The Prevalence and Characteristics of Arrhythmic Mitral Valve Prolapse in Patients With Unexplained Cardiac Arrest.

BACKGROUND: There is growing evidence that mitral valve prolapse (MVP) is associated with otherwise unexplained cardiac arrest (UCA). However, reports are hindered by the absence of a systematic ascertainment of alternative diagnoses. OBJECTIVES: This study reports the prevalence and characteristics of MVP in a large cohort of patients with UCA. METHODS: Patients were enrolled following an UCA, defined as cardiac arrest with no coronary artery disease, preserved left ventricular ejection fraction, and no apparent explanation on electrocardiogram. A comprehensive evaluation was performed, and patients were diagnosed with idiopathic ventricular fibrillation (IVF) if no cause was found. Echocardiography reports were reviewed for MVP. Patients with MVP were divided into 2 groups: those with IVF (AMVP) and those with an alternative diagnosis (nonarrhythmic MVP). Patient characteristics were then compared. The long-term outcomes of AMVP were reported. RESULTS: Among 571 with an initially UCA, 34 patients had MVP (6%). The prevalence of definite MVP was significantly higher in patients with IVF than those with an alternative diagnosis (24 of 366 [6.6%] vs 5 of 205 [2.4%]; P = 0.03). Bileaflet prolapse was significantly associated with AMVP (18 of 23 [78%] vs 1 of 8 [12.5%]; P = 0.001; OR: 25.2). The proportion of patients with AMVP who received appropriate implantable cardioverter-defibrillator therapies over a median follow-up of 42 months was 21.1% (4 of 19). CONCLUSIONS: MVP is associated with otherwise UCA (IVF), with a prevalence of 6.6%. Bileaflet prolapse appears to be a feature of AMVP, although future studies need to ascertain its independent association. A significant proportion of patients with AMVP received appropriate implantable cardioverter-defibrillator therapies during follow-up.

Paced P-wave morphology templates to guide atrial tachycardia localization: A derivation and validation study.

BACKGROUND: Surface ECG is a useful tool to guide mapping of focal atrial tachycardia (AT). OBJECTIVES: We aimed to construct 12-lead ECG templates for P-wave morphology (PWM) during endocardial pacing from different sites in both atria in patients with no apparent structural heart disease (derivation cohort), with the goal of creating a localization algorithm, which could subsequently be validated in a cohort of patients undergoing catheter ablation of focal AT (validation cohort). METHODS: We prospectively enrolled consecutive patients who underwent electrophysiology study, had no structural heart disease and no atrial enlargement. Atrial pacing, at twice diastolic threshold, was carried out at different anatomical sites in both atria. Paced PWM and duration were assessed. An algorithm was generated from the constructed templates of each pacing site. The algorithm was applied on a retrospective series of successfully ablated AT patients. Overall and site-specific accuracy were determined. RESULTS: Derivation cohort included 65 patients (25 men, age 37 ± 13 years). Atrial pacing was performed in 1025 sites in 61 patients (95%) in RA and in 15 patients (23%) in LA. The validation cohort included 71 patients (28 men, age 52 ± 19 years). AT were right atrial in 66.2%. The algorithm successfully predicted AT origin in 91.5% of patients (100% in LA and 87.2% in RA). It was off by one adjacent segment in the remaining 8.5%. CONCLUSIONS: A simple ECG algorithm based on paced PWM templates was highly accurate in localizing site of origin of focal AT in patients with structurally normal hearts.

Prevalence and management of electrical lead abnormalities in cardiac implantable electronic device leads.

Background: Electrical lead abnormalities (ELAs) can result in device malfunction, leading to significant morbidity in patients with cardiac implantable electronic devices (CIEDs). Objective: We sought to determine the prevalence and management of ELAs in patients with CIEDs. Methods: This was a retrospective cohort study of patients implanted with a CIED between 2012 and 2019 at a tertiary care center. The primary outcome was ELA defined as increased capture threshold (≥2× implantation value), decreased sensing (≤0.5 implantation value), change in impedance (>50% over 3 months), or nonphysiologic potentials. A secondary outcome of device clinic utilization was also collected. Results: There were 2996 unique patients (35% female) included with 4600 leads (57% Abbott, 43% Medtronic). ELAs were observed in 135 (3%) leads, including 124 (92%) Abbott and 10 (7%) Medtronic leads (hazard ratio 9.25, P < .001). Mean follow-up was 4.5 ± 2.2 years. ELAs were associated smaller lead French size, atrial location, and Abbott leads. Lead revision was required in 28% of cases. Patients with lead abnormalities had 38% more in-clinic visits per patient year of follow-up compared with those without (P < .001). Conclusion: ELAs were more frequent in certain models, which increased rates of revision and follow-up. Identification of factors that mitigate these abnormalities to improve lead performance are required to improve care for these devices and provide efficient healthcare.

