Acute regional changes in myocardial strain may predict ventricular remodelling after myocardial infarction in a large animal model

D S Mansell,V D Bruno,E Sammut,M S Suleiman,A N Cookson,S George,H S Gill,D Baz Lopez,T Krieg,A Chiribiri,T Johnson,K H Fraser,M Murphy,I Khaliulin,R Ascione

doi:10.1038/s41598-021-97834-y

Abstract

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. Changes in myocardial strain and strain rates were derived from CMRI data. Tissue proteomics was compared between infarcted and non-infarcted territories. Peak values of left ventricular (LV) apical circumferential strain (ACS) changed over time together with peak global circumferential strain (GCS) while peak GLS epicardial strains or strain rates did not change over time. Early LVR post-MI enhanced abundance of 39 proteins in infarcted LV territories, 21 of which correlated with LV equatorial circumferential strain rate. The strongest associations were observed for D-3-phosphoglycerate dehydrogenase (D-3PGDH), cysteine and glycine-rich protein-2, and secreted frizzled-related protein 1 (sFRP1). This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. More studies are needed to ascertain if the observed increase in tissue levels of D-3PGDH and sFRP1 might be casually involved in the pathogenesis of adverse LV remodelling.

Highlights

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI
Overall mean LVEF dropped from 56.6% ± 2.5% at baseline to 45.3% ± 7.6% at 4 to 72 h and to 49% ± 4.6% at 5–6 weeks
This study identifies an association between change in regional strain soon after MI, early LVR and abundance of D-3-phosphoglycerate dehydrogenase (D-3PGDH) and secreted frizzled-related protein 1 (sFRP1) myocardial proteins

Summary

Introduction

To identify predictors of left ventricular remodelling (LVR) post-myocardial infarction (MI) and related molecular signatures, a porcine model of closed-chest balloon MI was used along with serial cardiac magnetic resonance imaging (CMRI) up to 5–6 weeks post-MI. This study shows that early changes in regional peak ACS persist at 5–6 weeks post-MI, when early LVR is observed along with increased tissue levels of D-3PGDH and sFRP1. Studying global and regional changes in MS post-MI in a relevant experimental model may help with predicting early LVR. Global strain measures, calculated as averaged values, may result in loss of sensitivity due to missing key information on regional LV areas, a factor applicable to measurements of LVEF. Proteomics analysis of the myocardium has made the evaluation of cellular and cardiac extra-cellular matrix more approachable and reproducible allowing to study molecular signatures in health and disease including L VR17

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