Abstract 5936: Can Apoptosis Predict Functional Recovery in Acute Myocarditis?

Abstract

Background. Acute myocarditis is characterized by acute cardiac dysfunction followed by a variable recovery over time. Recent data have shown the presence of apoptosis in acute myocarditis. We hypothesized that the presence and extent of apoptosis evaluated at endomyocardial biopsy (EMB) could predict functional recovery in patients with acute myocarditis, with more apoptosis predicting less recovery. Methods. Sixteen patients with acute myocarditis were studied with EMB. Baseline and follow up echocardiography was obtained in all cases. The patients were retrospectively divided in 2 groups according to the final left ventricular ejection fraction (LVEF): LVEF>40% [recovery] and LVEF≤40% [no recovery]. Co-staining for DNA fragmentation (TUNEL) and caspase-cleaved cytokeratin-18 (CytoDeath) were performed to quantify the cardiomyocyte apoptosis in EMB specimens. Four subjects dying of non-cardiac causes were selected as control hearts at time of autopsy. Results. Six patients showed functional recovery (38%) while 8 did not (62%). The apoptotic rate (AR, expressed as % of double positive cardiomyocytes on total number per field) was significantly higher in the hearts of patients with acute myocarditis (1.1%[0.7–2.2] vs 0.01%[0.01–0.01] in control hearts, p<0.001). Unexpectedly, patients with functional recovery had a significantly higher AR than patients without recovery (3.2%[1.1–8.0] vs 0.5%[0.3–1.0], p=0.001), and the AR correlated with follow-up LVEF (R=+0.54, p=0.030). Six of the 8 patients (75%) with AR above average showed functional recovery vs 0 of the 8 patients (0%) with AR below average (p=0.007). Conclusions. This study surprisingly shows that the presence of greater apoptosis at EBM in patients with acute myocarditis predicts functional recovery at 12 months. Whether this represents a true cause-effect association or it simply represents a non-causal association remains unclear and warrants further studies.