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CLINICAL STUDIES

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation

Thomas J. Dengler, MD^*, Rainer Zimmermann, MD^*, Klaus Braun^*, Margit Müller-Bardorff, MD, J.örg Zehelein, MD^*, Falk-Udo Sack, MD, Philipp A. Schnabel, MD, Wolfgang Kübler, MD^* and Hugo A. Katus, MD

^* Department of Cardiology, University of Heidelberg, Heidelberg, Germany
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
Department of Pathology, University of Heidelberg, Heidelberg, Germany
Department of Cardiology, University of Lübeck, Lübeck, Germany

Manuscript received December 31, 1997; revised manuscript received March 31, 1998, accepted April 16, 1998.

Address for correspondence: Thomas J. Dengler, MD, Boyer Center for Molecular Medicine, Yale School of Medicine, 295 Congress Ave, room # 449, New Haven, Connecticut 06510
thomas.dengler{at}yale.edu

Objectives. This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection.

Background. Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis.

Methods. In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies.

Results. Mean troponin T serum concentrations were identical in control subjects (23.2 ± 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 ± 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 ± 1.8 ng/liter; grade 2: 33.2 ± 2.7 ng/liter; grade 3A: 54.6 ± 6.5 ng/liter; grade 3B and 4: 105.4 ± 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings.

Conclusions. The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection.

Abbreviations and Acronyms   CK = creatine kinase   ECG = electrocardiogram   ELISA = enzyme-linked immunosorbent assay   ISHLT = International Society for Heart and Lung Transplantation   LDH = lactate dehydrogenase   MRI = magnetic resonance imaging

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