Chanhee Seo, Connor Michie, Benjamin Hibbert, Darryl R. Davis
Abstract
Post-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.
Introduction
Post-operative atrial fibrillation (POAF) is a commonplace arrhythmia seen in a third of patients after coronary artery bypass grafting and almost half of patients after valve repair/replacement [1–3]. Albeit often transient, the impact of POAF on surgical outcomes is significant as it portends a 2-fold increase in mortality, greater hospital resource utilization and increased costs [4, 5]. Emerging evidence has shown that POAF arises from a combination of pre-existing cardiomyopathic changes in the atria, surgical-induced changes in atrial substrate and post-operative insults (such as inflammation, altered neural regulation and oxidative stress) [6–8]. These electrical and structural changes increase AF vulnerability by creating a pro-fibrillatory substrate while altered calcium handling increases the risk for delayed afterdepolarizations and the stimulation of ectopic atrial beats that trigger the arrhythmia [9–11].
Methods
Search strategy
We performed an electronic literature search of the Medical Literature Analysis and Retrieval System Online (MEDLINE) and the ExcerptaMedicadataBASE (EMBASE) from database inception to September 2020 using methods prospectively registered in the International Prospective Register of Systemic Reviews (PROSPERO, CRD42019155649). To maximize the sensitivity of the search strategy, we combined the terms: “animal experimentation,” “postoperative period,” and “atrial fibrillation” or any of their synonyms as either MeSH terms or key words (S1 Table in S1 File). The search strategy was designed to capture all animal studies relevant to the study question as previously described [12]. In addition, a manual screening of the bibliographies of all retrieved articles was performed to enable a broad evaluation of the current literature.
Discussion
In this study, we report the published work to date exploring pre-clinical therapies for POAF. Amongst clinical AF syndromes, POAF is unique as it is highly prevalent, clinically meaningful, and demonstrates predictable time-course [1–5]. Given that standard therapies are not useful or highly toxic, these attributes combine to make the development of effective prophylaxis both clinically and commercially attractive. Although our review identified several promising pre-clinical strategies, clinical translation has been limited which may reflect the quality of the evidence, the impractical nature of the interventions or the risks of off target (systemic) complications.
Citation: Seo C, Michie C, Hibbert B, Davis DR (2020) Systematic review of pre-clinical therapies for post-operative atrial fibrillation. PLoS ONE 15(11): e0241643. https://doi.org/10.1371/journal.pone.0241643
Editor: Daniel M. Johnson, The Open University, UNITED KINGDOM.
Received:July 18, 2020; Accepted: October 16, 2020; Published: November 4, 2020.
Copyright: © 2020 Seo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability:All relevant data are within the manuscript and its Supporting Information files.
Funding:This work was supported by the Canadian Institutes of Health Research (Project Grant 410103; awarded to DD; https://cihr-irsc.gc.ca/e/193.html). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests:The authors have declared that no competing interests exist.
