Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy : external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. Methods and results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.Methods and results In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.Conclusion Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs

Two to one cavotricuspid isthmus conduction block during coronary sinus pacing: What is the mechanism?

A 70-year-old woman was admitted for end-stage heart failure and cardiogenic shock, which required the implantation of a left ventricular assist device (LVAD, Heartmate 3, Abbott, St. Paul, MN, USA) as a bridge to transplant. During the hospital stay, she presented two episodes of paroxysmal complete atrioventricular block with prolonged asystole. No regular pacemaker could be implanted because of infectious contraindications and vascular access limitations. As a consequence, a leadless pacemaker was implanted and programmed in backup VVI mode at 50 bpm. This article is protected by copyright. All rights reserved

Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit

This case series assesses QT intervals for French patients with coronavirus disease 2019 (COVID-19) treated with hydroxychloroquine alone or in combination with azithromycin

SCN5A Overlap Syndromes: an open-minded approach.

SCN5A overlap syndromes are clinical entities that express a phenotype combining aspects of different canonical SCN5A-related arrhythmia syndromes or a variable arrhythmic phenotype among individuals carrying the same SCN5A mutation. We here review the literature addressing SCN5A overlap syndromes, as well as the principal mechanisms currently proposed. Among others, a multifactorial determination - encompassing an interaction between SCN5A variant(s), other genetic polymorphisms, and possibly environmental factors - seems the most plausible hypothesis

Prognostic significance of a low T/R ratio in Brugada Syndrome

International audienc

Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia

Background Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST‐segment‐elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling. Methods and Results In a case–control study, we recruited 953 patients with ST‐segment‐elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for ADRB1 Arg389Gly and Ser49Gly, ADRB2 Gln27Glu and Gly16Arg, and ADRA2C Ins322‐325Del. Within each minor allele‐containing genotype, haplotype, or 2‐genotype combination, patients with incident VF were compared with non‐VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly (P<0.05) reduced association with incident VF, and none was associated with increased VF risk except for ADRB1 Gly389 homozygotes in the subset of patients not receiving β‐blockers. ADRB1 Gly49 carriers (prevalence 23.0%) had an OR (95% CI) of 0.70 (0.49–0.98), and the ADRA2C 322–325 deletion (Del) carriers (prevalence 13.5%) had an OR of 0.61 (0.39–0.94). When present in genotype combinations (8 each), both ADRB1 Gly49 carriers (OR, 0.67 [0.56–0.80]) and ADRA2C Del carriers (OR, 0.57 [0.45– 0.71]) were associated with reduced VF risk. Conclusions In ST‐segment‐elevation myocardial infarction, the adrenergic receptor minor alleles ADRB1 Gly49, whose encoded receptor undergoes enhanced agonist‐mediated internalization and β‐arrestin interactions leading to cardioprotective biased signaling, and ADRA2C Del322‐325, whose receptor causes disinhibition of norepinephrine release, are associated with a lower incidence of VF. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT00859300

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus