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Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: a Systematic Review

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Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: a Systematic Review Journal of Clinical Medicine Article Outcomes of Mechanical Circulatory Support for Giant Cell Myocarditis: A Systematic Review Preeyal M. Patel 1, Abhiraj Saxena 1, Chelsey T. Wood 1, Thomas J. O’Malley 2 , Elizabeth J. Maynes 2, John W. C. Entwistle 2, H. Todd Massey 2, Preethi R. Pirlamarla 3, René J. Alvarez 3, Leslie T. Cooper 4 , J. Eduardo Rame 2 and Vakhtang Tchantchaleishvili 2,* 1 Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA; [email protected] (P.M.P.); [email protected] (A.S.); [email protected] (C.T.W.) 2 Division of Cardiac Surgery, Department of Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA; [email protected] (T.J.O.); [email protected] (E.J.M.); john.entwistle@jefferson.edu (J.W.C.E.); howard.massey@jefferson.edu (H.T.M.); eduardo.rame@jefferson.edu (J.E.R.) 3 Division of Cardiology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA; preethi.pirlamarla@jefferson.edu (P.R.P.); rene.alvarez@jefferson.edu (R.J.A.) 4 Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL 32224, USA; [email protected] * Correspondence: vakhtang.tchantchaleishvili@jefferson.edu; Tel.: +1-215-955-6996; Fax: +1-215-955-6010 Received: 20 October 2020; Accepted: 23 November 2020; Published: 1 December 2020 Abstract: Treatment of giant cell myocarditis (GCM) can require bridging to orthotopic heart transplantation (OHT) or recovery with mechanical circulatory support (MCS). Since the roles of MCS and immunotherapy are not well-defined in GCM, we sought to analyze outcomes of patients with GCM who required MCS. A systematic search was performed in June 2019 to identify all studies of biopsy-proven GCM requiring MCS after 2009. We identified 27 studies with 43 patients. Patient-level data were extracted for analysis. Median patient age was 45 (interquartile range (IQR): 32–57) years. 42.1% (16/38) were female. 34.9% (15/43) presented in acute heart failure. 20.9% (9/43) presented in cardiogenic shock. Biventricular (BiVAD) MCS was required in 76.7% (33/43) of cases. Of the 62.8% (27/43) of patients who received immunotherapy, 81.5% (22/27) used steroids combined with at least one other immunosuppressant. Cyclosporine was the most common non-steroidal agent, used in 40.7% (11/27) of regimens. Immunosuppression was initiated before MCS in 59.3% (16/27) of cases, after MCS in 29.6% (8/27), and not specified in 11.1% (3/27). Immunosuppression started prior to MCS was associated with significantly better survival than MCS alone (p = 0.006); 60.5% (26/43) of patients received bridge-to-transplant MCS; 39.5% (17/43) received bridge-to-recovery MCS; 58.5% (24/41) underwent OHT a median of 104 (58–255) days from diagnosis. GCM recurrence after OHT was reported in 8.3% (2/24) of transplanted cases. BiVAD predominates in mechanically supported patients with GCM. Survival and bridge to recovery appear better in patients on immunosuppression, especially if initiated before MCS. Keywords: myocarditis; mechanical circulatory support; immunosuppression; treatment; survival 1. Introduction Giant cell myocarditis (GCM) is a rare autoimmune disorder characterized by diffuse myocardial necrosis with multinucleated giant cells [1]. First described in 1905 by Saltikow [2], GCM is often mistaken for other infiltrative cardiomyopathies [3] such as cardiac sarcoidosis and lymphocytic myocarditis. Although these diseases may present similarly and share some histopathologic features, GCM is most associated with a poor prognosis [4], resulting in severe heart failure and ventricular arrhythmias. J. Clin. Med. 2020, 9, 3905; doi:10.3390/jcm9123905 www.mdpi.com/journal/jcm J. Clin. Med. 2020, 9, x FOR PEER REVIEW 2 of 12 histopathologic features, GCM is most associated with a poor prognosis [4], resulting in severe heart J. Clin. Med. 2020, 9, 3905 2 of 11 failure and ventricular arrhythmias. Given the rare incidence of GCM, there are limited data on the topic, with Cooper’s Multicenter GiantGiven Cell Myocarditis the rare incidence Registry of GCM,[5] as therethe largest are limited collection data of on data the topic,in this with population. Cooper’s GCM Multicenter affects Giantyoung Cellindividuals Myocarditis and is Registry associated [5] aswith the autoimmune largest collection disease of and data tumors, in this population.especially thymoma. GCM aff ectsThe youngmean age individuals at the time and of isdiagnosis associated is 52.5 with years autoimmune [6] for patients disease with and GCM, tumors, with especially some presenting thymoma. in Theyoung mean adulthood. age at the Heart time failure of diagnosis