Disparities in Referral and Utilization of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with reduced left ventricular ejection fraction (LVEF). We investigated sex disparities in a contemporary Canadian population for utilization of primary prevention ICDs. METHODS: This was a retrospective cohort study on patients with reduced LVEF admitted to hospitals from 2010 to 2020 in Nova Scotia (population = 971,935). RESULTS: There were 4406 patients eligible for ICDs: 3108 (71%) men and 1298 (29%) women. The mean follow-up time was 3.9 ± 3.0 years. Rates of coronary disease were similar between men and women (45.8% vs 44.0%; P = 0.28), but men had lower LVEF (26.6 ± 5.9% vs 27.2 ± 5.8%; P = 0.0017). The referral rate for ICD was 11% (n = 487), with 13% of men (n = 403) and 6.5% of women (n = 84) referred (P < 0.001). The ICD implantation rate in the population was 8% (n = 358), with 9.5% of men (n = 296) and 4.8% of women (n = 62) (P < 0.001) receiving the device. Men were more likely than women to receive an ICD (odds ratio 2.08, 95% confidence interval 1.61-2.70; P < 0.0001)). There was no significant difference in mortality between men and women (P = 0.2764). There was no significant difference in device therapies between men and women (43.8% vs 31.1%; P = 0.0685). CONCLUSIONS: A significant disparity exists in the utilization of primary prevention ICDs between men and women in a contemporary Canadian population.

Ventricular Tachycardia and ICD Therapy Burden With Catheter Ablation Versus Escalated Antiarrhythmic Drug Therapy.

BACKGROUND: Catheter ablation improves ventricular tachycardia (VT) event-free (time to event) survival in patients with antiarrhythmic drug (AAD)-refractory VT and previous myocardial infarction (MI). The effects of ablation on recurrent VT and implantable cardioverter-defibrillator (ICD) therapy (burden) have yet to be investigated. OBJECTIVES: This study sought to compare the VT and ICD therapy burden following treatment with either ablation or escalated AAD therapy among patients with VT and previous MI in the VANISH (Ventricular tachycardia AblatioN versus escalated antiarrhythmic drug therapy in ISchemic Heart disease) trial. METHODS: The VANISH trial randomized patients with previous MI and VT despite initial AAD therapy to either escalated AAD treatment or catheter ablation. VT burden was defined as the total number of VT events treated with ≥1 appropriate ICD therapy. Appropriate ICD therapy burden was defined as the total number of appropriate shocks or antitachycardia pacing therapies (ATPs) delivered. The Anderson-Gill recurrent event model was used to compare burden between the treatment arms. RESULTS: Of the 259 enrolled patients (median age, 69.8 years; 7.0% women), 132 patients were randomized to ablation and 129 patients were randomized to escalated AAD therapy. Over 23.4 months of follow-up, ablation-treated patients had a 40% lower shock-treated VT event burden and a 39% lower appropriate shock burden compared with patients who received escalated AAD therapy (P <0.05 for all). A reduction in VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation patients was only demonstrated in the stratum of patients with amiodarone-refractory VT (P <0.05 for all). CONCLUSIONS: Among patients with AAD-refractory VT and a previous MI, catheter ablation reduced shock-treated VT event burden and appropriate shock burden compared with escalated AAD therapy. There was also lower VT burden, ATP-treated VT event burden, and appropriate ATP burden among ablation-treated patients; however, the effect was limited to patients with amiodarone-refractory VT.

Perceived self-efficacy and empowerment in patients at increased risk of sudden cardiac arrest.

