# Large animal models of ischemic mitral regurgitation—systematic review and meta-analysis

## TL;DR

This study reviews large animal models to find the best way to induce ischemic mitral regurgitation, a heart condition, for testing new treatments.

## Contribution

The study identifies the ethanol injection strategy as the most effective and least harmful method for inducing IMR in large animal models.

## Key findings

- Ethanol injection in obtuse marginal arteries (EtOH-OMx) resulted in 87% IMR development with low mortality.
- Ligation under cardiopulmonary bypass had high mortality and inconsistent IMR severity.
- Reporting quality across studies was variable, with missing details on sex, randomization, and adverse events.

## Abstract

Ischaemic mitral regurgitation (IMR) is a significant complication of myocardial infarction associated with increased morbidity and mortality. Large animal models are essential for testing novel mitral valve therapies, yet no consensus exists on the optimal infarction strategy to induce IMR.

A systematic review and meta-analysis were conducted to evaluate infarction strategies used to induce IMR in large animal models. Studies were identified through database searches and screened according to predefined inclusion criteria. Subgroups were stratified by infarction strategy. Proportions of IMR development and severity were analysed using a random-effects model, and reporting quality was assessed across studies.

Forty-four studies met the inclusion criteria, comprising 869 animals across 52 subgroups. Ethanol injection in select obtuse marginal arteries (EtOH-OMx strategy) yielded the highest rate of IMR development (87%, 95% CI: 79%–96%) with the lowest associated mortality. Ligation of obtuse marginal arteries under cardiopulmonary bypass (CPB-OM2, OM3 and CPB-OMx) demonstrated high mortality and inconsistent IMR severity. Reporting quality was variable, with frequent omissions regarding sex, randomisation, and adverse event documentation.

This review identifies the EtOH-OMx strategy as a promising method for inducing IMR in large animal models, demonstrating favourable performance within the limitations of available data.

Chart depicting large animal models of ischemic mitral regurgitation. It includes two species: porcine and ovine. Four interventions are shown: ligation, cardiopulmonary bypass and ligation, intracoronary balloon occlusion, and intracoronary ethanol injection. Outcomes measured are ischemic mitral regurgitation severity and survival, illustrated by a heart diagram and survival graph, respectively.