Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.
OBJECTIVE
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.
Dengler
T J
TJ
Department of Cardiology, University of Heidelberg, Germany. thomas.dengler@yale.edu
Zimmermann
R
R
Braun
K
K
Müller-Bardorff
M
M
Zehelein
J
J
Sack
F U
FU
Schnabel
P A
PA
Kübler
W
W
Katus
H A
HA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000145:classification / Q000175:diagnosis; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014184:Transplantation, Homologous; D014336:Troponin / Q000097:blood*; D020107:Troponin T
D015415:Biomarkers; D008840:Microfilament Proteins; D014336:Troponin; D020107:Troponin T