Statement from the Asia Summit: Current state of arrhythmia care in Asia.

On May 27, 2022, the Asia Pacific Heart Rhythm Society and the Heart Rhythm Society convened a meeting of leaders from different professional societies of healthcare providers committed to arrhythmia care from the Asia Pacific region. The overriding goals of the meeting were to discuss clinical and health policy issues that face each country for providing care for patients with electrophysiologic issues, share experiences and best practices, and discuss potential future solutions. Participants were asked to address a series of questions in preparation for the meeting. The format of the meeting was a series of individual country reports presented by the leaders from each of the professional societies followed by open discussion. The recorded presentations from the Asia Summit can be accessed at https://www.heartrhythm365.org/URL/asiasummit-22. Three major themes arose from the discussion. First, the major clinical problems faced by different countries vary. Although atrial fibrillation is common throughout the region, the most important issues also include more general issues such as hypertension, rheumatic heart disease, tobacco abuse, and management of potentially life-threatening problems such as sudden cardiac arrest or profound bradycardia. Second, there is significant variability in the access to advanced arrhythmia care throughout the region due to differences in workforce availability, resources, drug availability, and national health policies. Third, collaboration in the area already occurs between individual countries, but no systematic regional method for working together is present.

Non-invasive mid-term electrocardiogram patch monitoring is effective in detecting atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a cause of serious morbidity such as stroke. Early detection and treatment of AF is important. Current guidelines recommend screening via opportunistic pulse taking or 12­lead electrocardiogram. Mid-term ECG patch monitors increases the sensitivity of AF detection. METHODS: The Singapore Atrial Fibrillation Study is a prospective multi-centre study aiming to study the incidence of AF in patients with no prior AF and a CHA2DS2-VASc score of at least 1, with the use of a mid-term continuous ECG monitoring device (Spyder ECG). Consecutive patients from both inpatient and outpatient settings were recruited from 3 major hospitals from May 2016 to December 2019. RESULTS: Three hundred and fifty-five patients were monitored. 6 patients (1.7%) were diagnosed with AF. There were no significant differences in total duration of monitoring between the AF and non-AF group (6.39 ± 3.19 vs 5.42 ± 2.46 days, p = 0.340). Patients with newly detected AF were more likely to have palpitations (50.0% vs 11.8%, p = 0.027). Half of the patients (n = 3, 50.0%) were diagnosed on the first day of monitoring and the rest were diagnosed after 24 h. On univariate analysis, only hyperlipidemia was associated with reduced odds of being diagnosed with AF (OR HR 0.08 CI 0.01-0.74, p = 0.025). In a group of 128 patients who underwent coronary artery bypass grafting and had post-operative ECG monitoring, 9 patients (7.0%) were diagnosed with post-operative AF. CONCLUSIONS: The use of non-invasive mid-term patch-based ECG monitoring is an effective modality for AF screening.

Improving the utilization of implantable cardioverter defibrillators for sudden cardiac arrest prevention (Improve SCA) in developing countries: Clinical characteristics and reasons for implantation refusal.

BACKGROUND: Despite available evidence that implantable cardioverter defibrillators (ICDs) reduce all-cause mortality among patients at risk for sudden cardiac death, utilization of ICDs is low especially in developing countries. OBJECTIVE: To summarize reasons for ICD or cardiac resynchronization therapy defibrillator implant refusal by patients at risk for sudden cardiac arrest (Improve SCA) in developing countries. METHODS: Primary prevention (PP) and secondary prevention (SP) patients from countries where ICD use is low were enrolled. PP patients with additional risk factors (syncope, ejection fraction < 25%, nonsustained ventricular tachycardia [NSVT], or frequent premature ventricular complexes) were further categorized as "1.5 PP patients." Candidates who declined implantation were asked for reasons for refusal. Baseline factors that may have influenced the implant decision were examined using logistic regression. RESULTS: Among 3892 patients, the implant refusal rate was 46.5% among PP patients (n = 2700), and 10.3% among SP patients (n = 1192). The most common refusal reason was inability to pay for the device (53.8%), followed by not believing in the benefits of the ICD (19.4%). Among PP ICD candidates, those with no syncope, no NSVT, no premature ventricular contractions, shorter QRS duration, no atrial arrhythmias, and no left bundle branch block were more likely to refuse implant. Among SP candidates, a history of cardiovascular surgery and no sinus node dysfunction were significant predictors of ICD refusal. Additionally, countries had significant differences in patient refusal rates among PP and SP groups. CONCLUSION: Implant refusal among PP patients is high in many countries. Increased reimbursement and better awareness of the benefits of an ICD could increase their utilization.

