Cardiac Rhythm News 41 – May 2018 EU edition

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Apixaban is a safe alternative to warfarin during catheter ablation of atrial fibrillation and may have a positive effect on cognitive function

Leslie Saxon:

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Apixaban and warfarin are equally safe during catheter ablation of atrial fibrillation, according to results of the AXAFA-AFNET 5 (Anticoagulation using the direct factor Xa inhibitor apixaban during Atrial Fibrillation catheter Ablation: Comparison to vitamin K antagonist therapy) (German Atrial Fibrillation NETwork (AFNET)) trial presented at European Heart Rhythm Association Congress (EHRA; 18–20 March 2018, Barcelona, Spain). There were similar rates of stroke and bleeding, and an improvement in cognitive function was shown for the first time.

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he AXAFA-AFNET 5 trial was the first randomised trial to examine whether continuous apixaban is a safe alternative to a vitamin K antagonists (VKA) during catheter ablation of atrial fibrillation and effective in the prevention of peri-procedural complications such as death, stroke, and major bleeding events. A total of 633 patients with atrial fibrillation and additional stroke risk factors scheduled to undergo atrial fibrillation ablation in Europe and the USA were randomised to receive either continuous apixaban or the locally used VKA (warfarin, phenprocoumon, acenocoumarol, or fluindione).

The study participants received the medicine for at least 30 days prior to the planned catheter ablation procedure and medication was continued for three months after the ablation procedure. All patients were treated following the current guidelines at the time.

The primary outcome was a composite of all-cause death, stroke, and major bleeding up to three months after ablation. The primary outcome occurred in 22 patients randomised to apixaban and 23 randomised to VKA. Paulus Kirchhof, international chief investigator of the trial, said: “The results show that apixaban is a safe alternative to warfarin during catheter ablation of atrial fibrillation in patients

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at risk of stroke.”

The researchers assessed cognitive function using the Montreal Cognitive Assessment test at the beginning and end of the trial and found a small but statistically significant improvement in cognitive function; it improved equally in both treatment groups. Kirchhof said: “This is the first randomised trial to show that cognitive function is improving after atrial fibrillation ablation. It is possible that this is due to continuous anticoagulation, although we did not test this specifically.”

A magnetic resonance imaging substudy in 335 patients showed a similar rate of silent strokes in the apixaban (27%) and VKA (25%) groups. Use of brain magnetic resonance imaging (MRI) was a unique feature of this study and was carried out in more than half of the study patients within 48 hours after ablation to quantify procedure-related acute ischaemic brain lesions. The results of the brain MRI substudy demonstrated no significant difference in clinically silent acute brain lesions between the treatment arms.

Kirchhof noted that patients in the trial were four years older than participants of previous studies with the non-vitamin K oral anticoagulants (NOACs) rivaroxaban and dabigatran.

Other features of the trial were that local investigators chose the VKA and catheter ablation procedure which

led to the use of a variety of drugs and techniques. He said: “These characteristics of the trial mean that the results apply to older patients and in different clinical settings.”

Kirchhof added: “The bleeding rate was half of what we have expected, with 22 patients experiencing events on apixaban, and 23 on VKAs, and there was a remarkably low rate of stroke, with only two events being observed in the trial (0.3%). In addition, seven episodes of cardiac tamponade–two with apixaban and five with a VKA–were managed with drainage, without the need for antidotes.”

Atrial fibrillation is associated with a high risk of stroke. Most patients with atrial fibrillation need anticoagulation therapy using VKAs or NOACs and around 5-15 % of the patients suffering from AF undergo catheter ablation treatment. During and after the ablation procedure they require anticoagulation to reduce the risk of procedure-associated stroke. Factor Xa inhibitors and direct thrombin inhibitors are new oral anticoagulants (NOACs) that provide an alternative treatment to vitamin K antagonists (VKAs) for stroke prevention in AF. Their use has previously been evaluated in several large clinical trials. Until now whether NOACs can be used in the setting of catheter ablation of AF had not been examined.

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AF detection with smarttechnology achieved >95% accuracy

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Stroke prevention drugs may help reduce dementia risk for atrial fibrillation patients, consensus document finds Patients with atrial fibrillation could reduce the risk of dementia by taking stroke prevention medications, according to recommendations from an international consensus document presented EHRA 2018.2 The international consensus document was published in EP Europace, HeartRhythm and the Journal of Arrhythmia.1

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he expert consensus statement on arrhythmias and cognitive function was developed by the European Heart Rhythm Association (EHRA), a branch of the European Society of Cardiology (ESC); the Heart Rhythm Society (HRS); the Asia Pacific Heart Rhythm Society (APHRS); and the Latin American Heart Rhythm Society (LAHRS).

Heart rhythm disorders (arrhythmias), as well as some procedures undertaken to treat them, can increase the risk of cognitive decline and dementia. The international consensus document was written for doctors specialising in arrhythmias and aims to raise awareness of the risks of Continued on page 2

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Stroke prevention drugs may help reduce dementia risk for atrial fibrillation patients, consensus document finds Continued from page 1

cognitive impairment and dementia and how to reduce them.

The document states that atrial fibrillation is associated with a higher risk for cognitive impairment and dementia, even in the absence of apparent stroke. This may be because atrial fibrillation is linked with a more than two-fold risk of silent strokes. The accumulation of silent strokes and the associated brain injuries over time may contribute to cognitive impairment.

Stroke prevention with oral anticoagulant drugs is the main priority in the management of patients with atrial fibrillation. The consensus document says that oral anticoagulation may reduce the risk of dementia.

Adopting a healthy lifestyle may also reduce the risk of cognitive decline in patients with atrial fibrillation. This includes not smoking and preventing or controlling hypertension, obesity, diabetes, and sleep apnea.

“Patients with atrial fibrillation may be able to reduce their risk of cognitive impairment and dementia by taking their oral anticoagulation medication and having a healthy lifestyle,” said Nikolaos Dagres, lead author and consultant, Department of Electrophysiology, Heart Centre Leipzig, Germany.

The document also reviews the association between other arrhythmias and cognitive dysfunction, including post-cardiac arrest, in patients with cardiac implantable devices such as implantable cardioverter defibrillators (ICDs) and pacemakers, and ablation procedures.

Editors-in-chief:

Treatment of atrial fibrillation with catheter ablation can itself lead to silent strokes and cognitive impairment. To reduce the risk, physicians should follow recommendations for performing ablation and for the management of patients before and after the procedure.3,4 The consensus document notes that physicians may suspect cognitive impairment if a patient’s appearance or behaviour changes—for example, if appointments are missed. Family members should be asked for collateral information. If suspicions are confirmed, the consensus document recommends tools to conduct an objective assessment of cognitive function.

The paper highlights gaps in knowledge and areas for further research. These include, for instance, how to identify atrial fibrillation patients at increased risk of cognitive impairment and dementia, the effect of rhythm control on cognitive function, and the impact of cardiac resynchronisation therapy (CRT) on cognitive function.

References 1. Dagres N, 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 on arrhythmias and cognitive function: what is the best practice? Europace. 2018. doi: 10.1093/europace/euy046.

2. EHRA 2018 session: Arrhythmias and cognitive impairment on 19 March 3. Kirchhof P, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–2962. doi:10.1093/eurheartj/ ehw210 4. Calkins H, et al. 2017 HRS/EHRA/ECAS/APHRS/ SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: Executive summary. Europace. 2018;20(1):157–208. doi: 10.1093/europace/eux275.

Binge drinking affects heart rhythm A new study has found that the more alcohol you drink, the higher your heart rate gets. Theses finding were presented at European Heart Rhythm Association Congress (EHRA; 18–20 March 2018, Barcelona, Spain).

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he Munich Beer Related Electrocardiogram Workup (MunichBREW) study was conducted by researchers from the LMU University Hospital Munich, Department of Cardiology (Germany), supported by the German Cardiovascular Research Centre (DZHK) and the European Commission. It was the first assessment of the acute effects of alcohol on electrocardiogram (ECG) readings. The study included more than 3,000 people attending the 2015 Munich Oktoberfest.

ECG readings were taken and breath alcohol concentrations were measured. Age, sex, heart disease, heart medications, and smoking status were recorded. Participants were, on average, 35 years old and 30% were women. The average breath alcohol concentration was 0.85g/kg. Increasing breath alcohol concentration was significantly associated with sinus tachycardia of more than 100 beats per minute in 25.9% of the cohort.

The current analysis of the MunichBREW study looked in more detail at the quantitative ECG measurements in 3,012 participants.

The researchers investigated the association between blood alcohol concentration and four ECG parameters: excitation (heart rate), conduction (PR interval, QRS complex), and repolarisation (QT interval).

Increased heart rate was associated with higher breath alcohol concentration, confirming the initial results of the MunichBREW study. The association was linear, with no threshold. Alcohol consumption had no effect on the other three parameters.

“The more alcohol you drink, the higher your heart rate gets,” said Stefan Brunner, a cardiologist at the University Hospital Munich, Munich, Germany, who is one of the

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paper's lead authors.

The researchers are currently investigating whether the increase in heart rate with alcohol consumption could lead to heart rhythm disorders in the longer-term.

Moritz Sinner, another lead author, said: “We cannot yet conclude that a higher heart rate induced by alcohol is harmful. But people with heart conditions already have a higher heart rate, which in many cases triggers arrhythmias, including atrial fibrillation.

So it is plausible that the higher heart rate following alcohol consumption could lead to arrhythmias.”

He added, “Most people in our study were young and healthy. If we conducted the same study in older people or heart patients we might have found an association between drinking alcohol and arrhythmias.”

The authors speculated that alcohol creates an imbalance between the sympathetic (fight or flight) and parasympathetic (rest and digest) nervous systems.

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Conference coverage

European Sudden Cardiac Arrest network will look at gender-based prevention and treatment Researchers will use a European network of 90,000 patients, including 20,000 DNA samples, to look at different approaches for prevention and treatment of sudden cardiac arrest for men and women.

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udden cardiac arrest is the consequence of the heart rhythm disorder ventricular fibrillation, and there are around 400,000 cases a year in Europe. If left untreated it is deadly within minutes and survival rates are just 5–20%, meaning that there is a large medical need to improve sudden cardiac arrest outcomes, including prevention and treatment.

Designing effective individualised prevention and treatment strategies requires knowledge on inherited, acquired, and environmental risk factors.

So far, these efforts have been hampered by the lack of sufficiently large study cohorts of sudden cardiac arrest patients with detailed information. Obtaining sudden cardiac arrest patient samples is challenging as the condition happens suddenly and unexpectedly.

The European Suddent Cardiac Arrest network (ESCAPE-NET) has pooled the patient populations of 16 organisations across Europe. The resulting database of sudden cardiac arrest in the community is sufficiently large to study causes, treatments and prevention strategies (such as AED [automated external defibrillator], lay rescuers and ventricular fibrillation analysis based resuscitation), and how these vary between women and men.

The main aims of the ESCAPE-NET project are to build a database of over 90,000 sudden cardiac arrest patients including 20,000 DNA samples of them, by combining existing European databases and infrastructures, to identify risk factors (inherited, acquired, environmental) and first-response treatment strategies that may explain the differences

in sudden cardiac arrest occurrence and survival between European countries, and to collaborate with professional networks, such as the European Heart Rhythm Association and European Resuscitation Council, to translate the outcomes into European clinical practice for the prevention of sudden cardiac arrest, and European infrastructures to improve survival after sudden cardiac arrest.

The electrical properties of the heart differ between men and women. The heart beats by an electrical conduction system in which the movement of potassium ions back and forth across channels in the membranes of heart cells plays an important role. Women have fewer potassium channels than men.

Commonly prescribed drugs that work by blocking ion channels can increase the risk of ventricular fibrillation and sudden cardiac arrest. For potassium channel blockers, such as selective serotonin reuptake inhibitors (SSRIs) for depression, antibiotics including erythromycin, antifungal medications, and domperidone, the increased risk of sudden cardiac arrest may be larger in women.

“Doctors want to know when these drugs can be safely prescribed in women in general, and to which individual with her specific set of inherited and acquired risk factors, in particular,” said Hanno Tan, ESCAPE-NET project leader and cardiologist, Academic Medical Centre, Amsterdam, the Netherlands.

One of the aims of ESCAPE-NET is to create a

risk score that includes age, sex, comorbidities and genetic profile. Doctors will be able to use the score to determine the risk, for example, of prescribing erythromycin for a female patient.

Tan said, “We think that sudden cardiac arrest is caused by the interaction of various risk factors.

Our research will uncover which factors are relevant in women and men and use this information to develop a risk score.”

There is also evidence that women are more likely to die from sudden cardiac arrest than men because they are less likely to be resuscitated by a bystander.

This appears to be due to sociological factors rather than biological sex. For example, women are more likely to be living alone because they have outlived their spouse. Such factors alone, however, cannot fully explain the difference between men and women. Thus, biological factors must also play a role.

ESCAPE-NET will identify specific reasons for differences in survival between men and women and which factors might be changed.

Tan said: “The major strength of ESCAPE-NET is the large number of patients. These cohorts are normally very difficult to collect because sudden cardiac arrest occurs quickly and unexpectedly.”

The European Sudden Cardiac Arrest network is backed by the European Heart Rhythm Association (EHRA), a branch of the European Society of Cardiology (ESC), and the European Resuscitation Council (ERC).

ESCAPE-NET has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No° 730731.

Analysis of the BRUISE CONTROL 1 and 2 trials shows no difference in clinically significant haematoma between DOACs and warfarin In a multivariate analysis including both BRUISE CONTROL 1 and BRUISE CONTROL 2 patients and adjusted for antiplatelet use, there was no difference in clinically significant haematoma between direct oral anticoagulants (DOACs) and warfarin.

Oral anticoagulant use is common among patients requiring pacemakers or defibrillator surgery. The Bridge or Continue Coumadin for Device Surgery Randomised Controlled (BRUISE CONTROL) trial demonstrated 80% fewer device pocket haematomas when surgery was performed without interruption of warfarin, compared to warfarin treated patients who had their anticoagulation interrupted and received heparin bridging but since the publication of the first BRUISE CONTROL trial the use of DOACs has drastically increased and they are now used in the majority of patients with atrial fibrillation. This led to the Strategy of Continued Versus Interrupted Novel Oral Anti-coagulant at Time of Device Surgery in Patients With Moderate to High Risk of Arterial

Thromboembolic Events (BRUISECONTROL 2) trial.

BRUISECONTROL 2 showed that the rates of clinically significant haematoma were the same in both continued and interrupted DOAC groups.

Device pocket haematomas have a significant impact on patients as it may be necessary to stop anticoagulation for a prolonged period of time, increasing the risk of thromboembolism and serious device system infection.

Both trials were multicentre singleblind randomised control trials. To be eligible for the BRUISE CONTROL 1 trial patients had to have a ≥5% annual predicted risk of thromboembolisms, be taking warfarin and be undergoing non-emergency device related surgery.

During treatment the continued-warfarin arm had a targeted INR of 3 or

less, except for patients with mechanical valves, their target INR was 3.5 or less. Patients in the heparin-bridge arm discontinued warfarin five days prior to procedure and started therapeutic heparin three days before the procedure. Heparin was restarted 24 hours post procedure and continued until a therapeutic INR was reached.

BRUISE CONTROL 2 patients were treated with dabigatran, rivaroxaban or apixaban and had a CHA2DS2-VASc score of ≥2. They were randomised to continued or interrupted DOAC. Patients in the continuous DOAC arm had their DOAC continued throughout the surgical period and took their morning dose prior to surgery. Those in the interrupted DOAC arm on rivaroxaban or apixaban had their drug discontinued after taking their last dose two days before surgery. Patients on dabigatran discontinued the drug at a time interval dependent on their glomerular filtration rate. All three drugs were resumed at the next regular dose

timing after 24 hours post-surgery.

In both studies the primary outcome was clinically significant haematoma, requiring surgery, resulting in prolonged hospitalisation or requiring interruption of anticoagulation for more than 24 hours.

To carry out the analysis the investigators were blinded. Each centre was required to identify two patient care teams. The unblinded team, had knowledge of treatment allocation and was responsible for device implantation and the blinded team, had no knowledge of treatment allocation and was responsible for diagnosing, following and making decision on haematomas.

The results show almost a doubling of clinically significant haematoma in the single/dual antiplatelet group compared to no antiplatelet. The multivariable analysis looked at the predictors of haematoma. When bridging with heparin, compared to continued warfarin there was a six-fold increase in the rate of haematoma and there was no significant difference with DOAC use compared to continuous warfarin. The study also found that those with diabetes had a lower rate of haematoma, which the investigators say is worth of further exploration. Significantly, they found that antiplatelet use doubled the rate of haematoma.

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Guidelines

New guidelines for anticoagulants and syncope launched at EHRA At European Heart Rhythm Association 2018 (EHRA; 18–20 March, Barcelona, Spain) two new guidelines were launched: one was the third edition of the EHRA Practical Guide on the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation, and the other was the European Society of Cardiology guidelines on syncope.

New practical guide on nonvitamin K antagonist oral anticoagulants

The third edition of the EHRA Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation has been published online in the European Heart Journal and an executive summary in EP Europace, and was presented at EHRA 2018.

“ESC [European Society of Cardiology] guidelines state that NOACs should be preferred over vitamin K antagonists, such as warfarin, for stroke prevention in patients with atrial fibrillation, except those with a mechanical heart valve or rheumatic mitral valve stenosis, and their use in clinical practice is increasing,” said first author Jan Steffel (Senior consultant in Cardiology, University Hospital Zurich, Switzerland).

The 2018 edition has several new chapters, including how to use NOACs in particular groups of patients, such as those with very low body weight, the very obese, athletes, frail patients where there are concerns about bleeding, and patients with cognitive impairment who may forget to take their pills.

The guide gives practical advice on how to use NOACs in specific clinical situations, with chapters on areas including patient eligibility for NOACs, ensuring adherence to prescribed oral anticoagulant intake

combined use of antiplatelets and NOACs in patients with coronary artery disease, particularly those with an acute coronary syndrome or patients scheduled for percutaneous coronary intervention with stenting. “We provide guidance around which and how many antiplatelets, for how long, with which NOAC, and at what dose of that NOAC,” said Heidbuchel.

There is also more scientific evidence on the use of anticoagulants around cardioversion. The document gives detailed advice on what to do in patients on long-term NOAC treatment who need cardioversion versus patients newly diagnosed with atrial fibrillation and started on a NOAC before cardioversion.

Since the previous edition of the guide was published, the first NOAC reversal agent has received market approval. Advice is given on how to use idarucizumab—which reverses the anticoagulant effect of dabigatran— when there is acute bleeding, when urgent surgery is required, or when the patient has a stroke. Guidance is also

syncope, which include keeping hydrated, avoiding hot crowded environments, tensing the muscles, and lying down. Advice is given on driving for patients with syncope, although the risk of accidents is low.

The document emphasises the value of video recording in hospital or at home to improve diagnosis. It recommends that friends and relatives use their smartphones to film the attack and recovery.

Angel Moya (Arrhythmia Unit, Hospital Vall d’Hebron, P Vall d’Hebron, Barcelona, Spain), Task Force co-chairperson, said, “There of the NOAC could be measured just are clinical clues, such as the duration before surgery to confirm that the of the loss of consciousness, whether anticoagulant effect has waned. the patient’s eyes are open or closed, The chapter on drug-drug and jerky movements, that can help interactions has been expanded with distinguish between syncope, epilepsy, anticancer and antiepileptic drugs, or other conditions.”

Steffel added, “While this is mostly Another diagnostic tool is the based on potential pharmacokinetic implantable loop recorder, a small interactions and case reports, it is the device inserted underneath the skin first of its kind. This is likely to be of the chest that records the heart’s adapted and become more complete electrical signals. The guidelines over the years as our experience recommend to extend its use for increases at this new frontier.” diagnosis in patients with unexplained falls, suspected epilepsy, or recurrent European Society of episodes of unexplained syncope and a Cardiology guidelines on low risk of sudden cardiac death. syncope launched A new section has been added to European Society of Cardiology the guidelines, as an addendum, with guidelines on syncope were launched at practical instructions for doctors on EHRA 2018 and published online in the how to perform and interpret diagnostic European Heart Journal. tests.

The challenge for doctors is to Brignole said, “The Task Force identify the minority of patients whose that prepared the guidelines was syncope is caused by a potentially truly multidisciplinary. A minority of deadly heart problem. The guidelines cardiologists were joined by experts recommend a new algorithm for in emergency medicine, internal emergency departments to stratify medicine and physiology, neurology and patients and discharge those at low autonomic diseases, geriatric medicine, and nursing.”

Moya added, “Syncope is very common and is usually not lifethreatening. We now have more tools to help us clarify the diagnosis and cause of syncope so that patients with benign forms can be reassured and those at risk of sudden cardiac death can receive treatment.”

Syncope is a transient loss of consciousness caused by risk. Patients at intermediate or high reduced blood flow to the brain. risk should receive diagnostic tests Approximately 50% of people have in the emergency department or an one syncopal event during their outpatient syncope clinic. lifetime. The most common type is Michele Brignole (head of vasovagal syncope, commonly known Cardiology, Arrhythmologic Centre, as fainting, triggered by fear, seeing Osped-ali Tigullio, Lavagna, Italy), blood, or prolonged standing, for Task Force chairperson, said, “The new example. pathway avoids costly hospitalisations These guidelines are endorsed by while ensuring the patient is properly the European Academy of Neurology diagnosed and treated.”

(EAN), the European Federation of Most syncope does not increase Autonomic Societies (EFAS), the the risk of death, but it can cause European Federation of Internal injury due to falls or be dangerous Medicine (EFIM), the European in certain occupations – such as Union Geriatric Medicine Society airline pilots. The guidelines provide (EUGMS) and the European Society recommendations on how to prevent of Emergency Medicine (EuSEM).

The Task Force that prepared the guidelines was truly multidisciplinary. A minority of cardiologists were joined by experts in emergency medicine, internal medicine and physiology, neurology and autonomic diseases, geriatric medicine, and nursing and NOACs in special situations.

Another new chapter briefly summarises the correct dosing of NOACs in conditions other than atrial fibrillation, such as prevention of deep venous thrombosis, treatment of venous thromboembolism, and treatment of ischaemic heart disease.

“The dosing for each condition is different, which may lead to confusion, so we have outlined this clearly,” said senior author Hein Heidbuchel (chair of Cardiology, Antwerp University, Antwerp, Belgium), who initiated the EHRA Practical Guide in 2013 and an update in 2015.

Updated advice is given on the

included on andexanet alfa, another reversal agent expected to receive market approval, with the caveat that the instructions on the label should be followed.

Unlike warfarin, NOACs do not require monitoring of plasma levels followed by dose adjustments. The guide describes rare scenarios in which physicians might want to know the NOAC plasma level. One scenario concerns patients undergoing major surgery in whom it is unclear, for example because of other drugs or renal dysfunction, whether the usual practice of stopping the NOAC 48 hours in advance is sufficient. The plasma level

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Advertorial

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Case report: Usefulness of high resolution mapping with mini-electrodes to select ablation site in complex arrhythmias

By Eduardo Franco, Daniel Rodríguez Muñoz, and Javier Moreno, University Hospital Ramón y Cajal (Madrid, Spain)

Figure 1: High-density electroanatomical map of the tachycardia (lateral view of the right atrium), on RHYTHMIATM mapping system. Left panel: Activation map showing a macroreentrant circuit with a figure-ofeight between the two cavotomy scars. Right panel: Bipolar voltage map (scar threshold: 0.5 mV). In both panels, white dots represent fragmented local electrograms, and green dots represent pacing sites with post-pacing intervals that matched tachycardia cycle length with concealed fusion.

Case description

A 62-year-old woman, with recent sinus venosus atrial septal defect correction surgery, developed a persistent macroreentrant atrial tachycardia and macroreentrant atrial tachycardia (MAT) ablation was performed. The diagnosis of this congenital heart defect was done in a cardiac magnetic resonance imaging scanner, performed after an uneventful percutaneous atrial fibrillation ablation carried out in another centre. The patient underwent open-heart sinus venosus defect closure. Early after cardiac surgery, the patient developed an atrial tachycardia and an ablation procedure was scheduled.

A 24-pole catheter (ORBITER®; Bard Medical) was placed around the tricuspid annulus with its distal part within the coronary sinus. Post-pacing intervals at the coronary sinus and right atrium were consistent with right atrial origin of the tachycardia. Right atrial highresolution activation map performed with the INTELLAMAP ORIONTM 64-poles catheter and RHYTHMIATM navigation system (Boston Scientific, Inc.) showed a macroreentrant circuit with a figure-ofeight involving a broad slow conduction area in the lateral wall of the right atrium (Figure 1): clockwise rotation around the superior vena cava, and counter-clockwise rotation around the inferior vena cava.

The area of slow conduction was located between the two pericaval scars performed at cardiac surgery for extracorporeal circulation, showing phrenic nerve capture along the majority of the line (Figure 2).

Linear ablation between the two cavotomy scars would have been sufficient to terminate the tachycardia, but that would have implied a high risk of phrenic nerve injury. Hence,

high-resolution mapping of this area (previously located with the INTELLAMAP ORIONTM catheter), was done using IntellaTip MIFITM open-irrigated ablation catheter (Boston Scientific, Inc.) in order to localise the critical isthmus of the tachycardia and attempt focal ablation. Spots with the most fragmented signals within the area of slow conduction in the distal dipole of the IntellaTip MIFITM catheter (i.e. potential targets for ablation) were marked in the electroanatomical map (white spots in Figure 1); concealed entrainment with post-pacing intervals that matched tachycardia cycle length was observed from all three locations (green spots in Figure 1).

Mini-electrode signals from these three spots permitted exclusion of false isthmuses (i.e. fragmented electrograms in the distal dipole of the ablation catheter and no fragmented signals in the mini-electrode dipoles, meaning

Figure 2: Activation map of the tachycardia (RHYTHMIATM mapping system, same view as in Figure 1). Spots with phrenic capture (black dots) were located nearly all along the slow conduction area in the lateral wall of the right atrium, between the two cavotomy scars.

fragmentation at the distal dipole was near-field but not local signal) and selection of the true critical isthmus of the tachycardia (i.e. fragmented electrograms in both the distal dipole of the ablation catheter and the mini-

electrode dipoles, meaning local fragmentation at the tip of the ablation catheter). A single application at the most fragmented MiFi electrograms, between the phrenic nerve spots, terminated the tachycardia.

Summary IntellaTip MIFITM open-irrigated ablation catheter has three mini-electrodes within the distal electrode that allows visualisation of the local electrograms at the catheter tip whilst avoiding near-field signals, which sometimes cannot be distinguished using only the conventional distal dipole signal. Concretely, in the field of MAT, precise location of slow conduction spots is of paramount importance as critical isthmuses that perpetuate the tachycardia usually display slow conduction,

represented by fragmented electrograms.

High-density mapping with INTELLAMAP ORIONTM 64-pole catheter and RHYTHMIATM system permits precise documentation of reentrant circuits. Minielectrodes embedded within the IntellaTip MIFITM open-irrigated ablation catheter allow distinguishing between local, near-field and far-field signals. This may help to select the target for focal ablation in complex tachyarrhythmias.

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Devices

Cybersecurity safety communications for implantable cardiac devices: Year in review LESLIE SAXON COMMENT & ANALYSIS Cyber security has become a hot topic in recent years.

Leslie Saxon writes in Cardiac Rhythm News about the cybersecurity risks for implantable cardiac devices.

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n the past year, the US FDA and a division of Homeland Security that responds to and coordinates disclosure of critical infrastructure cybersecurity vulnerabilities issued two cybersecurity Safety Communications for implantable cardiac pacemakers and implantable cardioverter defibrillators (ICD’s) that connect to a secure remote monitoring network using a home communicator.1,2 These addressed devices made by Abbott (formerly St. Jude Medical) and followed FDA’s issuance of post market guidance recommendations for industry for management of cybersecurity in medical devices.2 In total over one million patients were affected.

I chair the Cybersecurity Medical Advisory Board (CSMAB) for Abbott. The CSMAB was formed to provide clinical perspective and advice to the company on the impact of cybersecurity vulnerabilities

along with recommend mitigations on patient care and outcomes.