by contrast is 52.5 has years a mean [6] for age patients of diagnosis with GCM, at 75 withyears some [7]. Since presenting patients in youngaffected adulthood. by giant cell Heart myocarditis failure by contrastare younger has a meanthan the age average of diagnosis patient at 75 population years [7]. Sinceexperiencing patients aheartffected failure, by giant improved cell myocarditis management are guidelines younger thanmay themeaningfully average patient impact population their quality experiencing of life and heartlong-term failure, survival. improved management guidelines may meaningfully impact their quality of life and long-termMost survival.patients with GCM are treated with immunosuppression (IS) or orthotopic heart transplantationMost patients (OHT). with With GCM the aredevelopment treated with of du immunosuppressionrable, continuous-flow (IS) left or ventricular orthotopic assist heart transplantationdevices (CF-LVADs), (OHT). patients With thewith development end-stage heart of durable, failure can continuous-flow be mechanically left supported ventricular as assist they devicesawait OHT (CF-LVADs), [8]. When patients GCM withpresents end-stage as a fulminant heart failure myocarditis can be mechanically with acute supported heart failure, as they patients await OHTmay be [8]. placed When on GCM bridge-to-transplant presents as a fulminant mechanical myocarditis circulatory with acutesupport heart (MCS) failure, [9], patients and often, may the be placeddiagnosis on of bridge-to-transplant GCM is made via biopsy mechanical at the circulatory time of LVAD support implantation (MCS) [9 ],or and transplant often, the [10]. diagnosis Given the of GCMrarity isof made GCM, via there biopsy is limited at the time literature of LVAD discussi implantationng treatment or transplant outcomes [10 ].in Givenpatients the managed rarity of GCM, with thereMCS. isThe limited purpose literature of discussing this study treatment is to outcomes evaluate in patientsthe characteristics managed with and MCS. outcomes The purpose of ofimmunosuppression this study is to evaluate in mechanically the characteristics supported and patients outcomes with of giant immunosuppression cell myocarditis.in mechanically supported patients with giant cell myocarditis. 2. Experimental Section 2. Experimental Section 2.1. Literature Search 2.1. Literature Search An electronic search was performed in June 2019 in the Cochrane, MEDLINE, Scopus, and An electronic search was performed in June 2019 in the Cochrane, MEDLINE, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases to identify all and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases to identify reports of biopsy-proven giant cell myocarditis requiring mechanical circulatory support from 2009 all reports of biopsy-proven giant cell myocarditis requiring mechanical circulatory support from through 2019. The keyword “giant cell myocarditis” was used to perform the search. Of the 2646 2009 through 2019. The keyword “giant cell myocarditis” was used to perform the search. Of the articles identified, 27 articles, consisting of six case series and 21 case reports, with a total of 43 cases 2646 articles identified, 27 articles, consisting of six case series and 21 case reports, with a total of met inclusion criteria. A Preferred Reporting Items for Systematic Reviews and Meta-Analysis 43 cases met inclusion criteria. A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram outlining the literature search protocol is provided as Figure 1. No (PRISMA) flow diagram outlining the literature search protocol is provided as Figure1. No institutional institutional review board approval was required for this study, given that all data were collected review board approval was required for this study, given that all data were collected from previously from previously published articles. published articles. Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) diagram Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) diagram outlining literature search strategy for systematic review. outlining literature search strategy for systematic review. J. Clin. Med. 2020, 9, 3905 3 of 11 2.2. Inclusion Criteria Only biopsy-proven cases of giant cell myocarditis were included in this study. All adults 18 years or older with MCS, including CF-LVADs, biventricular assist devices (BiVAD), and total artificial hearts (TAH), were included in the study. Due to limited available data, case series and case reports were selected. 2.3. Data Extraction Patient-level data were extracted and pooled for statistical analysis from the body, figures, and tables of selected case series and case reports. In situations where data were not available, attempts were made to contact corresponding
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