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Therapies to limit myocardial injury in animal models of myocarditis: a systematic review and meta-analysis

Research output: Contribution to journalArticlepeer-review

Joshua A. Silverblatt, Oliver J Ziff, Luke Dancy, Allen Daniel, Benjamin Richard Carter, Paul Andrew Scott, Daniel Sado, Ajay Manmohan Shah, Daniel Ian Bromage

Original languageEnglish
Article number48
JournalBasic Research in Cardiology
Volume114
Issue number6
Early online date31 Oct 2019
DOIs
Accepted/In press7 Oct 2019
E-pub ahead of print31 Oct 2019
PublishedNov 2019

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Abstract

Aims
Current myocarditis guidelines do not advocate treatment to prevent myocardial injury and scar deposition in patients with myocarditis and normal left ventricular ejection fraction. We aimed to ascertain the utility of beta blockers, calcium channel blockers and antagonists of the renin-angiotensin system in ameliorating myocardial injury, scar formation and calcification in animal in vivo models of myocarditis.

Methods and Results
The project was prospectively registered with the PROSPERO database of systematic reviews (CRD42018089336). Primary outcomes (necrosis, fibrosis and calcification) were meta-analysed with random effects modelling. 52 studies were systematically reviewed. Meta-analysis was performed compared with untreated controls. In each study, we identified all independent comparisons of treatment versus control groups. The pooled weighted mean difference (WMD) indicated treatment reduced necrosis by 16.9% (71 controlled analyses, 95% CI 13.2 - 20.7%; P<0.001), however there was less evidence of an effect after accounting for publication bias. Treatment led to a 12.8% reduction in fibrosis (73 controlled analyses , 95% CI 7.6 – 18.0%; P<0.001). After accounting for publication bias this was attenuated to 7.8% but remained significant. Treatment reduced calcification by 4.1% (28 controlled analyses, 95% CI 0.2 – 8.0%; P<0.0395). We observed significant heterogeneity in effect size in all primary endpoints, which was predominantly driven by differences between drug categories. Beta blockers and angiotensin converting enzyme (ACE) inhibitors were the only agents that were effective for both necrosis and fibrosis, while only ACE inhibitors had a significant effect on calcification.

Conclusions
This study provides evidence for a role for ACE inhibitors and beta-blockers to prevent myocardial injury and scar deposition in in vivo models of myocarditis. There is a need for further well-designed studies to assess the translational application of these treatments.

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