Hypertrophic cardiomyopathy due to truncating variants in myosin binding protein C: a Spanish cohort

Abstract

Background Hypertrophic cardiomyopathy (HCM) is an inherited disorder whose causal variants involve sarcomeric protein genes. One of these is myosin-binding protein C (MYBPC3), being previously associated with a favourable prognosis. Our objective is to describe the clinical characteristics and events of a molecularly homogeneous HCM cohort associated with truncating MYBPC3 variants. Methods and results A cohort of patients and relatives with HCM diagnosis and carrying a truncating MYBPC3 variant were retrospectively recruited. Subjects had an average follow-up of 7.77 years, with an incident HCM phenotype of 10%. They were middle-aged adult patients (47±16.8 years) without significant comorbidities or symptoms. Hypertrophy was discrete with a significative difference between probands and relatives (17.5±4 mm vs 14.6±5 mm; p<0.0001). Ejection fraction was predominantly preserved (65%±10%). Despite it being the most common clinical event, relevant heart failure (observed in 8.1% of patients) was infrequent and commonly found in the presence of a second environmental precipitating agent. ESC-HCM risk calculator and modifier factors did not correlate with the risk of major events predicting events, which were low (1.51 per 100 patients/year) and associated with the severity of HCM, abnormal QRS in the ECG and age. Genetic factors and sex were not associated with major events. Conclusions This is the first molecularly homogeneous, contemporary cohort, including HCM patients secondary to MYBPC3 truncating variants. Patients showed a good prognosis with a low event rate. In our cohort, major arrhythmic events were not related to measured environmental or genetic factors.