Long-term outcome of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy after immunosuppressive therapy

AIM: To analyze the long-term outcome after immunosuppressive treatment of patients with virus-negative chronic myocarditis or inflammatory cardiomyopathy (CMi).

METHODS AND RESULTS: We investigated 114 patients with endomyocardial biopsy (EMB)-proven virus-negative chronic myocarditis or CMi, who were treated with prednisone and azathioprine for 6 months. Myocardial inflammation was assessed by quantitative immunohistology. We examined hemodynamic measurements after 6 months and long-term follow-up periods of up to 10 years {median 10.5 months [95 % confidence interval (CI) 11.69-59.16]}. At follow-up, the patients showed a significant improvement of left ventricular ejection fraction (LVEF) compared to baseline after 6-month period (LVEF rising from 44.6 ± 17.3 to 51.8 ± 15.5 %, p = 0.006) and in the long-term follow-up (LVEF 52.1 ± 15.6 %, p = 0.006). Simultaneously, EMB-analysis revealed significant reduction of quantified inflammatory infiltrates (CD3+ cells 16.03 ± 29.09-8.2 ± 9.0/mm2, p = 0.002; CD2+ cells 12.62 ± 20.01 to 6.61 ± 8.47/mm2, p = 0.001; perforin+ cells 3.94 ± 4.65-1.03 ± 1.47/mm2, p = 0.0001), and cell-adhesion molecule HLA-1 [9.91 ± 5.55-6.65 ± 2.81/area fraction (AF), p = 0.0001]. In a subgroup analysis, patients with initial LVEF ≤45 % (n = 53) significantly increased with LVEF at follow-up (29.3 ± 8.8-41.7 ± 13.2-42.1 ± 13.1 %, p < 0.0001, Group I), defined as CMi. Patients with initial LVEF >45-60 % (n = 25) significantly improved further or recovered completely, regarding LVEF (53.0 ± 3.6-59.0 ± 9.4-59.8 ± 10.0 %, p = 0.03, Group II). Patients with initial LVEF >60 % (n = 36) remained stable and did not deteriorate over long-term follow-up (68.8 ± 6.7-67.5 ± 10.9-68.8 ± 10.7 %, p = 0.5, Group III). Groups II and III were defined as chronic myocarditis.

CONCLUSIONS: In patients with virus-negative chronic myocarditis or CMi, we could show the effectiveness and beneficial effects of immunosuppressive treatment. Based on the normalization of the inflammatory process LVEF improvement is lasting for a long-term period of time.