https://doi.org/10.4081/monaldi.2025.3231
The role of genetics in the prognosis of acute myocarditis: a systematic review and meta-analysis
Submitted: October 18, 2024
Accepted: December 10, 2024
Published: February 25, 2025
Accepted: December 10, 2024
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SUPPLEMENTARY MATERIAL: 46
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Myocarditis is a heterogeneous disease with varying clinical presentations, etiologies, and courses. Apart from environmental factors, genetic factors may also play a role in its pathophysiology. Through a systematic review and meta-analysis, we aimed to characterize the relationship between acute myocarditis (AM), underlying genetic background, and prognosis. We searched on MEDLINE/PubMed and Web of Science for studies reporting clinical outcomes of patients presenting with AM and undergoing genetic testing. The prevalence of a positive genetic test result was 27.3%, with a higher proportion of males (61.3%). Patients with a positive genetic test often had a family history of cardiovascular events (53.3%) and late gadolinium enhancement on cardiac magnetic resonance (81.2%), suggesting that these clinical features may represent a population with a higher burden of genetic background and risk for worse outcomes. The risk of recurrence of AM among patients with a positive genetic test was four times greater than among non-carriers (RR=4.02, p<0.001), and the most frequently observed variants among AM carriers were in the TTN, DSP, PKP2, MYH7, BAG3, RMB20, DSG2, TNNT2, and SCN5A genes. Overall, these findings underscore the need to improve the criteria used for genetic testing in the setting of AM episodes and to identify affected individuals who may benefit from increased surveillance and genetic testing.
McNally EM, Selgrade DF. Genetic testing for myocarditis. JACC Heart Fail 2022;10:728-30.
DOI: https://doi.org/10.1016/j.jchf.2022.07.003
Baggio C, Gagno G, Porcari A, et al. Myocarditis: which role for genetics? Curr Cardiol Rep 2021;23:58.
DOI: https://doi.org/10.1007/s11886-021-01492-5
Caforio AL, Pankuweit S, Arbustini E, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;34:2636-48.
DOI: https://doi.org/10.1093/eurheartj/eht210
Lewis AJM, Burrage MK, Ferreira VM. Cardiovascular magnetic resonance imaging for inflammatory heart diseases. Cardiovasc Diagn Ther 2020;10:598-609.
DOI: https://doi.org/10.21037/cdt.2019.12.09
Monda E, Limongelli G. Is there a role for genetic testing in patients with myocarditis? Circ Genom Precis Med 2022;15:e003824.
DOI: https://doi.org/10.1161/CIRCGEN.122.003824
Sousa A, Moldovan O, Lebreiro A, et al. Recommendations for genetic testing in cardiology: Review of major international guidelines. Rev Port Cardiol 2020;39:597-610.
DOI: https://doi.org/10.1016/j.repce.2020.03.008
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
DOI: https://doi.org/10.1136/bmj.n71
Ader F, Elodie Surget, Charron P, et al. Inherited cardiomyopathies revealed by clinically suspected myocarditis: highlights from genetic testing. Circ Genom Precis Med 2020;13:e002744.
DOI: https://doi.org/10.1161/CIRCGEN.119.002744
Ammirati E, Raimondi F, Piriou N, et al. Acute myocarditis associated with desmosomal gene variants. JACC Heart Fail 2022;10:714-27.
DOI: https://doi.org/10.1093/eurheartj/ehac544.1682
Artico J, Merlo M, Delcaro G, et al. Lymphocytic myocarditis. J Am Coll Cardiol 2020;75:3098-100.
DOI: https://doi.org/10.1016/j.jacc.2020.04.048
Brown EE, McMilllan KN, Halushka MK, et al. Genetic aetiologies should be considered in paediatric cases of acute heart failure presumed to be myocarditis. Cardiol Young 2019;29:917-21.
DOI: https://doi.org/10.1017/S1047951119001124
Kontorovich AR, Patel N, Moscati A, et al. Myopathic cardiac genotypes increase risk for myocarditis. JACC Basic Transl Sci 2021;6:584-92.
DOI: https://doi.org/10.1016/j.jacbts.2021.06.001
Kontorovich AR, Tang Y, Patel N, et al. Burden of cardiomyopathic genetic variation in lethal pediatric myocarditis. Circ Genom Precis Med 2021;14:e003426.
DOI: https://doi.org/10.1161/CIRCGEN.121.003426
Lota AS, Hazebroek MR, Theotokis P, et al. Genetic architecture of acute myocarditis and the overlap with inherited cardiomyopathy. Circulation 2022;146:1123-34.
DOI: https://doi.org/10.1161/CIRCULATIONAHA.121.058457
Ollitrault P, Khoury M, Troadec Y, et al. Recurrent acute myocarditis: an under-recognized clinical entity associated with the later diagnosis of a genetic arrhythmogenic cardiomyopathy. Front Cardiovasc Med 2022;9:998883.
DOI: https://doi.org/10.3389/fcvm.2022.998883
Seidel F, Holtgrewe M, Al-Wakeel-Marquard N, et al. Pathogenic variants associated with dilated cardiomyopathy predict outcome in pediatric myocarditis. Circ Genom Precis Med 2021;14:e003250.
DOI: https://doi.org/10.1161/CIRCGEN.120.003250
Seidel F, Laser KT, Klingel K, et al. Pathogenic variants in cardiomyopathy disorder genes underlie pediatric myocarditis—further impact of heterozygous immune disorder gene variants? J Cardiovasc Dev Dis 2022;9:216.
DOI: https://doi.org/10.3390/jcdd9070216
Tiron C, Campuzano O, Fernandez-Falgueras A, et al. Prevalence of pathogenic variants in cardiomyopathy-associated genes in myocarditis. Circ Genom Precis Med 2022;15:e003408.
DOI: https://doi.org/10.1161/CIRCGEN.121.003408
Peretto G, Sommariva E, Di Resta C, et al. Myocardial inflammation as a manifestation of genetic cardiomyopathies: from bedside to the bench. Biomolecules 2023;13:646.
DOI: https://doi.org/10.3390/biom13040646
Martens P, Cooper LT, Wilson Tang WH. Diagnostic approach for suspected acute myocarditis: considerations for standardization and broadening clinical spectrum. J Am Heart Assoc 2023;12:e031454.
DOI: https://doi.org/10.1161/JAHA.123.031454
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.
DOI: https://doi.org/10.1038/gim.2015.30
Salvarani N, Peretto G, Silvia C, et al. Functional characterisation of the rare SCN5A p.E1225K variant, segregating in a Brugada syndrome familial case, in human cardiomyocytes from pluripotent stem cells. Int J Mol Sci 2023;24:9548.
DOI: https://doi.org/10.3390/ijms24119548
George CH, Jundi H, Thomas NL, et al. Ryanodine receptors and ventricular arrhythmias: emerging trends in mutations, mechanisms and therapies. J Mol Cell Cardiol 2007;42:34-50.
DOI: https://doi.org/10.1016/j.yjmcc.2006.08.115
Duan D, Goemans N, Takeda S, et al. Duchenne muscular dystrophy. Nat Rev Dis Primers 2021;7:13.
DOI: https://doi.org/10.1038/s41572-021-00248-3
Roy Choudhury A, Munonye I, Sanu KP, et al. A review of Alström syndrome: a rare monogenic ciliopathy. Intractable Rare Dis Res 2021;10:257-62.
DOI: https://doi.org/10.5582/irdr.2021.01113
Filippa R, Lorenzi P, Bergamo E, et al. Identification of nuclear retention domains in the RBM20 protein. FEBS Lett 2013;587:2989-95.
DOI: https://doi.org/10.1016/j.febslet.2013.07.018
Palpant NJ, Bedada FB, Peacock B, et al. Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies. Am J Physiol Heart Circ Physiol 2011;300:H356-65.
DOI: https://doi.org/10.1152/ajpheart.00774.2010
McNally EM, Mestroni L. Dilated cardiomyopathy. Circ Res 2017;121:731-48.
DOI: https://doi.org/10.1161/CIRCRESAHA.116.309396
Ye JZ, Delmar M, Lundby A, et al. Reevaluation of genetic variants previously associated with arrhythmogenic right ventricular cardiomyopathy integrating population‐based cohorts and proteomics data. Clin Genet 2019;96:506-14.
DOI: https://doi.org/10.1111/cge.13621
Bariani R, Rigato I, Cipriani A, et al. Myocarditis-like episodes in patients with arrhythmogenic cardiomyopathy: a systematic review on the so-called hot-phase of the disease. Biomolecules 2022;12:1324.
DOI: https://doi.org/10.3390/biom12091324
Monda E, Bakalakos A, Cannie D, et al. Prevalence of pathogenic variants in cardiomyopathy-associated genes in acute myocarditis: a systematic review and meta-analysis. JACC Heart Fail 2024;12:1101-11.
DOI: https://doi.org/10.1016/j.jchf.2024.02.012
How to Cite
Tomás, Maria João, Ana Isabel Pinho, Bernardo Sousa Pinto, and Elisabete Martins. 2025. “The Role of Genetics in the Prognosis of Acute Myocarditis: A Systematic Review and Meta-Analysis”. Monaldi Archives for Chest Disease, February. https://doi.org/10.4081/monaldi.2025.3231.
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