Abstract
Given the global burden of heart failure, strategies to understand the underlying cause or to provide prognostic information are critical to reducing the morbidity and mortality associated with this highly prevalent disease. Cardiomyopathies often have a genetic cause, and the field of heart failure genetics is progressing rapidly. Through a deliberate investigation, evaluation for a familial component of cardiomyopathy can lead to increased identification of pathogenic genetic variants. Much research has also been focused on identifying markers of risk in patients with cardiomyopathy with the use of genetic testing. Advances in our understanding of genetic variants have been slightly offset by an increased recognition of the heterogeneity of disease expression. Greater breadth of genetic testing can increase the likelihood of identifying a variant of uncertain significance, which is resolved only rarely by cellular functional validation and segregation analysis. To increase the use of genetics in heart failure clinics, increased availability of genetic counsellors and other providers with experience in genetics is necessary. Ultimately, through ongoing research and increased clinical experience in cardiomyopathy genetics, an improved understanding of the disease processes will facilitate better clinical decision-making about the therapies offered, exemplifying the implementation of precision medicine.
Key points
The frontier of genetics is rapidly advancing and, increasingly, genetic testing in heart failure clinics is associated with benefit for family screening and individual prognostication.
A focused evaluation of the clinical characteristics and inheritance pattern of heart failure or sudden cardiac death, in addition to consultation with a genetic counsellor when appropriate, can facilitate a successful genetic evaluation.
Genetic testing is recommended in all patients with familial dilated cardiomyopathy (DCM) to facilitate screening, whereas guideline recommendations for testing in patients with sporadic DCM differ, but specific clinical features might increase the yield of testing.
Genetic testing in DCM is currently associated with the identification of a culprit variant in approximately 15–25% of patients with sporadic DCM and approximately 20–40% of patients with familial DCM.
The identification of a pathogenic variant might have important predictive and therapeutic implications; however, expression of the phenotype might depend on environmental triggers.
All first-degree relatives of patients with familial DCM should undergo clinical screening; guidelines for screening of first-degree relatives of patients with sporadic DCM differ.
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Rosenbaum, A.N., Agre, K.E. & Pereira, N.L. Genetics of dilated cardiomyopathy: practical implications for heart failure management. Nat Rev Cardiol 17, 286–297 (2020). https://doi.org/10.1038/s41569-019-0284-0
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DOI: https://doi.org/10.1038/s41569-019-0284-0
