Excess mortality and sex differences in outcome in hypertrophic cardiomyopathy: a European multicentre study

Background. Contemporary survival studies in hypertrophic cardiomyopathy (HCM) have shown that the prognosis for most individuals with the disease is much better than described previously, but it remains unclear whether HCM conveys an excess mortality when compared to the general population. Methods. We conducted a retrospective, multicentre longitudinal cohort study of adult HCM patients from 7 European centers. To compare survival to the general population standardized mortality ratios (SMR) were calculated using data from Eurostat stratified by study period, country, sex and age, using a composite endpoint (all-cause mortality, sudden cardiac death (SCD) equivalent, and heart transplantation). Results. The study population consisted of 4893 patients (mean age 49.2 ± 16.4 years; 64% male). After a median follow up of 6.1 years (IQR 3.0-9.8), 796 (16.3%) patients reached the composite endpoint. HCM had an excess mortality compared to the general population (SMR 2.23 (95% Confidence Interval (CI):1.66-2.94)). Females were older at presentation, more symptomatic at baseline (NYHA III/IV: 17.1% vs 7.5%) and more likely to have left ventricular outflow tract obstruction and atrial fibrillation. Female patients had a greater excess mortality than males (SMR 2.87 (95% CI: 2.57-3.19) vs 1.92 (95% CI: 1.76-2.11); p<0.001). Excess mortality in females was present throughout the age spectrum while mortality in male patients after the age of 65 years was similar to the normal population. Female sex was independently associated with a worse prognosis in the multivariable model for the primary composite endpoint (HR 1.19, 95% CI:1.06-1.30;p=0.007) and HF death or transplantation (HR 1.44, 95% CI:1.25-1.59;p<0.001), but not SCD or equivalent. Conclusions. HCM is associated with a significant excess mortality throughout the life course. Women have a worse prognosis that is at least partly due to an excess HF mortality.