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


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.
Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany. felicitas.escher@charite.de.|Department of Cardiology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. felicitas.escher@charite.de.|Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany. felicitas.escher@charite.de.
Felicitas
F
Escher
Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany.|Department of Cardiology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Uwe
U
Kühl
Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany.
Dirk
D
Lassner
Department of Cardiology, CBF, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany.
Wolfgang
W
Poller
University Heart Center Hamburg, Hamburg, Germany.
Dirk
D
Westermann
Department of Cardiology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Department of Cardiology, Deutsches Herzzentrum Berlin (DHZB), Berlin, Germany.|Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany.
Burkert
B
Pieske
Department of Cardiology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.|Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.|Deutsches Zentrum für Herz-Kreislaufforschung (DZHK), Berlin, Germany.
Carsten
C
Tschöpe
Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany.|Department of Cardiology, CBF, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Heinz-Peter
HP
Schultheiss
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009205:Myocarditis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D020127:Recovery of Function; D012189:Retrospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D001379:Azathioprine; D011241:Prednisone
Endomyocardial biopsy; Immunosuppressive therapy; Inflammatory cardiomyopathy; Intramyocardial inflammation; Long-term follow-up