The Sex, Age, Medical History, Treatment, Tobacco Use, Race Risk (SAMe TT2R2) Score Predicts Warfarin Control in a Singaporean Population.

BACKGROUND: Warfarin reduces stroke risk in atrial fibrillation (AF) patients but requires ongoing monitoring. Time in therapeutic range (TTR) is used as a measure of warfarin control, with a TTR less than 60% associated with adverse patient outcomes. The Sex, Age, Medical history, Treatment, Tobacco use, Race (SAMe-TT2R2) score has been identified as a model able to predict warfarin control, but this has been tested in mainly Caucasian populations. Therefore, the aim of this study was to determine the ability of the SAMe-TT2R2 score to predict warfarin control in a Singaporean population consisting of Chinese, Malay, and Indian race. METHODS: Retrospective data were collected from the National Heart Centre Singapore for AF patients receiving warfarin between January and June 2014. The TTR and the SAMe-TT2R2 score were calculated for each patient. RESULTS: The 1137 non-valvular AF patients had a mean TTR of 58.0 ± 34.3% and a median SAMe-TT2R2 score of 3. The categorized SAMe-TT2R2 scores (2 versus >2) showed a significant reduction in mean TTR for the entire population (63.2% versus 55.8%, P = .0004) and also when categorized according to race for Chinese (62.7% versus 56.9%, P = .0075) and Malay (68.4% versus 50.6%, P = .0131) populations. CONCLUSION: The SAMe-TT2R2 tool is effective in predicting warfarin control in a Singaporean population as patients with a score greater than 2 had poor control. The minimum score for non-Caucasian patients is 2; thus, in these patients, the presence of any additional risk factors identified in the SAMe-TT2R2 tool categorizes them as unlikely to achieve adequate warfarin control and possible candidates for alternative anticoagulants.

Non-fluoroscopic navigation systems for radiofrequency catheter ablation for supraventricular tachycardia reduce ionising radiation exposure.

INTRODUCTION: The use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time. METHODS: We prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO® mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported. RESULTS: A total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 ± 11.1 minutes vs. 32.0 ± 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 ± 5,768 mGy*cm2 vs. CF: 21,070 ± 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups. CONCLUSION: The use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time.

Predictors of two-year mortality in Asian patients with heart failure and preserved ejection fraction.

INTRODUCTION: Mortality in patients with heart failure and preserved ejection fraction (HFpEF) remains high. Data from Asia is lacking. We aim to study the impact of ethnicity and other predictors of mortality in patients admitted for HFpEF in a multi-ethnic Asian country. MATERIAL AND METHODS: Consecutive patients admitted to two local institutions with heart failure and ejection fraction ≥50% on transthoracic echocardiogram from Jan 2008 to Dec 2009 were included. All patients were followed-up for 2 years. Overall mortality was obtained from the national registry of deaths in our country. RESULTS: A total of 1960 patients with heart failure were included. 751 (38.3%) patients had HFpEF. Overall mortality at two years was 26.6% (n=200) compared to 37.1% (n=449) in patients with reduced ejection fraction (HR 0.618 (95% CI 0.508-0.753), p<0.001). Ethnicity did not predict mortality. On multivariable Cox regression analysis, significant predictors of two-year mortality in HFpEF patients were older age (HR 1.027 (1.011-1.044)), prior myocardial infarction (HR 1.577 (1.104-2.253)), prior stroke (HR 1.475 (1.055-2.061)), smoking (HR 1.467 (1.085-1.985)), higher creatinine levels (HR 1.002 (1.001-1.003)) and use of mineralocorticoid receptor antagonists (HR 1.884 (1.226-2.896)). Use of warfarin (HR 0.506 (0.304-0.842)) and statins (HR 0.585 (0.435-0.785)) were associated with significantly lower mortality. CONCLUSIONS: In our Asian population presenting with HFpEF, two-year mortality was 26.6%. Ethnicity did not predict mortality. Older age, prior myocardial infarction, prior stroke, smoking, and higher creatinine levels were found to be significant predictors of mortality.

