Systematic review of pre-clinical therapies for post-operative atrial fibrillation.

Abstract

BackgroundPost-operative atrial fibrillation (POAF) is a frequent cardiothoracic surgery complication that increases hospital stay, mortality and costs. Despite decades of research, there has been no systematic overview and meta-analysis of preclinical therapies for POAF in animal models.MethodsWe performed a systematic search of MEDLINE and EMBASE from their inception through September 2020 to determine the effect of preclinical POAF therapies on primary efficacy outcomes using a prospectively registered protocol (CRD42019155649). Bias was assessed using the SYRCLE tool and CAMARADES checklist.ResultsWithin the 26 studies that fulfilled our inclusion criteria, we identified 4 prevention strategies including biological (n = 5), dietary (n = 2), substrate modification (n = 2), and pharmacological (n = 17) interventions targeting atrial substrate, cellular electrophysiology or inflammation. Only one study altered more than 1 pathophysiological mechanism. 73% comprised multiple doses of systemic therapies. Large animal models were used in 81% of the studies. Preclinical therapies altogether attenuated atrial fibrosis (SMD -2.09; 95% confidence interval [CI] -2.95 to -1.22; p ConclusionTreatments with therapies targeting atrial substrate, cellular electrophysiology or inflammation reduced POAF in preclinical animal models compared to controls. Improving the quality of outcome reporting, independently validating promising approaches and targeting complimentary drivers of POAF are promising means to improve the clinical translation of novel therapies for this highly prevalent and clinically meaningful disease.