Evolution of hypertrophic cardiomyopathy in sarcomere mutation carriers

ObjectiveThe early natural history of sarcomere mutations and the evolution to hypertrophic cardiomyopathy (HCM) are poorly characterised. To describe phenotypic progression, we compared mutation carriers who developed HCM to those who did not during prospective longitudinal investigation.MethodsSarcomere mutation carriers without baseline left ventricular hypertrophy (LVH) were studied during participation in a pilot clinical trial testing diltiazem versus placebo. 38 participants (mean±SD age 15.8±8.6 years) were followed for a median of 2.9 years (range 1.0–5.1 years) with imaging and biomarker analysis. 4 participants (mean baseline age 13.8±3.9 years) developed HCM and were compared to those without phenotypic progression.ResultsParticipants who developed HCM were all children/adolescents and members of families with more highly penetrant mutations. At baseline, participants who developed HCM had a higher left ventricular (LV) ejection fraction (74±2% vs 69±1%, p=0.02), lower global E′ velocity (11.2±0.5 vs 14.8±0.4 cm/s, p