Background: The role of multidisciplinary clinics for psychosocial care is increasingly recognized for those living with inherited cardiac conditions (ICC). In Canada, access to healthcare providers differ between clinics. Little is known about the relationship between access to specialty care and a patient's ability to cope with, and manage their condition. Methods: We leveraged the Hearts in Rhythm Organization (HiRO) to conduct a cross-sectional, community-based survey of individuals with ICC and their family members. We aimed to describe access to services, and explore the relationships between participants' characteristics, cardiac history and self-reported health status and self-efficacy (GSE: General Self-Efficacy Scale) and empowerment (GCOS-24: Genetic Counseling Outcome Scale). Results: We collected 235 responses from Canadian participants in 10 provinces and territories. Overall, 63% of participants reported involvement of a genetic counsellor in their care. Access to genetic testing was associated with greater empowerment [mean GCOS-24: 121.14 (SD = 20.53) vs. 105.68 (SD = 21.69); p = 0.004]. Uncertain genetic test results were associated with lower perceived self-efficacy (mean GSE: uncertain = 28.85 vs. positive = 33.16, negative = 34.13; p = 0.01). Low global mental health scores correlated with both lower perceived self-efficacy and empowerment scores, with only 11% of affected participants reporting involvement of psychology services in their care. Conclusion: Differences in resource accessibility, clinical history and self-reported health status impact the perceived self-efficacy and empowerment of patients with ICC. Future research evaluating interventions to improve patient outcomes is recommended.

Management of Inherited Arrhythmia Syndromes: A HiRO Consensus Handbook on Process of Care.

Inherited arrhythmia syndromes are rare genetic conditions that predispose seemingly healthy individuals to sudden cardiac arrest and death. The Hearts in Rhythm Organization is a multidisciplinary Canadian network of clinicians, researchers, patients, and families that aims to improve care for patients and families with inherited cardiac conditions, focused on those that confer predisposition to arrhythmia and sudden cardiac arrest and/or death. The field is rapidly evolving as research discoveries increase. A streamlined, practical guide for providers to diagnose and follow pediatric and adult patients with inherited cardiac conditions represents a useful tool to improve health system utilization, clinical management, and research related to these conditions. This review provides consensus care pathways for 7 conditions, including the 4 most common inherited cardiac conditions that confer predisposition to arrhythmia, with scenarios to guide investigation, diagnosis, risk stratification, and management. These conditions include Brugada syndrome, long QT syndrome, arrhythmogenic right ventricular cardiomyopathy and related arrhythmogenic cardiomyopathies, and catecholaminergic polymorphic ventricular tachycardia. In addition, an approach to investigating and managing sudden cardiac arrest, sudden unexpected death, and first-degree family members of affected individuals is provided. Referral to specialized cardiogenetic clinics should be considered in most cases. The intention of this review is to offer a framework for the process of care that is useful for both experts and nonexperts, and related allied disciplines such as hospital management, diagnostic services, coroners, and pathologists, in order to provide high-quality, multidisciplinary, standardized care.

Les syndromes d'arythmie héréditaires sont des troubles génétiques rares qui prédisposent des personnes en apparence en bonne santé à un arrêt cardiaque soudain et à la mort. L'organisation Hearts in Rhythm Organization est un réseau multidisciplinaire canadien qui regroupe des cliniciens, des chercheurs ainsi que des patients et leurs proches dans le but d'améliorer les soins prodigués aux patients atteints de maladies cardiaques héréditaires et à leur famille, en particulier dans le cas des maladies qui entraînent une prédisposition à l'arythmie et à un arrêt cardiaque soudain et/ou à la mort. Puisque ce champ de recherche évolue rapidement, la mise au point d'un guide pratique et simple à l'intention des professionnels de la santé pour le diagnostic et le suivi des patients enfants et adultes présentant une maladie cardiaque héréditaire serait donc un outil intéressant pour améliorer l'utilisation du système de santé et la prise en charge clinique de ces maladies tout en orientant la recherche à ce propos. La présente synthèse expose les trajectoires de soins faisant l'objet d'un consensus pour sept maladies, dont les quatre maladies cardiaques héréditaires les plus courantes qui prédisposent à l'arythmie. Elle présente aussi des scénarios pour orienter les examens, le diagnostic, la stratification du risque et la prise en charge des patients. Ces maladies sont le syndrome de Brugada, le syndrome du QT long, la cardiomyopathie arythmogénique du ventricule droit et les cardiomyopathies arythmogènes associées, et la tachycardie ventriculaire polymorphe catécholaminergique. En outre, une approche pour la prise en charge de l'arrêt cardiaque soudain, de mort subite inattendue et des membres de la famille immédiate de la personne touchée est proposée. L'orientation vers des cliniques spécialisées en cardiogénétique doit être envisagée dans la plupart des cas. L'objectif est d'établir un cadre de soins qui soit utile pour les experts et les non-experts ainsi que pour les professionnels des domaines connexes, par exemple le personnel de l'administration hospitalière et des services diagnostiques, les coroners et les pathologistes, en vue d'offrir des soins multidisciplinaires normalisés de grande qualité.

