane Database Syst Rev 2019; 1: CD003331. Taylor RS, Walker S, Smart NA, et al. Impact of exercise rehabilitation on

exercise capacity and quality-of-life in heart failure: individual participant meta-analysis. J Am Coll Cardiol 2019; 73: 1430-43. 4. Corrà U, Agostoni PG, Anker SD, et al. Role of cardiopulmonary exercise testing in clinical stratification in heart failure. Eur J Heart Fail 2018; 20: 3-15. 5. Dalal HM, Taylor RS, Jolly K, et al. The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: the REACHHF multicentre randomized controlled trial. Eur J Prev Cardiol 2019; 26: 262-72. 6. Ellingsen O, Halle M, Conraads V, et al. High-intensity interval training in patients with heart failure with reduced ejection fraction. Circulation 2017; 135: 839-49. 7. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from theory to practice. Eur J Heart Fail 2011; 13: 347-57. 8. Pelliccia A, Pelliccia A, Sharma S, Gati S, et al. 2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease. Eur Heart J 2020; 41: 1-10. 9. Gomes Neto M, Duraes AR, Conceicao LSR, et al. High intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis. Int J Cardiol 2018; 261: 134-41. 10. Gayda M, Ribeiro PAB, Juneau M, et al. Comparison of different forms of exercise training in patients with cardiac disease: where does high-intensity interval training Fit? Can J Cardiol 2016; 32: 485-94. 11. Cornelis J, Beckers P, Taeymans J, et al. Comparing exercise training modalities in heart failure: a systematic review and meta-analysis. Int J Cardiol 2016; 221: 867-76. 12. Giuliano C, Karahalios A, Neil C, et al. The effects of resistance training on muscle strength, quality of life and aerobic capacity in patients with chronic heart failure - a meta-analysis. Int J Cardiol 2017; 227: 413-23. 13. Wu J, Kuang L, Fu L. Effects of inspiratory muscle training in chronic heart failure patients: a systematic review and meta-analysis. Congenit Heart Dis 2018; 13: 194-202. 14. Adsett JA, Mudge AM, Morris N, et al. Aquatic exercise training and stable heart failure: A systematic review and meta-analysis. Int J Cardiol 2015; 186: 22-8. 15. Adams V, Reich B, Uhlemann M, et al. Molecular effects of exercise training in patients with cardiovascular disease: focus on skeletal muscle, endothelium, and myocardium. Am J Physiol Heart Circ Physiol 2017; 313: H72-88. 16. Kitzman DW, Brubaker PH, Morgan TM, et al. Exercise training in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Circ Heart Fail 2010; 3: 659-67. 17. Howden EJ, Sarma S, Lawley JS, et al. Reversing the cardiac effects of sedentary aging in middle age: a randomized controlled trial: implications for heart failure prevention. Circulation 2018; 137: 1549-60. 18. Grupper A, Gewirtz H, Kushwaha S. Reinnervation post-heart transplantation. Eur Heart J 2018; 39: 1799-1806. 19. Bachmann JM, Shah AS, Duncan MS, et al. Cardiac rehabilitation and readmissions after heart transplantation. J Heart Lung Transplant 2018; 37: 467-76. 20. Haykowsky MJ, Halle M, Baggish A. Upper limits of aerobic power and performance in heart transplant recipients: legacy effect of prior endurance training. Circulation 2018; 137: 650-2. 21. Anderson L, Nguyen TT, Dall CH, et al. Exercise-based cardiac rehabilitation in heart transplant recipients. Cochrane Database Syst Rev 2017; 4: CD012264. 22. Adamopoulos S, Corrà U, Laoutaris ID, et al. Exercise training in patients with ventricular assist devices: a review of the evidence and practical advice. Eur J Heart Fail 2019; 21: 3-13.

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| CHAPTER 3.10 |

Arterial disease of the lower limbs Pompilio Faggiano, Valentina Pescatore, Pier Luigi Temporelli

Peripheral Artery Disease (PAD) is a clinical syndrome linked to the reduction of the blood flow of the lower limbs, generally as a consequence of the formation of atherosclerotic plaques, eventually leading to significant hemodynamic stenosis in the arterial district starting from the abdominal aorta, along the iliac-femoral-popliteal axis up to the tibial arteries. The most frequent symptomatology is intermittent claudication, i.e. the onset of cramping pain (generally in the calf) during walking. The degree of severity of claudication is defined by the distance you can travel before the pain sets in1-6. Patients with PAD are at very high cardiovascular risk and should receive an individualized, multidisciplinary program aimed at reducing the risk of cardiovascular ischemic events and improving functional status7. Different types of intervention can be used for patients with PAD: drug therapy, lifestyle improvement, supervised exercise. In cases of severe claudication (symptom-free interval generally less than 50 meters), or in any case not tolerated by the patient, symptoms at rest or trophic lesions, there is an indication for possible percutaneous or surgical revascularization. The most common clinical classifications of PAD are Fontaine’s and Rutherford’s, which discriminate the stage of the disease based on the severity of claudication and the presence of any ischemic ulcers or gangrene.

Functional assessment Symptom severity and functional status can be assessed by exercise testing. The treadmill test (usually using the Strandness protocol at a speed of 3 km/h and 10% slope) is an excellent tool for the functional assessment of patients with PAD, as well as for the planning of physical exercise for preventive-therapeutic purposes. The test is stopped when the patient is no longer able to walk due to pain, defining the maximum distance that can be travelled. A decrease in post-exercise ankle systolic pressure >30 mmHg or a decrease in the ratio of measured arm systolic pressure/post-exercise ankle systolic pressure (Ankle/Brachial Index ABI) >20% are diagnostic for PAD8.

SPE in the PAD In patients with intermittent claudication, the prescription of SPE is effective and improves symptoms and quality of life and increases the maximum distance that can be walked. In 30 randomized trials including 1,816 patients with stable leg pain, SPE improved the maximum distance that could be walked on the treadmill by almost 5 minutes compared to usual care. The painfree distance and maximum walking distance had increased by an average of 82 meters and 109 meters, respectively. Improvement was observed for up to 2 years. In addition, SPE has improved quality of life. However, SPE has not improved the ABI and it is not yet clear whether it reduces CV events and improves life expectancy8. The mechanisms through which the clinical/functional improvement of SPE practising PAD patients is achieved are multifactorial and not yet fully understood. These include neo-angiogenesis with increased collateral circulation, increased endothelium-dependent vasodilation, increased oxygen extraction by ischemic muscle, increased nitric oxide activity, improved carnitine metabolism, reduced atherosclerotic risk factors, improved endothelial function, the reduction of markers of chronic inflammation, the modification of pain perception. Recommendations for exercise prescribing in these patients are represented in Table 1. The most widely used and recommended protocols in the literature include the so-called HIIT: walking sessions on treadmills interspersed with periods of rest when claudication pain becomes moderate/severe2. Alternatively, for the most compromised patients, constant load protocols can be used that provide, after adequate low-intensity warm-up, training at a speed slightly lower than that at which claudication occurs. This form of training “below ischemic threshold” has also been shown to significantly improve the claudication-free speed and the maximum tolerated speed over time. Although flat walking represents the first-line therapy for PAD patients with claudication, strength training seems to have favourable and additional effects compared to aerobic training,

Table 1. Indications for exercise prescription in PAD (modified by ACSM’S Guidelines for Exercise Testing and Prescription Eleventh Edition11). Intensity

Duration

Aerobic

Type

Minimum 3 times/week, Free way or on loaded preferably up to 5 times/ treadmill intermittent with week seated rest when pain becomes moderate and resumption of the journey when the pain is completely solved

Frequency

Moderate intensity or until pop-up of moderate pain or 50-80% of the maximum speed allowed

30-45 minutes (excluding periods rest) for a minimum of 12 weeks; Progressing up to 60 minutes

Strength

Up to 2 times per week in Focus on whole body on days non-consecutive large groups muscular; emphasis on the lower limbs if a short time available

Start with 40-60% of 1RM to get to 60-80% regime of 1RM

2-3 sets of 8-10 repetitions; 6-8 exercises that involve The main Muscle groups

Complementary

≥2-3 times the week, better Static stretching, dynamic and exercises proprioceptive daily neuromuscular

Stretch up to the point of feel tension or slight discomfort

Holding 10-30 seconds for the stretching static; 2-4 repetitions for each exercise

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prolonging claudication-free walking9,10. When starting a new strength program, the initial intensity should be 40%-60% of 1RM thus gradually increasing the resistance, number of sets and frequency of training sessions over time. This progressive increase in load is essential for the maintenance or continuous improvement of muscle adaptation and strength over time. The “2 for 2” rule can be used: when an individual can perform 2 more repetitions of a given exercise in 2 consecutive strength training sessions, the weight can be increased from 2% to 10%. After 6 months of strength training, individuals, unless specifically contraindicated, can use a wider range of repetitions and heavier loads, extending the recovery time between sets of exercises.

References 1.

Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382: 1329-40. Gornik HL, Aronow HD, Goodney PP, et al. CC/AHA/AACVPR/APMA/ ABC/ SCAI/SVM/SVN/SVS/SIR/VESS Guidelines for the Management of Lower Extremity Peripheral Artery Disease. JACC (2024); 83: 2497-2604. Diehm C, Schuster A, Allenberg JR, et al. High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study. Atherosclerosis 2004; 172: 95-105.

Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015; 116: 1509-26. 5. Fowkes FG, Murray GD, Butcher I, et al. Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta- analysis. JAMA 2008; 300: 197-208. 6. Conte MS, Pomposelli FB, Clair DG, et al. Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication. J Vasc Surg 2015; 61 (3 Suppl): 2s-41s. 7. Giada F, Biffi A, Agostoni P, et al. Exercise prescription for the prevention and treatment of cardiovascular diseases: part II. J Cardiovasc Med 2008, 9: 1-12. 8. Thomas SG, Marzolini S, Lin E, et al. Peripheral Arterial Disease. Supervised Exercise Therapy Through Cardiac Rehabilitation. Clin Geriatr Med 2019; 35: 527-37. 9. Aboyans V, Ricco JB, Bartelink ML, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Sugery (ESVS). Eur Heart J 2018; 39: 763-821. 10. Paluch AE, Boyer WR, Franklin BA, et al. Resistance Exercise training in Individuals with and without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association. Circulation 2024; 149: e217-e231. 11. Liguori G, Feito Y, Fountaine C, et al. ACSM’S Guidelines for Exercise Testing and Prescription. Eleventh Edition. Philadelphia: Lippincott Williams & Wilkins, 2021.

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| CHAPTER 3.11 |

Cardio-oncology Chiara Bennati, Maria Laura Canale, Elena Coletti Moia, Monica Tiberi, Eliana Tranchita, Isabella Zovatto

Introduction A sedentary lifestyle is a known risk factor for the development of oncological diseases and remaining physically inactive after a diagnosis of neoplasia increases the likelihood of getting sick again. Mechanisms by which physical activity reduces the risk of cancer include: • Reduction of sex hormones, associated with some types of cancer (breast and colon); • Reduction of obesity, in particular visceral fat which acts as a reserve of carcinogens (breast, endometrium, ovary); • Strengthening the immune system protects through the increase in the number and activity of macrophages and natural-killer lymphocytes; • Reduction of bile acid secretion and increase of intestinal motility with consequent reduction of the time of exposure of the intestinal mucosa to carcinogens (colon)1,2. Physical exercise also acts by modulating multiple mechanisms that can determine cardiotoxicity linked to cancer therapy and reduces the cardiovascular risk of the cancer patient by decreasing the onset of risk factors such as obesity, diabetes and arterial hypertension. Cardiotoxicity is cardiac dysfunction caused by the action of anticancer drugs and/or radiotherapy and cardiovascular risk factors already present. It can manifest

as an alteration in the contractility of the heart muscle or as an alteration in the conduction of the electrical impulse (arrhythmias, myocarditis, left ventricular dysfunction, cardiomyopathy) (table 1). Current recommendations from the American College of Sports Medicine (ACSM), the American Society of Clinical Oncology and the American Cancer Society (ASCO), Exercise and Sport Science Australia (ESSA) published between 2019 and 2022, suggest that cancer patients should practice at least 2 and a half hours (150 minutes, e.g. 30 minutes a day over 5 days a week) of moderate-intensity aerobic activity or at least 75 minutes of high-intensity aerobic activity per week. At least 2-3 sessions of muscle strengthening exercises should also be introduced, involving the major muscle groups. However, these generic recommendations require personalization based on the patient’s individual abilities that depend on the extent of the oncological disease and the adverse effects related to the treatment3,4. Recent studies in the literature have shown that the practice of physical activity under medical supervision is safe for cancer patients both during and after active treatment but requires a multidisciplinary approach between the different professionals involved. The physical activity protocol can therefore be proposed at different times:

Table 1. Cardiotoxicity of anticancer drugs. Drug categories

Examples of cancers

Possible side effect

Chemotherapy agents Anthracyclines (e.g., doxorubicin, epirubicin)

Breast, neuroendocrine lung tumors, lymphomas

Left ventricular dysfunction, heart failure

Antimetabolites (capecitabine, 5-fluorouracil)

Colon, stomach, breast

Myocardial ischemia, arterial vasospasm, thrombosis

Monoclonal antibodies Trastuzumab (anti-HER2)

Breast, stomach

Heart failure, left ventricular dysfunction

Bevacizumab (anti-VEGF)

Breast, colon

Hypertension, arterial or venous thromboembolism, QT prolongation

Tyrosine kinase inhibitors Lapatinib (anti-HER2)

Breast

Arterial hypertension

Sunitinib (anti-VEGF, PDGFR)

Kidney

Arterial hypertension, venous thromboembolism

Osimertinib (EGFR inhibitors)

Lung

Acute coronary syndrome, QT prolongation

Crizotinib, Ceritinib (ALK inhibitors)

Lung

QT prolongation, bradycardia

Lung, melanoma

Heart failure, arrhythmias

Trametinib (BRAF inhibitor)

Immunotherapy Atezolizumab, Pembrolizumab, Nivolumab (anti-PD-1/PD-L1)

Lung, bladder, kidney, colon, melanoma

Myocarditis, pericarditis, arrhythmias, heart failure

Ipilimumab, Tremelimumab (anti-CTLA-4)

Lung, melanoma

Myocarditis, pericarditis

HER2: epidermal growth factor receptor 2; VEGF: Endothelial vascular growth factor; PDGFR: platelet growth factor receptor; ALK: anaplastic lymphoma tyrosine kinase receptor; BRAF: serin/threonine protein kinase of the RAF protein family; PD1/PDL1: programmed death receptor 1 and its ligand; CTL4: Protein 4 associated with cytotoxic T lymphocytes. SPORTS MEDICINE JOURNAL | SUPPL. 1 - VOL 79 N 1 | MARCH 2026

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• Early intervention: from the diagnosis of the oncological pathology to the initiation of drug therapy and/or radiotherapy and/or surgery; • Maintenance activities: during anti-cancer therapies and/or surgery; • Rehabilitation: at the end of treatments for oncological pathology.

The prescription of physical exercise in the cancer patient The assessment for the prescription of the SPE of the cancer patient must be included in a multidisciplinary context including different figures (e.g. oncologist, cardiologist, surgeon, sports doctor, general practitioner, nurse, kinesiologist, nutritionist, psychologist). In the planning phase, it is necessary to evaluate the stage of oncological pathology, the presence of metastases, lymphedema, any scarring retractions, the drug therapy in progress, the presence of cardiovascular diseases, sarcopenia and osteoporosis5. In particular, attention should be paid to any conditions of fragility and possible cognitive impairment in the elderly. The medical examination should also include the administration of questionnaires aimed to identify the quality of life, the skills possessed by the patient (sedentary or sporty), expectations and factors limiting physical activity (e.g. economic or psycho-social). The accurate instrumental classification of the patient should include the performance of blood chemistry tests, including the dosage of BNP or NT-proBNP and hs-cTn and a cardiological evaluation, including evaluation with resting ECG and echocardiogram focused on the estimation of left ventricular function by determination of left ventricular EF and global longitudinal strain (fundamental data to be re-evaluated during follow-up to identify the presence of damage as well as the evaluation of valvulopathies, pulmonary hypertension or pericardial effusion. The other initial follow-up examinations (e.g. assessment of body composition, assessment of strength, determination of specific exercise intensities) are equally important, although they do not differ from the other categories of patients addressed in other chapters of this document. In cancer patients, it is very important to be able to identify and manage potential relative contraindications of exercise such as anaemia, neutropenia, thrombocytopenia, uncontrolled arterial hypertension, arrhythmias, bone or brain metastases. The patient should be made aware of any signs or symptoms of cardiorespiratory that appear during exertion, such as chest pain

or breathlessness due to mild exertion. The presence of angina, dizziness or pre-syncope, and oxygen saturation at rest in room air <88% are absolute contraindications to exercise. Dyspnoea is a fairly common symptom especially in smokers or patients with lung cancer; This does not contraindicate the activity, but rather it is necessary to encourage the patient to perform aerobic activity on a daily basis, preferably supervised. Another very common side effect is “fatigue”, i.e. a subjective feeling of physical and/or cognitive fatigue due to the pathology and/or drugs that is not related to the intensity of physical exertion that enters into a differential diagnosis with other conditions such as reduced tolerance to physical exercise due to various causes (poor training, heart disease, etc.) or loss of muscle mass. In this case, exercise was found to be the most effective non-pharmacological intervention to counteract it4. Considering the results of the clinical-instrumental evaluations, a physical exercise prescription can be structured. The American College of Sport Medicine in its latest guidelines offers an address for correctly planning a training proposal for cancer patients (table 2), to be adapted to the individual patient, based on his or her characteristics and needs6. As indicated by recent studies in the literature7, the intensity of both aerobic and strength training load should be modulated according to the patient’s initial fitness and then progressively increased as the weeks of training go by. In recent years, the concept of cardio-oncological rehabilitation “CORE” (Cardio-oncology rehabilitation) has also been introduced, which involves the identification of patients with cancer at high risk of cardiac dysfunction. The CORE program is based on a multidisciplinary approach that includes, in addition to physical exercise, lifestyle counselling, risk factor control and psychological support8. Finally, other studies have demonstrated the feasibility of a HIIT protocol in cancer patients treated with anthracyclines. It seems that this type of training where high-intensity exercises alternate with moments of low intensity may have a cardioprotective role in these patients. However, these results are still preliminary and need to be confirmed by further studies and this approach is not to be followed in cancer patients with clear cardiac dysfunction9. In the context of SPE in cancer patients, it is important to remind the patient that the most tangible progress will be achieved no earlier than 8-12 weeks; the patient should be encouraged to provide feedback and express their doubts, actively involving them in the choices, and to immediately notify the doctor of

Table 2. Indications for the prescription of physical exercise in cancer patients. Frequency

Time

Intensity

Type

Aerobic

3-5 days/week

Moderate or high (in selected 150 min/week if moderate; cases) 75 min/week if high

Prolonged activity and rhythmic using large muscle groups (walking, cycling, swimming...)

Strength

2-3 days/week

Start with light loads (<30% 1RM) and increase gradually

8-12 rep

Natural load or using weights and machines, elastics...

