CRY Research Highlights 2021

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Research Highlights 2021 Inside this issue. . .

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Conferences Interviews Papers/Articles CRY’s Research Programme

Offering help and support to affected families @CRY_UK CardiacRiskintheYoung www.c-r-y.org.uk

Conferences

CRY’s online International Medical Conference

Due to the ongoing COVID-19 pandemic, the CRY Conference was moved online again for 2021. On October 14 and 15, the conference was hosted in partnership by CRY and the European Association of Preventive Cardiology (EAPC).

We were thrilled to welcome leading experts in cardiology from around the globe for presentations, discussion of case-based scenarios, and interactive debates for the audience to follow and engage with online.

The first debate of Day 1 was “Athlete with an ICD; No way back to competition?” This was led by Andre La Gerche, a cardiologist and researcher at the Baker Heart and Diabetes Institute in Melbourne, Australia, who presented a case of whether an athlete should be allowed to return to competition. The athlete in this case was an elite 26-year old Australian Rules Footballer, who had previously been well with no family history of any medical problems. He collapsed during a match and after getting up was immediately taken to hospital. In the presentation, Professor La Gerche went on to show some of the tests the athlete went through. It was established that the athlete had no other symptoms before or after the incident, and he went on to have a subcutaneous implantable cardiac defibrillator.

Professor Rachel Lampert from Yale Medical Center joined to argue the case against the athlete returning to sport, while CRY Consultant Cardiologist Professor Sharma presented the case that the athlete could resume competing.

have long QT syndrome, and there is no evidence of higher risk attributable to the additional QT prolongation of athletes. In fact, most patients are low risk, Professor Behr added. Dr Silvia Castelletti from the Cardiomyopathy Unit and Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy followed to present the case against the athlete returning to competitive sport. Dr Castelletti presented more data and outlined some of the arguments against, such as how participating in sport can lead to a further prolonged QT which can correlate with the increased risk of a cardiac event occurring.

After a Q&A session with questions from audience members, the second session of the day got underway. This session included three different cases. Firstly, Dr Harald T. Jørstad began with “Veteran athlete with atrial fibrillation; pit stop or steady on?” The case looked at a 39-year-old man who is a former professional football player with atrial fibrillation. The former footballer contacted a clinic one morning to say that he had atrial fibrillation the night before and took his medication (flecainide). Now that he was feeling fine, he asked if it would be safe for him to play in a football match later that day. Dr Jørstad went on to discuss atrial fibrillation in more detail and how this case could be dealt with.

The second debate of the day was entitled “Athlete with LQTS and prolonged QT interval; Treat and release.” This case looked at an 18-year-old competitive swimmer with long QT, who had a syncope spell two years ago and whose mother had a syncope spell while skiing, meaning there was family history to consider. The swimmer underwent a variety of tests.

After 83% of the audience voted to say the athlete should not return to competitive sport, the debate began.

Next, Dr Michael Papadakis from St George’s University, London, looked at a case of an athlete with pre-excitation. In this instance, a 16-year-old sportswoman who attended a CRY screening. Her exercise regimen involves 13 hours of training per week, including competing in swimming and netball at county level. She reported some shortness of breath from exertion which had been attributed to hay fever, and she had no family history of concern. Dr Papadakis then looked at the ECG of the athlete to ask the audience what it showed, and discussed what tests could be done next.

Professor Elijah Behr had the task of convincing the audience otherwise, making the case that the athlete could be treated and return to sport. After discussing various data, Professor Behr concluded with a few key points, including that athletes have longer QT intervals, many with QT prolongation do not

For the third and final case of Day One, Dr Alessandro Zorzi from the Department of Cardiac, Thoracic and Vascular Sciences and Public Health at the University of Padova, Italy joined to give a presentation, entitled “Athlete with ventricular ectopy: it is a family thing.” Dr Zorzi looked at four members of

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CRY’s online International Medical Conference a family who were referred to his cardiac clinic for evaluation.