There are unique aspects of these first cybersecurity advisories that can be generalised to future cybersecurity as well as device hardware safety communications and recommendations. The lessons learned thus far are particularly important because there is no single comprehensive piece of legislation that has become law, establishing medical device cybersecurity standards.3 Most cybersecurity risks for implanted cardiac devices arise from the capability of the devices to communicate wirelessly using radiofrequency or Bluetooth connectivity from locations other than a medical facility. This capability has existed for over 10 years and studies evaluating patient outcomes with devices followed remotely have demonstrated improved patient outcomes,

including significant reductions in hospitalisation, mortality and medical costs.4 Interestingly, remotely collected data has also become the standard for surveillance and management of patients with devices that fall under a recall for a device hardware component malfunction. For these and other reasons, remote monitoring of implantable devices is a recommended standard of care and the promising potential of digitally collected health data and digital health product solutions is a current focus of the FDA .4,5 Although no cyber intrusions or exploits of the devices falling under the above mentioned advisories are known to have occurred, public disclosure of the vulnerabilities from a cybersecurity research firm and a short-selling investment fund led to software and firmware mitigations from Abbott. The mitigations are designed to prevent the potential for intrusions that could directly or indirectly result in patient harm by impacting the programming or essential functions of the device.

The first mitigation consisted of a software patch designed for the home unit that communicates with the implantable device and was deployed in January 2017.

The software patch prevented the communicator from being co-opted to transmit unauthorised commands to the device. The software patch was delivered remotely to approximately 300,000 home

communicators (greater than 80% of actively monitored patients) within two months of release and was not associated with any adverse events.

The second and third mitigations for pacemakers and ICD’s, are firmware upgrades to the actual devices that require a clinic visit and programmer to implement. The firmware upgrade for pacemakers was released in the fall of 2017, and the ICD upgrade in spring of 2018.

To date, the pacemaker ugrades have not been associated with any major adverse effects and no device has been rendered permanently inoperable as a result of the upgrade.

The upgrade has been implemented in approximatey 25% of patients that have had a clinic visit since the Safety Communication was issued. In addition to providing cyberprotections, the ICD firmware upgrade also includes a device-based battery performance alert notification for a subset of ICD’s subject to a 2016 Safety Communication for premature battery depletion.6 These patients are currently under active surveillance with remote monitoring. The alert is designed to provide additional notification of the potential for early battery depletion directly to the patient through the use of a vibratory notifier regardless of remote connectivity.

This year the clinical community has gained experience implementing software patches and firmware upgrades to hundreds of thousands of patients to enhance cybersecurity.

In particular, firmware updates to pacemakers appear to be without significant risk. Firmware updates also provide the opportunity to add additional safety protections for hardware safety issues. As experience accumulates with ICD firmware updates, remotely collected data can be queried to confirm that there are no short or long term risks to these mitigations.

Leslie Saxon is Professor of Medicine, Clincal Scholar Keck School of Medicine, University of Southern California, USA, and Executive Director, USC Center for Body Computing References:

1.U.S. Food and Drug Administration: Cybersecurity Vulnerabilities Identified in St. Jude Medical’s Implantable Cardiac Devices and Merlin@home Transmitter/Firmware Update to Address Cybersecurity Vulnerabilities Identified in Abbott’s (formerly St. Jude Medical’s) Implantable Cardiac Pacemakers: FDA Safety Communication [Internet]. U.S. Food Drug Adm. 2017 [cited 2017 Oct 26], p. 1. Available from: https://www. fda.gov/MedicalDevices/Safety/AlertsandNotices/ ucm553873.htm 2.Postmarket Management of Cybersecurity in Medical Devices Guidance for Industry and Food and Drug Administration Staff Additional Copies [Internet]. Silver Spring, 2016. Available from: https://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ UCM482022.pdf 3.U.S. Senate: Medical Device Cybersecurity Act of 2017 [Internet]. Congress.gov. 2017 [cited 2017 Oct 26].

Available from: https://www.congress.gov/bill/115thcongress/senate-bill/1656 4.Slotwiner D, Varma N, Akar JG, et al.: HRS Expert Consensus Statement on Remote Interrogation and Monitoring for Cardiovascular Electronic Implantable Devices. Hear Rhythm 2015; 12:e69–e100.

5.U.S. Food and Drug Administration: Digital Health Innovation Action Plan [Internet]. U.S. Food Drug Adm. [cited 2018 Jan 5]. Available from: https://www.fda.gov/ downloads/MedicalDevices/DigitalHealth/UCM568735. pdfU.S. 6.Food and Drug Administration: Premature Battery Depletion of St. Jude Medical ICD and CRT-D Devices: FDA Safety Communication [Internet]. U.S. Food Drug Adm. 2016

MOMENTUM 3: Need for surgical intervention reduced after two years with a fully magnetically levitated centrifugal-flow pump In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was found to be superior to a mechanicalbearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device.

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he HeartMate 3 left ventricular assist device (LVAD) markedly reduced the need for more surgery and reduced strokes in patients with advanced heart failure at two years after implantation, according to results of the MOMENTUM 3 trial presented by Mandeep R Mehra (Medical director of Brigham and Women’s Hospital Heart and Vascular Center in Boston, USA) at ACC.18 (ACC; 10–12 March, Orlando, USA). The study was simultaneously published in the New England Journal of Medicine.

The study showed low rates of “suspected” pump thrombosis (1.2%), none confirmed, and there were no reoperations or urgent transplants to replace a malfunctioning pump occurring at two years. The rate of stroke was almost half, compared to the HeartMate II LVAD (10%

vs. 19%).

HeartMate 3 is the first fully implantable heart pump that uses full magnetic levitation technology and has wide blood-flow passages to reduce shear stress, is frictionless with no mechanical bearings and produces an intrinsic pulse to reduce stasis and avert thrombosis. The MOMENTUM 3 study was conducted to ascertain over the long-term whether the HeartMate 3 could optimally support patients who wait for extended periods or are ineligible for heart transplantation.

The MOMENTUM 3 Investigation Device Exemption (IDE) study was a prospective, multi-centre, randomised, unblinded study evaluating the safety and effectiveness of the HeartMate 3 LVAD when used for the treatment of advanced, refractory, left ventricular heart failure.

The study included all-comers, which means researchers evaluated the device regardless of whether the patient needed a short-term support option while awaiting transplantation or a long-term support option for those who are not candidates for cardiac transplantation.

A total of 1,028 patients with New York Heart Association (NYHA) IIIB or IV heart failure at 69 centres in the USA were randomised to surgical implantation with either a HeartMate 3 or HeartMate II LVAD, a mechanical bearing axial continuous-flow blood pump. The primary endpoint was two-year survival free of disabling stroke or reoperation to replace or remove a malfunctioning device.

Six-month outcomes for the first 294 patients enrolled were reported in November 2016.

The current study reports outcomes for 366 patients (HeartMate 3, n=190; Heart Mate II, n=176) who completed two years of follow-up. The primary endpoint of success in the intention-to-treat analysis

was achieved by significantly more patients with HeartMate 3 compared with those with HeartMate II (79.5% vs. 60.2%).

Survival was 82.8% with HeartMate 3 vs.76.2% with HeartMate II (P=0.16).

Freedom from reoperation was achieved by significantly more patients with HeartMate 3 than with HeartMate II (98.4% vs. 83.0%). None of the HeartMate 3 patients had pump thrombosis requiring reoperation, but this was required in 12.2% of HeartMate II patients. Freedom from disabling strokes was similar in both groups (92.8% vs. 92.5%), but significantly more patients with HeartMate 3 vs. HeartMate II were free of any stroke (89.9% vs. 80.8%).

“All of the benefit seen with the HeartMate 3 was in reducing the rate of nondisabling strokes,” Mehra said.

“Disabling stroke was a low-frequency event—occurring in 5–7% of all patients in the trial. The overall stroke rate at two years is the lowest recorded to date in an LVAD trial.”

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Atrial fibrillation

Surgical treatment of atrial fibrillation results in higher complication rates when compared to catheter ablation The total procedure-related complications after surgical minimally invasive pulmonary vein isolations (MIPI) were higher; this was mainly due to more major complications. During a two-year followup there were three transient ischaemic attacks or cerebrovascular accidents after MIPI compared to zero after catheter ablation.

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ead-to-head randomised comparison of primary surgical and catheter ablation has not been performed before. Previous randomised studies comparing surgical and catheter ablation of atrial fibrillation (AF) always included patients with unsuccessful previous catheter ablation. The SCALAF (surgical vs. catheter ablation of paroxysmal and early persistent atrial fibrillation) trial compared surgical and catheter ablation of paroxysmal and early persistent AF. The current European Society of Cardiology/ European Heart Rhythm Society (ESC/EHRA) guidelines recommend both percutaneous catheter ablation and surgical ablation in the treatment of symptomatic drug refractory paroxysmal and early persistent AF with different classes and levels of evidence.

This was the first randomised controlled trial that randomised patients without structural heart disease with symptomatic AF to surgical or percutaneous ablation as a first invasive procedure. The follow-up strategy of this study comprised continuous rhythm monitoring with the use of implantable loop recorders in all patients.

Patients with paroxysmal or early persistent AF were randomised, with a 1:1 ratio, to undergo either percutaneous catheter ablation for pulmonary vein isolation without additional lesion sets or surgical pulmonary vein isolation and left atrial appendage. The primary outcome measure was freedom from atrial tachyarrhythmias off antiarrhythmic drugs and the safety endpoint was

procedure -elated complications.

Eighty patients were enrolled on the trial and received an implantable loop recorder (Reveal XT, Medtronic), leading to a total of 52 patients being randomised to the two groups. A total of 25 MIPI patients were analysed as one was lost to follow-up, 25 catheter patients were also analysed as one was excluded due to a left atrial volume index >50ml/m2.

The trial found that MIPI procedures had a higher procedure-related complication-rate after surgery (34.8% vs. 11.1%) and a higher rate of major complications (22% vs. 0%).

Hospitalisation was also longer for patients receiving surgical ablation with an average hospital stay of 9(6–10) days compared to 3 (2–3) days for catheter ablation.

After two years a significantly greater proportion of patients after percutaneous catheter ablation as compared to surgical pulmonary vein isolation had AF burden <0.5% without the use of antiarrhythmic drugs (60.0% vs. 27.3%, p=0.047).

The investigators concluded that percutaneous isolation of the pulmonary veins in the treatment of paroxysmal and early persistent atrial fibrillation is safer and results in higher long-term arrhythmia free survival compared to surgical pulmonary vein isolation with left atrial appendage ligation. Rhythm follow-up with continuous monitoring using implantable loop recorders is important to obtain the true and accurate outcome of invasive atrial fibrillation treatment.

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Gender impact on arrhythmia

How gender impacts pathophysiology treatment of cardiac arrhythmia CECILIA LINDE COMMENT & ANALYSIS Differences between men and women mean that outcomes after cardiac evenst can differ between the sexes. Cecilia Linde write in Cardiac Rhythm News about a new consensus document that looks to address these issues.

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here is an increasing awareness that sex is a major determinant of the incidence, aetiology and clinical presentation of arrhythmias and that there are sex differences in access and response to arrhythmia therapies. Women traditionally were under-represented in the clinical trials but trial results have been extrapolated to the female population assuming identical results in men and women.

Insufficient knowledge of physiology, epidemiology, and treatment outcome in women have led to lack of sexspecific recommendations and underutilisation of existing guideline-based therapies, in women1. In our document we emphasise when evidence indicates equal management and when the evidence is insufficient which in turn calls for further studies. The women in electrophysiology of the European Heart Rhythm Association (EHRA) chaired by Andrea Sarkosy and committee member Cecilia Linde initiated this consensus document which encompasses a wider range of arrhythmias and which was elaborated by key opinion leaders in the field from Europe, United States and Canada and Japan. We provide an overview of sex differences in the pathophysiology, epidemiology and management of cardiac arrhythmias, to highlight the factors limiting the access to contemporary therapies, and to develop the pathways that may improve quality of medical care in women with cardiac arrhythmias.

Each arrhythmia chapter is ended by key messages, consensus recommendations, gaps of knowledge and ideas for future clinical trials.

The best known sex differences regard the longer QT duration in women compared to men. Even though this difference primarily sets off at puberty and becomes less prominent after menopause, it leads to a higher risk in women for torsade de pointes (Tde) ventricular tachyarrhythmia in the acquired LQT syndrome and in the congenital LQT syndrome. The

document stresses the increased risk for Tde during the peripartum period due to stress and sleep deprivation and that beta-blockers should not be discharged during pregnancy or in the 9â&#x20AC;&#x201C;12 months peripartum period for this reason. In particularly vulnerable patients with QTc>500 ms, a wearable implantable cardiac defibrillators (ICD) could be considered in the absence of guidelines recommendations to prevent sudden cardiac death.

Regarding supraventricular tachyarrhythmia the risk of developing AV-nodal reentry tachycardia (AVNRT) is almost twice as high in women than in men which probably is linked to the shorter slow pathway refractoriness with a wider vulnerability in women.

Orthodromic reentrant tachycardia (ORT) is twice as common in men than in women. This correlates to the doubled incidence of accessory pathways in men as compared to women, and consequently, ventricular fibrillation (VF) due to an antegradely conducting accessory pathway occurs less often in women than men. Quality of life is impaired in all paroxysmal supraventricular tachycardia (PSVT) patients, but women have worse quality of life and suffer more often from tachycardia related anxiety which

in turn increases the risk of being misdiagnosed as panic disorders in women. There is evidence that referral or ablation is therefore delayed in women even though results are equally positive.

Regarding atrial fibrillation (AF) the age-adjusted incidence and prevalence is lower in women. Women with AF are older, have a higher prevalence of hypertension, valvular heart disease, and heart failure with a preserved ejection fraction and a lower prevalence of coronary heart disease in comparison with men.

Women are less likely to undergo rhythm control therapy than men (cardioversion, pulmonary vein (PV) ablation) and more likely to undergo AV-nodal ablation. When treated with antiarrhythmic drugs women are more likely to have life-threatening adverse events and to develop bradycardia and need a pacemaker. Regarding risk for thrombo-embolic disease, female sex is a stroke risk modifier that increases the risk of AF-related stroke in the presence of other conventional stroke risk factors. Female AF patients with acute stroke have a greater stroke severity and worse long-term outcome in terms of permanent disability, compared to males with AF. Anticoagulation with warfarin may be less well controlled in female AF patients, thus affecting the effectiveness of warfarin; moreover, females with AF have a greater . residual stroke risk even with well-controlled vitamin-K anticoagulants (VKAs). The efficacy and safety of non-vintamin-K oral anticoagulants (NOACs) relative to warfarin in the respective pivotal randomised control trails (RCTs) were consistent in both sexes, but females were largely underrepresented in those trials constituting about 20% of enrolled patients. Women with AF are referred for catheter ablation later than men which may reflect that AF occurs later in life in women. Women presenting with AF suffer worse symptoms than men and tend to have a less favourable result by pulmonary vein isolation (PVI).

