Efficacy of immunosuppressive therapy in myocarditis: A 30-year systematic review and meta analysis

Chun-Yan Cheng; Gang-Yi Cheng; Zhong-Gui Shan; Anna Baritussio; Giulia Lorenzoni; Agata Tyminska; Krzysztof Ozieranski; Sabino Iliceto; Renzo Marcolongo; Dario Gregori; Alida L P Caforio

doi:10.1016/j.autrev.2020.102710

Efficacy of immunosuppressive therapy in myocarditis: A 30-year systematic review and meta analysis

Autoimmun Rev. 2021 Jan;20(1):102710. doi: 10.1016/j.autrev.2020.102710. Epub 2020 Nov 13.

Affiliations

¹ Cardiology, Dept of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Padova, Italy.
² Department of Cardiac Surgery, The first affiliated hospital of XiaMen University, XiaMen, China.
³ Unit of Biostatistics, Epidemiology and Public Health, Dept of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Padova, Italy.
⁴ First Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
⁵ Hematology and Clinical Immunology, Dept of Medicine, University of Padova, Padova, Italy.
⁶ Cardiology, Dept of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Padova, Italy. Electronic address: alida.caforio@unipd.it.

PMID: 33197576
DOI: 10.1016/j.autrev.2020.102710

Abstract

Aims: Myocarditis is an inflammation of the heart muscle, due to infectious, toxic or autoimmune causes. Literature reported controversial results in relation to the effect of immunosuppression (IS)/immunomodulation (IM). We aimed at assessing the effect of IS/IM by meta analysis.

Methods and results: Using the P.R.I.S.M.A. approach, two researchers searched for relevant studies on PubMed, Embase, and the Central Registry of Controlled Trials of the Cochrane Library. Proposed MeSH terms were: "immunotherapy OR immune therapy OR immune modeling OR Immunosuppressive Agents" AND "combination OR combined with OR plus" AND "myocarditis OR cardiomyopathies OR inflammatory cardiomyopathy". The language was restricted to English. Reference lists of included articles and those relevant to the topic were hand searched for the identification of additional, potentially relevant articles. The cutoff date was from 1987 until 30th Nov 2019. Reported survival or mortality events or change of left ventricular ejection fraction (LVEF) after IS/IT were primary outcomes of the study; in addition, improvement of New York Heart Association class, follow-up biopsy (Bx) findings, viral genome clearance on Bx and recurrence of myocarditis were recorded if reported. Statistical analysis was conducted using Review Manager 5.3; 5452 studies were screened, of these 73 were assessed for eligibility, including 8 randomized control studies, 26 retrospective studies, 2 prospective studies and 1 case control study, 34 case reports and 2 case series. In prospective studies, the difference in mortality between the IS and control groups tended to be lower in the combined IS groups (12.5% vs. 18.2%) (95% CI of odds ratio 0.7(0.3, 1.64)) and the pooled difference of the increase of LVEF between the IS and control groups tended to be higher in the combined IS groups (95% CI 7.26 (-2.29, 16.81)). In retrospective studies, the difference of survival between the IS and control group was significantly in favor of IS (95%CI Hazard ratio 0.82(0.69, 0.96)).

Conclusions: A tailored IS may be considered in myocarditis, depending on the phase of the disease, and the type of underlying autoimmune or immune-mediated form.

Keywords: Autoimmunity; Immunomodulation; Immunosuppressive therapy; Inflammatory cardiomyopathy; Myocarditis.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Case-Control Studies
Humans
Immunosuppression Therapy*
Immunotherapy*
Myocarditis* / diagnosis
Myocarditis* / drug therapy
Prospective Studies
Retrospective Studies
Stroke Volume
Ventricular Function, Left