Prevalence of electrocardiographic abnormalities in an unselected young male multi-ethnic South-East Asian population undergoing pre-participation cardiovascular screening: results of the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol.

AIMS: Resting 12-lead electrocardiograms (ECGs) have been employed in the pre-participation evaluation of young asymptomatic subjects to detect pre-existing heart diseases. Although the incorporation of routine ECG in pre-participation screening remains controversial, there is increasing evidence that cardiomyopathies and ion channelopathies have ECG changes as the initial manifestation. The causes of sudden cardiac death in young people show significant geographical variation. We aim to determine the prevalence and spectrum of ECG abnormalities in a young male South-East Asian population. METHODS AND RESULTS: The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE) protocol is an ECG-based pre-participation cardiac screening programme modelled after the Italian system. From October 2008 to May 2009, a total of 18 476 young male conscripts (mean age 19.5 years old, range 16-27) underwent mandatory pre-enlistment medical screening at a single medical facility. Subjects with abnormal ECG findings were classified into two groups: Group A had ECG changes that fulfilled a pre-specified checklist to screen for hypertrophic cardiomyopathy and were referred for transthoracic echocardiogram; Group B had other ECG abnormalities [such as Brugada pattern, Wolff-Parkinson-White (WPW) pattern, long QTc] and were referred for secondary screening at a tertiary institution. Of the 18 476 subjects screened, 7.0% (n= 1285) had ECG abnormalities. Of note, 19 (0.10%) had Brugada pattern, 25 (0.14%) had WPW pattern, and 31 (0.17%) had prolonged QT interval on ECG. The prevalence of ECG abnormalities was significantly higher in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). CONCLUSION: The prevalence of ECG abnormalities in a young, South-East Asian male population was 7.0%. There were significant ethnic differences, with ECG abnormalities more prevalent in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). The inclusion of universal ECG, in addition to history and physical examination, may increase the sensitivity of a cardiovascular screening programme. Knowledge of the spectrum and prevalence of ECG abnormalities and disease conditions would be pivotal in designing customized screening programmes.

Prevalence of hypertrophic cardiomyopathy on an electrocardiogram-based pre-participation screening programme in a young male South-East Asian population: results from the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol.

AIMS: Hypertrophic cardiomyopathy is a leading cause of sudden cardiac death (SCD) in young people in the USA. Pre-participation screening for athletes might reduce the incidence of SCD. In Singapore, military service is compulsory for all young able-bodied male citizens. The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE) pre-participation screening protocol based on the Italian programme was introduced. This study evaluates the prevalence of hypertrophic cardiomyopathy (HCM) in a young male South-East Asian population. METHODS AND RESULTS: From October 2008 to May 2009, all male military conscripts underwent pre-participation screening. For all conscripts whose electrocardiogram (ECG) findings fulfilled any of these pre-specified criteria (Group A), direct referral for a transthoracic echocardiogram was mandatory. Conscripts with ECG findings other than pre-specified criteria (e.g. T-wave inversions, repolarization abnormalities) were referred for secondary screening by cardiologists (Group B), which could include echocardiography. Out of 18 476 subjects screened during the study period, 988 (5.3%) subjects were fast tracked for echocardiogram (Group A). Of them, there were three (0.3%) cases with severe abnormalities; there was one case each of HCM, bicuspid aortic valve with significant aortic valve regurgitation, and atrial septal defect with right ventricular systolic dysfunction. The patient with HCM had left axis deviation on ECG. None of the 215 patients who underwent echocardiography following cardiology consult (Group B) had HCM. CONCLUSION: The prevalence of HCM in our young male population (mean age 19.5, range 16-27) using an ECG-based screening protocol was 0.005%; this appeared lower than published data from other geographical cohorts. Possible explanations include a later age of phenotypic manifestation in our population, limitations of the ECG criteria for screening, or a truly lower prevalence of HCM. More population-based longitudinal studies would be needed to ascertain the true prevalence of HCM in our South-East Asian population.

Is there an association between external cardioversions and long-term mortality and morbidity? Insights from the Atrial Fibrillation Follow-up Investigation of Rhythm Management study.

BACKGROUND: Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. METHODS AND RESULTS: We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥ 1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥ 3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P < 0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P < 0.0001). CONCLUSIONS: In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.

Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation.