A balanced proportion of men and women corresponding to the prevalence of the studied disease should be included in RCTs. Regular statistical updates of therapy access and implementation should always be analysed by sex. Female cardiologists should be adequately represented in associations.

Importantly, women suffer significantly more procedural complications from AF ablation including perforation/ tamponade which was recently shown in the EurObservational Research Programme (EORP) registry in Europe.

There is also evidence to suggest that the substrate for AF may differ between sexes and be outside of pulmonary vein (PV) in women which needs further exploration.

Regarding sudden cardiac death (SCD) women have a lower incidence than men, even when accounting for predisposing risk factors such as coronary artery disease (CAD), myocardial infarction (MI) and heart failure (HF). Women are also less likely to have underlying coronary CAD as a risk factor for SCD and more likely than men to have a structurally normal heart, suggesting a sex difference in arrhythmic substrate.

In randomised studies of cardiac resynchronisation therapy (CRT) and implantable cardioverter defibrillators (ICD) women have constituted 20% making it difficult to draw firm conclusions. A common perception is that women benefit less from ICDs and more from CRT. Although women have a lower rate of appropriate shocks than men there is no interaction between treatment effect and sex. For CRT women with wide QRS and left bundle branch block (LBBB) have excellent results of CRT therapy and may derive a benefit at shorter QRS widths than men. Recently, height irrespective of sex has emerged as an important predictive factor of CRT benefit, with shorter persons with wide QRS having the greatest benefit. For antibradycardiapacing the most important knowledge gap is the risks of complications with leadless pacing which have been reported to be higher in women.

Finally, we conclude with suggestions for actions which could help in overcoming the low enrolment of women in trials. A balanced proportion of men and women corresponding to the prevalence of the studied disease should be included in RCTs. Regular statistical updates of therapy access and implementation should always be analysed by sex. Female cardiologists should be adequately represented in associations, steering committees of RCTs, in guideline task forces and scientific documents to ensure gender equality. Female patients should be equally included as patient representatives in such committee and guidelines elaboration.

Cecilia Linde is professor of Cardiology at Theme of Heart and Vessels at the Karolinska University Hospital in Stockholm, Sweden.

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Lead extraction

Patients undergoing lead extraction are more likely to survive superior vena cava tears when treatment includes endovascular balloon A study looking at patients undergoing lead extraction found that they were more likely to survive superior vena cava tears when treatment included the Bridge occlusion balloon. Lead author, Roger Carrillo (University of Miami, Miami, USA) concluded that when used properly the novel device has the potential to save lives.

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he aim of the study, carried out from from July 2016 to December 2017, was to assess the impact of the compliant endovascular balloon on the management of superior vena cava tears and survival outcomes after more than one year in clinical practise.

Each year in the USA there are between 15,000 and 20,000 lead extraction procedures, with 0.46% leading to superior vena cava tears.

The mandatory Manufacturer and User Facility Device Experience (MAUDE) database was used to collect data and additional demographic information was provided by the device manufacture and from telephone interviews with the extracting physician.

The data was then divided into three groups: Balloon cohort, not used/used improperly and non-superior vena cava events. To be included in the balloon cohort and balloon not used/used improperly cohort the superior vena cava tear needed to be surgically confirmed by sternotomy and the tear needed to occur between the innominate vein and right atrium. Patients were excluded if the superior vena cava tear was unconfirmed, the tear that occured was not a superior vena cava tear (e.g. right atrium, right ventricle, innominate vein, subclavian vein, etc) or if surgical repair was not attempted.

During the study period there were 91 confirmed superior vena cava events. In 36 cases an endovascular balloon was used and there were 55 cases where no balloon was used. When an endovascular balloon was used 91.7% of patients survived but when the balloon was not used the survival rate was only 56.4%. The difference was statistically significant (p=0.0003).

There was very little difference between the make-up of the groups, the age, indication for extraction and extraction tools were the same.

The balloon-use cohort were defined as having a stiff guidewire prepositioned from the right femoral vein to either the right internal jugular or right subclavian vein prior to extraction and the wire remained within the vein during deployment. The non-balloon cohort did not use the balloon, or the stiff guidewire was not in the vein during balloon deployment.

The superior vena cava tears occurred in a patient population identified as having a higher risk of complications

The study led to a summary of seven recommendations for best practise: 1) Guidewire: All patients should have a stiff 0.035” guidewire deployed from either femoral vein through the superior vena cava, preferably to the right internal jugular of subclavian vein prior to every lead extraction procedure 2) Introducer sheath: All patients should have either a 6F peel away or 12F femoral vein introducer sheath inserted for introduction of the stiff 0.035” guidewire prior to every lead extraction procedure 3) Immediate deployment: The occlusion balloon and prefilled inflation syringe must be ready for deployment, without delay, as soon as a superior vena cava tear is suspected 4) Tamponade and haemothorax: The occlusion balloon should be immediately deployed when there is evidence of either cardiac tamponade or haemothorax. Intrapericardial superior vena cava tears may also during lead extraction, including female patients (53.4%), as well as patients with implantable cardiac devices (ICDs;51.7%) and older leads (>10 years).

The death rate due to superior vena cava injuries without balloon usage during the study period was consistent with existing finding, at around 44% but balloon use significantly increased the likelihood of survival to 91.7% (p=0.0003).

cause cardiac tamponade.

5) Familiarity: All team member that are part of extraction cases should be familiar with the occlusion balloon and the deployment 6) Competence: Extracting physicians should become competent and comfortable in deployment and inflation of the occlusion balloon in nonemergent settings 7) Prophylaxis: prophylactic “During the procedure,” Carrillo commented, “We learnt that the wire must remain in the vein during the balloon deployment. We also learnt that we had to secure the introducer sheath into the femoral vein and over stiff guidewire prior to lead extraction and that balloon use does not substitute surgical repair.”

The study suggests that continued surveillance is needed to further assess the impact of the endovascular balloon

placement of the occlusion balloon may be considered for reasons including, but no limited to, procedures and patients deemed high risk, new physician practising lead extraction, low volume operators and intraprocedural increase in the perceived risk These recommendation were published in Heart Rhythm. Heart Rhythm. 2017 Oct;14(10):1574-1578.

and that future research should look at identifying risk factors for superior vena cava tears.

The study was limited because of the small sample size due to the rare occurrence of major complications during lead extraction.

Carillo concluded that, “A simple change in workflow and a well-rehearsed team can make a difference in patient safety.”

During the procedure. We learnt that the wire must remain in the vein during the balloon deployment. We also learnt that we had to secure the introducer sheath into the femoral vein and over stiff guidewire prior to lead extraction and that balloon use does not substitute surgical repair.

Roger Carrillo

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Lead extraction

CRT patients undergoing lead extraction are at no higher risk than non-CRT patients

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Transvenous lead extraction in cardiac resynchronisation therapy (CRT) patients is not associated with increased 30-day mortality vs. non-CRT patients. The study found that age, renal impairment and sepsis were independent predictors of 30-day mortality and sepsis was the main cause of 30-day mortality.

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he results of a 16 year singlecentre experience of transvenous lead and system extraction in patients with and without coronary sinus lead were presented by Justin Gould (Guy’s and St Thomas’ Hospital, London, UK and King’s College London, UK) at the European Heart Rhythm Association Congress (EHRA 2018; 18–20 March, Barcelona, Spain).

Transvenous lead extraction can be necessary for many reasons, such as system infection, erosion or lead malfunction. The study hypothesised that CRT patients with coronary sinus leads undergoing transvenous lead extraction are at a greater risk of major complications and 30-day mortality.

Data from all transvenous lead extractions carried out at Guy’s and St Thomas’ Hospital (London, UK) between 2001 and 2016 were prospectively collected and recorded onto a computer database and divided into two groups: CRT (n=227) and non-CRT (n=696). In total there were 923 patients in the database to compare. In the CRT group predominately had CRT defibrillators (78%, n=177) with CRT pacemakers making up 22% of the population (n=50). In the non-CRT group patients had predominantly either a dual chamber pacemaker (52%, n=363) or

a single or dual chamber implantable cardiac defibrillator (ICD) (37%, n=257).

The patient demographics, with the exception of means age, previous valve surgery or stroke, comorbidities were significantly more prevalent in the CRT group, with 84% of the CRT group having two or more comorbidities and 63% having three or more.

Among the clinical features and indication for transvenous lead extraction the only statistically significant difference was mean lead dwell time, with the CRT group having an average dwell time of 5.6±5.5 years and the non CRT group having an average dwell time of 7.5±7.1 months (p=0.003). Gould speculated why this might be, saying: “It probably reflects the sicker cohort of patients, possibly earlier lead displacement in CRT patients as well.”

Major complication rates were exactly the same (2.2%) between the two groups and 30-day mortality was not statistically significantly different between the two groups, being 3.1% (n=7) for the CRT group and 2.4% (n=17) for the non-CRT group.

The predominant cause of 30-day mortality was sepsis in both groups (57%, n=4 in the CRT group vs. 53%, n=9 in the non-CRT group). The

Justin Gould

other causes of death were ventricular fibrillation arrest post transvenous lead extraction (n=1 in both CRT and non-CRT group), superior vena cava tear (n=1 in the non-CRT group), pneumonia (n=1 in the non-CRT group), and myocardial infarction (n=1

in the non-CRT group). There were two non-procedure related deaths in the CRT group and four non-procedure related deaths in the non-CRT group.

Analysis of these result found that CRT did not predict mortality using univariate and multivariate analysis.

Risks of long dwell lead extraction Longer dwell times are related to higher rates of complication during lead extraction. There have been various studies looking at the risk factors for transvenous lead extraction but there is limited knowledge about extraction of leads that have been implanted for over 20 years.

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Andrzej Kutarski

ndrzej Kutarski (University of Lublin, Poland) and his colleagues have carried out a study to look at the risk of lead extraction after long dwell times. They aimed to compare the safety and feasibility of transvenous lead extraction in four different patient groups who had different lead dwell times.

To do this they carried out a retrospective analysis of their 12-year old transvenous lead extraction database (containing

data from 2,654 transvenous lead extraction procedures), comparing the effectiveness and complications of the extraction procedures in the four groups (˂10 years, 10–19 years, 20–29 years and ≥30 years). The lead extractions were carried out using standard mechanical systems. Laser and radiofrequency energy equipped sheaths were not use and mechanical energy powered sheaths with rotating threaded tip were used sporadically (3.6%). The predominant major

complication was cardiac tamponade, which occurred in 1.4% of cases.

Amongst the four groups, patients had comparable ages and there were more women in the 20–29 years and ≥30 years age group.

The analysis found that major complications and the need for rescue cardiac surgery increased as the lead dwell time increased and procedure success was higher the shorter the dwell time. Somewhat surprisingly the death rate was zero in the 20–29 years and ≥30 years age groups, although it was also very low in the ˂10 years age group (0.1%) and 10–19 years age group (0.7%) The study found that there was a clear relationship between

lead body dwell time and effectiveness and safety of the lead extraction procedure.

A higher number of leads, abandoned leads and percentage of female patients seemed to be related to the effectiveness of lead extraction in patients with long lead dwell times but they concluded that lead body dwell time is one of many factors that affect the effectiveness of lead extraction and that other factors should be considered.

As they found that major lead extraction complications could occur during procedures with a relatively short dwell time, long dwell time should not be a reason for not carrying out lead extraction, especially in patients with a long life prognosis.

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Profile

Profile

Dhanunjaya Lakkireddy Dhanunjaya Lakkireddy is executive medical director at The Kansas City Heart Rhythm Institute at HCA Midwest Health, Kansas, USA. He holds the title Professor Medicine, is board certified in Cardiology and Electrophysiology and is a renowned electrophysiologist. He spoke to Cardiac Rhythm News about the impact his family doctor had on his life, and his most memorable patient cases.

When did you first decide you wanted a career in medicine?

I decided that I wanted to be a doctor when I was in high school. Our family doctor had a profound impact on my leanings towards medicine. I remember, during high school, I contracted malaria. The doctor ordered an ice bath which, after three hours, controlled my body temperature. This reaffirmed my respect and fascination for the profession. The knowledge and compassion of our family physician Dr. Madhuvardhan Reddy left a lasting impression on me.

Why did you choose to specialise in atrial fibrillation and complex arrhythmias?

I always liked cardiology as the most dynamic field with a lot of creativity and innovation driving the science forwards. When I was in medical school interventional cardiology was still spreading its wings and acute percutaneous coronary intervention was just taking a foot hold in India. .

All through residency I thought I was going to be an interventionalist but in my first month during general cardiology fellowship I was fortuitously asked to switch my rotation to electrophysiology (EP) since the assigned fellow had a family emergency. I started working with Dr Huagui Li who was absolutely fantastic. He took me under his wing and taught me a lot about electrophysiology. By the end of the month I was placing pacemakers, implantable cardiac defibrillators (ICDs) and floating catheters.

The very idea that one can actually ablate around the pulmonary veins and stop atrial fibrillation was mind boggling. I thought that was the coolest thing in the world. The complexity of AF origin and maintenance all of a sudden seemed surmountable. The field was so young and the opportunity to advance it further was very exciting. The tools at the time were very clumsy and each case would take 6–8 hours but, at the end, patients going home in sinus rhythm was exhilarating. While my other colleagues in the fellowship hated long cases in EP, it became very appealing to me. By the end of the three months into the fellowship I found my calling.

Who were your mentors and what influence did they have on your career?

I had several mentors at every stage of my life. I would not have come this far without their support, kindness and guidance. During high school, Sisters Mabel and Emy, Mrs Gowri, Dr Jaganmohan Rao and Dr Anjireddy sowed the seed of interest in life sciences and importance of staying focused.

Professors Annapurna, Habeebullah and Rangareddy during medical school helped me learn the basic tenements of the art and science of medicine. Later during residency Dr James Vacek and Manohar Gowda shaped my interest in cardiology further. My interest in cardiovascular research was fostered by these two wonderful people whom I am indebted to. During cardiology fellowship Drs Huagui Li and Syed Mohiuddin at Creighton have provided with further clarity and direction leading up to my career

in 3lectrophysiology. Drs Andrea Natale and Sanjeev Saksena have been impactful on my career as an EP. Dr. Natale has been an inspiring influence on my career as an electrophysiologist. His leadership in clinical program building, high quality research and education has rubbed on all of us who were his fellows. My training years were very exciting with all the new developments in complex arrhythmia ablations, device extractions, robotic navigation and more. Dr Saksena has taught me the lessons of life and the importance of work life balance. He is someone I always reach out to when making a life decision. Dr Arun Kolli who was one year ahead of me from junior college through EP training has been an amazing source of guidance and fellowship. My parents and brothers have been a great influence on my personal and professional accomplishments. My wife Madhuri has been an unfettered supporter and stabiliser in my life.

