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Canadian Journal of Cardiology
Clinical Research| Volume 32, ISSUE 12, P1396-1401, December 2016

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The Canadian Arrhythmogenic Right Ventricular Cardiomyopathy Registry: Rationale, Design, and Preliminary Recruitment

Published:April 20, 2016DOI:https://doi.org/10.1016/j.cjca.2016.04.004

      Abstract

      Background

      Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex and clinically heterogeneous arrhythmic condition. Incomplete penetrance and variable expressivity are particularly evident in ARVC, making clinical decision-making challenging.

      Methods

      Pediatric and adult cardiologists, geneticists, genetic counsellors, ethicists, nurses, and qualitative researchers are collaborating to create the Canadian ARVC registry using a web-based clinical database. Biological samples will be banked and systematic analysis will be performed to examine potentially causative mutations, variants, and biomarkers. Outcomes will include syncope, ventricular arrhythmias, defibrillator therapies, heart failure, and mortality.

      Results

      Preliminary recruitment has enrolled 365 participants (aged 42.7 ± 17.1 years; 50% women), including 129 probands and 236 family members. Previous cardiac arrest occurred in 28 (8%) participants, syncope occurred in 43 (12%) participants, and 46% of probands had a family history of sudden death. Overall yield of genetic testing was 36% for a disease-causing mutation and 20% for a variant of unknown significance. Target enrollment is 1000 affected patients and 500 unaffected family member controls over 7 years. The cross-sectional and longitudinal data collected in this manner will allow a robust assessment of the natural history and clinical course of genetic subtypes.

      Conclusions

      The Canadian ARVC Registry will create a population-based cohort of patients and their families to inform clinical decisions regarding patients with ARVC.

      Résumé

      Introduction

      La cardiomyopathie arythmogène du ventricule droit (CAVD) est un trouble complexe et cliniquement hétérogène caractérisé par une irrégularité du rythme cardiaque. La pénétrance incomplète et l’expressivité variable sont particulièrement évidentes dans la CAVD, ce qui complique la prise de décisions sur le plan clinique.

      Méthodes

      Des cardiologues, des pédocardiologues, des généticiens, des conseillers en génétique, des éthiciens, des infirmiers et des spécialistes en recherche qualitative travaillent conjointement à la création d’un registre canadien sur la CAVD à partir d’une base de données cliniques sur le Web. Des échantillons biologiques seront mis en réserve et feront l’objet d’une analyse systématique destinée à mettre en évidence de possibles mutations causales, variants et biomarqueurs. La syncope, l’arythmie ventriculaire, la défibrillation, l’insuffisance cardiaque et la mortalité figureront au nombre des issues cliniques.

      Résultats

      Au départ, 365 participants (âgés de 42,7 ± 17,1 ans; 50 % de sexe féminin), incluant 129 proposants et 236 membres de leur famille ont été recrutés. De ces 365 participants, 28 (8 %) avaient des antécédents d’arrêt cardiaque et 43 (12 %) avaient déjà fait une syncope, alors que 46 % des proposants avaient des antécédents familiaux de mort subite. De façon globale, les tests génétiques ont révélé que la maladie était causée par une mutation dans 36 % des cas et qu’un variant dont la portée était inconnue était présent dans 20 % des cas. On espère recruter 1000 personnes atteintes et 500 témoins non atteints parmi les membres de leur famille sur 7 ans. Grâce aux données transversales et longitudinales ainsi recueillies, il sera possible d’évaluer de façon robuste l’évolution naturelle et clinique des sous-types génétiques.

      Conclusions

      Le registre canadien sur la CAVD va rassembler une cohorte composée de patients et des membres de leur famille afin d’éclairer les décisions cliniques entourant ce trouble.
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