Clinical and Cardiac Magnetic Resonance Phenotype of Probable Viral versus Probable Immune-mediated Acute Myocarditis

BACKGROUND: Endomyocardial biopsy can distinguish between immune-mediated and viral myocarditis, but is rarely performed in routine practice. It is unclear whether clinically defined probable viral myocarditis (pVM) and probable immune-mediated myocarditis (pIM) differ in presentation, cardiac magnetic resonance (CMR) phenotype, and prognosis. METHODS: Patients referred for CMR due to possible myocarditis were enrolled at two tertiary centers. pVM was defined as myocarditis within 14 days of a documented infectious disease. pIM was defined as acute myocarditis in patients with a known systemic autoimmune disease. Those not meeting either definition were excluded. Clinical characteristics, CMR features and clinical outcomes using a composite endpoint of first heart failure hospitalization, recurrent myocarditis, sustained ventricular tachycardia, or all-cause death were compared. RESULTS: Among 1122 patients referred for CMR for clinically suspected myocarditis, 379 met criteria for pVM and 116 for pIM. Compared with pIM, patients with pVM were younger (36.0 vs. 55.0 years, p<0.001) and more frequently presented with acute chest-pain and ST-segment elevation (17.9 vs. 7.8%, p=0.012). Late gadolinium enhancement (LGE) (83.6 vs. 70.2%, p=0.006) and basal septal LGE involvement (31.5 vs. 18.7%, p=0.006) were more common in pIM. pIM was associated with worse outcomes at median 3.3 years follow-up and independently predicted the composite endpoint (HRadj=1.89, 95%CI:1.03-3.48; p=0.041). In pIM, age was the only predictor of adverse events, while in pVM multiple clinical and CMR features were prognostically relevant. CONCLUSION: pVM and pIM were associated with distinct clinical and CMR phenotypes. While outcomes in pVM appeared closely linked to myocardial injury patterns, pIM was associated with poorer outcomes, largely independent of imaging findings, suggesting a more heterogeneous inflammatory cardiomyopathy driven by the underlying systemic disease.