Genetics and Heart Failure: A Concise Guide for the Clinician
Cecile Skrzynia, Jonathan S. Berg, Monte S. Willis and Brian C. Jensen
Affiliation: UNC Division of Cardiology, 160 Dental Circle, CB 7075, Chapel Hill, NC 27599-7075, USA.
Keywords: Cardiomyopathy, dilated, genetic counseling, genetics, medical, genetic testing, heart failure, pharmacogenetics.
The pathogenesis of heart failure involves a complex interaction between genetic and environmental factors.
Genetic factors may influence the susceptibility to the underlying etiology of heart failure, the rapidity of disease progression,
or the response to pharmacologic therapy. The genetic contribution to heart failure is relatively minor in most multifactorial
cases, but more direct and profound in the case of familial dilated cardiomyopathy. Early studies of genetic risk
for heart failure focused on polymorphisms in genes integral to the adrenergic and renin-angiotensin-aldosterone system.
Some of these variants were found to increase the risk of developing heart failure, and others appeared to affect the therapeutic
response to neurohormonal antagonists. Regardless, each variant individually confers a relatively modest increase
in risk and likely requires complex interaction with other variants and the environment for heart failure to develop.
Dilated cardiomyopathy frequently leads to heart failure, and a genetic etiology increasingly has been recognized in cases
previously considered to be “idiopathic”. Up to 50% of dilated cardiomyopathy cases without other cause likely are due to
a heritable genetic mutation. Such mutations typically are found in genes encoding sarcomeric proteins and are inherited
in an autosomal dominant fashion. In recent years, rapid advances in sequencing technology have improved our ability to
diagnose familial dilated cardiomyopathy and those diagnostic tests are available widely. Optimal care for the expanding
population of patients with heritable heart failure involves counselors and physicians with specialized training in genetics,
but numerous online genetics resources are available to practicing clinicians.
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