Interferon-β treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction

被引:351
作者
Kühl, U [1 ]
Pauschinger, M [1 ]
Schwimmbeck, PL [1 ]
Seeberg, B [1 ]
Lober, C [1 ]
Noutsias, M [1 ]
Poller, W [1 ]
Schultheiss, HP [1 ]
机构
[1] Free Univ Berlin, Klinikum Benjamin Franklin, Med Klin 2, Dept Cardiol & Pneumol, D-12200 Berlin, Germany
关键词
cardiomyopathy; viruses; biopsy; heart failure;
D O I
10.1161/01.CIR.0000072766.67150.51
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Viral infections are important causes of myocarditis and may induce cardiac dysfunction and finally lead to dilated cardiomyopathy. We investigated whether interferon (IFN)-beta therapy is safe and may achieve virus clearance and prevent deterioration of left ventricular (LV) function in patients with myocardial virus persistence. Methods and Results-In this phase II study, 22 consecutive patients with persistence of LV dysfunction (history of symptoms, 44 +/- 27 months) and polymerase chain reaction-proven enteroviral or adenoviral genomes were treated with 18 x 10(6) IU/week IFN-beta (Beneferon) subcutaneously for 24 weeks. Histological and immunohistological analysis of endomyocardial biopsies was used to characterize myocardial inflammation. LV diameters and ejection fraction were assessed by echocardiography and angiography, respectively. During the treatment period, IFN-beta was well tolerated by all patients. No patient deteriorated. Clearance of viral genomes was observed in 22 of 22 of patients after antiviral therapy. Virus clearance was paralleled by a significant decrease of LV end diastolic and end systolic diameters, decreasing from 59.7 +/- 11.1 to 56.5 +/- 10.0 mm (P < 0.001) and 43.2 +/- 13.6 to 39.4 +/- 12.1 mm (P < 0.001), respectively. LV ejection fraction increased from 44.6 +/- 15.5% to 53.1 +/- 16.8% (P < 0.001). Conclusions-A 6 months, IFN-beta treatment was safe in patients with myocardial enteroviral or adenoviral persistence and LV dysfunction and resulted in elimination of viral genomes (22 of 22 patients) and improved LV function (15 of 22 patients).
引用
收藏
页码:2793 / 2798
页数:6
相关论文
共 41 条
  • [1] MOLECULAR PROBES FOR DETECTION OF PERSISTING ENTEROVIRUS INFECTION OF HUMAN HEART AND THEIR PROGNOSTIC VALUE
    ARCHARD, LC
    BOWLES, NE
    CUNNINGHAM, L
    FREEKE, CA
    OLSEN, EGJ
    ROSE, ML
    MEANY, B
    WHY, HJF
    RICHARDSON, PJ
    [J]. EUROPEAN HEART JOURNAL, 1991, 12 : 56 - 59
  • [2] Characterization of Coxsackie B virus RNA in myocardium from patients with dilated cardiomyopathy by nucleotide sequencing of reverse transcription-nested polymerase chain reaction products
    Archard, LC
    Khan, MA
    Soteriou, BA
    Zhang, HY
    Why, HJF
    Robinson, NMK
    Richardson, PJ
    [J]. HUMAN PATHOLOGY, 1998, 29 (06) : 578 - 584
  • [3] ARETZ HT, 1987, HUM PATHOL, V18, P619
  • [4] Meta-analysis of the association of enteroviruses with human heart disease
    Baboonian, C
    Treasure, T
    [J]. HEART, 1997, 78 (06) : 539 - 543
  • [5] Badorff C, 2000, CIRCULATION, V102, P2276
  • [6] Enteroviral protease 2A cleaves dystrophin: Evidence of cytoskeletal disruption in an acquired cardiomyopathy
    Badorff, C
    Lee, GH
    Lamphear, BJ
    Martone, ME
    Campbell, KP
    Rhoads, RE
    Knowlton, KU
    [J]. NATURE MEDICINE, 1999, 5 (03) : 320 - 326
  • [7] Successful treatment of Epstein-Barr virus infection associated with myocarditis
    Baykurt, C
    Caglar, K
    Ceviz, N
    Akyuz, C
    Secmeer, G
    [J]. PEDIATRICS INTERNATIONAL, 1999, 41 (04) : 389 - 391
  • [8] BOWLES NE, 1986, LANCET, V1, P1120
  • [9] Pathophysiologically relevant concentrations of tumor necrosis factor-α promote progressive left ventricular dysfunction and remodeling in rats
    Bozkurt, B
    Kribbs, SB
    Clubb, FJ
    Michael, LH
    Didenko, VV
    Hornsby, PJ
    Seta, Y
    Oral, H
    Spinale, FG
    Mann, DL
    [J]. CIRCULATION, 1998, 97 (14) : 1382 - 1391
  • [10] The shift in the myocardial adenine nucleotide translocator isoform expression pattern is associated with an enteroviral infection in the absence of an active T-cell dependent immune response in human inflammatory heart disease
    Dörner, A
    Pauschinger, M
    Schwimmbeck, PL
    Kühl, U
    Schultheiss, HP
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 35 (07) : 1778 - 1784