Sarcomere gene mutations in hypertrophy and heart failure

Abstract

Despite considerable progress in identifying and modifying risk factors that cause cardiovascular disease, heart failure has emerged as an important medical and socioeconomic problem. Hypertrophic remodeling, a common response to many cardiovascular disorders, increases the risk of heart failure. Discovery of the genetic basis of hypertrophic cardiomyopathy has allowed consideration of whether these genes also contribute to pathologic remodeling that occurs in the context of common acquired cardiovascular disorders. Evidence supporting a shared etiology has emerged from the recent identification of sarcomere protein mutations and sequence variants in community-based populations with hypertrophy and heart failure. These findings imply that harnessing genetic testing for hypertrophic mutations may help define patients at risk for heart failure. In the future, mechanistic insights into hypertrophic remodeling, combined with strategies to prevent this pathology, are expected to reduce the burden of heart failure.

Figure 1

The diagnostic algorithm of HCM with genetic testing

Figure 2

The diagnostic algorithm of HCM without genetic testing