Sarcomere variants are a major cause of hypertrophic cardiomyopathy (HCM) and are associated with worse prognosis. In this longitudinal multicentre study from the SHaRe registry (6,120 genotyped HCM patients, 50% sarcomeric, median follow-up 5.3 years), the influence of genetic classification and comorbidities on disease trajectory, event timing and causes of death was examined. Sarcomeric HCM was diagnosed at a younger age (median 38.1 vs 54.3 years) and more often in women. Using time-varying models, the study maps the sequence of cardiovascular events to better inform prognosis and treatment in sarcomeric versus nonsarcomeric HCM.
BACKGROUND:Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM), and have been associated with worse prognosis. However, it is unclear how comorbidities influence clinical trajectories, the timing of events, and causes of death in sarcomeric and nonsarcomeric HCM.METHODS:We conducted a multicenter longitudinal cohort study of genotyped patients with HCM in the Sarcomeric Human Cardiomyopathy registry (SHaRe). Patients were classified as sarcomeric HCM (pathogenic/likely pathogenic sarcomere variant) or nonsarcomeric HCM (genetically elusive). The influence of genetic classification and comorbidities on the sequence of cardiovascular events were assessed in time-varying Cox proportional hazards models.RESULTS:Among 6120 patients (40% women; 87% probands; 50% sarcomeric HCM), followed for a median of 5.3 years, sarcomeric HCM (n=3082) was associated with a younger age at diagnosis (median 38.1 versus 54.3 years;P<0.001), a higher proportion of women and les
