Abstract 14403: Echocardiographic Predictors of Phenotype Development in Hypertrophic Cardiomyopathy Mutation-Carriers

Introduction: Hypertrophic cardiomyopathy (HCM) is a hereditary disease characterized by unexplained left ventricular (LV) hypertrophy (LVH). Genetic family screening of probands identifies mutation carriers (Gen+) without phenotype (Phen-), who require clinical follow-up.

Hypothesis: Identification of early phenotype signs may facilitate clinical management of Gen+/Phen-. We assessed if echocardiography LV global longitudinal strain (GLS) and strain rate (SR) may predict LVH development in Gen+/Phen- HCM.

Methods: We identified 16 Gen+/Phen- (25% women; age 20±11 years). Echocardiogram was performed at baseline, when no phenotype was evident, and repeated yearly. The end of follow up was the HCM diagnosis date in subjects who developed HCM (FU-Phen+) and the last visit date in those who didn’t develop HCM (FU-Phen-). Mitral inflow peak E and A velocities and Tissue Doppler E’ and A’ peak velocities were measured. LV GLS and SR-peak during isovolumic relaxation (SRIVR) were calculated offline independently by two investigators blind to the clinical data.

Results: GLS and SRIVR were not age-dependent (p=0.08 and 0.55, respectively), whereas E/E’ ratio was directly related to age (p=0.011). During follow-up (8±5 years, interquartile range 5-10 years) 5 subjects became FU-Phen+. At baseline, FU-Phen+ compared to FU-Phen- were older and had higher maximal wall thickness, higher EF, less negative GLS and lower SRIVR (Table). Abnormal baseline GLS, despite a normal EF, and reduced SRIVR indicate reduced systolic deformation and covert diastolic dysfunction which may be caused by disarray preceding LVH and fibrosis.

Conclusions: This is the first HCM preclinical study to compare at baseline HCM Gen+/Phen- subjects who will develop to those who will not develop LVH. We identified sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.