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

Abstract

This study sought to investigate the effects of immunosuppression on arrhythmic myocarditis. 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. 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. A total of 58 matched patient couples (age 42 ± 13 years; 67% male) were analyzed in the main study cohort. IST duration was 12 ± 1months. 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 ± 21months of follow-up. 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.