He explained their various symptoms, looked at their ECG results, and discussed what further testing or treatment they may need. To bring Day One to a close, Dr Papadakis hosted The Great ECG Quiz.

The first session of Day Two got started with a talk from Professor Martin Halle, examining the case of a 52-year-old male who suffered a non-ST-elevation myocardial infarction.

In the three months since, the man underwent cardiac rehabilitation with moderate intensity exercise three to four times per week and had no symptoms. Before his acute myocardial infarction, though, he was more active – he went jogging for 45-60 minutes five times a week and took part in several half marathons and marathons, and wanted to return to a similar level of physical activity. So, Professor Halle discussed some of the testing the patient had and asked the question whether participation in high-volume sports, such as a marathon, could be recommended.

Dr Meagan M. Wasfy from the Cardiovascular Performance Program at the Massachusetts General Hospital in Boston, USA argued the case for the runner to return to this kind of sport. Dr Wasfy did say that personally she would not recommend training for a marathon, but did look at why cases need to be individualised and consider the goals of the patient. To counter, Professor Mats Börjesson argued why the runner should not return to such significant levels of sport.

The next case, presented by Professor Antonio Pelliccia, looked at a 43-year-old male football player with no symptoms or family history. The only finding with the footballer was abnormalities on his ECG, including markedly increased voltages. After Professor Pelliccia explained the footballer’s test results and low risk score, former CRY Research Fellow Dr Sabiha Gati from the Royal Brompton Hospital argued the case for a return to sport. Dr Gati closed with a few key arguments, such as how moderate exercise reduces cardiac risk factors and improves fitness, and how a sedentary lifestyle can have detrimental effects on people including those with hypertrophic cardiomyopathy. To conclude, Dr Jonathan Drezner gave his presentation to make the argument against the footballer returning to play. Dr Drezner looked at a few key points, such as how exercise can be safer for older patients with HCM but not necessarily younger patients, and that restricting participation in sports can reduce the risk of SCD. The session finished with a Q&A and

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discussion amongst the panel of experts.

The second and final session of Day Two began with a case presented by Dr Guido Claessen, “Athlete with dilated LV and reduced/borderline LVEF.” The athlete in this case was a 23-year-old elite runner who had reported some atypical chest pain when in a resting state. His clinical examination was normal, he had no personal medical history and takes no medication. There was some family history, though, as his father was a runner who was diagnosed with dilated cardiomyopathy at 44 years old. Dr Claessen discussed the testing the runner underwent and the panel of experts weighed in on the findings.

The next case of the session was presented by Dr Elena Cavarretta from Sapienza University of Rome, Italy on “An athlete with mitral valve prolapse.” Dr Cavarretta looked at the case of a 40-year-old competitive triathlete diagnosed with mitral valve prolapse, and discussed his condition and to what degree he should be able to participate in sports.

The final presentation of the conference was given by CRY Research Fellow Dr Raghav Bhatia. Dr Bhatia’s case looked at a 20-year-old semi-professional cricketer after being infected with COVID-19. The cricketer was typically fit and well but went to his local Accident and Emergency department after having a two-day history of chest pains and a few other symptoms.

The athlete had received two doses of the Pfizer-BioNTech vaccine and had mild illness with COVID a week after his first dose. Dr Bhatia looked at how to diagnose the athlete and how long they may need to wait before returning to sport, along with discussion from the expert panel.

The 2021 CRY Conference featured so many brilliant presentations and we are grateful to all the experts who took part. We would also like to thank all of our sponsors for the conference, as well as Wondr Medical, our digital partner who streamed the event.

Research Highlights 2021

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COVID-19 and the CRY Experience An interview with CRY Research Fellow Dr Raghav Bhatia

Interviews

CRY Research Fellow Dr Raghav Bhatia’s primary research interests include evaluating the role and efficacy of cardiovascular screening in individuals aged 14-35, which incorporates the challenges and opportunities catalysed by the COVID-19 pandemic.

