Genotype Positive Status in Patients With Hypertrophic Cardiomyopathy Is Associated With Higher Rates of Heart Failure Events

Study Questions:

Is genotype status related to prognosis in patients with hypertrophic cardiomyopathy (HCM)?


Genetic testing was performed in 558 consecutive proband HCM patients. Clinical and echocardiographic data were obtained at baseline and 6-year follow-up.


Pathogenic mutations were identified in 198 (35.4%) patients. Genotype-positive (G+) patients were more likely to be female (44% vs. 30%, p = 0.001), younger (39 vs. 48 years, p < 0.001), and have a family history of HCM (53% vs. 20%, p < 0.001) as well as family history of sudden cardiac death (SCD) (17% vs. 7%, p = 0.002). There were no significant differences in the rates of atrial fibrillation, stroke, or septal reduction procedures. Multivariate analysis demonstrated that G+ status was an independent risk factor for the development of combined heart failure endpoints (left ventricular ejection fraction [LVEF] <50%, New York Heart Association class III or IV in the absence of obstruction, heart failure-related hospital admission, transplantation, and heart failure-related death) (hazard ratio, 4.51; p < 0.001). No difference was seen in heart failure events between the MYH7 and MYBPC3 G+ patients.


The presence of a pathogenic sarcomere mutation in patients with HCM was associated with an increase in heart failure events, with no differences in event rates seen between MYH7 and MYBPC3 genotype-positive patients.


HCM is a heterogenous disease with variable penetrance. A previous study demonstrated that in patients with HCM, identification of a pathogenic sarcomere mutation was associated with worse combined outcomes compared to patients in which a mutation was not identified. This current study extends these findings by demonstrating in a relatively large cohort that genotype-positive patients are specifically at risk for heart failure-related endpoints. Furthermore, in contrast to some previous studies, the specific mutation (MYH7 vs. MYBPC3) did not affect outcomes. The identification of a disease-causing mutation appears more relevant than the type of mutation, although further studies including more extensive genetic screening as well as phenotyping (i.e., magnetic resonance imaging) may provide additional insight into genotype-phenotype relationships.

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