BACKGROUND: Ablation of long-standing persistent atrial fibrillation (AF) remains challenging, with a lower success rate than paroxysmal AF. A reliable ablation endpoint has not been demonstrated yet, although AF termination during ablation may be associated with higher long-term maintenance of sinus rhythm (SR). OBJECTIVE: The purpose of this study was to determine whether the method of AF termination during ablation predicts mode of recurrence or long-term outcome. METHODS: Three hundred six patients with long-standing persistent AF, free of antiarrhythmic drugs (AADs), undergoing a first radiofrequency ablation (pulmonary vein [PV] antrum isolation and complex fractionated atrial electrograms) were prospectively included. Organized atrial tachyarrhythmias (AT) that occurred during AF ablation were targeted. AF termination mode during ablation was studied in relation to other variables (characteristics of arrhythmia recurrence, redo procedures, the use of adenosine/isoproterenol for redo, and comparison of focal versus macroreentrant ATs). Long-term maintenance of SR was assessed during the follow-up. RESULTS: During AF ablation, six of 306 patients converted directly to SR, 172 patients organized into AT (with 38 of them converting in SR with further ablation), and 128 did not organize or terminate and were cardioverted. Two hundred eleven of 306 patients (69%) maintained in long-term SR without AADs after a mean follow-up of 25 +/- 6.9 months, with no statistical difference between the various AF termination modes during ablation. Presence or absence of organization during ablation clearly predicted the predominant mode of recurrence, respectively, AT or AF (P = .022). Among the 74 redo ablation patients, 24 patients (32%) had extra PV triggers revealed by adenosine/isoproterenol. Termination of focal ATs was correlated with higher long-term success rate (24/29, 83%) than termination of macroreentrant ATs (20/35, 57%; P = .026). CONCLUSION: AF termination during ablation (conversion to AT or SR) could predict the mode of arrhythmia recurrence (AT vs. AF) but did not impact the long-term SR maintenance after one or two procedures. AT termination with further ablation did not correlate with better long-term outcome, except with focal ATs, for which termination seems critical.

Relationship between catheter forces, lesion characteristics, "popping," and char formation: experience with robotic navigation system.

INTRODUCTION: Popping, char and perforation are complications that can occur following catheter ablation. We measured the amount of grams (g) applied to the endocardium during ablation using a sensor incorporated in the long sheath of a robotic system. We evaluated the relationship between lesion formation, pressure, and the development of complications. METHODS: Using a robotic navigation system, lesions were placed in the left atrium (LA) at six settings, using a constant duration (40 seconds) and flow rate of either 17 cc/min or 30 cc/min with an open irrigated catheter (OIC). Evidence of complications was noted and lesion location recorded for later analysis at necropsy. RESULTS: Lesions using 30 Watts (W) were more likely to be transmural at higher (>40 g) than lower (<30 g) pressures (75% vs 25%, P < 0.001). Significantly higher number of lesions using >40 g of pressure demonstrated "popping" and crater formation as compared with lesions with 20-30 g of pressure (41% vs 15%, P = 0.008). A majority of lesions placed using higher power (45 W) with higher pressures (>40 g) were associated with char and crater formation (66.7%). No lesions using 10 g of pressure were transmural, regardless of the power. Lesions placed with a power setting less than 35 W were more likely to result in "relative" sparing of the endocardial surface than lesions at a power setting higher than 35 W (62% vs 33.3%, P = 0.02) regardless of the pressure. CONCLUSIONS: When using an OIC, lower power settings (

Pulmonary vein calcification by EBCT in patients with drug refractory nonvalular atrial fibrillation.

INTRODUCTION: Pulmonary veins in patients with atrial fibrillation (AF) have been shown to be highly arrhythmogenic. Calcification in these veins may play an adjunctive role in the pathogenesis of AF. METHODS AND RESULTS: A case control study was performed in patients with drug refractory nonvalvular AF whose preablation computed tomography chest scans demonstrated pulmonary vein (PV) calcification. Eight out of 48 patients with PV calcification were compared to 50 patients without AF who underwent electron beam computed tomography coronary artery calcium scores. These patients were matched for age, gender, coronary artery calcium scores, and the presence of PV calcification. The mean age of the combined group was 57 +/- 9 years and 60% were men. The mean total PV calcium score was significantly higher at 199 +/- 112 in patients with AF compared to 106 +/- 52 in controls (p = 0.018). Men had significantly higher total PV calcium score than women in both groups. CONCLUSION: Total PV calcium score was significantly higher in patients with atrial fibrillation. Increased PV calcification may play an adjunctive role in the pathogenesis in initiating and maintaining AF.