Earlier on in the pandemic, Dr Bhatia led on consensus recommendations, aimed at providing practical answers to pertinent questions being posed by the sporting community around safe participation in exercise. (“Exercise in the Severe Acute Respiratory Syndrome Coronavirus-2 [SARS-CoV-2] era: A Question and Answer session with the experts Endorsed by the section of Sports Cardiology & Exercise of the European Association of Preventive Cardiology [EAPC].” Bhatia RT, Marwaha S, Malhotra A, et al. Eur J Prev Cardiol. 2020) The recommendations were endorsed by the European Association of Preventive Cardiology (EAPC) and widely adopted and utilised by sporting bodies which included the Rugby Football Union (RFU), English Institute of Sport (EIS), and the English Football Association (FA).

A twinned review (“The Impact of COVID-19 on the Continuity of Cardiovascular Care.” Bhatia RT, Gati S, Papadakis M, Sharma S. Eur Heart J. 2021) provided an overview of the challenges posed by the pandemic on cardiovascular services, whilst suggesting potential solutions based on current models of care.

With the above in mind, Dr Bhatia joined us in conversation to discuss all things COVID-19 related.

What are the main ways COVID-19 has impacted people with cardiovascular conditions?

Whilst COVID-19 can be contracted by all individuals, multiple studies have demonstrated that individuals with established cardiovascular disease, and those with risk factors such as diabetes mellitus, hypertension and obesity, are associated with an increased morbidity and mortality.

Case fatality is also higher in older age groups, with the highest mortality in those aged ≥80 years in whom mortality is six times higher than in younger patients. Furthermore, patients with heart failure have significantly poorer outcomes including in-hospital complications.

What are your current research interests, specifically around COVID-19?

Firstly, in my capacity as a Research Fellow I am grateful to the families and supporters who fund our screening events and research. It is with this support that I am currently working on two large scale projects which 1) address the

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impact of COVID-19 infection in young individuals aged 14-35, who attend our screening events and 2) outcomes of cardiac screening in athletes following COVID-19 infection.

Overall, we aim to address current knowledge gaps around the epidemiological aspects of the disease and impact on individuals who engage in regular physical activity, as well as enhance our understanding around the optimal screening strategies.

How much do you think the increased use of remote technology during the pandemic can help us moving forward with new remote care for people with cardiovascular conditions?

Largely due to necessity, aspects of e-health, which includes utilising information technology and communication technology to aid patient care, have been broadly adopted by healthcare systems. Telemedicine has been responsible for the buoyancy in maintaining outpatient services through virtual consultations.

Meanwhile, mobile applications and wearable technologies continue to empower patients in their management. For example, cardiac rehabilitation services, which have traditionally been delivered in a hospital setting, saw an effective shift towards home-based cardiac rehabilitation.

Whilst the pandemic has accelerated the utilisation of remote technologies, it has emphasised the importance of 1) risk stratifying patient groups in whom more traditional models of care with face-to-face encounters would provide safer and more effective care; 2) comparing clinical outcomes in specific patient groups using different models of care; 3) evaluating patient experiences where remote care has been delivered; and 4) ensuring adequate infrastructure, training, and investment.

Specifically, with reference to our CRY screening programme, we are evaluating the potential incorporation of remote technologies in tandem to our nationwide mobile screening units. This takes into account potential logistical issues such as connectivity, evaluation of licensed platforms, technologies for ECG acquisition, and most importantly governance.

Online meetings and conferences have been used more than ever through the pandemic as well. How could this continue and help us with education in the future?

The online shift in medical education has been positively received by colleagues. However, we do miss the interaction and networking opportunities from in person meetings!

We recently held the 7th EAPC Sports Cardiology Course & CRY International Conference virtually in liaison with Wondr Medical, over two afternoon sessions. 242 delegates joined us from over 30 countries, with attendees spanning a broad range of medical specialities.

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In my opinion, where feasible, adaptive online learning interfaces should complement in-person meetings and conferences. One of the biggest positives the pandemic has brought, has been subsidised or free access to online events, whereby traditionally access to in-person events might have been limited due to financial constraints, including registration fees and travel. Perhaps the pandemic has accelerated industry and societies to strive towards optimal access to medical education, which balances financial and geographical constraints.

