Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies.

AIMS: Outcome predictors in myocarditis are not well defined; we aimed at identifying predictors of death, heart transplantation (HTx) and relapse before the introduction of immunosuppression. METHODS AND RESULTS: From 1992 to 2012, 466 consecutive patients (68% male, mean age 37 ± 17 years, single centre recruitment, median follow-up 50 months) were included, of whom 216 had clinically suspected and 250 biopsy-proven myocarditis. Serum anti-heart (AHA) and anti-intercalated disk (AIDA) autoantibodies were measured by indirect immunofluorescence. Univariable and multivariable analyses of clinical and diagnostic features at diagnosis were performed. Survival free from death or HTx at 10 years was 83% in the whole study population and was lower in biopsy-proven versus clinically suspected myocarditis (76% vs. 94%, p < 0.001). Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.5), fulminant presentation (HR 13.77, 95% CI 9.7-261.73), high-titre organ-specific AHA (HR 4.2, 95% CI 1.2-14.7) and anti-nuclear antibodies (ANA) (HR 5.2, 95% CI 2.1-12.8) were independent predictors of death or HTx; higher echocardiographic left ventricular ejection fraction (LVEF) at diagnosis was protective, with a 0.93-fold risk reduction for each 1% LVEF increase (95% CI 0.89-0.96). History of myocarditis at diagnosis (HR 8.5, 95% CI 3.5-20.7) was an independent predictor of myocarditis relapse at follow-up; older age was protective (HR 0.95, 95% CI 0.91-0.99). Predictors of death, HTx and relapse did not differ in biopsy-proven versus clinically suspected myocarditis. CONCLUSIONS: Young age and a previous myocarditis were independent relapse predictors; female gender, fulminant onset, lower LVEF at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features predict worse prognosis.