Myocarditis

Gabriel, Franck; Luo, Honglin; Qiu, Ye; Yang, Decheng; McManus, Bruce M.

doi:10.1161/circresaha.115.306573

Cited by 405 publications

(413 citation statements)

References 250 publications

(210 reference statements)

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“…Separating AVM from DCM has long posed a significant clinical challenge (27,28). When AVM presents in childhood, as it often does, the meaning of a history of recent viral infections is dubious given their prevalence in that age group.…”

Section: Discussionmentioning

confidence: 99%

Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis

Belkaya

Kontorovich

Byun

et al. 2017

Journal of the American College of Cardiology

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BACKGROUND Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon- (IFN) α/β immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3, a potent inducer of IFNs, were proposed to underlie AVM. OBJECTIVES We evaluated the hypothesis that human genetic factors might underlie AVM in previously healthy children. METHODS We tested the role of TLR3-IFN immunity utilizing human-induced pluripotent stem cell-derived cardiomyocytes. We then performed whole exome sequencing of 42 unrelated children with acute myocarditis (AM), some with proven viral etiologies. RESULTS We found that TLR3- and STAT1-deficient cardiomyocytes were not more susceptible to coxsackievirus B3 (CVB3) infection than control cells. Moreover, CVB3 did not induce IFN-α/β and IFN-α/β-stimulated genes in control cardiomyocytes. Finally, exogenous IFN-α did not substantially protect cardiomyocytes against CVB3. We did not observe a significant enrichment of rare variations in TLR3- or IFN-α/β-related genes. Surprisingly, we found that homozygous, but not heterozygous, rare variants in genes associated with inherited cardiomyopathies were significantly enriched in AM-AVM patients compared with healthy individuals (p = 2.22E-03) or patients with other diseases (p = 1.08E-04). Seven of 42 patients (16.7%) carried rare biallelic nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes (BAG3, DSP, PKP2, RYR2, SCN5A, or TNNI3). CONCLUSIONS Previously silent recessive defects of the myocardium may predispose to acute heart failure presenting as AM, notably after common viral infections.

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Section: Discussionmentioning

confidence: 99%

Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis

Belkaya

Kontorovich

Byun

et al. 2017

Journal of the American College of Cardiology

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“…Many centers perform heart biopsies with a high degree of safety and with the clear benefit of guiding diagnosis and treatment although the issue is still controversial (7*; 8). A review of the available evidence that persistent virus can contribute to cardiac pathology has been laid out in an extensive review of two decades of research by Fung and colleagues (9**). A number of in vitro mechanisms by which persistent virus can produce damage to the myocardium directly or indirectly has been described.…”

Section: Introductionmentioning

confidence: 99%

Viral myocarditis

Rose¹

2016

Current Opinion in Rheumatology

127

103

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Purpose of the review This article traces the pathways leading from viral infection of the heart by coxsackievirus B3 to autoimmune myocarditis in its various manifestations. Recent findings Myocarditis can be induced by a number of different infectious agents and represents a significant cause of death especially in young individuals. Following infection patients may develop lymphocytic, eosinophilic, or giant cell/granulomatous myocardial inflammation. It can lead to infectious dilated cardiomyopathy, a disease frequently requiring cardiac transplantation. Although acute viral myocarditis is frequently sub-clinical and recovery may be spontaneous, treatment of chronic myocarditis is presently unsatisfactory. Ongoing disease may be due to persistent virus in the heart or to immunopathic attack. Depending on the etiology, treatment may be antiviral or immunosuppressive. Endomyocardial biopsy is proving of value in determining etiology and deciding future therapy. A great deal of information about the pathogenesis of myocarditis has been gained from experimental models in rodents using heart disease induced by infection using coxsackievirus B3 or by immunization with cardiac myosin. Summary Treatment of myocarditis is still problematic and may depend on etiologic diagnosis to distinguish infectious from immune mediated disease. Both pathogenic mechanisms may co-occur in individual patients. In the future, treatment may depend upon endomyocardial biopsy, immunohistologic testing, improved imaging, and molecular genetic analysis for providing more precise diagnoses.

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“…Nevertheless, infection with enteroviruses is thought to be one leading cause of the disease [3, 5], especially infection with cardiotropic Coxsackievirus B3 (CVB3) in young patients [6]. Acute viral myocarditis is described by focal cellular infiltrates with necrosis or fibrosis, primarily consisting of macrophages, CD4 + T cells, and CD8 + T cells with B cells, mast cells, dendritic cells, and natural killer cells [3, 6–12]. There exists evidence that especially B cells, T-helper cells, and macrophages are infected during the acute myocarditis suggesting indirect transport of virus particles into organs, which in turn leads to infection of resident cells [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

Becher¹,

Gotzhein

Klingel

et al. 2017

Journal of Immunology Research

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Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

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Myocarditis

Cited by 405 publications

References 250 publications

Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis

Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis

Viral myocarditis

Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

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