Finally, central to patient care, the digital transformation has enhanced methods of conducting multidisciplinary team meetings and has encouraged participation from an even broader audience, compared to historical meetings which were held in confined spaces.

Dr Raghav Bhatia’s presentation during the 2021 CRY International Medical Conference

In addition, our MSc in Sports Cardiology, the only programme of its kind in the UK and Europe, taught by world-leading experts from the Centre for Inherited Cardiovascular Conditions and Sports Cardiology at St George’s NHS Foundation Trust, has incorporated hybrid models of teaching, which include in-person and remote sessions, in an attempt to balance and maximise learning opportunities for students.

These examples from our own experience, have been positively received by audiences.

Such practices have the potential to improve both patient care and healthcare professional education through sharing expertise, particularly outside the context of specialised referral centres.

“Sudden Death in Female Athletes: Insights From a Large Regional Registry in the United Kingdom” An interview with Dr Gherardo Finocchiaro Former CRY Research Fellow Dr Gherardo Finocchiaro completed research into the incidence of sudden cardiac death in female athletes, using data gathered at the CRY Centre for Cardiac Pathology.

In this interview, he explains the main findings of this research: What data was reviewed and how did you carry out this research?

We reviewed a database of 6,847 cases of sudden cardiac death (SCD) which were referred to the CRY Centre for Cardiac Pathology at St George’s, University of London between 1994 and 2020.

SCD was defined as death occurring within 12 hours of apparent wellbeing. We retrieved a subgroup of 748 (10.9%) decedents who engaged in sport activities, defined as >3 hours of organized physical training per week.

What are the main takeaways from this paper?

Females constituted 98 (13%) of the 748 SCDs among individuals engaging in regular sports activities. More than

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40% of female athletes die at rest or during daily activities.

Sudden arrhythmic death syndrome (SADS), which means that the heart is structurally normal at post-mortem examination, was the most common finding in female athletes.

Is there anything else you’d like to mention about this research?

There is consistency among studies that females are less prone to exercise-related SCD than males, however knowledge pertaining to the specific cause and precipitating circumstance is sparse.

The increase in the number of women participating in various sports, including disciplines historically dominated by males, calls for a more focused perspective surrounding exercise related SCDs in female athletes. This study is the first to focus on a large cohort of female athletes who died suddenly and provides important insights on prevalence and causes of sudden death.

What are you focusing on in your work next?

My researches continues on causes and incidence of sudden death in young individuals and in athletes. The next step is to focus on hypertrophic cardiomyopathy and on the circumstances of death in individuals affected by this condition.

Research Highlights 2021

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Papers/Articles

Research • “2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease.” Pellicia A, Sharma S, Gati S, et al. European Heart Journal, January 2021.

“The overarching aim of these recommendations was to minimize the risk of adverse events in highly trained athletes. It is important to recognize, however, that most of the exercising population engages in leisure sport and solo recreational exercise and, unlike elite athletes, these individuals have a higher prevalence of risk factors for atherosclerosis and established CVD [cardiovascular disease].”

• “The Impact of COVID-19 on the Continuity of Cardiovascular Care.” Bhatia RT, Gati S, Papadakis M, et al. European Heart Journal, January 2021.

“In this article, we aim to provide an overview of these challenges [to cardiovascular care due to the impact of COVID-19] and suggest potential solutions based on current models of care.”

• “Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.” Walsh R, Lahrouchi N, Tadros R, et al. Genetics in Medicine: Official Journal of the American College of Medical Genetics, January 2021.

• “The 2020 ESC Guidelines on Sport Cardiology.” Pellicia A, Sharma S. European Heart Journal, January 2021.

“The initiative for producing the first Guidelines (GLs) on Sport Cardiology was prompted by the European Society of Cardiology (ESC) to facilitate appropriate risk stratification and safe decision-making when prescribing exercise programmes and sport participation in patients with CV [cardiovascular] diseases/abnormalities.”

• “The ‘Ten Commandments’ for the 2020 ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease.”