Complementary

>2-3 day/week

Increase more and more the ROM until maximum tolerated

Keep for at least 10-30 sec Exercises of elongation and/ a location elongation (about or articulation, especially for those districts that have 10 min total) immediately treatments surgical or radiation

HRmax: Maximum heart rate; RPE: Rating of Perceived Exertion; VO2R: Reserve oxygen consumption; 1RM: 1 maximum repetition.

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the onset of cardiovascular symptoms (chest pain, dyspnoea, palpitations, presyncope and/or syncope). It is very important to schedule an evaluation some time after the start of the training protocol, to monitor progress and make changes to the prescription; Therefore, patient feedback is equally important during follow-up, especially in order to monitor progress and make changes to prescribing. Supervised activity can be carried out in a hospital, in the community or at home. Studies have shown that supervised activity has greater advantages than unsupervised activity3. Patients who can benefit from home training are patients at low cardiovascular risk who do not need to be supervised during training, or immunosuppressed patients who cannot attend crowded places or even those patients who for personal reasons (economic, psycho-social, logistical, etc.) cannot benefit from a facility.

References 1.

Spanoudaki M, Giaginis C, Karafyllaki D, et al. Exercise as a Promising Agent against Cancer: Evaluating Its Anti-Cancer Molecular Mechanisms. Cancers (Basel) 2023; 15: 5135. Tong L, Jiménez-Cortegana C, Tay AHM, et al. NK cells and solid tumors:

Therapeutic potential and persisting obstacles. Mol. Cancer 2022; 21: 206. Patel AV, Friedenreich CM, Moore SC, et al. American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control. Med Sci Sports Exerc 2019; 51: 2391-2402. Hayes SC, Newton RU, Spence RR, et al. The Exercise and Sports Science Australia position statement: Exercise medicine in cancer management. J Sci Med Sport 2019; 22: 1175-99. D’Ascenzi F, Anselmi F, Fiorentini C, et al. The benefits of exercise in cancer patients and the criteria for exercise prescription in cardio-oncology. Eur J Prev Cardiol 2021; 28: 725-35. Liguori G, Feito Y, Fountaine C, et al. ACSM’S Guidelines for Exercise Testing and Prescription. Eleventh Edition. Philadelphia: Lippincott Williams & Wilkins, 2021. Murri A, Vitucci D, Tranchita E, et al. “Operation Phalco”. Adapted Physical Activity for Breast Cancer Survivors: Is It Time for a Multidisciplinary Approach? Cancers (Basel) 2022; 15: 34. Bisceglia I, Venturini E, Canale ML, et al. Cardio-oncology rehabilitation: are we ready? Eur Heart J Suppl 2024; 26 (Suppl 2): ii252-ii263. Tranchita E, Murri A, Grazioli E, et al. The Beneficial Role of Physical Exercise on Anthracyclines Induced Cardiotoxicity in Breast Cancer Patients. Cancers (Basel) 2022; 14: 2288.

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| CHAPTER 3.12 |

The prescription of physical exercise in post-acute cardiac patients and in patients awaiting cardiac surgery: prehabilitation Marco Ambrosetti, Carmine Riccio

Patients who are candidates for cardiac surgery (both coronary and on valves and large vessels) or percutaneous correction procedures for valvulopathies (TAVI, MitraClip) have epidemiological and clinical characteristics appropriate for pre-rehabilitation. Compared to non-cardiac surgery, these patients are often older and with a greater burden of comorbidities, at greater risk of physical deconditioning and cognitive impairment, not infrequently frail, sarcopenic and with higher rates of post-operative complications and mortality1. The National Agency for Regional Health Services (Agenas)2 reports in the pre-pandemic period the execution in Italy of about 14,000 isolated coronary artery bypass graft interventions with a thirty-day mortality of 2%; Valvuloplasty or valve replacement surgeries, on the other hand, were about 37,000, with a thirty-day mortality of 2.2%. Although it is not possible to have a precise selection of elective interventions and the distinction between open and transcatheter valve methods, it is reasonable to believe that cardiac surgery patients eligible for prehabilitation may be a few tens of thousands each year, in charge of the 94 hospitals with cardiac surgery surveyed in 2022 by ANMCO3 (46 in the North, 17 in the Centre and 31 in the South). Prehabilitation can be defined as a multidisciplinary intervention aimed at improving the physical and mental state before surgery and promoting the post-operative course, both for faster recovery and to reduce adverse events. Physical exercise is an indispensable component of prehabilitation pathways, to be combined with respiratory training, nutritional support, psycho-social intervention, lifestyle modification, educational counselling and

of course, in structured health contexts, adequate clinical stabilization and titration of drug therapy. No recommendations are currently available from the major international cardiology scientific societies on prehabilitation, a topic that will be adequately covered by the next guidelines of the European Society of Cardiology on Cardiac Rehabilitation scheduled for 2026. In this context, therefore, there is a lack of definitive instructions for prescribing, administering and supervising physical exercise prior to cardiac surgery. Some indications can be extracted from the guidelines on perioperative management4,5, from consensus statements on frailty6 and from the exercise protocols most used in the available intervention trials, already the subject of some meta-analyses7,8 and a dated Cochrane review of 20129, in anticipation of a forthcoming update10. As far as the effectiveness of training is concerned, it should be considered that studies have mostly involved supplementation with breathing exercises (especially inspiratory exercises, incentive spirometry, diaphragmatic breathing and controlled cough) for the prevention of the dreaded postoperative pulmonary complications, such as pneumonia and atelectasis. The programs include the activation of both aerobic and resistance exercise (often combined) and a minimum duration of 90 minutes/ week, for a total duration of at least two weeks with completion of at least six sessions7. Most of the few studies available are in any case placed on a supervised program of about 4 weeks. A significant heterogeneity with regard to the use of continuous and interval aerobic training protocols and above all for the intensity of aerobic training (from very mild to high and very high)

Table 1. Indications for exercise prescribing in patients who are candidates for elective cardiac surgery. Frequency

Intensity

Time

Aerobic

3 times/week (2-8 weeks of duration)

Moderate with progression or reduction individualized

Duration of the session: from 15 min in the patient more deconditioned (e.g. frail elderly candidate for TAVI) 40-60 minutes in the subject with capacity global functional preserved

Strength

3 times/week (2-8 weeks of duration)

Moderate with progression or reduction individualized

Identification of force circuit with work of agonists/ antagonists and predilection for muscle groups involved in the life activities daily (especially for elderly subjects)

Complementary

3 times/week (2-8 weeks of duration)

Heating of 15 minutes to start of each session and cooldown of 10 minutes to go

Breathing exercises and balance/ coordination/ flexibility

Type Aerobic work continuous intensity constant and possibilities of HIIT

Exclusion criteria: unstable angina, acute decompensation, myocardial infarction in the previous two weeks, left coronary stenosis >50%, ischemic threshold <50W, left ventricular EF <35%, ventricular arrhythmias, myocarditis, hypertrophic obstructive cardiomyopathy, coronary cardiac surgery in the previous six months, neurological or orthopaedic comorbidities precluding training, distance from the center >1 hour of travel (if outpatients).

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is still evident in the experiences in the literature. Despite this variability, the latest evidence7 suggests that patients enrolled in a prehabilitation program based on physical exercise before cardiac surgery (especially coronary surgery) show an increase in functional capacity assessed by the 6-minute walk test (which persists even after surgery), a shorter duration of hospitalization and a lower risk of postoperative complications (including frequent AF). These benefits are most evident in patients under the age of 65. The effect of preventing post-operative respiratory complications, especially atelectasis and logistics, appears to be significantly related to the presence and modality of respiratory training11. On the other hand, clear evidence is not currently available on changes in re-hospitalization and mortality rates following prehabilitation intervention. Operationally, a training protocol should not derive solely from the type of intervention (although some specificities must naturally be taken into account, especially with regard to the degree of invasiveness of the same) or from the underlying pathology (with the obvious exception of an unstable clinical state, especially ischemic or arrhythmic), but rather from the global functional capacity, the presence of frailty/sarcopenia and logistical aspects (hospital or home context). An assessment by direct test of CRF and muscle strength should always be obtained, also for the purpose of a more precise outcome assessment, with gold standard methods if available (CPET for the calculation of VO2peak or dynamometer for the measurement of 1RM), renouncing as much as possible prescriptions based solely on indirect methods (e.g. theoretical HR ranges or scales of subjective perception of fatigue). The adjuvant intervention to nutritional and psychological training is also particularly important and hopefully to be carried out through the involvement of experienced health professionals. Table 1 presents a prescription scheme for preoperative physical exercise on the basis of the experiences already present in the literature, potentially applicable in supervised settings, including outpatient or non-inpatient settings, with the relative exclusion criteria. Alongside the structured program, it is important to counteract a sedentary lifestyle throughout the

entire period of waiting for the intervention, also in order to reduce preoperative anxiety/stress and with adequate involvement of the caregiver.

References 1.

