Aims: Mitral valve (MV) abnormalities are recognized features of hypertrophic cardiomyopathy (HCM), and there is preliminary evidence suggesting they are intrinsic phenotypic manifestations of sarcomere mutations, present in mutation carriers without left ventricular (LV) hypertrophy (subclinical HCM). However, further study is required to characterize the nature of these changes and their functional impact. Thus, we performed comprehensive echocardiographic analysis of MV structure and function on a genotyped population.

Methods and results: MV and papillary muscle echocardiographic parameters were measured in 192 genotyped individuals, including 50 overt HCM, 79 subclinical HCM, and 63 mutation-negative, healthy relatives as normal controls. Compared to controls, subclinical HCM subjects had elongated anterior MV leaflets relative to LV end-diastolic volume index (0.57 ± 0.02 vs. 0.51 ± 0.02 mm/mL/m2, P = 0.013) and anteriorly displaced papillary muscles [decreased papillary-septal separation (31.1 ± 0.7 vs. 34.2 ± 0.9 mm, P = 0.004) and relative antero-posterior position ratio of the papillary muscles (0.67 ± 0.01 vs. 0.71 ± 0.01, P = 0.011]. Similar findings were identified comparing overt HCM to controls. These MV changes were associated with an increased prevalence of systolic anterior motion (SAM) of the MV amongst subclinical HCM subjects.

Conclusions: Sarcomere mutations are associated with primary abnormalities of the MV apparatus, specifically excess anterior leaflet length relative to LV cavity size and anterior displacement of the papillary muscles; both features predisposing to SAM. These abnormalities appear to be early phenotypic consequences of sarcomere mutations, observed in mutation carriers with normal LV wall thickness.