Sharma S, Pelliccia A, Gati S. European Heart Journal, January 2021.

• “Defining the Normal Spectrum of Electrocardiographic and Left Ventricular Adaptations in Mixed-Race Male Adolescent Soccer Players.” Malhotra A, Oxborough D, Rao P, et al. Circulation, January 2021.

“We examined the electric and structural adaptations in the heart in healthy mixed-race male soccer players and compared them with those of White and Black male soccer players.”

• “Diagnostic yield and financial implications of a nationwide electrocardiographic screening programme to detect cardiac disease in the young.” Dhutia H, Malhotra A, Finocchiaro G, et al. Europace, February 2021.

“The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.”

• “Medical care and first aid: an interassociation consensus framework for organised non-elite sport during the COVID-19 pandemic.” Hodgson L, Phillips G, Saggers RT, et al. British Journal of Sports Medicine, February 2021.

“The ongoing prevalence of SARS-CoV-2 and subsequent ‘second waves’ require urgent best practice guidelines to be developed to return recreational (non-elite) sports as quickly as possible while prioritising the well-being of the participants and support staff.”

• “Familial Evaluation in Idiopathic Ventricular Fibrillation: Diagnostic Yield and Significance of J Wave Syndromes.” Mellor GJ, Blom LJ, Groeneveld SA, et al. Circulation: Arrhythmia and Electrophysiology, March 2021.

“The yield of family screening in relatives of IVF [idiopathic ventricular fibrillation] probands is low when the proband is comprehensively investigated. The significance of J wave syndromes in relatives and the role for systematic sodium channel blocker provocation are, however, uncertain and require further research.”

• “Multi-catheter cryotherapy compared with radiofrequency ablation in long-standing persistent atrial fibrillation: a randomized clinical trial.” Gallagher MM, Yi G, Gonna H, et al. Europace, March 2021.

“Multi-catheter cryotherapy can restore SR [sinus rhythm] by ablation alone in more cases and more quickly than RF [radiofrequency] ablation. Long-term success is difficult to achieve by either methods and is similar with both.”

• “Innovative Cardiac Resynchronization: Deployable Lead as an Anchor to Facilitate Guidewire Advancement.” Akhtar Z, Chen Z, Leung LWM, et al. Journal of the American College of Cardiology. Case Reports, March 2021.

• “Finding the heart of the problem: A letter to the editor on ‘Detection of oesophageal course during left atrial ablation’ by Santoro et al.” Leung LW, Akhtar Z, Gallagher MM. Indian Pacing and Electrophysiology Journal, March-April 2021.

• “Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.” van Buuren F, Gati S, Sharma S, et al. European Journal of Preventive Cardiology, April 2021.

“This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals.”

• “EAPC Core Curriculum for Preventive Cardiology.” Wilhelm M, Abreu A, Adami PE, et al. European Journal of Preventive Cardiology, April 2021.

“This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe.”

• “Percutaneous management of lead-related cardiac perforation

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Papers/Articles with limited use of computed tomography and cardiac surgery.”

Elbatran AI, Akhtar Z, Bajpai A, et al. Pacing and Clinical Electrophysiology, April 2021.

• “Future of preventive cardiology: EAPC vision 2020-22.” Halle M, Davos CH, Dendale P, et al. European Journal of Preventive Cardiology, May 2021.

• “Prolonged QT predicts prognosis in COVID-19.” Akhtar Z, Gallagher MM, Yap YG, et al. Pacing and Clinical Electrophysiology, May 2021.

“Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc).”

• “Leadless cardiac resynchronization therapy: a distant Utopia.”

Akhtar Z, Leung LWM, Sohal M, et al. Europace, May 2021.

• “Genetics and genomics of arrhythmic risk: current and future strategies to prevent sudden cardiac death.” Scrocco C, Bezzina CR, Ackerman MJ, et al. Nature Reviews. Cardiology, May 2021.

