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Canadian Journal of Cardiology

Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management

Published:January 21, 2021DOI:https://doi.org/10.1016/j.cjca.2021.01.016

      Abstract

      Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel–based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.

      Résumé

      Les cardiomyopathies sont une cause importante d’insuffisance cardiaque; elles touchent souvent les jeunes et ont des conséquences importantes pour les membres de la famille. Le dépistage génétique des cardiomyopathies constitue un parcours de soins bien établi dans la pratique actuelle en cardiologie. Les principales cardiomyopathies pour lesquelles un dépistage génétique est indiqué sont les cardiomyopathies hypertrophique, dilatée, arythmogène et restrictive, la non-compaction ventriculaire gauche étant un variant phénotypique. Le dépistage précoce et l’instauration rapide d’un traitement chez les patients ayant une cardiomyopathie héréditaire permet de cibler les patients asymptomatiques et présymptomatiques dont la maladie est au stade A ou B selon la classification de l’insuffisance cardiaque de l’American College of Cardiology/American Heart Association. La stratégie de dépistage génétique actuelle fait appel à l’analyse d’une batterie de gènes et, dans de rares cas, au séquençage de l’exome ou du génome complet. Les principales composantes de l’analyse génétique comprennent la définition des fondements génétiques du diagnostic, l’établissement d’un pronostic, et la possibilité d’effectuer un dépistage chez les membres de la famille du patient et de les stratifier en fonction du risque auquel ils sont exposés. Le dépistage génétique des cardiomyopathies devrait être coordonné par une équipe multidisciplinaire formée notamment de cardiologues pour adultes et enfants, de conseillers en génétique et de généticiens, ayant accès à des spécialistes de l’imagerie et de l’électrophysiologie cardiaques. Il importe en outre d’adopter une approche pragmatique pour la prise en charge des variants génétiques dont la signification est mal connue. Nous abordons ici les types de cardiomyopathies dans lesquels un dépistage génétique est indiqué, l’importance d’un diagnostic précoce et de l’instauration rapide d’un traitement, le dépistage familial, et le parcours de soins relatif au counseling en génétique et au dépistage.
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