What is your most memorable patient case?

I can say there are probably several, of which two cases stand out.

One was from the Spring of 2005: A 56 year old patient with ventricullar tachycardia (VT) storm.

Bob Schweikert was the attending physician. We started the case around 7:30pm. There were five different VTs, the Impella was not available at that time. We knew right away that we were going to be there for a long time. After we chased three out of the five VTs. We still had two more that we continued inducing. It was 1:30am and Bob was still going at it. I finally had to ask him what our plan B was going to be?

His answer was simple and stern—“We go after them until we are done. If we do not take care of it, the patient has no place else to go”. We ablated all the areas that were arrhythmogenic and homogenised the scar.

This is probably the early beginings of VT substrate modification. We got done at 3am to go talk to the anxious family. Five days later the patient walked out of the hospital VT free.

The second case was when I was a young attending at

Kansas University, USA. We had a 17 year old Hispanic patient who presented to our emergency room with repeated syncopal spells related to WolffParkinson-White syndrome, with rapid AF and he was uninsured. It was obvious that we needed to get rid of his accessory pathway to give him a chance to

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Profile

survive. I had to talk to the hospital to underwrite his procedural costs and the EP ablation company to donate their catheters and I went to work. Patient and family were very thankful for helping them, I did not think about this patient for another seven years.

Last Christmas I got a card from this young man, thanking me for what I have done for him and that he is entering medical school and wishes to pursue cardiology for a career. It gave me goose bumps that what little I paid forwards had such profound impact on a person’s life.

experience in JACC EP as a full peer reviewed manuscript.

This is a good example of collaborative research involving electrophysiology and gastroenterology.

Our work on understanding the impact of patient adherence to oral anticoagulation using pharmacy databases yielded some very interesting observations that are very important to decision making in patient care. This data will be presented as a late breaking clinical trial at the Heart Rhythm Society meeting (HRS) 2018.

What are your current areas of research?

In my opinion access to quality care is the biggest problem we face in taking care of patients. All the factors that limit access at various levels need to be addressed. It should start with providing high quality training to young people that are joining the EP practice pool around the world. Educating and empowering patients to take charge of their lives and treatment is very critical to the success of arrhythmia care. Standardising quality and creating benchmarks to ensure streamlined care is another important piece in the puzzle. We need to work towards equalising the differences between the developing and developed countries. There are still many countries where lifesaving therapies are not accessible to majority of the population. One such item is access to an automated external defibrillator (AED) in public places. The general awareness about sudden cardiac death, basic life support and access to AED in public places is something we can work on. This requires engagement of local physicians, governments and strong legislation. I have been working with several state governments in India for a start.

I take a multi-disciplinary approach to most of the questions in front of us. For example, for a long time I have been frustrated with lack of options for treating AF patients with gastrointestinal (GI) arteriovenous malformations who need to be on oral anticoagulation. After several discussions and extensive research we found octreotide to be a reasonable option to use. Indeed, we found over 70% of patients with lower GI bleed related to AV malformations seem to respond to this therapy allowing us the breathing room to consider more durable therapeutic options like left atrial appendage closure. We published this

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Fact File

What are the best ways to improve patient care for those with arrhythmia?

You have varied research interests.

What is the most interesting or unusual way you have come across treating arrhythmia?

Recently we have been trying to understand the relation between myocarditis and ventricular arrhythmia. What started off as a mere observation has piked our interest and we systematically studied a few hundred patients presenting with VTs and premature ventricular contractions to find that a vast majority of these patients have underlying myocarditis.

The MAVERIC registry looks at this particular question and we have some exciting results to report during the late breaking clinical trial during HRS 2018 in Boston.

What conferences are you most looking forward to in 2018?

I am looking forward to Heart Rhythm Society annual meeting in Boston. There are several excellent late-breaking trials and amazing sessions that very practical. There has been special emphasis on practical and clinically relevant science. Kansas City Heart Rhythm Symposium is in its tenth edition. We have John Camm receiving the EP Pioneer Award with several other superstars of EP coming to participate in the meeting on 17–19 August in Kansas City, USA. Annual Sessions at ESC, APHRS and ACC are other big meetings I am looking forward to.

How do you like to spend your time outside of work?

I wish the day had more than 24 hours so that I could do more outside things. I hang out with my 12 and 15 years old daughters whenever I can. I love to watch cricket on TV. Recently I have been coaching my daughter’s science bowl team (since I am really not good at any sports in general). Oh yes! I do like to see my wife sometimes.

Current appointments

Professor of Medicine Director, Center for Excellence in AF and Complex Arrhythmias Medical School, Osmania Medical College, Hyderabad India Residency, University of Missouri Kansas City, St. Luke’s Hospital, Kansas City Missouri Fellowship, Creighton University, Omaha Nebraska (Cardiology) Fellowship, Cleveland Clinic Foundation, Cleveland Ohio (Electrophysiology)

Employment and Qualifications

1996- Medicine Bachelor Bachelor Science

(MBBS), Osmania Medical College,

University of Health Sciences,

Hyderabad, India 1998-2001 Internship/Residency, University of

Missouri Kansas City, Kansas City,

Missouri, USA 2002-04 Fellow in Cardiology, Creighton

University, Omaha, Nebraska, USA 2004-06 Fellow in Electrophysiology,

Cleveland Clinic Foundation,

Cleveland, Ohio, USA

Research Interests

Atrial fibrillation and ventricular tachycardia.

Investigational devices and drugs for treatment of cardiac arrhythmias Role of yoga in the treatment of cardiac arrhythmias and syncope Cardiac resynchronisation therapy—effects on outcomes, predictors of positive response Radiofrequency ablation—effects on outcomes and patient quality of life Role of vitamin deficiency in cardiac arrhythmia

Awards

2005Bakken Heart Brain Institute—Best Research of the Year Award 2005- Joseph Cash Award—Best Clinical Research of the Year 2011- Prevention Magazine Integrative

Medicine Award 2014- Ingram’s Heroes in Healthcare and

Icons of Education Award 2016- Ingram’s 2016 Top Doctor

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May

Wearable cardiac devices

VEST trial shows wearable defibrillator cuts total mortality but failed to show reduction in sudden deaths

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A phase 3 trial of Zoll Medical’s LifeVest has missed its primary endpoint. The study found that people who started using the wearable defibrillator the week after they had a heart attack did not experience a statistically significant reduction in sudden cardiac death in the next three months as patients who received conventional therapy; however, patients did experience a statistically significant reduction in the secondary endpoint of total mortality.

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he investigators designed the 2,300-patient trial to show that the LifeVest reduces the sudden death rate by monitoring the wearer’s heart rhythms and delivering a treatment shock if they go awry.

However the study found the device did not statistically significantly reduce sudden death mortality.

Investigators claim this result may be due to decreased power for the primary outcome of sudden death due to difficulty in misclassification of cause of death.

“While the VEST Trial did not meet the endpoint of sudden death mortality, the ability to determine the cause of death as sudden when unwitnessed is difficult and could result in misclassification,” Jeffrey Olgin, co-principal investigator of the trial, said as a potential explanation for not seeing a statistically significant reduction in sudden death.

Olgin’s assessment is supported by data from a secondary endpoint that looked at all-cause mortality. The

all-cause mortality rate in the control arm was 4.9%, compared to 3.1% in the LifeVest cohort. That difference amounts to a 36% reduction in mortality and a p-value of 0.04, giving the wearable cardiac defibrillator (WCD) a data point that, while having delimited clinical significance, doesn’t suggest the study was an outright failure and could make the point for further investigation.

The study concluded that the wearable cardioverter-defibrillator did not statistically significantly reduce sudden death mortality but it did reduce total mortality in the first 90 days postmyocardial infarction in patients with left ventricular ejection fraction 35% and there was a relative risk reduction of 35.5%.

Prescribing the wearable cardioverter-defibrillator is reasonable to protect high-risk patients with a low left ventricular ejection fracture postmyocardial infarction until evaluation for an implantable cardioverter defibrillator at 40–90 days

The study only investigated the impact of the WCD in patients who suffered a recent heart attack (MI) and had a low ejection fraction: other indications (such as non-ischemic cardiomyopathy or patients with explanted ICDs) were not studied in this trial.

The study enrolled 2,302 post myocardial infarction patients (13,774 patients were screened) with low ejection fractions who were randomised in a 2:1 ratio to either receive a wearable cardiac device and optimal medical therapy (n=1,524) or optimal medical therapy alone (n=778). The patients were followed up after 90 days and they had a mean age of 61 years and were 27% female.

The inclusion criteria were being within seven days of hospital discharge for acute myocardial infraction and having an ejection fracture of less than 35%. The exclusion criteria were having an existing implantable cardioverter-defibrillator, significant valve disease, unipolar pacing system,

The rise of smartphones and wearables for AF detection: WATCH-AF and DETECT-AF pro How to best combine optimal screening and diagnosis for atrial fibrillation (AF) has long been a challenge. At European Heart Rhythm Association Congress (EHRA; 18–20 March 2018, Barcelona, Spain) Jens Eckstein (University of Basel, Basel, Switzerland) presented the case for how modern technology can help to address this issue.

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trial fibrillation (AF) is the most common cardiac arrhythmia and incidence increase with age. Those with atrial fibrillation have a three to five fold increase in risk of stroke and are more likely to die or suffer disability if they do suffer a stroke.

There were already different ways to diagnose AF— traditional resting electrocardiogram (ECG), 24-72h Holter ECG and implantable loop recorders—but there are now novel ways that make the most of modern technology.

Recently internet enabled mobile ECGs (iECG), an ECG band for Apple watch and smart detection of AF and cameras of mobile phones and smartwatches became available for AF screening too.

Two trials looked at these new technologies to see if they could accurately detect AF: the DETECT AF pro (Enhanced Diagnostics for Early Detection of Atrial Fibrillation–Prospective Validation) trial and the WATCH AF (SmartWATCHes for Detection of Atrial Fibrillation) trial.

The three methods tested in the WATCH-AF trial and DETECT AF Pro trial (smartwatch, smartphone and iECG)

have varying availability and all three showed that long term screening is possible without inconvenient sticker electrodes that are needed for most traditional methods.

The intriguing aspect of a purely smartphone-based AF screening solution is the global availability, particularly as different models of phone can be used with the tested app. The disadvantage is that patients need to be active in assessing their heart rhythm.

This aspect could be solved by using a smartwatch which allows a similar degree of accuracy without active intervention on the part of the patient. With a suitable wrist worn device, and the tested algorithm, there is the potential for an almost ideal AF screening device.

Ecktein commented, "For all three technologies there is a huge potential for them to be used as efficient AF screening devices. Efforts have to be undertaken to achieve an optimal signal quality. We therefore fully support the already implemented signal quality check in the commercial version of the Heartbeats app. The next step will be a trial validating these technologies in a population based international trial to evaluate their beneficial use for our patients."

Zoll's LifeVest

chronic haemodialysis, a chest too small or large to wear the wearable cardiac device, discharge to a skilled nurse facility for more than seven days and pregnancy.

In the wearable cardioverterdefibrillator group the vest was worn on average for 14.1 hours a day, give 1.4% appropriate shocks, 0.6% inappropriate shocks and 4.6% aborted shocks.

The DETECT AF Pro trial The trial was carried out at the University Hospital Basel and Greifswald (Basel and Greifswald, Germany) with 660 inpatients (330 with a history of AF and 330 matched controls). The inclusion criteria were patients of 18 years or older. Exclusion criteria included having a pacemaker.

Patients underwent a five-minute iECG with automated analysis and validation by a cardiologist, as well as a five minute photoplethysmographic (PPG) pulse wave recording with a smartphone camera (without information on signal quality or diagnosis). The data was analysed by the Preventicus Heartbeats algorithm in a blinded fashion.

A total of 672 subjects were assed for eligibility, of which 657 subjects were included and 594 underwent final analysis. There were 250 patients with AF and 344 patients with sinus rhythm.

The smartphone PPG readings were analysed with the Heartbeats algorithm for one, three and five minutes files.

Based on one-minute files, the analysis was 95.3% accurate, a threeminute analysis was 95.7% accurate and a five minute analysis was 96.5% accurate.

The study investigators speculated

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Wearable cardiac devices

Algorithm can accurately detect atrial fibrillation and differentiate from sinus rhythm

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The KardiaBand (AliveCor) is a wristband for Apple Watches that can detect atrial fibrillation

The algorithm (Kardiaband, AliveCor) for atrial fibrillation (AF) detection, when supported by physician review can accurately differentiate AF from sinus rhythm (SR). This technology can help screen patients prior to elective cardioversion and avoid unnecessary procedures.

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ne hundred patients were enrolled in the study from March 2017 until June 2017. Cardioversion was performed in 85% of study participants. Of the 15 patients who did not undergo cardioversion, eight were cancelled due to presentation in sinus rhythm. There were 169 simultaneous 12-lead electrocardiogram (ECG) and band recordings obtained from study participants, and 57 band recordings were determined as unclassified by the band algorithm. Of the 57 unclassified band tracings, 16 (28%) were due to baseline artefact and low amplitude of the recording, 12 (21%) were due to a recording of less than 30 seconds in duration, six (10%) were due to a heart rate of less than 50 bpm, five (9%) were due to a heart rate of greater than 100 bpm, and the remaining 18 (32%) were unclassified due to an unclear reason.

Electrophysiologist interpreted 12-lead ECGs were all interpretable.

In order to test the ability of the

algorithm to detect atrial fibrillation (AF), automated band rhythm interpretations and electrophysiologist interpreted 12-lead ECGs were compared.

Among the 112 recordings where the band provided a diagnosis, it correctly diagnosed AF with 93% sensitivity, 84% specificity and a K coefficient of 0.77 (95% confidence interval 0.65-0.89) when compared to the electrophysiologist interpreted 12-lead ECG. To determine whether the automated band recordings labelled as “unclassified” by the algorithm were still clinically useful, these tracings were interpreted by blinded electrophysiologists and compared to the electrophysiologist interpreted 12-lead ECGs. Of the 57 automated unclassified band recordings, the interpreting electrophysiologists were able to correctly diagnose AF with 100% sensitivity, 80% specificity and a K coefficient of 0.74.