Pahwa S, Bernabei A, Schaff H, et al. Impact of postoperative complications after cardiac surgery on long-term survival. J Card Surg 2021; 36: 2045-52. 2. https://pne.agenas.it/assets/documentation/report/agenas_pne_report_2023.pdf. 3. Oliva F, Di Pasquale G, Lucci D, et al. 8th Census of Cardiology Facilities in Italy. National Association of Hospital Cardiologists (ANMCO). Year 2022. G Ital Cardiol 2024; 25 (2 Suppl. 1): 19S-103S. 4. Engelman DT, Ben Ali W, Williams JB, et al. Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg 2019; 154: 755-66. 5. Mertes PM, Kindo M, Amour J, et al. Guidelines on enhanced recovery after cardiac surgery under cardiopulmonary bypass or off-pump. Anaesth Crit Care Pain Med 2022; 41: 101059. 6. Niebauer J, Bäck C, Bischoff-Ferrari HA, et al. Preinterventional frailty assessment in patients scheduled for cardiac surgery or transcatheter aortic valve implantation: a consensus statement of the European Association for Cardio- Thoracic Surgery (EACTS) and the European Association of Preventive Cardiology (EAPC) of the European Society of Cardiology (ESC). Eur J Prev Cardiol 2024; 31: 146-81. 7. Marmelo F, Rocha V, Moreira-Gonçalves D. The impact of prehabilitation on post-surgical complications in patients undergoing non-urgent cardiovascular surgical intervention: Systematic review and meta-analysis. Eur J Prev Cardiol 2018; 25: 404-17. Erratum in: Eur J Prev Cardiol. 2018 Jun; 25(9):NP2. PMID: 29338307. 8. Steinmetz C, Bjarnason-Wehrens B, Walther T, et al. Efficacy of Prehabilitation Before Cardiac Surgery: A Systematic Review and Meta-analysis. Am J Phys Med Rehabil 2023; 102: 323-30. Epub 2022 Sep 23. PMID: 36149383; PMCID: PMC10010695. 9. Hulzebos EH, Smit Y, Helders PP, et al. Preoperative physical therapy for elective cardiac surgery patients. Cochrane Database Syst Rev 2012; 11: CD010118. 10. Skorupska N, Perry R, Collis P, et al. Prehabilitation for people undergoing cardiac surgery (Protocol). Cochrane Database Syst Rev 2024; 1: Art. No.: CD015336. 11. McCann M, Stamp N, Ngui A, et al. Cardiac prehabilitation. J Cardiothorac Vasc Anesth 2019; 33: 2255-65.

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Organizational and medical-legal aspects 1. Prescription and administration of physical exercise: a multidisciplinary approach 2. Informed consent 3. Professional liability

| CHAPTER 4.1 |

Prescription and administration of physical exercise: a multidisciplinary approach Flavio D’Ascenzi, Franco Giada, Marco Scorcu

Introduction The prescription and administration of SPE in patients requires an integrated approach involving different professionals. Multi-disciplinary work is essential to ensure that SPE is safe, effective and adapted to the specific clinical and functional conditions of each individual patient. Furthermore, depending on the pathology from which the patient is suffering or any complications or comorbidities, it is necessary to modulate the multidisciplinary group, in order to respond dynamically to the specific needs of each individual patient.

Benefits of multidisciplinary work Multidisciplinary work is a key element in the prescribing and administration of SPE in patients. The collaboration between the professionals involved in the different phases of the program guarantees a complete and effective approach, improving clinical outcomes and the quality of life of patients. Investing in organizational models that encourage interaction between different professional figures is essential for the success of health promotion strategies through physical activity. • The multidisciplinary approach to exercise prescription offers numerous advantages and in particular: • Increased safety: reduction of the risk of adverse events thanks to monitoring by different professionals in the various phases of the program, from initial risk stratification to evaluation during operation; • Personalization of treatment: each patient is required to receive a tailor-made program based on his or her physical and clinical condition. The presence of comorbidities or treatment with drugs of interest to specialists requires the support of ad hoc specialists to identify the best therapeutic windows for administering SPE. A typical example in this area is cardiac oncology, where the interaction between sports doctor, cardiologist and oncologist is fundamental from the initial stages of the SPE program; • Better adherence to the program: the support of several figures increases motivation and adherence to the exercise program, reducing the dropout rate, also through a periodic remodelling of the activity to be carried out, for example, in the gym, by the kinesiologist, in accordance with the patient’s predisposition and requests; • Optimization of outcomes: the combination of different skills leads to an overall improvement in health, outcomes and quality of life.

tween the GP and the P with the centres where SPE is prescribed and/or administered is essential to direct the patient where his or her specific needs can be adequately met clinical and personal. In addition, in some non-specialist contexts, the GP and the P with specific skills and knowledge can directly promote and prescribe physical exercise in the context of primary prevention, responding directly to the request for health and well-being of their patient, in accordance with defined work protocols. In addition, the GP and the P play a decisive role in promoting correct lifestyles for the entire general population. In the evaluation and prescription phase of SPE in the cardiological patient, the Sports Physician and the Sports Cardiologist play a fundamental role, in order to study the patient in detail and provide precise indications on the SPE program that the patient can carry out safely, with specific reference to the analysis of the cardiovascular response during exertion, as well as the identification of the appropriate type, dose and specific and personalized intensity of exercise intensity, to be identified in accordance with specific evaluation protocols. Depending on the pathology the patient is suffering from and any complications or comorbidities, individual specialists will be fundamental in supporting the prescription of the training program or adapting the initial prescription, responding to the specificities and needs of each individual. In cardiology, prescribing SPE requires specific knowledge and skills, including those essential for accurate risk stratification of exercise-related adverse events. This is a focal point to be shared with the patient and with all the professionals who will intervene in the SPE program.

Kinesiologist The Kinesiologist specializes in adapting physical exercise to the patient’s needs. It works in close collaboration with doctors and especially with sports doctors to develop and adapt personalized programs that achieve the set objectives. By working closely with the patient in the gym, taking into account the initial prescription of SPE made by the doctor, the kinesiologist has the opportunity to adapt and adjust the administration based on the patient’s feedback and their response to gym activity. The role of the kinesiologist is equally important in sharing with the prescriber the time in which to repeat the functional assessment during the follow-up, in order to evaluate the effects of the training carried out up to that moment and possibly modify what was initially set, see for example a new re-evaluation of the thresholds and respective modification of the appropriate training HR references.

Nutritionist The role of the different professional figures Prescription of physical exercise in the cardiological patient The general practitioner (GP) and Paediatricians (P) are often the first point of contact for the patient and play a crucial role in identifying the need for exercise as part of treatment. The link be-

Nutrition is a key element in optimizing the effects of exercise. The nutritionist provides support to ensure adequate energy intake and a qualitatively correct diet, helping to improve physical performance. In addition, the nutritionist is essential to promote the correct management of conditions such as diabetes or obesity. An ad hoc nutritional plan is important in order to achieve the set goals, enhancing the beneficial effects of physical exercise.

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Psychologist Motivation and adherence to the exercise program are influenced by psychological factors. The psychologist helps overcome any emotional or behavioural barriers, improving the patient’s approach to adopting a healthy lifestyle (first and foremost, quitting

cigarette smoking) and adherence to the SPE program, thereby reducing the dropout rate. In addition, psychological support is essential to help the patient in the management (coping) of the chronic disease from which he is suffering, with respect to himself but also with respect to the social and environmental context.

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| CHAPTER 4.2 |

Informed consent Maurizio Casasco, Francesco De Ferrari, Andrea Verzeletti

Information is the fundamental prerequisite for any medical/ therapeutic act and represents a way of respecting the personality and free will of the citizen. And this is especially true in the case of prescription of physical exercise in subjects with CVD, a situation in which the work of the doctor takes on a meaning of prevention and treatment within a global concept of health protection. The need for the patient’s consent for every health service has always been an issue that has also been the focus of forensic doctors; remember what Fallani stated in a report to the Congress of Forensic Medicine back in 1972: “... The doctor’s freedom to act appears clearly to be subordinated to the patient’s primary will to be the object of the health service, so that it is essential to examine even before the contents of the faculty of treatment how it is made available and through what mechanisms it is conferred”. The regulatory references in Italian legislation are found first of all in some articles of the Constitution: art. 32 (“The Republic protects health as a fundamental right of the individual and interest of the community and guarantees free care to the indigent. No one can be forced to undergo a specific health treatment except by law. The law may in no case violate the limits imposed by respect for the human person”), art. 2 (“The Republic recognizes and guarantees the inviolable rights of man, both as an individual and in the social formations where his personality develops, and requires the fulfilment of the mandatory duties of solidarity political, economic and social law”) and art. 13 (“Personal freedom is inviolable. No form of detention, inspection or personal search, or any other restriction of personal liberty is permitted, except by a motivated act by the judicial authority and only in the cases and ways provided for by law”). Furthermore, in art. 50 of the Criminal Code. (“Anyone who harms or endangers a right with the consent of the person who can validly dispose of it is not punishable”) and art. 5 of the Civil Code (“Acts of disposition of one’s own body are prohibited when they cause a permanent decrease in physical integrity or when they are otherwise contrary to the law, public order or morality”). The importance of informed consent is increasingly binding under the Council of Europe Convention (Strasbourg 19/11/1996) for the protection of human rights and the dignity of the human being with regard to the application of biology and medicine, signed in Oviedo on 04/04/1997 and ratified in Italy with Law 145/2001; in particular, art. 5 provides: “Any intervention in the health field cannot be carried out unless the person concerned has given his or her free and informed consent. This person receives appropriate information in advance about the purpose and nature of the intervention as well as its consequences and risks. The data subject may freely withdraw his or her consent at any time”, and Art. 10 “Everyone has the right to respect for his or her private life when it comes to information relating to his or her health. Everyone has the right to know all relevant information to one’s health”. For some time now, the Court of Cassation has ruled that “… for the formation of the contract concerning a health service, it is necessary that the doctor’s proposal is fully and consciously

