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(Circulation. 2007;116:1274-1282.)
© 2007 American Heart Association, Inc.

Transplantation

Prognostic Impact of Microvasculopathy on Survival After Heart Transplantation

Evidence From 9713 Endomyocardial Biopsies

Nicola E. Hiemann, MD; Ernst Wellnhofer, MD; Christoph Knosalla, MD, PhD; Hans B. Lehmkuhl, MD; Julia Stein, MSc; Roland Hetzer, MD, PhD; Rudolf Meyer, MD, PhD

From the Departments of Cardiothoracic and Vascular Surgery (N.E.H., C.K., H.B.L., J.S., R.H., R.M.) and Cardiology (E.W.), Deutsches Herzzentrum Berlin, Berlin, Germany.

Reprint requests to Nicola E. Hiemann, MD, Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail hiemann{at}dhzb.de

Received June 20, 2006; accepted July 3, 2007.

Background— Epicardial vasculopathy has been shown to be associated with poor outcome after heart transplantation. We demonstrate that histologically proven stenotic microvasculopathy is a novel prognostic factor for long-term survival.

Methods and Results— In 9713 biopsies harvested within the first posttransplantation year from 873 patients (83% male; mean age, 49.1±0.6 years), light microscopic evaluations (x200) were performed for microvasculopathy, defined as stenotic endothelial and/or medial disease. Prevalence of severe epicardial vasculopathy was defined by presence of 75% luminal stenosis in coronary angiography (available in 611 of 873 patients), which was present in 118 of 611 patients (19%). For Kaplan-Meier analysis, we defined fatal cardiac events as lethal acute myocardial infarction, sudden cardiac death, and graft failure. Stenotic microvasculopathy was present in 379 of 873 patients (43%) and was due to medial (345/379; 91%) rather than endothelial disease (2/379; 1%) or a combination of both (31/379; 8%; P<0.001). Endothelial disease (median [95% CI], 12.07 [10.69 to 13.44] versus 12.73 years [10.16 to 15.30]; P=0.3329) and nonstenotic medial disease (12.44 [11.14 to 13.74] versus 12.43 years [10.51 to 14.35]; P=0.4047) did not decrease overall survival or time to fatal cardiac event. Stenotic microvasculopathy was associated with poor overall survival (10.90 [9.16 to 12.60] versus 13.40 years [11.79 to 15.07]; P=0.0374) and decreased freedom from fatal cardiac events (1, 5, 10 years, 95.6±1.4%, 86.9±2.3%, 75.5±3.1% versus 99.1±0.5%, 96.8±1.0%, 89.8±1.9%; P<0.0001). This finding was independent of epicardial transplant vasculopathy (P=0.0031).

Conclusions— Stenotic microvasculopathy is frequent in routinely processed biopsies and a new prognostic factor for long-term survival after heart transplantation.

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