Immunosuppressive Therapy and Risk Stratification of Patients With Myocarditis Presenting With Ventricular Arrhythmias

Objectives: This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis. Background: The effects of immunosuppressive therapy (IST) on ventricular arrhythmia (VA) have not been reported in patients with immune-mediated biopsy-proven myocarditis. Furthermore, myocarditis arrhythmic risk is still unpredictable. Methods: We enrolled 255 patients with biopsy-proven virus-negative myocarditis and VA (major: ventricular fibrillation, ventricular tachycardia; minor: nonsustained ventricular tachycardia, Lown grade ≥2 premature ventral complexes) at presentation. Serum cardiac autoantibodies (antiheart antibodies, anti–intercalated disk autoantibodies [AIDA]) were detected by a standardized indirect immunofluorescence technique. Whenever accepted and noncontraindicated, IST was started. Control individuals (IST−) were chosen after 1:1 matching to IST+ patients by age, sex, ethnicity, left ventricular ejection fraction, VA type, and treatment. Results: A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1 months. By the 24-month prospective follow-up, major VA occurred in 6 IST+ versus 10 IST− patients (p = 0.42), with no episodes following IST termination. As compared to IST− patients, IST+ patients showed a significant reduction in minor VA burden, as well as improvement in clinical, laboratory, and imaging findings (all p < 0.05). Major VA onset and positive AIDA status were independently associated with major VA at follow-up (hazard ratio [HR]: 14.2; 95% confidence interval [CI]: 2.9 to 68.7 and HR: 8.0; 95% CI: 2.6 to 25.2, respectively; both p < 0.001). Furthermore, in the whole study population (N = 255), IST was independently associated with protection from major VA (HR: 0.3; 95% CI: 0.2 to 0.7; p = 0.01) at 38 ± 21 months of follow-up. Conclusions: In patients with immune-mediated virus-negative myocarditis presenting with VA, IST is associated with positive effects on minor VA and nonarrhythmic endpoints. Short-term effects are limited on major VA, which were independently associated with major VA onset and positive AIDA.