Levine, R. A. | Search bioRxiv

bioRxiv2019

Mechanical effects of MitraClip on leaflet stress and myocardial strain in functional mitral regurgitation: A finite element modeling study.

PurposeMitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD).\n\nMethodsSimulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume ({uparrow}LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated.\n\nResultsMitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3{+/-}7.1 kPa (p<0.0001) in AL and 14.8{+/-}1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1{+/-}2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09{+/-}0.04 (p<0.0001)). Furthermore, MitraClip in {uparrow}LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9{+/-}14.4 kPa (p=0.0268) and in PL by 22.5{+/-}23.7 kPa (p=0.0101).\n\nConclusionsMitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement.

bioengineering↗

bioRxiv2018

GWAS-driven Pathway Analyses and Functional Validation Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse

Nonsyndromic Mitral valve prolapse (MVP) is a common degenerative valvular heart disease with severe health consequences, including arrhythmia, heart failure and sudden death. MVP is characterized by excess extracellular matrix secretion and cellular disorganization which leads to bulky valves that are unable to co-apt properly during ventricular systole. However, the triggering mechanisms of this process are mostly unknown. Using pathway enrichment tools applied to GWAS we show that genes at risk loci are involved in biological functions relevant to cell adhesion and migration during cardiac development and in response to shear stress. Through genetic, in silico and in vivo experiments we demonstrates the presence of several genes involved in gene regulation, including GLIS1, a transcription factor that regulates Hedgehog signaling. Our findings define genetic, molecular and cellular mechanisms underlying non-syndromic MVP and implicate disrupted endothelial to mesenchymal transition and cell migration as a potential common cause to this disease.

genetics↗