To assess the fidelity and overall quality of the band tracings produced by

the smartwatch, electrophysiologist interpreted band recordings were compared to corresponding 12-lead ECG tracings. Twenty-two recordings were determined to be non-interpretable by the reading electrophysiologist, and these were predominately due to baseline artifact. Of the remaining 147 simultaneous recordings, the electrophysiologist interpreted 12-lead ECGs and electrophysiologist interpreted band recordings, physician interpretation of the band tracings demonstrated 99%

sensitivity, 83% specificity and a K coefficient of 0.83.

The band automated algorithm interpretation was compared to physician interpretation of the same recordings. Of the cases where both methods were interpretable, the band automated algorithm was 93% sensitive and 97% specific in detecting AF with a K coefficient of 0.88.

The study concluded that KardiaBand smartwatch automated algorithm for AF detection, supported by physician review of these recordings, can reliably differentiate AF from sinus rhythm.

Avoiding scheduling unnecessary electrical cardioversions is one example of a clinical application of the KB system.

Many other potential applications warrant further investigation and might transform care of AF patients.

The WATCH AF trial

that with a recording time of up to five minutes, compliance could be low, so they compared one minute analyses of the smartphone camera method/PPG using the Heartbeats algorithm for five minutes and one minute only in a predefined fashion.

The Kardia (AliveCor) algorithm (iECG) analysis took one minute and had an accuracy of 98.7%, but had a higher percentage of recordings without an automated diagnosis.

When both were compared with a one minute test PPG had a sensitivity of 90.0% (85.6–93.8) compared to 99.6% (97.9-100) for iECG. The specificity was 99.1% (97.5–99.8) for PPG and 97.8% (95.3–99.2) for iECG. The accuracy was 95.3% for PPG and 98.7% for iECG. Taking into account the number of files not classified by the two technologies, the number of correctly classified cases was higher for the PPG technology (88.7% vs. 82.1%).

This trial was also carried out at the University Hospital Basel and Greifswald, with another 660 patients and the same inclusion and exclusion trial of the DETECT AF Pro trial.

The trial design was the same for DETECT AF PRO, using simultaneous five-minute recordings of a pulse wave with a smartwatch in one arm and an activity tracker with PPG sensor for pulse wave recording Modern technology can be used to improve patient health on the other arm and iECG to record an ECG from the fingertips. The PPG files were analysed

by Preventicus in a blinded fashion. The automated iECG results were documented and the ECGs validated cardiologists.

There were 672 patients that were assessed for eligibility resulting in 508 subjects being available for analysis. This broke down into 239 subjects with AF and 269 subjects with sinus rhythm.

After a oneminute test the smartphone had sensitivity of 90.0% (85.6-93.4) and accuracy of 95.3%. The iECG had a sensitivity of 99.6% (97.9-100) and an accuracy of 98.7% with a high number of ECGs without automated results.

May

Stroke - the need for interdisciplinary concepts WOLFRAM DÖHNER COMMENT & ANALYSIS The link between cardiac diseases and stroke is well known and reported. Wolfram Dӧhner writes in Cardiac Rhythm News about the needs for interdisciplinary thinking and collaboration.

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troke is a leading cause of death and the main cause of physical disability, dementia (second to Alzheimers disease), depression and falls. Up to about one third of patients die within the first weeks after stroke but 60% of patients live with at least minor handicap and about 25% of patients with severe disability and substantial disruption of their previous life. Thus stroke is a major burden to patients and families as much as to the health care systems and the society. Despite improving therapies and decreasing mortality rates in recent years, hospitalisation numbers are increasing.

Therefore, long-term care and secondary prevention of stroke will be of increasing importance in respond to the increasing prevalence.

The strong interaction between cardiac diseases and cerebrovascular incidents is well established. About 25% of the ischaemic stroke are of cardioembolic origin and a further 20–25% are of suspected cardiac origin or involvement.

Virtually any cardiac pathology (structural, functional, rhythmogenic) may account for an increased risk of stroke. Accordingly, stroke patients frequently have pre-existing cardiac/cardiovascular diseases, that may or may not be diagnosed at the incident of a stroke. But this is not the only and not the foremost reason why a close cooperation of cardiologists with neurologists in comprehensive stroke care is of high and increasing relevance.

fibrillation and ventricular arrhythmias), temporary breakdown of blood pressure regulation, myocardial damage and elevated troponin levels, or acute complications of pre-existing cardiac pathologies such as infective endocarditis, myocardial infarction or exacerbated heart failure. Previous studies have shown that presence of cardiac complications account for increases in mortality compared to patients without them.

While the detection of atrial fibrillation is predominantly pursued to clarify the potential cardio-embolic origin of the stroke, the rhythm monitoring at stroke units is also required to observe potentially life threatening ventricular arrhythmias.

Another complication is the stroke induced myocardial injury identified by increased troponin levels than can be observed in up to 60% of patients when using high sensitivity assays. Of course not all of these patients require immediate (invasive) cardiovascular diagnostic workup, but the number of patients with a culprit coronary lesion has been reported to be 24%. It therefore requires consequent and qualified cardiologic involvement to decide the further diagnostic and therapeutic path of these patients. The pathophysiologic mechanisms of stroke triggering myocardial damage are not completely understood but neuronal signals may be similar to those of the Tako Tsubo Syndrome, only with somatic brain injury. Notably, particularly involvement of the right insular cortex is often seen in strokes with accompanying Cardiologic expertise is needed by myocardial injury. Monitoring dynamic in stroke care changes in troponin levels rather than singly In the acute, subacute and chronic phase time measurement and the combination after stroke there are multiple complications of biomarker assessment with clinical and sequelae of stroke that require the symptoms, ECG and further information involvement of cardiologic expertise. such as risk profile and case history may Monitoring and immediate response to be required to come to a conclusive picture stroke induced complications is the main about the need for further cardiac workup. purpose of the stroke unit treatment that is a Beside neuroendocrine activation after corner stone in modern stroke therapy and stroke also inflammatory immune response that substantially contributes to improved may trigger multiple pathways resulting outcome. together in a range of cardiac complications Many of these complications relate to including plaque instability, calcium cardiac function, rhythm control or preoverload, blood pressure peaks, endothelium existent cardiac diseases. The most common Wolfram dysfunction, Dӧhner (Center microcirculatory for failure, and cardiac complication in the acute phase electrical instability (Figure 2). after stroke include arrhythmias (both, atrial A key diagnostic tool to evaluate cardiac

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Stroke

comorbidity is of course echocardiography.

Depending on the clinical question to be addressed the decision on the appropriate method (transthoracic or transesophageal echocardiography) may as well have practical implications on patient handling and resources. In a case of suspected infective endocarditis the stroke—that accounted for hospital admission and that is the most overt clinical problem of the patient— represents only one minor criteria of the Duke criteria and further efforts with particular emphasis on cardiac imaging are required to establish the true underlying disease. Again, a close cooperation between strokeologists and cardiologists is required to coordinate these appropriated diagnostic measures.

The stroke patient is a chronic patient who needs continued specialised medical treatment

After the acute phase of stroke continued efforts are required to establish previously undetected cardiac diseases and to target risk factors with consequent and long term strategies of secondary prevention.

Cardiologist 's collaboration in the long term care of patients after stroke is urgently required as complications are particularly prevalent in patients with stroke.

ESC Council on stroke

The European Society of Cardiology (ESC) aimed to improve awareness of stroke among cardiologists in Europe and to promote clinical education and scientific efforts towards stroke. On that basis, the ESC Council on stroke was founded in 2016 and an extensive agenda of activities has been implemented by the council including joint sessions with partner societies, position papers, webinars and cardiovascular round tables. A major activity is the annual international “ESC Heart & Stroke” conference of the ESC Council on stroke that has been established as a clinical educational meeting. All ESC members with interest in stroke are encouraged to get involved to contribute to the stroke council activities.

More work is needed to improve collaboration and integrated treatments concepts in the field of stroke bringing together all specialties involved in comprehensive modern stroke care.

Wolfram Dӧhner, Stroke Research Berlin and Department of Cardiology , DZHK (German Centre for Cardiovascular Research), partner site Berlin, Charité Universitätsmedizin Berlin, Germany

Post Stroke CV Complication

CV Risk profile • Atrial fibrillation • Hypertension

• All the sbove (secondary prevention)

• Atherosclerosis • Myocardial infarction • Myocarditis • Endocarditis • LV Aneurysm • Chronic heart failure



Stroke

• Valvular disease



• Valve replacement

• Cardiopulm. function



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• Congenital heart disease

• Arrhythmias inadequate RR regulation • Cardiac / vascular re-embolism • Myocardial Infarction • CHF exacerbation

• Thrombosis 2 • Figure Overt foramen ovale Cerebro-cardiac signalling after stroke (adaped from Doehner et al, EJHF 2018

Figure 1: Cardiovascular risk factors and complications linking heart and stroke. Adapted from Widimskoy et al EHJ 2017

Ischaemic stroke

Haemorrhagic stroke

(insular cortex involvement)

Inflammatory response

Sympatho-vagal imbalance

Central immunodepression Systemic cytocine overflow

Coronary plaque instability

Cathecolamine levels

Intracellular calcium overload Myocardial necrosis

Myocardial injury

Acute coronary syndrome

Strain related cardiomyopathy

Arterial baroreflex

+LJK %3 variability

(OHFWULFDO instability

Ventricular/atrial strain

Ventricular Arrhythmia

Atrial fibrillation

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Figure 2: Cerebro-cardiac signalling after stroke. Adaped from Doehner et al, EJHF 2018

May

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His bundle pacing

His bundle pacing is associated with reduced morbidity and mortality when compared to right ventricle pacing His bundle pacing was successful in 92% of patients and the primary endpoint of death, heart failure hospitalisation or upgrade to biventricular pacing was significantly reduced in the His bundle pacing group. Right ventricular pacing is associated with heart failure and increased mortality; His bundle pacing is an alternative.

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two-centre study compared the clinical outcomes of His bundle pacing to right ventricular pacing.

Consecutive patients referred to Geisinger Wyoming Valley Medical Center, Wilkes-Barre, USA and Geisinger Medical Center, Danville, USA from October 2013 to December 2016 for permanent pacemaker implantation for standard indications were included, totalling 765 patients.

The study, published in the Journal of the American College of Cardiology, concluded that permanent His bundle pacing was feasible and safe in a large real-world population requiring permanent pacemakers. His bundle pacing was associated with reduction in the combined endpoint of death, heart failure hospitalisation or upgrade to biventricular pacing compared to right ventricular pacing in patients requiring permanent pacemakers.

His bundle pacing was attempted in 332 consecutive patients while 433 patients underwent right ventricular pacing. The mean age was 75.7±11 years with males accounting for 55.8% of the study cohort. Prior history of heart failure and atrial fibrillation was present in 28.8% and 50%, respectively. Mean baseline left ventricular ejection fraction of the entire cohort was 54.5±9.5% and mean QRS duration was 108±27ms. Indication for pacemaker implantation was sinus node dysfunction

and atrioventricular conduction disease (35% vs. 65%, respectively). Patients were considered as lost to follow up if they didn’t have an event and were not seen in the Geisinger Health system in 2017. In the His bundle patient group 16 (4.8%) patients were lost to follow-up compared to 15 (3.5%) in the right ventricular patient group. The mean follow-up duration for the entire cohort was 725±423 days. The median follow-up in the right ventricular pacing group was 648 days compared to 754 days in the His bundle pacing group (p = 0.01). Demographics were similar in the His bundle pacing and the right ventricular pacing groups, except for higher prevalence of males (60% vs. 52%, p<0.05) and atrial fibrillation (57% vs. 45%, p<0.05) in the His bundle pacing group. Mean baseline QRS duration was slightly longer in the right ventricular

19

pacing group compared to His bundle pacing (110±28 vs.

105±25 ms, p<0.01).

The results of the study show that permanent His bundle pacing is associated with a significant reduction in the primary endpoint of all-cause mortality or heart failure hospitalisation or upgrade to biventricular pacing as compared to conventional right ventricular pacing in patients undergoing permanent pacemaker implantation for bradycardia. The primary outcome was driven by a significant reduction in the incidence of heart failure hospitalisations associated with His bundle pacing.

Additionally, the significant reduction in the primary endpoint was entirely due to the differences in the outcomes for patients with greater than 20% ventricular pacing burden. These findings address the need to determine the best ventricular pacing site in patients requiring permanent pacemakers for bradycardia therapy.

This study is supportive of the concept that His bundle pacing can prevent ventricular dyssynchrony by facilitating conduction through the native His-Purkinje system.

His bundle pacing was associated with reduction in the combined endpoint of death, heart failure hospitalisation or upgrade to biventricular pacing compared to right ventricular pacing in patients requiring permanent pacemakers.

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COMPASS trial

COMPASS trial suggests that the combination of low-dose rivaroxaban and aspirin significantly lowers the incidence of both major adverse cardiovascular and limb events, and reports the adverse prognosis of patients after major adverse limb events

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lowered the incidence of major adverse limb events by 43% (p=0.01), total vascular amputations by 58 % (p=0.01), peripheral vascular interventions by 24% (p=0.03) and all peripheral vascular outcomes by 24% (p=0.02).

Of note, researchers said that “While the risk of death did not change after a major adverse limb event in participants randomised to receive rivaroxaban and aspirin combination, there was a sixfold risk of death after a major adverse limb event for participants randomised to receive aspirin alone.” Similarly, the risk of composite major adverse Findings from the Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or cardiovascular events or total vascular Peripheral Artery Disease (COMPASS) trial suggest that the combination of low-dose rivaroxaban amputation in participants randomised and aspirin significantly lowers the incidence of both major adverse cardiovascular events and to receive aspirin alone was 10-fold major adverse limb events in patients with lower extremity peripheral artery disease. The results following a major adverse limb event. were presented by Sonia Anand, at ACC.18 (ACC; 10–12 March, Orlando, USA) and published in the "Among individuals with stable lower Journal of the American College of Cardiology. Rivaroxaban is currently used for stroke prevention in extremity peripheral artery disease, atrial fibrillation. the development of major adverse limb events is associated with a dire prognosis, making its prevention of he study analysed outcomes and aspirin compared with aspirin alone events. Overall, the incidence of major utmost importance," researchers say. As in 6,391 patients with lower on the incidence of major adverse limb adverse limb events was highest (3.8%) such, they urge consideration of low-dose extremity peripheral artery events, peripheral vascular interventions, in peripheral artery disease patients rivaroxaban and aspirin "As an important disease who were randomised to and all peripheral vascular outcomes over with a prior history of intervention therapy for patients with peripheral artery receive either a low-dose rivaroxaban a median follow-up of 21 months. (i.e., peripheral revascularisation or (2.5 mg/twice daily) and aspirin Researchers found the independent amputation) and lowest (0.5%) in patients disease."

The dosage of 2.5 mg twice-daily combination, rivaroxaban alone, or predictors of major adverse limb events with asymptomatic peripheral artery rivaroxaban used together with aspirin, aspirin alone. Researchers looked to included “severe ischaemia symptoms at disease (Ankle-brachial index<0.90). see if hospitalisations, major adverse baseline, prior limb or foot amputation According to researchers, 128 patients lower than the one currently approved for stroke prevention in atrial fibrillation, cardiovascular events, amputations and at baseline, prior history of peripheral experienced major adverse limb events, may have hit the sweet spot. It balances deaths were higher after the first episode revascularisation surgery or angioplasty, putting them at significantly increased efficacy and safety by favourably of major adverse limb events compared and randomisation to the aspirin arm of one-year cumulative risk of subsequent affecting the residual risk in patients with with peripheral artery disease patients trial.” They noted that diabetes, smoking, hospitalisations (95.4%), amputations established stable cardiovascular disease who did not experience major adverse female sex and history of peripheral (22.9%) and death (8.7%). However, limb events. They also studied the impact artery disease were not independently compared with aspirin alone, the on an appropriate background medical of treatment with low-dose rivaroxaban predictive of major adverse limb combination of rivaroxaban and aspirin regimen.

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Ablation

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Ultralow temperature ablation: Results from the Cryocure I and Cryocure II trials The trials found that ultralow temperature cryoablation is feasible and shows excellent safety and efficacy. The clinical outcomes for flutter ablation show a 94% success rate at three months.

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ltralow temperature ablation uses near-critical nitrogen. The catheter operates at the nearcritical point between liquid and vapour for nitrogen, or –196°C. Liquid nitrogen can't circulate through a small 8-French catheter below the liquidvapour line because evaporation of the liquefied gas results in enormous expansion up to a factor of 200, causing vapour lock, explained lead investigator Tom De Potter (Cardiovascular Center, Onze-Lieve-Vrouw Hospital, Aalst, Belgium).

"If you increase the pressure in the catheter dramatically up to the critical point of nitrogen, this phenomenon disappears. The gas no longer expands from the heating and it allows you to use these ultralow liquid nitrogen temperatures in a percutaneous catheter. This is what this technology does," he says.

This decreased viscosity allows for a smaller sized catheter to be used than is used in conventional cryoablation. The catheter can also be changed to different shapes, allowing for personalised ablation and a more targeted procedure.

Both trials were two-centre, prospective and observational. Cryocure I looked at typical right atrial flutter in 17 patients and were followed up at three months. The cryocure II trial looked at paroxysmal, long standing persistent atrial fibrillation (AF) in 27 patients who were followed up at 12 months.

Oesophageal warming balloons were used for all catheters, and no tamponade, fistula, or mechanical adverse events were reported.

In Cryocure I, bidirectional isthmus block was achieved after a 30-minute waiting period in all 17

Tom De Potter

patients, with the flutter catheter pouch approach used in 14.

The average ablation time to bidirectional isthmus block was 2.7±3.2 minutes, including a 14-second bonus freeze to the bidirectional isthmus block. The best-case scenario was bidirectional isthmus block real-time isolation in one patient in 14 seconds, De Potter says.

On average, 2.8±3.2 applications were used to reach bidirectional isthmus block with 12±5.0 minutes of X-ray time, resulting in a total procedure time of

85±16.0 minutes, including the 30-minute waiting period.

As for acute safety, there was one transient STsegment elevation, presumed due to right coronary artery spasm that lasted for two minutes with no sequelae on further evaluation.

At three months, 94% of the 17 patients were free of recurrence. Additional electrophysiology studies conducted in three patients for other reasons at three and 12 months confirmed cavotricuspid isthmus block in all.

For Cryocure II, the 27 patients (63% male; mean age, 64 years) had a history of AF for an average of 29 months, and had, on average, a left atrial diameter of 46±6mm. Extreme left atrial diameter was an exclusion criteria.

Pulmonary vein isolation (PVI) ablation was performed in all 27 patients and cavotricuspid isthmus block in seven of the 10 patients with persistent AF. At the discretion of the physician, left atrial posterior wall isolation was also performed in seven patients.

PVI was achieved in 101 of 105 veins (95%), with the procedure aborted after isolation of one of four veins in one patient after the catheter malfunctioned and a replacement was unavailable.

Posterior wall and/or cavotricuspid isthmus block isolation was achieved in all seven patients, adding an additional five minutes of ablation time. The total procedure time averaged 134 minutes.

Among 13 patients treated with PVI only using the first-generation catheter and no cryomapping, there were two cases of phrenic nerve palsy that persisted for some time, but with full recovery.

Among 13 patients treated with PVI with or without linear lesions using the second-generation catheter, there were no complications.

Thoracoscopic ablation and left atrial appendage excision found to be superior to catheter ablation for long-term freedom from Symptomatic atrial fibrillation (AF) patients with previous failed catheter ablation or structural changes associated with higher recurrence of AF could benefit from thoracoscopic ablation and left atrial appendage excision. The thoracoscopic approach was associated with higher initial rates of peri-procedural events, but there was no difference in long-term major adverse clinical outcomes during follow-up and less need for additional rhythm control. Dipak Kotecha (University of Birmingham, Birmingham, UK) presented the findings at the European Heart Rhythm Association Congress (EHRA; 18–20 March 2018, Barcelona, Spain) on behalf of the FAST team.

T

he FAST trial (Thoracoscopic vs. catheter ablation for AF) was a two country (Spain and The Netherlands) randomised controlled trial.

It looked at patients with failed catheter ablation or hypertension with a dilated left atrium and patients were randomised to receive thoracoscopic ablation (n=63) or catheter ablation (n=66), which consisted of pulmonary vein isolation with optional additional lines. The one year outcomes were published in 2012, and showed higher rates of success but more perioperative complications with

thoracoscopic ablation.

The follow-up study looked at all patients and they were reassessed in 2016 and 2017. All of the patients without clinical recurrence of AF underwent a further seven day ambulatory ECG. Major adverse clinical outcomes were confirmed by medical records and central government databases.

The primary rhythm endpoint was the recurrence of any atrial arrhythmia lasting more than 30 seconds during followup. The primary clinical endpoint was composite death, myocardial infarction or

cerebrovascular event (transient ischaemic attach or ischaemic/haemorrhagic stroke).

The principal finding was that atrial arrhythmia recurrence was significantly lower in the thoracoscopic ablation group, 56% (34/61), compared to 87% (55/63) in the catheter ablation group (adjusted hazard ratio 0.40, 95% CI 0.25-0.64, p˂0.001). The rate of death, myocardial infarction or cerebrovascular events was similar in both groups: 15% in the thoracoscopic group and 16% in the catheter ablation group (adjusted hazard ratio 1.11, 95% CI 0.40-3.10). All cause mortality was 7% in the thoracoscopic group and 8% in the catheter ablation group (adjusted hazard ratio 0.94, 95% CI 0.18-4.94).

Recurrence of atrial arrhythmia increased sharply after around a year.

The catheter ablation arm had a very progressive decline whereas it stabilised in the thoracoscopic ablation arm. At a mean follow-up period of seven years, the difference between them was statistically significant, with a p˂0.001. At final follow-

Dipak Kotecha

up, antiarrhythmic drugs were used in 19% of the thoracoscopic arm compared to 39% in the catheter ablation arm. Additional ablation procedures were needed in 13% of the thoracoscopic arm and 49% of the catheter ablation arm.

The primary safety endpoint showed no difference in long-term outcomes between the two arms despite the higher initial perioperative risk in the thoracoscopic group. Ten percent of the thoracoscopic ablation arm had received pacemakers, double the 5% rate of the catheter ablation arm, but this wasn’t statistically significant (p=0.27).

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Autonomic modulation

Autonomic modulation for refractory ventricular arrhythmias: Going beyond the heart JASON S BRADFIELD AND KALYANAM SHIVKUMAR COMMENT & ANALYSIS Patients with scar-related ventricular tachycardia (VT) do not often achieve a cure. Jason S Bradfield and Kalyanam Shivkumar write in Cardiac Rhythm News about how to tackle this issue.

S

uccess with medical therapy or catheter ablation may involve long periods of VT-freedom or “remission” after a single or multiple treatments.

The treatment of life-threatening ventricular arrhythmias has important parallels to the treatment of cancer (and indeed has a mortality worse than many cancers).

VT treatment has a number of parallels. We historically have treated VT with medications with significant side-effect/toxicity risk, such as amiodarone, and when medications are unsuccessful or

untolerated, with VT ablation. VT ablation is not toxic/destructive to a large number of the patient’s normal cells as is chemotherapy.

However, we are ablating regions of the heart that while having the potential for supporting VT may never do so in hopes on minimising the chance of recurrence. Much like cancer patients, VT patients can often have recurrences after a period of “remission” and overall treatment success (VT-free survival) is modest. VT occurs in structural heart disease because of a combination of predominantly scar-related re-entry in combination

with a “maladaptive” autonomic response leading to a relative hyeradrenergic state.1 Further, there are different “kinds” of VT (monomorphic vs. polymorphic, fast vs. slow, focal vs. reentrant, etc) and yet we often treat them with the same modality.

The oncology community has begun to move outside their comfort zone of chemotherapy to explore immunotherapy for many cancers including lymphoma and lung cancer. This concept of programming T cells to more aggressively target cancer cells is revolutionising cancer treatment and as this technique is developed for more and more types of cancer, has the potential to save millions of lives.

As electrophysiologists we must be equally willing to think outside our comfort zone and perhaps outside our area of training. Given the limited options available, the approach to VT reoccurrence has often been ablate, and if that fails ablate some more. Yet, the data for neuromodulation as a treatment for VT is growing.

The body’s autonomic nervous system responds to insults such

as infarction in a way that it thinks is adaptive, but from an arrhythmia standpoint is maladaptive and pro-arrhythmic.2 Autonomic imbalance—increased sympathetic output relative to parasympathetic—is a clear trigger and modulator of VT. By intervening with neuromodulation we have the ability to counter this maladaptive response and potentially control VT. While not as specific a target at its current stage as is immunotherapy for cancer, there is clear data demonstrating benefit either in conjunction with or as an alternative to current treatment with medical therapy and ablation.

In the acute setting, thoracic epidural anesthesia3 and percutaneous stellate block4 are useful tools to manage VT storm as a bridge to more definitive therapy.

Intermediate and long-term benefits are seen with cardiac sympathetic denervation via bilateral stellate ganglionectomy.5 Additionally, renal denervation show early promising data.6 Medical therapy and catheter ablation will remain cornerstones of arrhythmia management for

the foreseeable future. Yet, scientific advancements in neurocardiology and data for clinical neuromodulation therapy for VT continues to grow. Much like our oncology colleagues, we must embrace the opportunity to expand our understanding of a life-threatening disease and the treatment options, even when the science and treatment modalities involve areas outside our original training.

Jason S. Bradfield and Kalyanam Shivkumar, University of California, Los Angeles Cardiac Arrhythmia Center, Los Angeles, CA References:

1. Bradfield JS, Ajijola OA, Vaseghi M and Shivkumar K. Mechanisms and management of refractory ventricular arrhythmias in the age of autonomic modulation. Heart Rhythm. 2018.

2. Huang WA, Boyle NG and Vaseghi M. Cardiac Innervation and the Autonomic Nervous System in Sudden Cardiac Death. Card Electrophysiol Clin.

2017;9:665-679.

3. Do DH, Bradfield J, Ajijola OA, Vaseghi M, Le J, Rahman S, Mahajan A, Nogami A, Boyle NG and Shivkumar K. Thoracic Epidural Anesthesia Can Be Effective for the Short-Term Management of Ventricular Tachycardia Storm. J Am Heart Assoc. 2017;6.

4. Meng L, Tseng CH, Shivkumar K and Ajijola O. Efficacy of Stellate Ganglion Blockade in Managing Electrical Storm: A Systematic Review. JACC Clin Electrophysiol. 2017;3:942-949.

5. Vaseghi M, Barwad P, Malavassi Corrales FJ, Tandri H, Mathuria N, Shah R, Sorg JM, Gima J, Mandal K, Saenz Morales LC, Lokhandwala Y and Shivkumar K. Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. J Am Coll Cardiol.

2017;69:3070-3080.

6. Bradfield JS, Vaseghi M and Shivkumar K. Renal denervation for refractory ventricular arrhythmias. Trends Cardiovasc Med. 2014;24:206-13.

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Product news

Product News Battery performance alert and cybersecurity firmware updates for certain Abbott implantable cardiac devices: FDA safety communication The US Food and Drug administration (FDA) has approved a firmware update that is now available and is intended as a corrective action (recall), to reduce the risk of patient harm due to premature battery depletion and potential exploitation of cybersecurity vulnerabilities for certain Abbott implantable cardiac defibrillators (ICDs) and cardiac resynchronisation therapy defibrillator (CRT-Ds). “Firmware” is a specific type of software embedded in the hardware of a medical device (e.g. a component in the defibrillator).

This firmware update includes mitigations to address two separate issues: 1) a device-based Battery Performance Alert to detect rapid battery depletion in devices subject to the Battery Advisory from October 2016, and 2) updates to address cybersecurity vulnerabilities across Abbott’s radio frequency (RF) enabled ICDs and CRT-Ds. Abbott’s (formerly St. Jude Medical) ICDs and cardiac resynchronisation therapy defibrillators CRT-Ds are devices that provide pacing for slow heart rhythms, and electrical shock or pacing to stop dangerously fast heart rhythms.

ICDs and CRT-Ds are both implanted under the skin in the upper chest area with connecting insulated wires (“leads”) that go into the heart. A patient may need an ICD or CRT-D if their heartbeat is too slow (bradycardia), too fast (tachycardia), or needs coordination to treat heart failure.

The FDA recommends that all eligible patients receive the firmware update at their next regularly scheduled visit or when appropriate, depending on the preferences of the patient and physician.

For the purposes of this safety communication, cybersecurity focuses on protecting patients’ medical devices and their associated computers, networks, programs, and data from unintended or unauthorised threats.