“In this Review, we assess the current understanding of the epidemiology and causes of SCD and evaluate both the monogenic and the polygenic contributions to the risk of SCD in the young and SCD associated with drug therapy. Finally, we analyse the potential clinical role of genomic testing in the prevention of SCD in the general population.”

• “Cardiac magnetic resonance in patients with ARVC and family members: the potential role of native T1 mapping.” Georgiopoulos G, Zampieri M, Molaro S, et al. The International Journal of Cardiovascular Imaging, June 2021.

“This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 firstdegree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping.”

• “2020 APHRS/HRS expert consensus statement on the investigation of decedents with sudden unexplained death and patients with sudden cardiac arrest, and of their families.” Stiles MK, Wilde AAM, Abrams DJ, et al. Journal of Arrhythmia, June 2021.

• “The labyrinth of nomenclature in Cardiology. Eternal dilemmas and new challenges on the horizon in the personalized medicine era.”

Finocchiaro G, Sinagra G, Papadakis M, et al. European Journal of Heart Failure, July 2021.

• “The heart of the ageing endurance athlete: the role of chronic coronary stress.” Parry-Williams G, Gati S, Sharma S. European Heart Journal, July 2021.

“Studies in lifelong male athletes aged above 40 years old show a higher prevalence of high coronary artery calcium scores (>300 Agatston units), a higher coronary plaque burden, and myocardial fibrosis compatible with subclinical myocardial infarction compared with relatively sedentary healthy controls, raising speculation that

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lifelong intense exercise imposes chronic coronary stress on the heart.

This review article will provide a critical analysis of the existing data.”

• “Arrhythmogenic potential of myocardial disarray in hypertrophic cardiomyopathy: genetic basis, functional consequences and relation to sudden cardiac death.” Finocchiaro G, Sheikh N, Leone O, et al.

Europace, July 2021.

• “Age matters: differences in exercise-induced cardiovascular remodelling in young and middle aged healthy sedentary individuals.”

Torlasco C, D’Silva A, Bhuva AN, et al. European Journal of Preventive Cardiology, July 2021.

“Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing.”

• “Cardiac hypertrophy at autopsy.” Basso C, Michaud K, d’Amati G, et al. Virchows Archiv: An International Journal of Pathology, July 2021.

“Since cardiac hypertrophy may be considered a cause of death at autopsy, its assessment requires a uniform approach. Common terminology and methodology to measure the heart weight, size, and thickness as well as a systematic use of cut off values for normality by age, gender, and body weight and height are needed.”

• “An updated approach to sudden cardiac death, the AECVP perspective.” Michaud K, van der Wal AC, Banner J, et al. International Journal of Legal Medicine, July 2021.

• “The anti-cancer drug dabrafenib is not cardiotoxic and inhibits cardiac remodelling and fibrosis in a murine model of hypertension.”

Meijles DN, Cull JJ, Cooper STE, et al. Clinical Science (London, England: 1979), July 2021.

• “Management of Congenital Long-QT Syndrome: Commentary From the Experts.” Kaufman ES, Eckhardt LL, Ackerman MJ, et al.

Circulation. Arrhythmia and Electrophysiology, July 2021.

“We explored the diversity of opinion among 24 clinicians with expertise in long-QT syndrome. Experts from various regions and institutions were presented with 4 challenging clinical scenarios and asked to provide commentary emphasizing why they would make their treatment recommendations.”

• “The use of cardiac imaging in the evaluation of athletes in the clinical practice: A survey by the Sports Cardiology and Exercise Section of the European Association of Preventive Cardiology and University of Siena, in collaboration with the European Association of Cardiovascular Imaging, the European Heart Rhythm Association and the ESC Working Group on Myocardial and Pericardial Diseases.”

D’Ascenzi, Anselmi F, Mondillo S, et al. Circulation. Genomic and Precision Medicine, July 2021.

“This survey aimed to map the use of imaging in the setting of [pre-participation evaluation] PPE and explore physician beliefs and potential barriers that may influence individual practices.”

• “Genotype-Phenotype Correlation of SCN5A Genotype in Patients Research Highlights 2021

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Papers/Articles With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands.” Milman A, Behr ER, Gray B, et al.