Mutation screening in KCNQ1, HERG, KCNE1, KCNE2 and SCN5A genes in a long QT syndrome family.

INTRODUCTION: Long QT syndrome (LQTS), an inherited cardiac arrhythmia, is a disorder of ventricular repolarisation characterised by electrocardiographic abnormalities and the onset of torsades de pointes leading to syncope and sudden death. Genetic polymorphisms in 5 well-characterised cardiac ion channel genes have been identified to be responsible for the disorder. The aim of this study is to identify disease-causing mutations in these candidate genes in a LQTS family. MATERIALS AND METHODS: The present study systematically screens the coding region of the LQTS-associated genes (KCNQ1, HERG, KCNE1, KCNE2 and SCN5A) for mutations using DNA sequencing analysis. RESULTS: The mutational analysis revealed 7 synonymous and 2 non-synonymous polymorphisms in the 5 ion channel genes screened. CONCLUSION: We did not identify any clear identifiable genetic marker causative of LQTS, suggesting the existence of LQTS-associated genes awaiting discovery.

Impact of left ventricular epicardial and biventricular pacing on ventricular repolarization in normal-heart individuals and patients with congestive heart failure.

AIMS: Malignant ventricular arrhythmias can arise in a subset of congestive heart failure (CHF) patients after they undergo cardiac resynchronization therapy (CRT), thus counteracting the haemodynamic benefits typically associated with biventricular pacing. This study seeks to assess whether alteration of the ventricular transmural repolarization and conduction due to reversal of the depolarization sequence during epicardial or biventricular pacing facilitate the development of ventricular arrhythmias. METHODS AND RESULTS: ECGs and monophasic action potential (MAP) were recorded during programmed stimulation from right ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or both (biventricular, Bi-V) in 15 individuals without structural heart diseases. In patients with severe CHF and CRT (n=21), ECGs were collected during RV-Endo, LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT, and T(peak)-T(end) intervals on ECGs at different pacing sites were measured and compared. In subjects with or without structural heart disease, compared with RV-Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+/-61.97 ms with LV-Epi, 325.86+/-59.69 ms with Bi-V vs. 286.14+/-38.68 ms with RV-Endo in CHF individuals, P<0.0001) or T(peak)-T(end) interval (121.55+/-19.88 ms with LV-Epi, 117.71+/-42.63 ms with Bi-V vs. 102.28+/-12.62 ms with RV-Endo in normal-heart subjects, P<0.0001; 199.70+/-62.44 ms with LV-Epi, 184.89+/-74.08 ms with Bi-V vs. 146.41+/-31.06 ms with RV-Endo in CHF patients, P<0.0001), in addition to prolonged myocardial repolarization time and delayed endocardial activation. During follow-up, sudden death and arrhythmia storm occurred in two CHF patients after CRT. CONCLUSION: Epicardial and biventricular pacing prolong the time and increase the dispersion of myocardial repolarization and delay the transmural conduction. All of these should be considered as potential arrhythmogenic factors in CHF patients who receive CRT.

Congenital long QT syndromes: clinical features, molecular genetics and genetic testing.

Congenital long QT syndrome (LQTS) is a primary electrical disease characterized by a prolonged QT interval in the surface electrocardiogram and increased predisposition to a typical polymorphic ventricular tachycardia, termed Torsade de Pointes. Most patients with LQTS are asymptomatic and are diagnosed incidentally based on an electrocardiogram. Symptomatic patients may suffer from severe cardiac events, such as syncope and/or sudden cardiac death. Autosomal dominant forms are caused by heterozygous mutations in genes encoding the components of the ion channels. The autosomal recessive form with congenital deafness is also known as Jervell and Lang-Nielsen syndrome. It is caused by homozygous mutations or certain compound heterozygous mutations. Depending on the genetic defects, there are differences in the age of onset, severity of symptoms, and number of cardiac events and event triggers. With advances in gene technology, it is now feasible to perform genetic testing for LQTS, especially for those with family history. Identification of the mutation will lead to better management of symptoms and more targeted treatment, depending on the underlying genetic defect, resulting in a reduction of mortality and cardiac events.