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.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Arrhythmogenic right ventricular dysplasia/cardiomyopathy: a review.Pacing Clin Electrophysiol. 1995; 18: 1298-1314
- Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology.Br Heart J. 1994; 71: 215-218
- Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia. Proposed modification of the Task Force Criteria.Circulation. 2010; 31: 806-814
- Prevalence and pathophysiologic attributes of ventricular dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy.J Am Coll Cardiol. 2009; 54: 445-451
- Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: results from the North American Multidisciplinary Study.Heart Rhythm. 2009; 6: 984-992
- Desmosomal dysfunction due to mutations in desmoplakin causes arrhythmogenic right ventricular dysplasia/cardiomyopathy.Circ Res. 2006; 99: 646-655
- Clinical presentation, long-term follow-up, and outcomes of 1001 arrhythmogenic right ventricular dysplasia/cardiomyopathy patients and family members.Circ Cardiovasc Genet. 2015; 8: 437-446
- Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers.Eur Heart J. 2015; 36: 847-855
- Pathogenesis of arrhythmogenic cardiomyopathy.Can J Cardiol. 2015; 31: 1313-1324
- Arrhythmogenic right ventricular cardiomyopathy/dysplasia: an update.Curr Cardiol Rep. 2008; 10: 367-375
- Arrhythmogenic right ventricular cardiomyopathy type 5 is a fully penetrant, lethal arrhythmic disorder caused by a missense mutation in the TMEM43 gene.Am J Hum Genet. 2008; 82: 809-821
- Arrhythmogenic right ventricular cardiomyopathy with recessive inheritance related to a new homozygous desmocollin-2 mutation.Can J Cardiol. 2014; 30: 696.e1-696.e3
- Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER).Circulation. 2009; 120: 278-285
Krahn AD. Canadian Genetic Heart Rhythm Network. 2009;2010. Available at: https://arvc.ca/arvc/info/. Accessed June 10, 2016.
- Outcome in phospholamban R14del carriers: results of a large multicentre cohort study.Circ Cardiovasc Genet. 2014; 7: 455-465
- The ICD for primary prevention in patients with inherited cardiac diseases: indications, use, and outcome: a comparison with secondary prevention.Circ Arrhythm Electrophysiol. 2013; 6: 91-100
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Genet Med. 2015; 17: 405-424
- Diagnosis of unexplained cardiac arrest: role of adrenaline and procainamide infusion.Circulation. 2005; 112: 2228-2234
- Complications associated with revision of Sprint Fidelis leads: report from the Canadian Heart Rhythm Society Device Advisory Committee.Circulation. 2010; 121: 2384-2387
- Phenotypic analysis of arrhythmogenic cardiomyopathy in the Hutterite population: role of electrocardiogram in identifying high-risk desmocollin-2 carriers.J Am Heart Assoc. 2014; 3: e001407
- Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause arrhythmogenic cardiomyopathies in the UK and Canada.Eur Heart J. 2013; 34: 1002-1011
- The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43.Clin Genet. 2013; 83: 321-331
Article info
Publication history
Published online: April 20, 2016
Accepted:
April 11,
2016
Received:
February 28,
2016
Footnotes
See page 1401 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
