772 Genotype-Phenotype Correlations According to Clinical and Echocardiographic Characteristics in Hypertrophic Cardiomyopathy

Many mutations among genes encoding sarcomeric proteins have been identified in hypertrophic cardiomyopathy (HCM) leading to a heterogenic phenotype. Studies demonstrate negative outcomes associated with positive genetic testing but data on specific genotype-phenotype correlations are limited and highly variable. Identified mutations in genes TNNI3 (troponin I), TNNT2 (troponin T), MYBPC3 (myosin-binding protein C) and MYH7 (myosin heavy chain) were screened in 284 patients at the Cardiovascular Genetic Clinic of the Montréal Heart Institute. Mutations were identified in 113 patients (40%) and 84 patients (74%) were included for analysis. Five cardiac transplant recipients without previous echocardiographic images available were analysed according to clinical characteristics only. We excluded 16 patients without HCM phenotype and 13 patients with follow-up outside of our center. MYH7 (40%) and MYBPC3 (40%) mutations were the most common (Table 1). Only one patient was identified with a TNNI3 (1%) mutation and was excluded from further analysis. Patients with MYH7 mutations were younger at diagnosis and presented more often with a familial history of sudden cardiac death (76%) and defibrillator implantation (59%). Patients with MYH7 mutations were also more likely to progress to “burn-out” HCM (ejection fraction less than 50%) (27%) and cardiac transplantation (18%). Significant mitral insufficiency was more prevalent in patients with MYBPC3 mutations (33%). Patients with TNNT2 (18%) mutations showed an increased probability of having a significant resting and provocable left outflow tract obstruction (47%) with systolic anterior movement of the mitral valve (53%) leading to septal myomectomy (27%). Genotype did not affect septal morphology with an overall predominance of the midseptal form (73% overall). No difference was observed in our patient population for left ventricular end-diastolic dimension, degree of septal thickening, left ventricular mass, indexed left atrial volume and pulmonary artery systolic pressure.Tabled 1 This retrospective study suggests that TNNT2 mutations are associated with obstructive HCM while MYH7 mutations are related with arrhythmic complications. Moreover, septal morphologies do not appear to be influenced by any specific gene mutation.