PhD Scientific Days 2018

Budapest, April 19–20, 2018

Genetic determination of myocardial mechanics: towards a deeper understanding of heart failure with preserved ejection fraction?

Kovács, Attila

Attila Kovács MD, PhD, Semmelweis University Heart and Vascular Center, Budapest
Andrea Ágnes Molnár MD, PhD, Semmelweis University Heart and Vascular Center, Budapest

Language of the presentation


Text of the abstract

Genetic effects in the determination of left ventricular (LV) mechanics are scarcely characterized. The present study was performed to assess heritability of LV function and to reveal possible common genetic background of different LV functional phenotypes as measured by advanced echocardiographic parameters in a cohort of Caucasian twins.

Ninety-two twin pairs were recruited (54 monozygotic and 38 same-sex dizygotic twin pairs, mean age 56±9 years). Siblings with obstructive coronary artery stenosis assessed by coronary CT angiography or siblings with any cardiomyopathy or severe valvular disease were excluded. Beyond conventional echocardiographic parameters, global longitudinal (GLS), circumferential strain, apical counter-clockwise, basal clockwise rotation and longitudinal early diastolic strain rate were measured by speckle-tracking echocardiography.

The univariate genetic and environmental effects model showed high genetic component in the variance of LV systolic deformation (62–77%), however, heritability of LV diastolic functional parameters was low (31–46%), whilst unique environmental effects dominated. Cholesky decomposition was carried out to calculate the magnitude of covariation between the investigated phenotypes and to estimate the proportion of shared and unique genetic factors. Despite high heritability of LV systolic deformation parameters, no shared genetic background could be revealed between these parameters (p=0.99). Even though LV diastolic parameters showed low genetic determination, we found a significant common latent phenotype responsible for the heritability of these parameters (p<0.001). Furthermore, GLS and LV diastolic function showed also common heritability (p<0.001).

Our work demonstrated high heritability of LV systolic deformation in Caucasian twins. These findings support further investigation of potential candidate genes determining LV systolic function. Different directions of LV deformation are inherited independently. However, GLS shares common genetic background with diastolic function. This points at the importance of systolo-diastolic coupling of myocardial mechanics and may provide further insights into the understanding of heart failure with preserved ejection fraction.

Data of the presenter

Semmelweis University Heart and Vascular Center
New National Excellence Program (ÚNKP)