New analyses show that AdaptivCRT algorithm reduces AF episodes in patients

Two real-world analyses featuring the AdaptivCRT algorithm reinforce that its use is linked to a reduction in atrial fibrillation (AF) episodes, as well as tied to higher patient activity levels. The results, involving

408 patients with heart failure and a cardiac resynchronisation therapy (CRT) device at 26 centres in Italy, were unveiled at the European Heart Rhythm Association (EHRA) Scientific Sessions 2018 in Barcelona, Spain.

The first analysis revealed a significant reduction in the incidence of AF episodes of all measured durations (greater than: one hour, six hours, 12 hours, one day and seven days; p=0.017 for episodes lasting longer than six hours) in 210 patients with AdaptivCRT ON compared to 198 patients with conventional CRT. “Atrial fibrillation is a common comorbidity among patients with heart failure,” says Alessandro Proclemer, of University Hospital Santa Maria della Misericordia, Udine, Italy. “Progression of AF is linked to an increased risk of stroke and death, so it is encouraging to see additional clinical data that again links AdaptivCRT with a reduction in the incidence of AF in these patients.”

The second analysis showed AdaptivCRT was significantly and independently associated with a higher daily activity level for patients with the feature ON compared to those with conventional CRT (AdaptivCRT ON at 3.1 hours vs.

AdaptivCRT OFF at 2.6 hours; p=0.010).

“This finding is important since heart failure patients with low activity levels are more likely to be hospitalised, or even die,” says Saverio Iacopino, of Maria Cecilia Hospital in Cotignola, Italy. “We want our patients to be as active as possible, given the seriousness of their heart condition.”

Heart failure is a progressive condition, affecting more than 26 million people worldwide. CRT is an established treatment for some heart failure patients that uses an implantable defibrillator (CRT-D) or pacemaker (CRT-P) to improve the pumping efficiency of the heart.

The AdaptivCRT algorithm—first available on Medtronic CRT-Ds in 2013 and CRT-Ps in 2014— adjusts the way the implanted device paces the heart according to minute-to-minute evaluations of each patient’s rhythm. Evidence from the randomised clinical trial demonstrated that AdaptivCRT increases CRT response rate, reduces unnecessary right ventricular pacing, and improves clinical outcomes for patients with normal AV conduction .1-4 Additional analyses showed AdaptivCRT reduces patients’ odds of a 30-day heart failure readmission, and reduced their risk of AF.1,5 Continued on page 24

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atrial fibrillation

Product News Continued from page 23

References

1.Martin D, et al. Clinical outcomes with adaptive cardiac resynchronization therapy: Long-term outcomes of the Adaptive CRT Trial. HFSA Annual Scientific Meeting.

September 23, 2013.

2.Martin D, Lemke B, Birnie D, et al. Investigation of a novel algorithm for synchronized left ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: results of the adaptive CRT trial. Heart Rhythm. 2012; 9(11): 1807-1814.

3.Birnie D, et al. Clinical outcomes with synchronized leftventricular pacing: analysis of the adaptive CRT trial. Heart Rhythm 2013; 10(9): 1368-1374.

4.Singh JP, Abraham WT, Chung ES, et al. Clinical response with adaptive CRT algorithm compared with CRT with echocardiography-optimized atrioventricular delay: a retrospective analysis of multicentre trials. Europace 2013; 15(11): 1622-1628.

5.Starling RC, Krum H, Bril S, et al. Impact of a Novel Adaptive Optimization Algorithm on 30-Day Readmissions: Evidence From the Adaptive CRT Trial. JACC Heart Fail. July 2015;3(7):565-572.

Study shows positive results with cryoballoon for patients with persistent

Atrial fibrillation detection with smartwatch or smartphone camera achieved >95% accuracy

T

he results of the WATCH AF trial, the world’s first international, prospective and doubleblinded clinical trial (ClinicalTrials. gov ID: NCT02956343) evaluating the accuracy of a smartwatch to detect atrial fibrillation were announced at the European Heart Rhythm Association Congress. (EHRA 2018; 18–20 March, Barcelona, Spain). Preventicus, a German based company, provided the application for blinded analysis of one minute plethysmographic raw data (recorded with Samsung Gear Fit II smartwatch) of 636 study participants.

Total accuracy of the application was 95.7% with a positive predictive value of 97.8% in comparison to the ECG based diagnosis of two cardiologists by mutual agreement.

The smartwatch application “Preventicus Nightwatch®” incorporates that algorithm. It can continuously 24/7 analyse plethysmographic raw data and document atrial fibrillation events lasting at least one minute. The application will be launched in Europe as a certified medical device.

The same atrial fibrillation detection algorithm is already available in a smartphone camera application (“Preventicus® Heartbeats”, a CE marked medical device in the EU). The results of the corresponding DETECT AF PRO trial (ClinicalTrials.gov ID: NCT02949180) were introduced for the first time at EHRA as well. DETECT AF PRO is a separate trial from WATCH AF and is a prospective, double-blinded,

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Product news

international study as well with 672 participants. Total accuracy of the smartphone camera application to detect atrial fibrillation was 96.5% with a positive predictive value of 99.3% compared to the ECG based diagnosis of two cardiologists by mutual agreement.

Atrial fibrillation events detected by the Preventicus algorithm are accessible on a dedicated ICT platform, allowing medical professionals to oversee their patients using the new technology. The Preventicus algorithm analyses every single heartbeat recorded and classifies it as regular or irregular. The resulting report enables medical professionals to beat by beat comprehend the recorded events.

The WATCH AF trial used the Preventicus Nightwatch smartwatch application.

The one-year results from the CRYO4PERSISTENT AF study of ablation with the Arctic Front Advance Cryoballoon to isolate the pulmonary veins in patients with symptomatic persistent atrial fibrillation (AF) ahve been announced. The Arctic Front Advance Cyroablation System (Medtronic) is not approved for treating persistent AF in the USA. The study results, presented at the European Heart Rhythm Association (EHRA) Scientific Sessions 2018 in Barcelona, Spain, showed 60.7% of persistent AF patients were free from all atrial arrhythmias (adjudicated AF, atrial flutter or atrial tachyarrhythmias) lasting more than 30 seconds, at one year following a single ablation procedure. These clinically meaningful results are on par with outcomes seen in the FIRE AND ICE trial of paroxysmal AF patients (approximately 70% at 12 months), and are encouraging given these patients are in a more advanced disease state.

The study findings also demonstrated short and predictable procedure times of 53±22 minutes with the cryoballoon and a low device- and/or procedure-related complication rate of 4%.

“The findings demonstrate the benefits of cryoablation therapy in reducing the significant burden patients experience once AF progresses, and hold promise for physicians to realise efficient procedure times and a low rate of adverse events for their persistent AF patients,” says Serge Boveda, codirector of the Cardiac Arrhythmias Department in Clinique Pasteur, Toulouse, France, and co-principal investigator in the trial. “These results are encouraging and demonstrate the reproducibility of the cryoballoon procedure even in patients with persistent AF.” “This is the first study of its kind to closely observe patients with persistent AF using a PVI-only strategy with the cryoballoon,” says Pascal Defaye, Arrhythmia Unit, Department of Cardiology, Grenoble-Alpes University Hospital, Grenoble, France, and co-principal investigator in the trial. “The results are noteworthy and provide valuable insights for the physician community.”

Clinical trial data further demonstrate safety and effectiveness of RHYTHMIA mapping system

The DETECT AF PRO trial used the Preventicus Heartbeats smartphone camera application.

Data from the TRUE-HD study has been announced during a late-breaking clinical trial session at the annual congress of the European Heart Rhythm Association (EHRA) in Barcelona, Spain. The data demonstrated the RHYTHMIA Mapping System (Boston Scientific), when paired with the INTELLAMAP

ORION Mapping Catheter, continues to be safe and effective for mapping and to support treatment of a wide variety of arrhythmias, including a cohort of patients who had unsuccessful ablation of atrial fibrillation using other techniques.

The global TRUE-HD study examined procedural process, acute success and safety for the mapping and ablation of various clinical arrhythmias. Depending on the arrhythmia type, study data showed an acute success rate of up to 95.7%.

In 222 patients, procedure process included the creation of validation maps to confirm the termination of an arrhythmia. Utilisation of the RHYTHMIA Mapping System vMap feature allowed physicians to rapidly assess therapy efficacy and determine if other arrhythmias were present.

When completed, validation mapping identified the need for additional ablations in 73.% of patients.

“This study was the first to perform systematic data collection on a range of arrhythmia types using the RHYTHMIA Mapping System,” said Gerhard Hindricks, principal investigator and head of the electrophysiology department at Leipzig University Heart Center in Germany. “Importantly, validation mapping allowed for precise views of therapy success and the identification of new areas in the heart requiring additional ablations that would have otherwise gone untreated.”

The observational, prospective, non-randomized study enrolled 572 patients eligible for cardiac mapping and ablation to treat an arrhythmia, with the exception of those diagnosed with de novo atrial fibrillation. The ablation-related complications were low and similar to those reported in recent literature1, with only 0.57% potentially related to the mapping catheter.

References

Haegeli LM, Catheter ablation of atrial fibrillation: an update.

Eur Heart J., 2014(36): p. 2454-9.

Medtronic: class I recallmanufacturing error preventing electrical shock delivery

Medtronic is recalling certain implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy defibrillators (CRT-Ds) due to a defect in the manufacturing process. This defect causes an out of specification gas mixture inside the device and may prevent the device from delivering the electrical shock needed to pace a patient’s heartbeat or revive a patient in cardiac arrest.The delay or inability to deliver a shock to a patient in cardiac arrest or pace a patient’s heart whose heartbeat is too slow could result in serious injury and/or death.

On January 22 2018 Medtronic sent an Urgent Medical Device Recall notice to affected customers.

Medtronic will offer a supplemental device warranty for affected devices.

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Clinical News HeartSciences announces publication of clinical study results A medical device company has announced the results of a clinical study serially conducted at The Icahn School of Medicine, Mount Sinai Hospital, New York, USA and the West Virginia University (WVU) Heart and Vascular Institute, Morgantown, USA. The were published in the April 17, 2018 issue of Journal of the American College of Cardiology (JACC), a peer-reviewed journal in cardiovascular medicine.

The article titled “Prediction of Abnormal Myocardial Relaxation from Signal Processed Surface ECG” presents the results from the investigator-initiated clinical study that focused on evaluating the feasibility of MyoVista Wavelet ECG (wavECG) as a diagnostic tool for predicting myocardial relaxation abnormalities. Abnormal relaxation is an early feature of many types of heart disease and a key characteristic

of left ventricular diastolic dysfunction (LVDD). It is typically detected using echocardiographic imaging. LVDD is a strong predictor of cardiovascular and all-cause mortality.1 Ischaemia, hypertension, diabetes, valvular disease and reduced systolic function are all associated with LVDD. 1, 2 Results from the feasibility study demonstrate MyoVista patented technology can detect myocardial relaxation abnormalities associated with LVDD. The study results demonstrated 80% sensitivity and 84% specificity with an area under the curve of 91% for the prediction of low (e’), an echocardiographic parameter widely used in determination of LVDD. Prediction of low (e’) also correctly identified 23 out of 28 study subjects (82%), with significant underlying coronary artery disease.

Additionally, MyoVista wavECG prediction of relaxation abnormalities also allowed recognition of subjects with more advanced stages of

diastolic dysfunction and concurrent coronary artery disease with significantly more incremental value compared with clinical variables and conventional ECG information.

The feasibility study was performed using machine learning analysis often described as artificial intelligence or AI. The study included a limited number of patients as well as other limitations and future studies were recommended to address these limitations.

Conclusions of the trial suggest a potential role for the MyoVista wavECG Device as a screening tool for patients at risk for LVDD that would benefit from echocardiographic evaluations.

Partho Sengupta, professor, chief of Cardiology and Chair of Cardiac Innovation, WVU Heart & Vascular Institute and Principal Investigator in the study, comments, “These data are extremely encouraging as they suggest a potential role of signal processed ECG in early cardiac disease detection. It is quite remarkable that MyoVista demonstrated a high diagnostic precision in detecting a state of cardiac muscle dysfunction only previously detectable using cardiac ultrasound techniques. This

can eventually help in appropriate cardiac testing and reduce overall healthcare costs.”

A total of 188 subjects referred from outpatient clinics to the Icahn School of Medicine, Mount Sinai Hospital for coronary computed tomography (CT) angiography also undertook in the same visit, comprehensive two-dimensional echocardiography (including tissue Doppler) that included assessment of LVDD. Subjects with arrhythmias, unstable angina, previous cardiac surgery, a pacemaker, chest deformity, or an inability to express well-defined mitral annular velocities due to severe mitral annular calcifications were excluded. Additional analysis was conducted related to a comparison cohort that were evaluated at WVU, Heart and Vascular Institute, which further validated MyoVista wavECG healthy patient characteristics ,as well as age and population distribution information References

1.LV Diastolic Dysfunction and Prognosis, Dalane W. Kitzman, et al., Circulation, 2012 February 14: 125(6): 743-745. doi:10.1161.CIRCULATIONAHA.111.086843 2. Diastolic Dysfunction and Diastolic Heart Failure: Diagnostic, Prognostic and Therapeutic Aspects, Maurizio Galderisi, Cardiovascular Ultrasound, 2005, 3-9 doi:10.1186/14767120-3-9

Calendar of events 10–12 March

ACC: American College of Cardiology - Scientific Session Orlando, USA W: www.accscientificsession.acc.org

18–20 March

EHRA: Annual congress of the European Heart Rhythm Association Barcelona, Spain W: www.escardio.org/EHRA

9–12 May

17–20 October

Heart Rhythm Scientific Sessions Boston, USA

APHRS: Asia Pacific Heart Rhythm Society Scientific Session

W: www.hrssessions.org

Taipei, Taiwan W: www.aphrs2018.tw

26–29 May

22–24 October

Heart Failure 2018

27th European Cardiology Conference

Vienna, Austria

Rome, Italy

W: www.escardio.org

W: www.cardiologyconference.cardiologymeeting.com

3–5 October

28–31 October

21–24 April

ISCAT: 12th International symposium on catheter ablation techniques Paris, France

IDSS: 14th International Dead Sea Symposium - Innovations and Controversies in Cardiac Arrythmias

Prague, Czech Republic

W: www.iscat.net

Tel-Aviv, Israel

21st Prague Workshop on Catheter Ablation W: www.ablationworkshop.com

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Clinical news

W: www.idss-ep.com

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