Genotype Positive Status in Patients with Hypertrophic Cardiomyopathy is Associated with Higher Rates of Heart Failure Events
Background—The aim of the study was to clarify the relationship between genotype status and major cardiovascular outcomes in a large cohort of Hypertrophic Cardiomyopathy (HCM) patients.
Methods and Results—Genetic testing was performed in 558 consecutive proband HCM patients. Baseline and follow up (mean follow up 6.3 years) clinical and echocardiographic data were obtained. 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 end points (LVEF<50%, NYHAIII or IV in the absence of obstruction, heart failure related hospital admission, transplantation, and heart failure related death) (HR=4.51, CI 2.09-9.31, p<0.001). No difference was seen in heart failure events between the MYH7 and MYBPC3 G+ patients.
Conclusions—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. The presence of a disease-causing mutation appears more clinically relevant than the specific mutation itself.
- Received July 2, 2013.
- Revision received March 17, 2014.
- Accepted May 4, 2014.