Different Phases of Disease in Lymphocytic Myocarditis: Clinical and Electrophysiological Characteristics

Background: Endomyocardial biopsy (EMB) is required to make a definite diagnosis of lymphocytic myocarditis (LM), to identify its etiology, and to classify LM into different phases. Objectives: This study aims to characterize and compare clinical and electrophysiological characteristics of different biopsy-proven LM phases, namely acute myocarditis (AM), chronic active myocarditis (CAM), and healed myocarditis (HM). Methods: All patients with a diagnosis of LM at 3 Italian referral centers were prospectively enrolled. According to EMB findings, LM was classified as AM, CAM, or HM; per-group comparisons of clinical presentations, noninvasive, and invasive findings are reported. Results: Among the 122 enrolled patients (AM, n = 44; CAM, n = 42; HM, n = 36), complex ventricular arrhythmias were very common overall (n = 109, 89%), but ventricular fibrillation was slightly more prevalent in AM (P = 0.028). Cardiac magnetic resonance imaging showed late gadolinium enhancement in more patients with HM and CAM than AM (94.4% vs 92.9% vs 50%; P < 0.001), whereas edema was more common in AM than in CAM, being absent in HM (90.9% vs 50% vs 0%; P < 0.001). Accordingly, edema was the strongest independent clinical predictor of EMB-proven active inflammation. Electroanatomical mapping revealed a lower prevalence of low-voltage areas in AM than in CAM or HM. We observed a strong association between edema at a specific myocardial segment and normal voltages at that site (odds ratio: 0.24; 95% CI: 0.10-0.54; P < 0.01), as well as between late gadolinium enhancement and low-voltage areas (odds ratio: 2.86; 95% CI: 1.19-6.97; P = 0.019). Conclusions: LM is a highly heterogeneous disease, and its different phases are characterized by diverse clinical, morphological, and electrophysiological features. Further research is required to identify electroanatomical markers of inflammation.