Histopathological Patterns of Myocarditis and Their Association with Viral Etiologies: A Systematic Review and Meta-Analysis
Background: Myocarditis is an inflammatory disease of the myocardium with diverse histopathological patterns. Viral infections are the leading cause, yet the strength of association between histopathological subtypes and specific viral agents remains unclear. Objective: To systematically review and quantitatively synthesize available evidence on the relationship between histopathological patterns of myocarditis and viral etiologies detected in myocardial tissue. Methods: PubMed, Embase, Scopus, and Web of Science were searched up to March 2025 for studies reporting histopathological subtypes of myocarditis with concomitant viral testing of myocardial tissue by PCR, immunohistochemistry, or in situ hybridization. Eligible studies included cohorts, case-control studies, and case series (≥5 patients). Data were pooled using random-effects models to estimate odds ratios (OR) for associations between histological patterns (lymphocytic, eosinophilic, giant cell, granulomatous) and viral detection. Heterogeneity was quantified by I², and publication bias by Egger’s test. Results: Thirty-two studies comprising 4,256 patients (3,112 with endomyocardial biopsy, 1,144 with autopsy samples) were included. Lymphocytic myocarditis was the predominant pattern (61.8%), followed by eosinophilic (9.2%), granulomatous (6.5%), and giant cell myocarditis (3.8%). Viral genomes were detected in 53.4% of biopsies overall. Pooled analysis showed that lymphocytic myocarditis was strongly associated with viral detection (OR 3.12, 95% CI 2.25-4.32, I² = 28%). In contrast, eosinophilic (OR 0.54, 95% CI 0.33-0.88, I² = 12%) and giant cell myocarditis (OR 0.41, 95% CI 0.19-0.88, I² = 0%) were negatively associated with viral presence. Granulomatous myocarditis, often reflecting sarcoidosis or tuberculosis, showed no significant association with viral genomes (OR 0.92, 95% CI 0.55-1.56, I² = 35%). Subgroup analysis revealed parvovirus B19 and enteroviruses as the most frequently associated viruses with lymphocytic myocarditis. Conclusions: Histopathological patterns of myocarditis correlate strongly with underlying etiology. Lymphocytic myocarditis is significantly associated with viral detection, especially parvovirus B19 and enteroviruses, whereas eosinophilic and giant cell forms are typically non-viral. Recognition of these associations is essential for diagnostic interpretation and therapeutic decision-making