shared by the patient; to this end, the information must be divided into each individual phase of the intervention and its performance and extended to the risks, the achievable results and the possible negative consequences, according to the qualified diligence of the professional” (Sec. III Civ. 21 September 2012 no. 16047). The regulation of informed consent was then organically systematized in our country with Law no. 219 of 22 December 2017 (“Rules on informed consent and advance treatment provisions”), according to the such as consent to any health service represents the essential meeting point between “the patient’s decision-making autonomy and the competence, professional autonomy and responsibility of the doctor”. In the case of minors, Article 316 of the Civil Code (Parental responsibility) is recalled: “Both parents have parental responsibility which is exercised by mutual agreement taking into account the capacities, natural inclinations and aspirations of the child ... In the event of a dispute on issues of particular importance, either parent may appeal to the court without formalities, indicating the measures he or she considers most appropriate. The judge, after hearing the parents and ordering the hearing of the minor child who has reached the age of twelve and even younger if capable of discernment, suggests the determinations that he considers most useful in the interest of the child and the family unit. If the conflict persists, the judge assigns the power of decision to that of the parents who, in the individual case, he considers the most suitable to look after the interests of the child” and art. 315 bis of the Civil Code (“the minor child who has reached the age of twelve, and even younger if capable of discernment, has the right to be heard in all matters and procedures concerning him”). Moreover, the need for the involvement of the minor is also expressly provided for in art. 3 of Law no. 219 of 22 December 2017 (“The minor or incapacitated person has the right to the enhancement of his or her ability to understand and make decisions (...). She must receive information on the choices relating to her health in a way that is appropriate to her abilities in order to be put in a position to express her will. Informed consent to the medical treatment of the minor is expressed or refused by the persons exercising parental responsibility or by the guardian taking into account the will of the minor, in relation to his age and degree of maturity, and having as its purpose the protection of the psychophysical health and life of the minor in full respect of his dignity”). The Code of Medical Deontology also provides in art. 33 (Information and communication with the assisted person): “The doctor guarantees the assisted person or his legal representative comprehensible and exhaustive information on prevention ... ... on the foreseeable risks and complications, as well as on the behaviours that the patient will have to observe in the treatment process. The doctor adapts the communication to the ability of the assisted person or his or her legal representative to understand ... The doctor provides the child with useful information so that he or she understands his or her health condition ... in order to involve him in the decision-making process”; and in art.

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35 (Informed consent and dissent): “... The doctor does not undertake or continue diagnostic procedures and/or therapeutic interventions without the prior acquisition of informed consent or in the presence of informed dissent… The doctor takes into adequate consideration the opinions expressed by the child in all decision-making processes that concern him”. The medico-legal literature has long emphasized the importance of adequate information for valid consent; over twenty years ago Turillazzi, considering the information process as an essential element at the foundation of the doctor-patient therapeutic alliance, hoped for the transition from the phrase “informed consent” to “conscious participation”, just as Buccelli, in the same years, underlined the need for personalized information calibrated on the characteristics of the individual patient. In summary, consent can only come from the recipient of the health service, who is legally and de facto capable of providing it (there is no power of representation of close relatives, except for parents and guardians for minors or in any case unable to consent). In particular, in the prescription of physical exercise in subjects with CVD, it is essential that the information relating to the expected benefits and the associated risks (balanced benefit/ risk assessment) includes the useful elements so that the sub-

ject (and the parents in the case of a minor) is put in a position to understand the limit of the commitment of exercise and the importance of not exceeding it, also making him aware of any alterations and “alarm” symptoms and the ways in which to deal with them, including the importance of physical exercise as a primary and secondary prevention tool, when prescribed by the doctor in a personalized form after a careful evaluation of the clinical and functional parameters of the subject himself (in accordance with specific guidelines and protocols), as well as implemented in suitable facilities (gyms or adequately equipped centres) and with staff competent in the subject (e.g. Graduate in Sports Science LM67) able to have it performed correctly and monitor its effects. It is also advisable that there is documentary evidence of this informative contribution (also to parents in the case of minors) and that it be as detailed as possible (in the same way as the strictly technical aspects of the prescription), also taking into account that the “information moment” with respect to any health service is considered by now consolidated jurisprudence as an integral part of the health service itself and the inadequacies on this side constitute an autonomous source of responsibility for the doctor.

INFORMATION SHEET (TEMPLATE) INTRODUCTION Before you decide to participate in this structured exercise prescription and administration program, it is important that you read and understand the following information. In detail, this document describes the purpose, expectations, and risks associated with it. Your participation is voluntary and you can decide to leave the program at any time. You must independently evaluate the information in this informed consent document before deciding whether you wish to participate in the program. If you choose to participate, you will need to sign this informed consent form. RATIONALE A Structured Physical Exercise (SPE) program is an individualized exercise prescription intended for individuals suffering from chronic non-communicable diseases or presenting health risk factors (e.g., arterial hypertension, dyslipidemia, diabetes, obesity), aimed at improving well-being and quality of life, preventing recurrences, reducing mortality risk, and promoting social interaction among participants. A structured exercise prescription program includes: [Describe the specific activities planned within the SPE prescription program, using the examples below as a guide] •

Aerobic physical activity cycle: Characterized by exercises performed over a prolonged period, aimed at improving the capacity to sustain muscular activity for as long as possible.

•

Strength training cycle: Characterized by exercises designed to overcome external resistance, with the objective of increasing muscle strength and metabolic rate.

•

Flexibility and balance cycle: Characterized by exercises aimed at improving joint mobility, posture, and movement execution.

To ensure adequate control over the effectiveness and safety of the program, an initial assessment and subsequent

SPORTS MEDICINE | SUPPL.1 - VOLthrough: 79 N 1 | MARCH 2026 periodicJOURNAL re-evaluations are scheduled

•

Self-assessment questionnaires regarding physical condition and perceived well-being;

• •

Strength training cycle: Characterized by exercises designed to overcome external resistance, with the objective of increasing muscle strength and metabolic rate. E XE RC I SE PRE S C RI PT ION I N C ARDIOLO GY Flexibility and balance cycle: Characterized by exercises aimed at improving joint mobility, posture, and movement execution.

To minimize risks, the program will be tailored and adapted to specific individual physical conditions, ensuring an appropriate progression in workloads alongside careful monitoring during and after training sessions. [Describe the planned follow-up activities, using the examples below as a guide] To ensure adequate control over the effectiveness and safety of the program, an initial assessment and subsequent periodic re-evaluations are scheduled through: •

Self-assessment questionnaires regarding physical condition and perceived well-being;

•

Periodic clinical measurements (e.g., heart rate, blood pressure, body composition);

•

Functional tests to monitor progress.

The administered questionnaires are tools used to gather useful health status information and consist of a series of multiple-choice questions where you are asked to select the option that best reflects your situation. Assessment tests serve as fitness indicators and are useful for evaluating improvements gained from physical exercise; they are straightforward to perform, and some may involve exertion tests (e.g., flat walking, stationary cycling, bodyweight exercises). BENEFITS [Describe the expected benefits associated with the SPE prescription schedule, using the examples below as a guide] The benefits expected upon completion of the program can be summarized as follows: •

Adaptation and improvement of the cardiovascular and respiratory systems;

•

Adaptation and improvement of the oxygen transport system;

•

Increased muscular capillarization (improved blood circulation);

•

Enhanced control of cardiovascular risk factors, such as obesity, hypertension, hyperlipidemia, and diabetes;

•

Increased mechanical performance (ability to coordinate movements more naturally and with less effort);

•

Improvement of balance, posture, and joint mobility;

•

Body weight management and improved metabolism;

•

Enhancement of psychological well-being and overall quality of life.

RISKS [Describe the potential risks associated with the SPE prescription schedule, using the examples below as a guide] Although the program is specifically designed to be safe, certain risks associated with physical exercise may still arise: •

Muscle fatigue, which can be significant if poorly conditioned;

•

Acute musculoskeletal/articular injuries and overload;

•

Potential episodes of hypertension or hypotension—the latter of which may be accompanied by symptoms such as sweating and blurred vision;

•

Onset of cardiac arrhythmias in rare cases;

•

In very rare cases, acute cardiovascular events (e.g., myocardial infarction, stroke), exclusively in patients at very high cardiovascular risk and/or with known cardiovascular diseases.

It is critical that if any symptoms occur during physical exercise (such as chest pain, breathing difficulties, palpitations, or a feeling of faintness), you immediately inform both the staff supervising the exercise session and the prescribing physician. Prescribing Physician: _______________________________________ Contact Details (Email/Phone): _____________________________________ INFORMED CONSENT (TEMPLATE) I, the undersigned (First and Last Name in block letters): __________________________________________________________________________ •

I confirm that I have read and understood the information sheet relating to the structured physical exercise prescription program, and that I have had the opportunity to ask questions and receive all necessary clarifications from the prescribing physician;

•

I understand that my participation is voluntarySPORTS and that IMEDICINE am free to withdraw from| the program at any79time JOURNAL SUPPL. 1 - VOL N 1 | MARCH 2026 without providing any reason;

•

I understand that if I leave the program, I can decide whether to withdraw my consent regarding the processing

It is critical that if any symptoms occur during physical exercise (such as chest pain, breathing difficulties, palpitations, or a feeling of faintness), you immediately inform both the staff supervising the exercise session and the prescribing EXERC I SE PRESCR physician.IP TION IN C A R DIOLO G Y Prescribing Physician: _______________________________________ Contact Details (Email/Phone): _____________________________________ INFORMED CONSENT (TEMPLATE) I, the undersigned (First and Last Name in block letters): __________________________________________________________________________ •

•

I understand that my participation is voluntary and that I am free to withdraw from the program at any time without providing any reason;

•

I understand that if I leave the program, I can decide whether to withdraw my consent regarding the processing of my personal and special categories of data;

•

I am fully aware of the requirement to immediately inform medical staff or instructors should any discomfort or symptoms arise during the exercise sessions.

