Treatment of virus negative chronic myocarditis: long term follow-up of TIMIC trial

Abstract

Abstract Background The TIMIC trial demonstrated the short term efficacy of immunosuppression (IMS) in virus-negative inflammatory cardiomyopathy. However long term outcome of patients responsive to this treatment is still unclear. Purpose To assess the long term outcome of patients enrolled in the TIMIC trial. Methods The 85 (51 M, 34 F, 42.7±14.7 years) patients with endomyocardial biopsy proven virus-negative chronic inflammatory cardiomyopathy, enrolled in the TIMIC trial and treated either with prednisone and azathioprine (prednisone 1mg kg–1 day–1 for 4 weeks followed by 0.33 mg kg–1 day–1 for 5 months and azathioprine 2 mg kg–1 day–1 for 6 months) or placebo for 6 months, were evaluated in a long-term follow-up of up to 18 years (mean 15.2±2.0 SD, range 12–18 ys). Patients treated with placebo at the end of the 6-month enrollment because of the lack of improvement received IMS for further 6 months. Results At 6 months' follow-up 89% patients showed a significant improvement of left ventricular ejection fraction compared to baseline (LVEF rising from 27.0±5.7 to 46.2±6.4, % p<0.001). This improvement was maintained in the long term follow-up (LVEF 51.1±6.4%, p<0.001). Importantly, the 42 patients initially on placebo showed an improvement comparable to the branch on IMS either on short (EF from 27.7% to 46.8±6.2%) and on long term follow up (LVEF from 27.7% to 50.6±5.6%, p<0.001). Nine patients (11%) did not show a significant improvement of LVEF either at short and long term follow-up and among them 4 died and 2 had a cardiac transplantation. Five patients (5.8%) had a relapse of the cardiac inflammatory process that promptly responded to a new TIMIC dose treatment. Four of them (4F, 41.2±9.4 ys age) had concomitant autoimmune diseases and the relapse was within the first 2 years after IMS discontinuation. One patient (M, 56 ys) had a relapse after 10 years following a flu-like syndrome. Conclusion Immunosuppressive therapy of virus negative inflammatory cardiomyopathy warrants in susceptible patients a long term recovery of heart function with very low incidence of recurrences, that respond to a new TIMIC protocol dose treatment. Long term efficacy of TIMIC-IMS therapy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIFA