Genetic Evaluation of Cardiomyopathy—A Heart Failure Society of America Practice Guideline

Abstract

This guideline describes the approach and expertise needed for the genetic evaluation of cardiomyopathy. First published in 2009 by the Heart Failure Society of America (HFSA), the guideline has now been updated in collaboration with the American College of Medical Genetics and Genomics (ACMG). The writing group, composed of cardiologists and genetics professionals with expertise in adult and pediatric cardiomyopathy, reflects the emergence and increased clinical activity devoted to cardiovascular genetic medicine. The genetic evaluation of cardiomyopathy is a rapidly emerging key clinical priority, because high-throughput sequencing is now feasible for clinical testing and conventional interventions can improve survival, reduce morbidity, and enhance quality of life. Moreover, specific interventions may be guided by genetic analysis. A systematic approach is recommended: always a comprehensive family history; an expert phenotypic evaluation of the proband and at-risk family members to confirm a diagnosis and guide genetic test selection and interpretation; referral to expert centers as needed; genetic testing, with pre- and post-test genetic counseling; and specific guidance as indicated for drug and device therapies. The evaluation of infants and children demands special expertise. The approach to managing secondary and incidental sequence findings as recommended by the ACMG is provided.

The Diagnosis and Evaluation of Dilated Cardiomyopathy

“…The Diagnosis and Evaluation of DCM J U N E 2 8 , 2 0 1 6 : 2 9 9 6 -3 0 1 0 first-degree relatives of DCM patients who lack a clear underlying etiology. As DCM exhibits age-dependent penetrance, repeated screening is advocated (e.g., every 2 to 5 years until 50 to 60 years of age) to detect late-onset disease (47,48). Identification of a pathogenic gene mutation rationalizes screening by allowing mutation-specific cascade testing of family members.…”

Investigation of de novo variation in pediatric cardiomyopathy

“…Recommendations for cardiac screening in the first degree relatives of an individual with cardiomyopathy are largely based on the assumption of autosomal dominant disease (Hershberger et al, 2018). Improved understanding of the contribution of de novo variants to cardiomyopathy may impact family screening recommendations and improve familial recurrence risk counseling.…”

Restrictive cardiomyopathy: an unusual phenotype of a lamin A variant

“…Restrictive cardiomyopathy (RCM) has been linked to variants in several genes, 1,2 whereas dilated cardiomyopathy (DCM) has been linked to an even larger number of gene variants. 1 A few gene variants have been linked to both DCM and RCM, even within the same family. 3 Familial and sporadic cases of DCM have been associated with variants of lamin A (LMNA).…”