Circulation. Genomic and Precision Medicine, August 2021.

• “Biventricular Myocardial Fibrosis and Sudden Death in Patients With Brugada Syndrome.” Miles C, Asimaki A, Ster IC, et al. Journal of the American College of Cardiology, October 2021.

• “Return to play with hypertrophic cardiomyopathy: are we moving too fast? A critical review.” Drezner JA, Malhotra A, Prutkin JM, et al.

British Journal of Sports Medicine, September 2021.

“This study sought to characterize the presence and distribution of ventricular myocardial fibrosis in a cohort of decedents experiencing sudden cardiac death caused by BrS.”

“This review explores the potential harms and benefits of sports disqualification in athletes with HCM and details the challenges and limitations of shared decision-making when all parties may not agree.”

• “Sudden Death in Female Athletes: Insights From a Large Regional Registry in the United Kingdom.” Finocchiaro G, Westaby J, Bhatia R, et al. Circulation, November 2021.

• “Role of subcutaneous implantable loop recorder for the diagnosis of arrhythmias in Brugada syndrome: A United Kingdom single-center experience.” Scrocco C, Ben-Haim Y, Devine B, et al. Heart Rhythm, September 2021.

• “Risk of atrial fibrillation in athletes: a systematic review and metaanalysis.” Newman W, Parry-Williams G, Wiles J, et al. British Journal of Sports Medicine, November 2021.

• “Higher spatial resolution improves the interpretation of the extent of ventricular trabeculation.” Riekerk HCE, Coolen BF, Strijkers GJ, et al. Journal of Anatomy, September 2021.

“In conclusion, higher spatial resolution may affect the sensitivity of diagnostic measurements and in addition could allow for novel measurements such as counting of trabeculations.”

• “Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.”

Finocchiaro G, Barra B, Molaro S, et al. The international journal of cardiovascular imaging, September 2021.

• “The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.” Belhassen B, Laredo M, Roudijk RW, et al. Europace, September 2021.

“In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics.”

• “Supraventricular Tachycardia Causing Left Ventricular Dysfunction.” Zaffalon D, Pagura L, Cannatà A, et al. The American Journal of Cardiology, November 2021.

“There is limited evidence on characterization and natural history of supraventricular tachycardia (SVT)-induced left ventricular (LV) dysfunction. The aim of this work was to characterize clinical features and long-term evolution of SVT-induced LV dysfunction.”

• “Hourly variability in outflow tract ectopy as a predictor of its site of origin.” Waight MC, Li AC, Leung LW, et al. Journal of Cardiovascular Electrophysiology, November 2021.

“Before ablation, predicting the site of origin (SOO) of outflow tract ventricular arrhythmia (OTVA), can inform patient consent and facilitate appropriate procedural planning. We set out to determine if OTVA variability can accurately predict SOO.” • “Athletes with valvular heart disease and competitive sports: a position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology.” van Buuren F, Gati S, Sharma S, et al. European Journal of Preventative Cardiology, December 2021.

• “Preventing esophageal complications from atrial fibrillation ablation: A review.” Leung LWM, Akhtar Z, Sheppard MN, et al. Heart Rhythm O2, September 2021.

“This article provides an overview of the recommendations from the Sports Cardiology section of the European Association of Preventive Cardiology on sports participation in individuals with valvular heart disease (VHD). The aim of these recommendations is to encourage regular physical activity including sports participation, with reasonable precaution to ensure a high level of safety for all affected individuals.”

• “Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands.” Milman A, Behr ER, Gray B, et al.

Circulation. Genomic and precision medicine, October 2021.

• “Results of a nationally implemented cardiac screening programme in elite cricket players in England and Wales.” MacLachlan H, Dhutia H, Bhatia R, et al. Journal of Science and Medicine in Sport, December 2021.

“Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event.”

“We assessed the diagnostic yield and costs of an electrocardiogrambased national screening programme in elite cricket players and the incremental value of transthoracic echocardiography and periodic evaluation.”

