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

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.

SUBMITTER: Mansell DS

PROVIDER: S-EPMC8443552 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Mansell D S DS Bruno V D VD Sammut E E Chiribiri A A Johnson T T Khaliulin I I Lopez D Baz DB Gill H S HS Fraser K H KH Murphy M M Krieg T T Suleiman M S MS George S S Ascione R R Cookson A N AN

Scientific reports 20210915 1

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 ...[more]

PMID: 34526592

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Project description:We report a genome-wide survey of early responses of the mouse heart transcriptome to acute myocardial infarction (AMI). For three regions of the left ventricle (LV), namely ischemic/infarcted tissue (IF), the surviving LV free wall (FW) and the interventricular septum (IVS), 36,899 transcripts were assayed at six time points from 15 min to 48 h post-AMI in both AMI and sham surgery mice. For each transcript, temporal expression patterns were systematically compared between AMI and sham groups, which identified 515 AMI-responsive genes in IF tissue, 35 in the FW, 7 in the IVS, with three genes induced in all three regions. Using the literature, we assigned functional annotations to all 519 nonredundant AMI-induced genes and present two testable models for central signaling pathways induced early post-AMI. First, the early induction of 15 genes involved in assembly and activation of the activator protein-1 (AP-1) family of transcription factors implicates AP-1 as a dominant regulator of earliest post-ischemic molecular events. Second, dramatic increases in transcripts for arginase 1 (ARG1), the enzymes of polyamine biosynthesis and protein inhibitor of nitric oxide synthase (NOS) activity indicates that NO production may be regulated, in part, by inhibition of NOS and coordinate depletion of the NOS substrate, L-arginine. ARG1 was the single most highly induced transcript in the database (121-fold in IF region) and its induction in heart has not been previously reported. Keywords: heart attack, mouse, time course, regional responses We report temporal and regional changes in steady state mRNA levels in the mouse LV following a surgically-induced AMI. Three regions of the infarcted LV were surveyed: IF, FW and IVS. For each region, mRNA levels were assayed at t=0 and six time points after occlusion of the left anterior descending coronary artery (t = 15 min, 1 h, 4 h, 12 h, 24 h, 48 h). As control, an identical time course was carried out in the mouse LV after sham surgery in which the suture was passed under the artery, but not ligated. For sham surgical mice and naïve mice (t=0), the IVS and the LV free wall were harvested and assayed. The AMI and sham time courses were repeated for a total of two independent repetitions of the experiment. For each repetition, 96 GeneChips were hybridized. Thus, for two repetitions, 192 GeneChips (2 x 96) were hybridized. In addition, the naïve time point was assayed a second time during Repetition 1 for six additional GeneChips (two tissues x three chips). The overall total number of samples is 198 GeneChips (192 + 6). Total RNA was isolated from each individual tissue sample. Equal weights of total RNA from 4-10 mice were combined for each LV region, time point and treatment. Copy RNA mixtures were synthesized from each total RNA pool and hybridized to the Affymetrix GeneChip set MG U74 v2 (A, B, and C) that carries 36,899 probe sets. The global normalization of fluorescence emissions for the 198 GeneChips used in this study and their conversion to relative transcript concentrations measured in relative fluorescence units (RFU) was conducted using Robust Multi-array Averaging (RMA; www.bioconductor.org). Each of the 198 Accessions is titled as follows: time point / treatment / tissue, repetition, GeneChip. The additional assays of naïve mice in Repetition 1 are labeled “Naive2”.

Project description:AimsLeft ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling.Methods and resultsThis prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model.ConclusionsLV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.

Dataset Information

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

Publications

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

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