Impact of Systolic Dysfunction in Genotyped Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere, and approximately 5% of cases of HCM show systolic dysfunction with poor prognosis. Few data exist regarding the systolic dysfunction in a large population of genotyped HCM subjects. Hypothesis: The aim of this study was to assess the systolic dysfunction and prognosis in sarcomere gene mutation carriers. Methods: The study included 157 sarcomere gene mutation carriers from 69 unrelated HCM families (87 males; mean age, 46.5 ± 20.5 years). After exclusions for systolic dysfunction at baseline, 107 subjects underwent serial echocardiograms. Results: At a mean follow‐up of 7.0 years, 12 subjects experienced systolic dysfunction. In multivariate Cox analysis, systolic dysfunction was related to age and ejection fraction at initial evaluation (P < 0.001 and P = 0.020, respectively), and was associated with the absence of mutations in the cardiac myosin‐binding protein C gene (MYBPC3) (P = 0.042). When the subjects were divided into MYBPC3 and non‐MYBPC3 mutation carriers, and time from birth to development of systolic dysfunction was compared, the rate of systolic dysfunction was higher in the non‐MYBPC3 group than in MYBPC3 group (Kaplan‐Meier, log‐rank test, P = 0.010). After the onset of systolic dysfunction, 11 of 12 subjects died during a mean follow‐up of 8.3 years. Conclusions: Non‐MYBPC3 mutation carriers developed left ventricular systolic dysfunction more frequently than MYBPC3 mutation carriers, and the majority of sarcomere gene mutation carriers with systolic dysfunction had fatal outcomes during follow‐up. This suggests that subjects with mutations in sarcomeric genes require careful management for systolic dysfunction. This work was supported in part by a Grant‐in‐Aid for Scientific Research, the Ministry of Education, Culture, Sports, Science, and Technology (KAKENHI 16790414, 19590807, 22590808, Tokyo, Japan), and the Research Grant for Cardiovascular Diseases (20C‐4) from the Ministry of Health, Labour, and Welfare (Tokyo, Japan). The authors have no other funding, financial relationships, or conflicts of interest to disclose.