Incremental value of the signal-averaged ECG for diagnosing arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is currently diagnosed using a combination of clinical features, imaging, electrocardiography, and genetic investigations. An abnormal signal-averaged electrocardiogram (SAECG) is defined as a minor diagnostic criterion by the 2010 Task Force Criteria, but doubts remain about the value of this investigation. OBJECTIVE: We evaluated the utility of the SAECG in diagnosing ARVC using the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry, a population representative registry of probands with ARVC and relatives, less influenced by referral bias. METHODS: Probands with ARVC and family members from the Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry underwent phenotype review. SAECG parameters were compared individually and in combination between those with varying degrees of ARVC severity and healthy controls (family members of probands with ARVC and unexplained sudden death, free of evidence of cardiac disease). RESULTS: A total of 196 patients with ARVC and 205 controls were included (mean age 44 ± 15 years; 186 of 401 men [46%]). SAECG abnormalities were seen in 83 of 205 controls (40%), 33 of 68 patients with ARVC and mild disease (51%), and 31 of 42 with severe disease (74%). The SAECG associated strongly with imaging abnormalities (major: odds ratio 3.0, 95% confidence interval 1.3-6.9; minor: odds ratio 3.5, 95% confidence interval 0.7-16.5) but not with other aspects of phenotype. Patients carrying pathogenic variants but with minimal phenotype had similar SAECGs to healthy controls (filtered QRS duration 111.2 ± 11.2 ms vs 111 ± 7.6 ms, P = .93; duration of low amplitude signals < 40 µV 32.3 ± 8.9 ms vs 34.2 ± 7.2 ms, P = .32; root mean square of the terminal 40 ms of the filtered QRS complex 43.1 ± 25.2 ms vs 38.2 ± 20.2 ms, P = .38). CONCLUSION: The SAECG appears to be a surrogate marker for structural abnormalities seen on imaging in those with ARVC. Great caution is required in interpreting SAECG findings in those without other corroborating evidence of an ARVC phenotype.

Identification and in-silico characterization of splice-site variants from a large cardiogenetic national registry.

Splice-site variants in cardiac genes may predispose carriers to potentially lethal arrhythmias. To investigate, we screened 1315 probands and first-degree relatives enrolled in the Canadian Hearts in Rhythm Organization (HiRO) registry. 10% (134/1315) of patients in the HiRO registry carry variants within 10 base-pairs of the intron-exon boundary with 78% (104/134) otherwise genotype negative. These 134 probands were carriers of 57 unique variants. For each variant, American College of Medical Genetics and Genomics (ACMG) classification was revisited based on consensus between nine in silico tools. Due in part to the in silico algorithms, seven variants were reclassified from the original report, with the majority (6/7) downgraded. Our analyses predicted 53% (30/57) of variants to be likely/pathogenic. For the 57 variants, an average of 9 tools were able to score variants within splice sites, while 6.5 tools responded for variants outside these sites. With likely/pathogenic classification considered a positive outcome, the ACMG classification was used to calculate sensitivity/specificity of each tool. Among these, Combined Annotation Dependent Depletion (CADD) had good sensitivity (93%) and the highest response rate (131/134, 98%), dbscSNV was also sensitive (97%), and SpliceAI was the most specific (64%) tool. Splice variants remain an important consideration in gene elusive inherited arrhythmia syndromes. Screening for intronic variants, even when restricted to the ±10 positions as performed here may improve genetic testing yield. We compare 9 freely available in silico tools and provide recommendations regarding their predictive capabilities. Moreover, we highlight several novel cardiomyopathy-associated variants which merit further study.

Sex Differences and Utility of Treadmill Testing in Long-QT Syndrome.

Background Diagnosis of congenital long-QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal-to-borderline resting QT interval. A 3-step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3-step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex-specific cutoffs beyond the resting QTc. Methods and Results We identified 208 LQTS likely pathogenic or pathogenic KCNQ1 or KCNH2 variant carriers in the Canadian NLQTS (National Long-QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal-to-borderline range. The 4-minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4-minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1-minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1-minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients. Conclusions The 3-step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS.

Importance of genetic testing in unexplained cardiac arrest.