I hereby consent to participate in the program described above under the terms outlined in the attached information sheet. Participant's Full Name (Block Letters): _________________________________ Participant's Signature: ________________________ Date: _____ / ____ / ______ Privacy and Data Processing Consent (GDPR) Participant's Signature: ________________________ Date: _____ / ____ / ______ Having information note provided pursuant to Articles 13 and/ 14 of Regulation Participant's Signature: ________________________ Date: _____ ____ / ______ (EU) 2016/679 (GDPR) Privacyread andthe Data Processing Consent (GDPR) attached to this form, I hereby consent to the processing of my personal and health data for the purposes specified Privacy andthe Data Processing Consent (GDPR) Having information note provided pursuant to Articles 13 and 14 of Regulation (EU) 2016/679 (GDPR) therein. read attached to this form, I hereby consent to the processing of my personal and health data for the purposes specified Having read the information note Letters): provided pursuant to Articles 13 and 14 of Regulation (EU) 2016/679 (GDPR) Participant's Full Name (Block _________________________________ therein. attached to this form, I hereby consent to the processing of my personal and health data for the purposes specified Participant's Signature: ________________________ Date: _____ / ____ / ______ therein. Participant's Full Name (Block Letters): _________________________________ INFORMED CONSENT FOR MINORS (TEMPLATE) Participant's Signature: Full Name (Block Letters): _________________________________ Participant's ________________________ Date: _____ / ____ / ______ We, the undersigned: Participant's Signature: Date: _____ / ____ / ______ INFORMED CONSENT________________________ FOR MINORS (TEMPLATE) Parent/Guardian 1 (Full Name): ____________________________________________ INFORMED CONSENT FOR MINORS (TEMPLATE) We, the undersigned: Born in:undersigned: _________________________ Date of Birth: _____ / ____ / ______ We, the Parent/Guardian 1 (Full Name): ____________________________________________ Resident at: ________________________________________________________________ Parent/Guardian 1 (Full Name): ____________________________________________ Born in: _________________________ Date of Birth: _____ / ____ / ______ Parent/Guardian 2 (Full Name): ____________________________________________ Born in: _________________________ Date of Birth: _____ / ____ / ______ Resident at: ________________________________________________________________ Born in: _________________________ Date of Birth: _____ / ____ / ______ Resident at: ________________________________________________________________ Parent/Guardian 2 (Full Name): ____________________________________________ Resident at: ________________________________________________________________ Parent/Guardian 2 (Full Name): ____________________________________________ Born in: _________________________ Date of Birth: _____ / ____ / ______ exercising responsibility over theDate minor: Born in: _________________________ of Birth: _____ / ____ / ______ Resident at:parental ________________________________________________________________ Minor's Name: ______________________________________________________ Resident at:parental ________________________________________________________________ exercisingFull responsibility over the minor: Born in: _________________________ of Birth: _____ / ____ / ______ exercising parental responsibility over theDate minor: Minor's Full Name: ______________________________________________________ Minor's Fullconfirm Name: that ______________________________________________________ We we have read and understood the information sheet regarding the exercise prescription Born•in: _________________________ Date of Birth: _____ / ____ / ______ program to be administered to the minor, and that we have been able to request and obtain all necessary Born•in: _________________________ Date of Birth: _____ / ____ / ______ We confirm that wethe have read and understood the information sheet regarding the exercise prescription clarifications from prescribing physician; program to be administered to the minor, and that we have been able to request and obtain all necessary • We confirm that we have read and understood the information sheet regarding the exercise prescription • We are aware from that the participation is entirely voluntary and that they are free to withdraw from the clarifications theminor's prescribing physician; program to be administered to the minor, and that we have been able to request and obtain all necessary program at any time without providing any reason; theminor's prescribing physician; • clarifications We are aware from that the participation is entirely voluntary and that they are free to withdraw from the • We understand the minor leaves the program at any that timeifwithout providing anyprogram, reason; we may choose to withdraw consent for the processing of • We are aware that the minor's participation is entirely voluntary and that they are free to withdraw from the their personal and special categories of data; at any that timeifwithout providing anyprogram, reason; we may choose to withdraw consent for the processing of • program We understand the minor leaves the • We are aware of the requirement to immediately inform the physician or staff if the minor experiences any their personal and special categories of data; • We understand that if the minor leaves the program, we may choose to withdraw consent for the processing of discomfort or symptoms during the exercise program. personal andthe special categories of data; • their We are aware of requirement to immediately inform the physician or staff if the minor experiences any Signature of Minor (if over 12 years of age): _________________________________ discomfort or symptoms during the exercise program. • We are aware of the requirement to immediately inform the physician or staff if the minor experiences any Date: _____ ____ /or ______ discomfort symptoms during exercise program. Signature of /Minor (if over 12 years of the age): _________________________________ Signatures Parents /over Legal 1) ___________________________________ Signature ofof/Minor 12Guardians: years of age): _________________________________ Date: _____ ____ / (if ______

2) __________________________________________ SPORTS MEDICINE JOURNAL SUPPL.1 - VOL 79 N1) 1 ___________________________________ | MARCH 2026 Date: _____ /|______ Signatures of/ ____ Parents / Legal Guardians: Signatures Parents / Legal Guardians: 1) ___________________________________ Date: _____of/ ____ / ______ 2) __________________________________________

program at any time without providing any reason; •

XE RC I SE PRE Sfor C RI ION I N of C ARDIOLO GY We understand that if the minor leaves the program, we may choose toEwithdraw consent thePT processing their personal and special categories of data;

•

We are aware of the requirement to immediately inform the physician or staff if the minor experiences any discomfort or symptoms during the exercise program.

Signature of Minor (if over 12 years of age): _________________________________ Date: _____ / ____ / ______ Signatures of Parents / Legal Guardians: 1) ___________________________________ 2) __________________________________________ Date: _____ / ____ / ______

Privacy and Data Processing Consent for Minors (GDPR) Having read the information note provided pursuant to Articles 13 and 14 of Regulation (EU) 2016/679 (GDPR) attached to this form, we hereby consent to the processing of the minor's personal and health data for the purposes specified therein. Full Names of Parents / Legal Guardians (Block Letters): ___________________________________________________________________________ Signatures of Parents / Legal Guardians: 1) _____________________________________ 2) __________________________________________ Date: _____ / ____ / ______

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| CHAPTER 4.3 |

Professional liability Maurizio Casasco, Francesco De Ferrari, Andrea Verzeletti

Scientific evidence indicates that physical exercise represents a preventive (both in terms of primary and secondary prevention) and therapeutic tool of undoubted efficacy and low cost for CVD. In this context, there is no specific regulatory perimeter within which the Doctor must operate, unlike what occurs for the certification of fitness for sports practice (of any nature); This is because the medical service is not functional to guarantee the possibility of practicing a given sporting activity in “safety”, but is aimed at preserving/improving the state of health of the subject (not necessarily an athlete or a non-registered subject). Moreover, it is equally clear that physical exercise, especially in heart patients, can potentially lead to an alteration in the state of health and therefore its prescription, which is a real medical act, must necessarily be such as to avoid the recurrence of this situation. Therefore, the evaluation rigor on the actual types of physical exercise and methods of practice of the same that the subject will be able to carry out safely and with benefit will have to be even more stringent. The perspective between the healthy subject on the one hand and the sick person on the other is different: for the healthy subject, the prescription, in the first place, must be such as not to compromise his state of health, for the sick subject the prescription must be such as not to aggravate the pathology from which he is affected, as far as possible to counteract a worsening evolution and not determine the onset of new diseases, as well as, where possible, contribute to the recovery and improvement of health conditions. The prescription of physical exercise in subjects with CVD or with risk factors therefore requires specialized skills, such as those that are intrinsic to the Specialist in Sports Medicine and/ or the Cardiologist or the Specialist in the branch inherent to the pathology subject to the prescription, alone or in collaboration. Profiles of imprudence could, therefore, emerge in the prescription of physical exercise by doctors who do not possess adequate skills in the subject. The prescription of physical exercise must be as precise, articulated and unequivocal as possible, also taking into account the fact that the administration of the same may be the prerogative of other professionals who may possibly follow the subject (with particular regard to graduates in motor sciences and techniques of preventive and adapted motor activities). In such contexts, profiles of individual or team responsibility will be envisaged, having to assess the intrinsic adequacy of the prescription with respect to the characteristics of that given subject, together with the ways in which the physical exercise was then followed by other figures and the adherence of the same to what was actually prescribed. In this regard, it is appropriate that the prescription itself is also accompanied by the indication that the physical exercise itself must be carried out in facilities appropriate to the individual case, at least in terms of minimum safety requirements and competent personnel. The operational context where physical exercise will then be provided can be multifaceted: from real medical centres (similar to rehabilitation cardiology facilities) to

structures of sports associations and clubs and gyms organized in such a way as to ensure a more widespread and homogeneous implementation of a medical/therapeutic act of great social value, which is to be considered, as previously pointed out, the prescription of physical exercise in CVDs. The elements on which medical professional liability is based, also with reference to the prescription of physical exercise, are: • the health service not performed correctly • the damage claimed by the recipient of the service • the causal relationship between the medical conduct and the consequent damage. The two classic areas in which professional liability can materialize, which are not mutually exclusive to each other, are criminal and civil law. Criminal liability is personal (art. 27 of the Constitution), not delegable, and takes the form of the possibility that the doctor may be called to answer for the crime of culpable personal injury rather than manslaughter, with the related sanctioning regime provided for the aforementioned crimes. Civil liability, on the other hand, consists of the obligation to compensate for damages, it is personal but transferable to other parties (e.g. with an insurance contract) and the regulatory references that govern it are essentially art. 2043 of the Italian Civil Code (Compensation for unlawful act): “Any intentional or negligent act, which causes unjust damage to others, obliges the person who committed the act to compensate for the damage” and art. 185 of the Criminal Code (Restitution and compensation for damages): “Every crime obliges restitution, in accordance with civil laws”. In order to assess the adequacy of the conduct held by the doctor, the regulatory reference is art. 43 of the Criminal Code: “The crime: ... it is culpable, or against the intention, when the event, even if foreseen, is not desired by the agent and occurs due to negligence or imprudence or inexperience, or due to non-compliance with laws, regulations, orders or disciplines...”. Liability deriving from “inexperience, imprudence, negligence” (generic negligence) is assessed with reference to the “average” behaviour of professionals of the same level, experience, specialization and qualification, while liability deriving from “non-compliance with laws, regulations, orders and disciplines” (specific negligence) may constitute “inexcusable” negligence and may consist in the simple violation of the rule (e.g. in relation to the certification of suitability). The Civil Code also provides for the concept of gross negligence, understood as an inexcusable error, in art. 2236 of the Italian Civil Code (Liability of the service provider): “If the service involves the solution of technical problems of particular difficulty, the service provider is not liable for damages, except in the case of wilful misconduct or gross negligence”. In the event of suspected inappropriate behaviour, the criterion for evaluating both the conduct of the doctor and the consequences of incorrect behaviour must necessarily start from a careful and punctual reference to the recommendations contained in the guidelines. The definition of guidelines was coined in 1992 by the Institute of Medicine: “Recommendations of clinical behaviour, produced through a systematic process for the

