CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis

Objectives: The aim of this study was to determine whether clinical presentation and type of cell death in acute myocarditis might contribute to cardiac magnetic resonance (CMR) sensitivity. Background: Growing evidence indicates CMR is the reference noninvasive tool for the diagnosis of acute myocarditis. However, factors affecting CMR sensitivity are still unclear. Methods: We retrospectively evaluated 57 consecutive patients with a diagnosis of acute myocarditis made on the basis of clinical history (≤3 months) and endomyocardial biopsy evidence of lymphocytic infiltrates (≥14 infiltrating leukocytes/mm² at immunohistochemistry) in association with damage of the adjacent myocytes and absence or minimal evidence of myocardial fibrosis. CMR acquisition protocol included T2-weighted (edema), early (hyperemia), and late (fibrosis/necrosis) gadolinium enhancement sequences. Presence of ≥2 CMR criteria denoted myocarditis. Type of cell death was evaluated by using in situ ligation with hairpin probes. Results: Three clinical myocarditis patterns were recognized: infarct-like (pattern 1, n = 21), cardiomyopathic (pattern 2, n = 21), and arrhythmic (pattern 3, n = 15). Tissue edema was observed in 81% of pattern 1, 28% of pattern 2, and 27% of pattern 3. Early enhancement was evident in 71% of pattern 1, 67% of pattern 2, and 40% of pattern 3. Late gadolinium enhancement was documented in 71% of pattern 1, 57% of pattern 2, and 47% of pattern 3. CMR sensitivity was significantly higher in pattern 1 (80%) compared with pattern 2 (57%) and pattern 3 (40%) (p <0.05). Cell necrosis was the prevalent mechanism of death in pattern 1 compared with pattern 2 (p <0.001) and pattern 3 (p <0.05), whereas apoptosis prevailed in pattern 2 (p <0.001 vs. pattern 1 and p <0.05 vs. pattern 3). Conclusions: In acute myocarditis, CMR sensitivity is high for infarct-like, low for cardiomyopathic, and very low for arrhythmic clinical presentation; it correlates with the extent of cell necrosis-promoting expansion of interstitial space.