AIMS: Genetic testing is recommended in specific inherited heart diseases but its role remains unclear and it is not currently recommended in unexplained cardiac arrest (UCA). We sought to assess the yield and clinical utility of genetic testing in UCA using whole-exome sequencing (WES). METHODS AND RESULTS: Survivors of UCA requiring external defibrillation were included from the Cardiac Arrest Survivor with Preserved Ejection fraction Registry. Whole-exome sequencing was performed, followed by assessment of rare variants in previously reported cardiovascular disease genes. A total of 228 UCA survivors (mean age at arrest 39 ± 13 years) were included. The majority were males (66%) and of European ancestry (81%). Following advanced clinical testing at baseline, the likely aetiology of cardiac arrest was determined in 21/228 (9%) cases. Whole-exome sequencing identified a pathogenic or likely pathogenic (P/LP) variant in 23/228 (10%) of UCA survivors overall, increasing the proportion of 'explained' cases from 9% only following phenotyping to 18% when combining phenotyping with WES. Notably, 13 (57%) of the 23 P/LP variants identified were located in genes associated with cardiomyopathy, in the absence of a diagnosis of cardiomyopathy at the time of arrest. CONCLUSIONS: Genetic testing identifies a disease-causing variant in 10% of apparent UCA survivors. The majority of disease-causing variants was located in cardiomyopathy-associated genes, highlighting the arrhythmogenic potential of such variants in the absence of an overt cardiomyopathy diagnosis. The present study supports the use of genetic testing including assessment of arrhythmia and cardiomyopathy genes in survivors of UCA.

Ventricular tachycardia characteristics and outcomes with catheter ablation vs. antiarrhythmic therapy: insights from the VANISH trial.

AIMS: Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. METHODS AND RESULTS: All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [<150 b.p.m., 89/259, hazard ratio (HR) 1.7 (1.02-3.13)]. This effect was more pronounced among those taking amiodarone at baseline [HR of 2.22 (1.19-4.16)]. Presentation with VT storm (32/259) did not affect the primary outcome between groups. However, those presenting with VT storm on amiodarone had a trend towards worse outcomes with escalated antiarrhythmic therapy [HR 4.31 (0.55-33.93)]. CONCLUSION: The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.

Return of Results Policies for Genomic Research: Current Practices and the Hearts in Rhythm Organization (HiRO) Approach.

Research teams developing biobanks and/or genomic databases must develop policies for the disclosure and reporting of potentially actionable genomic results to research participants. Currently, a broad range of approaches to the return of results exist, with some studies opting for nondisclosure of research results and others following clinical guidelines for the return of potentially actionable findings from sequencing. In this review, we describe current practices and highlight decisions a research team must make when designing a return of results policy, from informed consent to disclosure practices and clinical validation options. The unique challenges of returning incidental findings in cardiac genes, including reduced penetrance and the lack of clinical screening standards for phenotype-negative individuals, are discussed. Finally, the National Hearts in Rhythm Organisation (HiRO) Registry approach is described to provide a rationale for the selective return of field-specific variants to those participating in disease-specific research. Our goal is to provide researchers with a resource when developing a return of results policy tailored for their research program, based on unique factors related to study design, research team composition, and availability of clinical resources.

Short-coupled ventricular fibrillation represents a distinct phenotype among latent causes of unexplained cardiac arrest: a report from the CASPER registry.

AIMS: The term idiopathic ventricular fibrillation (IVF) describes survivors of unexplained cardiac arrest (UCA) without a specific diagnosis after clinical and genetic testing. Previous reports have described a subset of IVF individuals with ventricular arrhythmia initiated by short-coupled trigger premature ventricular contractions (PVCs) for which the term short-coupled ventricular fibrillation (SCVF) has been proposed. The aim of this article is to establish the phenotype and frequency of SCVF in a large cohort of UCA survivors. METHODS AND RESULTS: We performed a multicentre study including consecutive UCA survivors from the CASPER registry. Short-coupled ventricular fibrillation was defined as otherwise unexplained ventricular fibrillation initiated by a trigger PVC with a coupling interval of <350 ms. Among 364 UCA survivors, 24/364 (6.6%) met diagnostic criteria for SCVF. The diagnosis of SCVF was obtained in 19/24 (79%) individuals by documented ventricular fibrillation during follow-up. Ventricular arrhythmia was initiated by a mean PVC coupling interval of 274 ± 32 ms. Electrical storm occurred in 21% of SCVF probands but not in any UCA proband (P < 0.001). The median time to recurrent ventricular arrhythmia in SCVF was 31 months. Recurrent ventricular fibrillation resulted in quinidine administration in 12/24 SCVF (50%) with excellent arrhythmia control. CONCLUSION: Short-coupled ventricular fibrillation is a distinct primary arrhythmia syndrome accounting for at least 6.6% of UCA. As documentation of ventricular fibrillation onset is necessary for the diagnosis, most cases are diagnosed at the time of recurrent arrhythmia, thus the true prevalence of SCVF remains still unknown. Quinidine is effective in SCVF and should be considered as first-line treatment for patients with recurrent episodes.

