Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy

Background: Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM. Methods: Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age-and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients. Results: Average indexed AML was significantly longer for HCM than for controls (17.2 +/- 2.3 vs. 13.3 +/- 1.6 mm/m(2), P < 0.001). Average AML length correlated with body surface area (BSA), left ventricular (LV) end-systolic volume (P < 0.001) and LV mass by CMR (P < 0.001). Average indexed AML by BSA of pure-apical HCM was significantly shorter than other typed HCM (16.6 +/- 2.0 vs. 17.4 +/- 2.4 mm/m(2), P = 0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9 +/- 3.8 vs. 29.6 +/- 3.8 mm, P = 0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P > 0.05). Conclusion: AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.