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

• Published in: Open heart Vol. 11; no. 2; p. e002891
• Main Authors: Melendo-Viu, Maria, Salguero-Bodes, Rafael, Valverde-Gómez, María, Larrañaga-Moreira, Jose María, Barriales, Roberto, Díez-Lopez, Carles, Limeres Freire, Javier, Peña-Peña, Maria Luisa, Garcia Pavia, Pablo, Ripoll, Tomas, Climent-Payá, Vicente, Gallego Delgado, Maria, Zorio, Esther, Bermudez Jimenez, Francisco José, García-Pinilla, José Manuel, Méndez Fernández, Irene, Sabater-Molina, Maria, Perez Asensio, Ana, Marchán-Lopez, Álvaro, Arribas Ynsaurriaga, Fernando, Bueno, Hector, Palomino Doza, Julián A
• Format: Journal Article
• Language: English
• Published: England British Cardiovascular Society 24.11.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Aged; Cardiac arrhythmia; Cardiomyopathy; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic - diagnosis; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - physiopathology; Carrier Proteins - genetics; Female; Follow-Up Studies; Genetic Diseases, Inborn; Genetic Predisposition to Disease; Genotype & phenotype; HEART FAILURE; Heart Failure and Cardiomyopathies; Humans; Male; Middle Aged; Morphology; Mutation; Original Research; Pedigree; Phenotype; Prognosis; Proteins; Retrospective Studies; Risk assessment; Spain - epidemiology; Stroke Volume - physiology; Variables; Ventricular Function, Left - physiology; Spain; HEART FAILURE; Genetic Diseases, Inborn; Cardiomyopathy, Hypertrophic
• ISSN: 2053-3624; 2398-595X; 2053-3624
• DOI: 10.1136/openhrt-2024-002891

BackgroundHypertrophic 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 resultsA 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.ConclusionsThis 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.