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/m2, 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/m2, 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.