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E XE RC I SE PRE S C RI PT ION I N C ARDIOLO GY

purpose of assisting physicians and patients in deciding which are the most appropriate modes of care in specific clinical circumstances” (Institute of Medicine, Guidelines for clinical practice: from development to use, Washington D.C., 1992). We can indeed distinguish: • Guidelines: recommendations of clinical behaviour indicative of the most appropriate care modalities in specific clinical circumstances. • Care pathway: logical sequence of diagnostic tests and/or therapeutic treatments indicated and/or suggested in the specific case according to evidence-based medicine. • Diagnostic-therapeutic protocol: predefined diagnostic-therapeutic behaviour scheme designed to guarantee the validity and certainty of a given technique. Here, therefore, the guidelines represent an important reference for the evaluation of the doctor’s work. They must never rise to the value of a mandatory norm but must be placed in the concrete reality of the individual subject and must be adequately modulated and applied to it. In other words, precisely because they are general indications, following them slavishly cannot in itself represent an exemption from liability for the doctor but, conversely, moving away from them must always be adequately motivated and fully documented by the prescribing doctor. Moreover, the centrality of the guidelines in the evaluation of conduct, already present in Law No. 189 of 8 November 2012 (the so-called Balduzzi Law), was systematized with Law No. 24 of 8 March 2017 (the so-called Gelli-Bianco law): the doctor, without prejudice to the specificities of the concrete case, must comply with the recommendations provided for by the guidelines contained in the “National System of Guidelines” (SNLG - https:// snlg.iss.it). These guidelines therefore represent an unavoidable

operational reference for the doctor, who is therefore required to know them and apply them critically taking into account any specificities of the concrete case. On the other hand, the professional’s knowledge of the guidelines is certainly an indication of his diligence and becomes a concrete expression of the need for continuous education in medicine and constant updating understood, as well as regulatory obligations, also as essential deontological duties for the doctor. In fact, we recall that the code of medical ethics, in art. 13 provides that: “The doctor takes into account the diagnostic therapeutic guidelines accredited by authoritative and independent sources as recommendations and assesses their applicability to the specific case” and, in art. 19, underlines that: “The doctor, throughout his professional life, pursues constant updating and continuous training for the development of knowledge and skills technical and non-technical professionals, encouraging their dissemination to learners and collaborators”. For what has been argued above, it can be deduced that a prescription for SPE, having been formulated by the doctor who has the specialized skills after an in-depth classification of the clinical condition, from a diagnostic and prognostic point of view, and the performance of the diagnostic tests indicated herein, represents both for the subject-patient and for the personnel responsible for the surveillance/implementation of the physical exercise program the document to refer to. Of course, after the initial classification, it is prudent to advise/recommend the re-evaluation of the subject at an appropriate distance of time in order to concretely evaluate how the prescribed physical exercise is acting on that given subject and possibly remodulate the prescription on the basis of the effects themselves.

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EXERC I SE PRESCR IP TION IN C A R DIOLO G Y

STRUCTURED EXERCISE PRESCRIPTION TEMPLATE For For _________________________________________________________________________ _________________________________________________________________________ Date of of birth birth _____________________ _____________________ Telephone Telephone ____________________ ____________________ E-mail E-mail _____________________ _____________________ Date Weight: Weight: ___________ ___________ Height: Height: ___________ ___________ BMI: BMI: ___________ ___________ DIAGNOSIS/CLINICAL HISTORY: HISTORY: _______________________________________________________________ DIAGNOSIS/CLINICAL _______________________________________________________________

_________________________________________________________________________________________ _________________________________________________________________________________________ CURRENT THERAPY: THERAPY: ________________________________________________________________________ ________________________________________________________________________ CURRENT _________________________________________________________________________________________ _________________________________________________________________________________________ TRAINING TRAINING PLAN PLAN This This training training plan plan has has aa duration duration of of _____ _____ months, months, unless unless changes changes in in the the patient's patient's clinical clinical status status require require aa new new medical medical evaluation. evaluation. To To be be performed performed at: at: ☐ Health/Fitness ☐ Health/Fitness club club with with facilities facilities and and qualified qualified personnel personnel specialized specialized in in structured structured physical physical exercise exercise programs; programs; ☐ ☐ Exercising Exercising in in aa protected/supervised protected/supervised environment; environment; ☐ ☐ Indipendently. Indipendently.

AEROBIC AEROBIC TRAINING TRAINING FREQUENCY FREQUENCY (sessions per (sessions per week) week) SESSION DURATION DURATION SESSION (in (in minutes) minutes)

☐ ☐1 1 ☐ ☐2 2 ☐ ☐3 3

TOTAL TOTAL DURATION DURATION

☐ ☐ _____ _____ minutes/week minutes/week ☐ Plan for ☐ Plan for aa possible possible progressive progressive increase increase in in the the duration duration of of the the sessions sessions and and the the weekly weekly frequency frequency of of the the sessions sessions

☐ ☐4 4

☐ ☐ 30 30 ☐ ☐ 45 45 ☐ ☐ 60 60 ☐ ☐ 90 90

☐ ☐… …

☐ ☐ walking walking (jogging, (jogging, nordic nordic walking, walking, treadmill…) treadmill…) ☐ running (jogging, running on treadmill…) treadmill…) ☐ running (jogging, running on ☐ swimming swimming ☐ ☐ cycling (cycling, (cycling, stationary stationary bike, bike, spin spin bike) bike) ☐ cycling TYPE TYPE ☐ dancing ☐ dancing ☐ elliptical elliptical ☐ ☐ _____________ ☐ _____________ ☐ ☐ _____________ _____________ ☐ ☐ mild mild ☐ ☐ moderate moderate ☐ ☐ high high INTENSITY HR INTENSITY HR of of exercise exercise between between _____ _____ bpm bpm and and _____ _____ bpm, bpm, with with average average HR HR to to be be maintained maintained at at about about _____ _____ bpm bpm ☐ ☐ intermittent intermittent cardiovascular cardiovascular training training cannot cannot be be performed performed ☐ ☐ intermittent intermittent cardiovascular cardiovascular training training at at moderate moderate intensity intensity can can be be performed performed ☐ ☐ intermittent intermittent cardiovascular cardiovascular training training at at high high intensity intensity can can be be performed performed Notes: Notes: ________________________________________________________________________________ ________________________________________________________________________________ _____________________________________________________________________________________ _____________________________________________________________________________________

PROGRESSION PROGRESSION

[or] [or]

☐ ☐ Add Add _____ _____ minutes minutes every every ________________, ________________, if if possible possible based based on on perceived perceived fatigue fatigue ☐ Once the duration of _____ minutes/session, add a weekly, shorter session (_____ minutes), with progression as in the previous point Provide a short warm-up phase before the aerobic training session and a cool-down phase at the end (maintaining an intensity lower than the minimum HR of exercise). Notes: __________________________________________________________________________________

MUSCLE STRENGTH TRAINING

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FREQUENCY (sessions per week)

☐1 ☐2 ☐3 ☐…

previous point Provide a short warm-up phase before the aerobic training session and a cool-down phase at the end (maintaining an intensity lower than the minimum HR of exercise). E XE RC I SE PRE S C RI PT ION I N C ARDIOLO GY Notes: __________________________________________________________________________________

MUSCLE STRENGTH TRAINING FREQUENCY (sessions per week) SESSION DURATION (in minutes) TYPE

INTENSITY TOTAL DURATION

PROGRESSION

☐1 ☐2 ☐3 ☐… ☐ 20 ☐ 30 ☐ 40

☐ floor exercise ☐ specific weights ☐ machinery ☐ _____________

☐ Between _____% and _____% of single maximal repetition (1RM, in kg) [or]

☐ Between _____ and _____ of the modified Borg Scale (0-10)

☐ _____ minutes/week Train the main muscle groups at a moderate intensity, alternating the upper district than the lower one. Provide for a progressive increase, before the number of repetitions (from _____ to and series (from _____ to _____) and finally the load intensity (from _____% to _____% of 1RM), if possible.

Pay attention to breathing during the execution of the exercises: exhalation during the pushing phase, avoid Valsalva's manoeuvre. Slow execution: 2 sec for the push phase and 2 sec for the release phase. Cooldown time between sets: ____ min. Prefer, at first, multi-joint exercises with the execution of 4-5 sets of 10-12 repetitions for a single exercise; then it is possible to move on to monoarticular exercises. Notes: __________________________________________________________________________________

FLEXIBILITY TRAINING FREQUENCY (sessions per week) SESSION DURATION (in minutes) TYPE

☐1 ☐2 ☐3 ☐… ☐ 10 ☐ 20 ☐ 30 ☐ static stretching ☐ dynamic stretching ☐ ……………………………..

