Hypertrophic Cardiomyopathy: The Impact of Age at Diagnosis of the Proband on Genetic Yield, Clinical Presentation, Outcomes, and Yield of Family Screening

BACKGROUND: Hypertrophic cardiomyopathy is a complex disease with variable clinical presentation and familial impact. Age at diagnosis may influence phenotypic expression, but it is unclear if age also affects clinical outcomes, genetic findings, and yield of family screening.

METHODS: This was a retrospective cohort study of families screened for hypertrophic cardiomyopathy in eastern Denmark (2006-2023). Probands were analyzed by age at diagnosis both continuously and in quartiles: 18 to 45, 46 to 56, 57 to 65, and >65 years.

RESULTS: A total of 612 probands (62% men; median age, 56 years; median follow-up, 9 years) and 919 relatives (45% men; median age, 42 years) were studied. A higher proband age at diagnosis was associated with more left ventricular outflow tract obstruction (odds ratio [OR], 1.19/10 years), hypertension (OR, 1.57/10 years) and atrial fibrillation (OR, 1.24/10 years), but less left ventricular hypertrophy (wall thickness ≥30 mm; OR, 0.52/10 years), and ventricular arrhythmias (OR 0.81/10 years). Older age at diagnosis was associated with higher all-cause death, but similar cardiovascular death. Sarcomere variants were less common in the oldest versus youngest quartile of probands (13% versus 42%, P<0.001). The yield of family screening at baseline was higher in probands diagnosed at a younger age (OR, 1.34/10-year decrease). Long-term hypertrophic cardiomyopathy incidence in relatives was not associated with proband age at diagnosis, and overall yield of family screening was comparable across all proband ages at diagnosis.

CONCLUSIONS: The proband's age at hypertrophic cardiomyopathy diagnosis was associated with clinical and genetic findings, but the cardiovascular death and the yield of family screening were similar across all ages at diagnosis, supporting the presently recommended follow-up and family screening irrespective of the proband's age at diagnosis.