For a full list of CRY’s research visit www.c-r-y.org.uk/research/crys-contribution-to-research 8

Research Highlights 2021

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Professor Sanjay Sharma, CRY Consultant Cardiologist The CRY Research Programme is overseen by Professor Sanjay Sharma, Professor of Inherited Cardiovascular Disease and Sports Cardiology at St George’s Hospital, London; Virgin Money London Marathon Medical Director; and the London 2012 Olympic Cardiologist.

The CRY Research Fellowship Programme funds doctors for up to three years who choose to specialise in the fields of inherited cardiac diseases, young sudden cardiac death, screening and sports cardiology. It is our unique expertise in sports cardiology and how athleticism, ethnicity and gender affect the ECG that has made CRY a leading international authority on cardiac screening. “Sports cardiology” is cardiac research and clinical practice applied to fit and healthy

young people. The knowledge gained from studying athletes better informs the diagnosis and management of all young people at risk from cardiac conditions.

CRY’s Research Fellows at St George’s Hospital divide their time between NHS clinics, CRY screenings and research. As well as the Fellows CRY are currently funding, more than 30 former Fellows have been trained as specialists by CRY and are now working in the NHS throughout the UK, and many more have received international grants to return to hospitals around the world.

Professor Sharma oversees the CRY National Screening Programme in which the CRY Research Fellows play a central role. Every person that CRY tests is asked to consent to having their data used anonymously for research purposes. This has developed a symbiotic relationship between research and screening; identifying young individuals at risk whilst learning from our experience and publishing these findings.

CRY’s Research Programme CRY research has shown: • Every week in the UK at least 12 young people die of undiagnosed heart conditions (Papadakis M et al. 2009) • 1 in 300 young people that CRY tests will have a potentially life-threatening heart condition (Wilson MG et al. 2008)

Transforming the way we understand the causes and incidence of young Causes sudden cardiac death.

Transforming the way we prevent young sudden cardiac deaths Prevention and save young lives.

• 80% of SADS deaths occur at rest or during sleep (Mellor G et al. 2014)

Treatment

• ARVC is the cardiac condition most likely to cause sudden death during exercise (Finocchiaro G et al. 2016)

Transforming treatment for young people who are living with cardiac conditions.

In 2021 29.5% of CRY’s funding supported research CRY research grants fund fast-track, expert referral services at the CRY Centre for Cardiac Pathology (CRY CCP) and the CRY Centre for Inherited Cardiovascular Conditions and Sports Cardiology.

Research 29.5% Support 12.5% Screening 23.5%

Awareness 16.5%

CRY research grants fund original research using data gathered from the CRY Centres and through the CRY National Screening Programme.

CRY research grants fund clinical doctors who are present at every CRY screening event to examine the results of young people tested and provide a consultation on the same day.

Governance 3% Fundraising In 2021, CRY received significant contributions to support our research team in memory of: 15%

Kyle Hancock Bruce Cousins Laura Hillier Jake Dean Due to the anticipated impact of COVID-19 on Stewart Howard fundraising in 2020/2021 CRY reduced the Matthew number of research fellowship grants awarded.

Kieran Joyce Dewhirst Eleanor Keeler Adam Donnelly Neil Bradbury Tiffany Andrews Joe Kellogg Josh Fell David Bramwell Gideon Baws Graeme Jannik Lam Richard Brember Anthony Fitzgerald Blenkinsop Jonathan Leigh Ben Forsyth Jordan Burndred Ian Bowen Alan Lumley Shamil Hamid Nathan Butler

Cardiac Risk in the Young

Amy Osborne Andrew Macleod Robert Poysor Jack Maddams Alex Reid James Markham James McGowan Suanu Saro-Wiwa Mike Scott Richard Merriman Robert Smith Adam Middleton Jonathan Morgan Philip Standing Ryan Terry Bethany Mycroft Andrew Oliver

Scott and Mike Thurlow Ryan Tilley Fraser Vaughan Neil Ward George Watson Julian Wort Sam Wright

Research Highlights 2021

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