Notes: __________________________________________________________________________________ ****

In case of changes in the clinic, it is recommended to suspend the activity and contact the prescribing doctor. If you experience major symptoms, contact the emergency system. Date and place: _______________________ Stamp and Signature of the Doctor ________________________________

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Glossary Aerobic physical activity. During this type of activity, the muscle cell uses the metabolic pathway to produce energy, which involves the use of Oxygen. It generally consists of rhythmic movements of large muscle masses (walking, jogging, swimming, cycling, dancing) performed at low or high intensity depending on the subject’s exercise capacity, for example a subject with good cardiorespiratory training is able to perform aerobic activity even at high intensity. Regular practice of aerobic physical activity improves cardiorespiratory efficiency. Anaerobic physical activity. During this type of activity, the demand for energy in the muscles is satisfied by anaerobic metabolic pathways (anaerobic glycolysis and high energy phosphates). Anaerobic activity can only be maintained for a short period of time, the duration of which depends on the intensity. Sprinting, jumping (high and long) and weightlifting are examples of different types of anaerobic physical activity. Balance. Ability to maintain the body’s center of gravity within the base of support, in static (static balance) or dynamic (dynamic balance) conditions. Body composition. It indicates the main body components (fat mass [adipose tissue] and lean mass [muscle, bone, water]) expressed as a percentage or in kg. Borg scale. It is a means of evaluating the effort perceived by a subject, also called Rating Perceived Exertion (RPE). It is a scale with values ranging from 6 (no effort) to 20 (maximum effort). It represents a tool (albeit empirical) that can be used by the subject to estimate the intensity of the exercise he is performing on the basis of personal perception and is therefore influenced by multiple elements such as fatigue of the cardiorespiratory system, psychological factors, thermal sensations, muscle fatigue, motivation.

Counseling. Activity aimed at orienting, supporting and promoting active attitudes towards possible solutions to a problem. The fundamental purpose is the development of the autonomy of the person, who always remains the protagonist of the counselling process and who is put in a position to make choices after being guided to examine the situation from different points of view. Dose of physical activity. Term used to define the amount and intensity of physical activity or physical exercise carried out or to be carried out. It depends on the induced energy expenditure of physical exercise (generally expressed in METs), the frequency and duration of the exercise itself. All things being equal, mechanical workload, and therefore of METs, the intensity will vary depending on the functional capacity of the individual. Energy expenditure. It is the amount of energy (expressed in Kilojoules or Kilocalories) needed to perform a given muscle work. It varies according to the characteristics of physical, sporting or work activities and depends mainly on the type and intensity of exercise and partly also on intrinsic variables such as training status (mechanical efficiency) and body mass and extrinsic variables such as climate and environment. It is typically measured by oxygen consumption (indirect calorimetry). Ergometer. An instrument used to measure the amount of mechanical work performed in a unit of time by an organism during the performance of a physical exercise. It can be used to perform ergometric tests for sports and cardiology purposes, to assess aerobic capacity, to carry out cardiovascular and/or upper or lower limb training. The most commonly used ergometers are:

Calisthenics exercises. Physical exercises that involve short muscle contractions aimed at increasing flexibility and muscle strength using only one’s own body weight as an overload. Cardiorespiratory efficiency (cardiorespiratory fitness). Cardiorespiratory efficiency expresses the ability of the cardiovascular and respiratory systems to ensure an adequate supply of Oxygen to the muscles during exercise, together with the ability of muscle tissues to use it. It is quantified through the measurement or estimation of maximum aerobic power (maximum oxygen consumption or VO2max). Cardio-respiratory endurance. Cardio-respiratory ability to sustain physical exercises or athletic performance for long periods of time that engage important muscle masses, mainly using aerobic metabolism. In general, it is a discursive term for expressing maximum aerobic power (maximal Oxygen uptake - VO2max). Coordination. Ability to perform motor tasks, simple or complex, in a fluid and precise way, i.e. with an appropriate temporal activation of the different muscles.

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• Cycle ergometer: reproduces locomotion on a bicycle, allows you to measure the work in the unit of time (power delivered) applied to the lower limbs. The resistance to the movement of the pedals can be increased by means of friction or electromagnetic brake systems that slow down the rotation of the flywheel (metal disc of variable weight and size) to which the pedals are connected. • Modified cycle ergometer where the subject has a comfortable seat. It is particularly suitable for individuals with significant excess weight or spinal problems. • Crank ergometer: it allows you to measure the work in the unit of time applied by the upper limbs and consists of two cranks that move in opposite and circular ways. It is ideal for people who have difficulty using other ergometers, such as people who are obese or have any kind of limitation to the use of their lower limbs. • Elliptical ergometer: produces a movement of the lower limbs halfway between a “stepper”, a cycle ergometer and a treadmill requiring both circular and pushing gestures with good simulation of the running action while avoiding the possible negative effects of impacts on the ground. The movement is produced on the basis of an elliptical-ovoid flywheel and not circular.

E XE RC I SE PRE S C RI PT ION I N C ARDIOLO GY

• Treadmill (treadmill, conveyor belt): instrument equipped with a sliding rubberized belt, moved by a motor, on which it is possible to run or walk. It is equipped with a monitor that, thanks to different devices, sensors and software, allows you to view and then control numerous training parameters, including HR, walking speed, incline percentage, training time, distance of run. Compared to the cycle ergometer, it engages a greater number of muscle masses and is less affected by local fatigue in the lower limbs. Fatigue. State of asthenia and psycho-physical fatigue. A term often used in the field of oncology to indicate the symptoms associated with the chemotherapy (and non-chemotherapy) treatment to which the cancer patient is subjected. Fitness. It includes the qualitative and quantitative level of physical efficiency, in specific aspects of health such as maximum aerobic power (cardiovascular capacity), muscle strength and endurance, flexibility and body composition. Frequency Intensity Time Type (FITT). Frequency, intensity, duration and type of physical activity are variables that characterize the individual exercise session and/or training. They must be taken into account in order to correctly structure physical exercise programs based on individual characteristics, physical efficiency and any pathologies present. Flexibility. Ability to move body segments for the entire range of motion (RoM) of joint. Game. Set of psychophysical activities carried out with playful and recreational intent. Health gym. A non-health facility, both public and private, where SPE and AFA programs are carried out. Intensity of Activity/Exercise. It indicates the fatigue (effort) required to perform a certain exercise. It is defined as a percentage of the person’s maximum functional capacity compared to that type of physical activity, for example, maximal oxygen uptake or maximal HR for aerobic dynamic activities and maximal voluntary contraction for muscle strength activities. It can also be expressed through subjective parameters such as the Borg scale score (see below) or talk test. Kinesiologist. Professional with a degree in Exercise and Sports Sciences (class L-22) whose professional activity has as its object the conduct, management and evaluation of individual and group motor activities of an educational, recreational-compensatory and sporting nature for the improvement of the quality of life through physical exercise. Kinesiologist of Preventive and Adapted Motor Activities (AMPA). Kinesiologists with a master’s degree in Science and Techniques of Preventive and Adapted Motor Activities (class LM-67) whose professional activity has as its object the design and implementation, in synergy with other health professionals, physical activity programs aimed at achieving and maintaining the best conditions of psychophysical well-being for individuals in various age groups and in different physical conditions, as well as the organization and

planning of particular activities and lifestyles aimed at preventing diseases and improving the quality of life through physical exercise. Maximum Oxygen uptake (VO2max). The body’s ability to introduce, transport, and use oxygen per unit of time during maximal exertion involving the dynamic contraction of large muscle groups expressed in millilitres/minute and often normalized per kg of body weight (ml/kg/min). It can be expressed in METs and is also known as maximal aerobic power. Maximum oxygen uptake is typically measured during incremental exercise tests conducted until exhaustion (cardiopulmonary testing). MET (Metabolic Equivalent of Tasks). Normalized measure of energy expenditure for resting energy metabolism in a sitting position and per kilogram (kg) of body mass. A MET is equivalent to Oxygen consumption of 3.5 ml/kg/min (this Oxygen consumption value is considered average for the population). The MET is used as a multiplier to quantify the energy expenditure of each physical activity. A physical activity whose energy expenditure corresponds to 5 METs, for example, it requires, to be carried out, 5 times the Oxygen uptake at rest. Muscle conditioning. Improvement of muscle contraction capacity, resistance to fatigue, muscle recovery obtained through training. Muscle deconditioning. Loss of muscle adaptations obtained through training. Muscular efficiency (muscle fitness). Muscle efficiency is characterized by strength, speed and therefore power, i.e. the product of these two variables and muscular endurance (ability to repeat submaximal muscle contractions or maintain a given sub-maximal load). It is linked to the function of the musculoskeletal system (osteo-arthro-muscular), therefore the term “musculoskeletal efficiency” is often adopted to give a broader definition. Physical efficiency. Physical efficiency is the ability to perform a certain physical work with the least expenditure of energy and resources, achieving the maximum result. It depends on the amount of work done compared to the energy expended and can be influenced by various factors such as technique, physical endurance and muscle coordination. Physical inactivity. Lower than recommended levels of physical activity for health, well-being and the prevention of numerous chronic diseases. Sarcopenia. Progressive and generalized syndrome characterized by reduced muscle strength and mass and physical performance, related to advancing age and other possible causes such as malnutrition, hormonal imbalances, neurological and oncological diseases and hypomobility. Stretching. Technique aimed at stretching muscles and increasing flexibility and joint mobility (RoM) that can be performed in different ways.

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