Biopsy-proven myocarditis: independent predictors of dismal prognosis, relapse and role of immunosuppressive therapy

Abstract Background Biopsy-proven myocarditis may be infectious or autoimmune. Risk stratification in biopsy-proven myocarditis and the role of immunosuppressive therapy in autoimmune forms have not been completely defined. Purpose To identify clinical, instrumental and immunological predictors of death, cardiac transplantation and relapse in a prospective cohort of 314 biopsy-proven myocarditis patients, and describe the effect of immunosuppressive treatment on secondary outcome measures, e.g. left ventricular ejection fraction (LVEF), in a subgroup of 45 consecutive patients with biopsy-proven autoimmune myocarditis diagnosed in our Cardiology Clinic. Methods Univariate and multivariate Cox regression analysis were used to identify predictors of death, heart transplant, and relapse in a cohort of 314 patients with biopsy-proven myocarditis (male 75%, median age 37). Actuarial survival free from death or transplant was calculated by the Kaplan-Meier method. Results Actuarial survival free from death or heart transplantation was 83% at 5 years. Among the clinical, instrumental and immunological features at diagnosis, independent predictors of death or heart transplantation by multivariable analysis were a lower transthoracic echocardiographic biplane LVEF% (p=0.001) and high serum titre for anti-nucler (ANA) and anti-cardiac endothelial cell autoantibodies (AECA). The only independent predictor of relapse was previous history of myocarditis. Immunosuppressive therapy was associated with a significantly favorable effect on LVEF (LVEF pre-therapy 37% (26; 50 interquartile range) vs. LVEF post-therapy 59% (48; 65 interquartile range), respectively, p=0.000). Conclusions In biopsy-proven myocarditis left ventricular dysfunction at diagnosis and autoimmune pathogenesis are associated with dismal prognosis, immunosuppressive therapy with improved LVEF in autoimmune patients.