Variant Reinterpretation in Survivors of Cardiac Arrest With Preserved Ejection Fraction (the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry) by Clinicians and Clinical Commercial Laboratories.

BACKGROUND: Following an unexplained cardiac arrest, clinical genetic testing is increasingly becoming standard of care. Periodic review of variant classification is required, as reinterpretation can change the diagnosis, prognosis, and management of patients and their relatives. METHODS: This study aimed to develop and validate a standardized algorithm to facilitate clinical application of the 2015 American College of Medical Genetics and Association for Molecular Pathology guidelines for the interpretation of genetic variants. The algorithm was applied to genetic results in the Cardiac Arrest Survivors With Preserved Ejection Fraction Registry, to assess the rate of variant reclassification over time. Variant classifications were then compared with the classifications of 2 commercial laboratories to determine the rate and identify sources of variant interpretation discordance. RESULTS: Thirty-one percent of participants (40 of 131) had at least 1 genetic variant with a clinically significant reclassification over time. Variants of uncertain significance were more likely to be downgraded (73%) to benign than upgraded to pathogenic (27%; P=0.03). For the second part of the study, 50% (70 of 139) of variants had discrepant interpretations (excluding benign variants), provided by at least 1 team. CONCLUSIONS: Periodic review of genetic variant classification is a key component of follow-up care given rapidly changing information in the field. There is potential for clinical care gaps with discrepant variant interpretations, based on the interpretation and application of current guidelines. The development of gene- and disease-specific guidelines and algorithms may provide an opportunity to further standardize variant interpretation reporting in the future. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00292032.

Potential Role of Life Stress in Unexplained Sudden Cardiac Arrest.

BACKGROUND: The etiology of sudden cardiac arrest (SCA) in individuals without known cardiovascular heart disease remains elusive in nearly half of all patients after systematic testing. We investigated the relationship between stressful life events and SCA risk in cases of explained and unexplained SCA (USCA) events. METHODS: Individuals who previously experienced SCA were enrolled prospectively and divided into a USCA or explained SCA (ESCA) subgroup dependent on whether a diagnosis was ascribed after SCA. Participants completed either the 1997 Recent Life Changes Questionnaire, Student Stress Scale, or Social Re-adjustment Rating Scale for Non-Adults recalling events during the year preceding their SCA, depending on age at SCA presentation; all measure stress in life change units (LCUs). SCA group scores were compared with an age- and sex-matched control group. RESULTS: We compared 36 SCA group participants (22 USCA, 14 ESCA, age 47 ± 15 years, age at SCA 40 ± 14 years, 50% male) with 36 control participants (age 47 ± 15 years, 50% male). There was no significant difference in LCU score between the control group and the SCA group (248 ± 181 LCU vs 252 ± 227 LCU; P > .05). The ESCA subgroup had significantly lower mean LCU scores than the USCA subgroup (163 ± 183 LCU vs 308 ± 237 LCU; P = .030). CONCLUSIONS: Stressful life events, especially those producing chronic stress, might predispose otherwise healthy individuals to lethal arrhythmias. Further investigation into the role of stress in SCA precipitation is warranted.

