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. A total of 1357 initially healthy subjects (women 51.6%; 48.2 ± 14.1 years) were included in this study from 20 years follow-up after the 4th 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/ASE/Industry Task Force. Layer-specific global longitudinal strain (GLS) and global circumferential strain (GCS) (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 (respectively 30 and 45%). In contrast, GLSEndo/GLSEpi ratio had a high level of heritability (65%). Except for GLSendo/GLSepi ratio, a large percentage of variance remained unexplained (greater than 50%). 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.