Incidence and predictors of major ventricular arrhythmias after myocarditis: a systematic review and meta-analysis

Abstract Introduction The arrhythmic risk and long-term outcomes after an acute myocarditis episode remain unclear. Recent data indicate that ventricular arrhythmias (VAs) may be frequently observed both in the acute phase and years after the initial event, making sudden cardiac death a prominent cause of death in these patients. The latest European and American guidelines support implantable cardioverter-defibrillator (ICD) implantation as secondary prevention independently on the underlying substrate and evolution. The initial and subsequent management of myocarditis patients remains debated. Purpose To assess the incidence and predictors of major arrhythmic events (MAEs) after myocarditis. Methods We conducted a systematic literature review and meta-analysis of 12 eligible studies (11 retrospective, 1 prospective), including 3450 patients with prior myocarditis, with and without MAEs at presentation, followed for a median of 24 months (IQR 18–41). MAEs were defined as a composite of sudden death (SD), aborted cardiac arrest (ACA), sustained ventricular tachycardia (SVT) and appropriate ICD interventions. The primary endpoint was the incidence of MAEs, while secondary endpoint included the occurrence of each one of components of MAEs, all-cause mortality and heart transplantation (HTx). Results Among 3450 patients (52.5% male, mean age 46.5 years), the majority (66%) had lymphocytic myocarditis, followed by giant cell myocarditis (5%). At presentation, 38% (IQR 23–52%) experienced ventricular fibrillation or SVT, with a mean left ventricular ejection fraction (LVEF) of 42% (IQR 38–49%). Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) was reported in 94% of cases. Notably, most patients (67%; IQR 44–91%) belonged to the acute myocarditis group, while only 9% (IQR 0–43%) had chronic myocarditis. At discharge, 60% (IQR 36–92%) required ICD implantation, and 88% (IQR 84–94%) were prescribed beta-blocker therapy. During follow-up, the incidence of MAEs was 36% (95% CI 23–49), including 5 SDs (1%). The median time to MAE occurrence was 12 months (IQR 11–18). The combined rate of all-cause mortality and HTx was 13% (95% CI 8–19%). Meta-regression analysis identified atrioventricular block at presentation as a significant predictor of MAEs (p = 0.046) during follow up, while giant cell myocarditis showed a trend toward higher MAE risk, though without statistical significance (p = 0.067). Conclusions Based on currently available studies, the recurrence of MAEs after myocarditis is high, regardless the phase of disease (acute or chronic), with a mortality/HTx rate of 13% over two years. Atrioventricular block at presentation appears to be risk factor for MAEs, while giant cell myocarditis is associated with a trend toward increased risk. Future prospective studies are needed to better stratify high-risk patients and guide decisions regarding early ICD implantation or other antiarrhythmic strategies.