CONTEXTE: La cause de l'arrêt cardiaque subit (ACS) chez les personnes n'ayant pas de maladie cardiovasculaire connue demeure nébuleuse dans près de la moitié des cas, même après des examens systématiques. Nous avons étudié la relation entre les événements stressants de la vie et le risque d'ACS chez des patients présentant un ACS expliqué (ACSe) ou inexpliqué (ACSi). MÉTHODOLOGIE: Des sujets ayant déjà subi un ACS ont été recrutés de manière prospective et répartis en deux sous-groupes (ACSe et ACSi), selon qu'un diagnostic a pu ou non être posé après l'ACS. On a demandé aux participants de répondre au questionnaire RLCQ (Recent Life Changes Questionnaire, questionnaire sur les changements de vie récents, version de 1997), au questionnaire SSS (Student Stress Scale, échelle d'évaluation du stress vécu par les étudiants) ou au questionnaire SRRS (Social Readjustment Rating Scale, échelle d'évaluation du réajustement social) pour les non-adultes en repensant aux événements survenus dans l'année précédant l'ACS, selon leur âge au moment de l'ACS; tous ces questionnaires mesurent le stress en unités de changement de vie (UCV). Les scores des patients ayant subi un ACS ont été comparés à ceux de sujets témoins appariés selon l'âge et le sexe. RÉSULTATS: Nous avons comparé 36 sujets ayant subi un ACS (22 ACSi et 14 ACSe; âge : 47 ± 15 ans; âge au moment de l'ACS : 40 ± 14 ans; proportion d'hommes : 50 %) à 36 sujets témoins (âge : 47 ± 15 ans; proportion d'hommes : 50 %). Il n'y avait pas de différence significative quant au score UCV entre le groupe témoin et le groupe ACS (248 ± 181 UCV vs 252 ± 227 UCV; p > 0,05). Les sujets du sous-groupe ACSe avaient un score UCV moyen significativement plus faible que ceux du sous-groupe ACSi (163 ± 183 UCV vs 308 ± 237 UCV; p = 0,030). CONCLUSIONS: Les événements stressants, plus particulièrement ceux qui entraînent un stress chronique, peuvent prédisposer des personnes autrement en bonne santé aux arythmies mortelles. Une étude plus poussée du rôle du stress dans la survenue précipitée d'un ACS s'impose.

A virtual platform to deliver ambulatory care for patients with atrial fibrillation.

Background: There are little data on the use of virtual care for patients with arrhythmia. We evaluated a virtual clinic platform, in conjunction with specialist care, for patients with symptomatic atrial fibrillation (AF). Methods: This was a prospective, observational cohort study evaluating an online educational and treatment platform, with a randomized sub-study examining the use of an ambulatory single-lead electrocardiogram heart monitor (AHM). Follow-up was 6 months. The main outcome was patients' platform use; success was defined as 90% of patients using the platform at least once, and 75% using it at least twice. The primary outcome in the AHM sub-study was Atrial Fibrillation Symptom Severity (AFSS) score. Other outcomes included patient satisfaction questionnaires, quality of life, emergency department visits, and hospitalizations for AF. Results: We enrolled 94 patients between July 2018 and May 2019; 83% of patients logged in at least once and 54.3% more than once. Patients who were older, were male, or had new-onset AF were more likely to log in to the platform. Satisfaction scores were high; 70%-94% of patients responded favorably. Quality-of-life scores improved at 3 and 6 months. In the AHM sub-study (n = 71), those who received an AHM had lower AFSS scores (least square mean difference -2.52, 95% CI -4.48 to -0.25, P = .03). There was no difference in emergency department visits or hospitalizations. Conclusion: The online platform did not reach our feasibility target but was well received. Allocation of an AHM was associated with improved quality of life. Virtual AF care shows promise and should be evaluated in further research.

The Hearts in Rhythm Organization: A Canadian National Cardiogenetics Network.

BACKGROUND: The Hearts in Rhythm Organization (HiRO) is a team of Canadian inherited heart rhythm and cardiomyopathy experts, genetic counsellors, nurses, researchers, patients, and families dedicated to the detection of inherited arrhythmias and cardiomyopathies, provision of best therapies, and protection from the tragedy of sudden cardiac arrest. METHODS: Recently, existing disease-specific registries were merged into the expanded National HiRO Registry, creating a single common data set for patients and families with inherited conditions that put them at risk for sudden death in Canada. Eligible patients are invited to participate in the registry and optional biobank from 20 specialized cardiogenetics clinics across Canada. RESULTS: Currently, there are 4700 participants enrolled in the National HiRO Registry, with an average of 593 participants enrolled annually over the past 5 years. The capacity to enable knowledge translation of research findings is built into HiRO's organizational infrastructure, with 3 additional working groups (HiRO Clinical Care Committee, HiRO Active Communities Committee, and HiRO Annual Symposium Committee), supporting the organization's current goals and priorities as set alongside patient partners. CONCLUSION: The National HiRO Registry aims to be an integrated research platform to which researchers can pose novel research questions leading to a better understanding, detection, and clinical care of those living with inherited heart rhythm and cardiomyopathy conditions and ultimately to prevent sudden cardiac death.

