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Clinical Research in Cardiology

, Volume 105, Issue 12, pp 1011–1020 | Cite as

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

  • Felicitas EscherEmail author
  • Uwe Kühl
  • Dirk Lassner
  • Wolfgang Poller
  • Dirk Westermann
  • Burkert Pieske
  • Carsten Tschöpe
  • Heinz-Peter Schultheiss
Original Paper

Abstract

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.

Keywords

Inflammatory cardiomyopathy Immunosuppressive therapy Endomyocardial biopsy Intramyocardial inflammation Long-term follow-up 

Abbreviations

AF

Area fraction

CAMs

Cell-adhesion molecules

CMi

Inflammatory cardiomyopathy

DIA

Digital image analysis

EMB

Endomyocardial biopsy

HLA-1

Human leukocyte antigen-1

IH

Immunohistology

LVEDD

Left ventricular end-diastolic diameter

LVESD

Left ventricular end-systolic diastolic diameter

LVEF

Ejection fraction

Npcr

Nested polymerase chain reaction

RT-PCR

Reverse transcription PCR

Notes

Acknowledgments

This study was supported by the Deutsche Forschungsgesellschaft (DFG; SFB/TR-19). We thank Ms. E. Hertel, M. Willner (Charité-Universitätsmedizin Berlin), K. Winter, S. Ochmann, and C. Seifert (IKDT Berlin) for excellent assistance.

Compliance with ethical standards

Conflict of interest

None declared.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Felicitas Escher
    • 1
    • 2
    • 7
    Email author
  • Uwe Kühl
    • 1
    • 2
  • Dirk Lassner
    • 1
  • Wolfgang Poller
    • 3
    • 7
  • Dirk Westermann
    • 4
  • Burkert Pieske
    • 2
    • 5
    • 7
  • Carsten Tschöpe
    • 2
    • 6
    • 7
  • Heinz-Peter Schultheiss
    • 1
    • 3
  1. 1.Institute for Cardiac Diagnostics and Therapy (IKDT)BerlinGermany
  2. 2.Department of Cardiology, Campus Virchow-KlinikumCharité-Universitätsmedizin BerlinBerlinGermany
  3. 3.Department of Cardiology, CBFCharité-Universitätsmedizin BerlinBerlinGermany
  4. 4.University Heart Center HamburgHamburgGermany
  5. 5.Department of CardiologyDeutsches Herzzentrum Berlin (DHZB)BerlinGermany
  6. 6.Berlin-Brandenburg Center for Regenerative Therapies (BCRT)BerlinGermany
  7. 7.Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)BerlinGermany

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