Clinical Effect of Genetic Testing in Inherited Cardiovascular Diseases: A 14-Year Retrospective Study

The clinical impact of genetic testing in a contemporary real-life cohort of patients with heritable cardiomyopathies or arrhythmias is not well defined. Additionally, the genetic spectrum of these conditions in the French-Canadian population is unknown, and interpretation of genetic variants can be challenging because of a known founder effect.

This study sought to evaluate the clinical utility of arrhythmia and cardiomyopathy genetic testing and assess the utility of allele frequency data from a local reference population.

The study included consecutive probands seen at the Montreal Heart Institute Cardiovascular Genetics Centre (Montreal, Quebec, Canada) for suspected heritable cardiomyopathies or arrhythmias for which both clinical data and genetic testing results were available. The study analyzed the enrichment of recurrent rare genetic variants by comparing their prevalence in the case cohort with that of a local population cohort.

A total of 2,062 probands (mean age at diagnosis 47 ± 17 years) were included. Overall, genetic testing identified a pathogenic/likely pathogenic (P/LP) variant in 496 (24%) probands. A total of 9 variants had their classification changed after comparing their prevalence (case control enrichment) using a local population-based cohort. Genetic testing resulted in diagnostic refinement with a potential impact on clinical management in 168 (8%) probands.

Genetic testing in a clinical context identified a disease-causing variant in 24% of probands, thus highlighting the high yield of rare variant genetic testing. Beyond the impact on family screening, the genetic testing result affected clinical management. Access to allele frequency data from a local population refines variant interpretation and classification.