Layer myocardial strain is the most heritable echocardiographic trait

Abstract

Aims: Myocardial deformation assessed by strain analysis represents a significant advancement in our assessment of cardiac mechanics. However, whether this variable is genetically heritable or whether all/most of its variability is related to environmental factors is currently unknown. We sought to determine the heritability of echocardiographically determined cardiac mechanics indices in a population setting.

Methods and results: A total of 1357 initially healthy subjects (women 51.6%; 48.2 ± 14.1 years) were included in this study from 20-year follow-up after the fourth visit of the longitudinal familial STANISLAS cohort (Lorraine, France). Data were acquired using state-of-the-art cardiac ultrasound equipment, using acquisition and measurement protocols recommended by the EACVI (European Association of Cardiovascular Imaging)/ASE (American Society of Echocardiography)/Industry Task Force. Layer-specific global longitudinal strain (GLS) and global circumferential strain (full-wall, subendocardial, and subepicardial) and conventional structural and functional cardiac parameters and their potential heritability were assessed using restricted maximum likelihood analysis, with genetic relatedness matrix calculated from genome-wide association data. Indices of longitudinal/circumferential myocardial function and left ventricular (LV) ejection fraction had low heritability (ranging from 10% to 20%). Diastolic and standard LV function parameters had moderate heritability (ranging from 20% to 30%) except for end-systolic and end-diastolic volumes (30% and 45%, respectively). In contrast, global longitudinal subendocardial strain (GLSEndo)/global longitudinal subepicardial strain (GLSEpi) ratio had a high level of heritability (65%). Except for GLSEndo/GLSEpi ratio, a large percentage of variance remained unexplained (>50%).

Conclusions: In our population cohort, GLSEndo/GLSEpi ratio had a high level of heritability, whereas other classical and mechanical LV function parameters did not. Given the increasing recognition of GLSEndo/GLSEpi ratio as an early/sensitive imaging biomarker of systolic dysfunction, our results suggest the possible existence of individual genetic predispositions to myocardial decline.

Keywords: cardiac mechanics; echocardiography; genetics; heritability; strain.