CONTEXTE: La Hearts in Rhythm Organization (HiRO) est une équipe d'experts canadiens en matière de rythmes cardiaques et de cardiomyopathies héréditaires, de conseillers en génétique, d'infirmières, de chercheurs, de patients et de familles qui se consacrent à la détection des arythmies et des cardiomyopathies héréditaires, à la mise en place des meilleures thérapies et à la protection contre la tragédie que représente une mort subite d'origine cardiaque. MÉTHODES: Récemment, les registres existants relatifs à des maladies spécifiques ont été fusionnés en un registre national élargi de l'HiRO, créant ainsi un ensemble de données commun unique à destination des patients et leurs familles, atteints de maladies héréditaires, qui sont à risque de mort subite au Canada. Les patients admissibles sont invités à s'associer au registre et à la biobanque facultative regroupant 20 cliniques spécialisées en cardiogénétique au Canada. RÉSULTATS: Actuellement, 4 700 participants sont inscrits au registre national de l'HiRO, avec une moyenne de 593 participants inscrits chaque année au cours des cinq dernières années. La capacité à favoriser l'application des connaissances issues de la recherche fait partie de la structure organisationnelle de l'HiRO, avec trois groupes de travail supplémentaires (comité des soins cliniques de l'HiRO, comité des communautés cctives de l'HiRO et comité du symposium annuel de l'HiRO), soutenant les objectifs et les priorités actuels de l'organisation tels qu'ils ont été fixés en partenariat avec les patients. CONCLUSION: Le registre national de l'HiRO vise à devenir une plateforme de recherche intégrée au sein de laquelle les chercheurs peuvent exposer des questions de recherche inédites permettant de mieux comprendre, détecter et soigner les personnes atteintes de troubles du rythme cardiaque et de cardiomyopathie héréditaires et, à terme, de prévenir la mort subite d'origine cardiaque.

The effect of revascularization on mortality and risk of ventricular arrhythmia in patients with ischemic cardiomyopathy.

BACKGROUND: There is clear evidence that patients with prior myocardial infarction and a reduced ejection fraction benefit from implantation of a cardioverter-defibrillator (ICD). It is unclear whether this benefit is altered by whether or not revascularization is performed prior to ICD implantation. METHODS: This was a retrospective cohort study following patients who underwent ICD implantation from 2002 to 2014. Patients with ischemic cardiomyopathy and either primary or secondary prevention ICDs were selected for inclusion. Using the electronic medical record, cardiac catheterization data, revascularization status (percutaneous coronary intervention or coronary bypass surgery) were recorded. The outcomes were mortality and ventricular arrhythmia. RESULTS: There were 606 patients included in the analysis. The mean age was 66.3 ± 10.1 years, 11.9% were women, and the mean LVEF was 30.5 ± 12.0, 58.9% had a primary indication for ICD, 82.0% of the cohort had undergone coronary catheterization prior to ICD implantation. In the overall cohort, there were fewer mortality and ventricular arrhythmia events in patients who had undergone prior revascularization. In patients who had an ICD for secondary prevention, revascularization was associated with a decrease in mortality (HR 0.46, 95% CI (0.24, 0.85) p = 0.015), and a trend towards fewer ventricular arrhythmia (HR 0.62, 95% CI (0.38, 1.00) p = 0.051). There was no association between death or ventricular arrhythmia with revascularization in patients with primary prevention ICDs. CONCLUSION: Revascularization may be beneficial in preventing recurrent ventricular arrhythmia, and should be considered as adjunctive therapy to ICD implantation to improve cardiovascular outcomes.

Prospective Assessment of an Automated Intraprocedural 12-Lead ECG-Based System for Localization of Early Left Ventricular Activation.

BACKGROUND: To facilitate ablation of ventricular tachycardia (VT), an automated localization system to identify the site of origin of left ventricular activation in real time using the 12-lead ECG was developed. The objective of this study was to prospectively assess its accuracy. METHODS: The automated site of origin localization system consists of 3 steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. RESULTS: In 19 patients undergoing 21 catheter ablation procedures of scar-related VT, site of origin localization accuracy was estimated using 552 left ventricular endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8±17.0 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2±4.1 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VTs, the site of origin localization system achieved accuracy within 4 mm. CONCLUSIONS: In this prospective validation study, the automated localization system achieved estimated accuracy within 10 mm and could thus provide clinical utility.