In this retrospective analysis of all pediatric heart transplant recipients in the UNOS data registry for whom there are recorded donor cardiac troponin I levels from April 2007-April 2009, there was no correlation between donor troponin I levels and graft survival after transplantation. Indeed, grafts from donors with even the highest pre-procurement troponin I levels demonstrated survivability on par with the rest of the data set. In addition, we demonstrate that donor pre-procurement troponin I levels do not correlate with recipient length of stay from transplant to discharge, ejection fraction after transplantation, shortening fraction after transplantation, or whether the recipient was treated for rejection within 1 year of transplantation. The results of this large study examining the relationship between donor troponin levels and recipient outcomes in heart transplantation call into question the prognostic relevance of donor troponin levels.
Previous studies on this subject have been inconsistent. Several studies suggest that donor troponin levels may be used as a surrogate for functional assessment in potential donors. For example, Riou and colleagues prospectively linked increasing troponin T values with decreasing ejection fractions in 100 brain dead potential heart donors aged 16 to 68 years (3
). In a prospective analysis of 79 potential heart donors, Venkateswaran and colleagues found that those with a troponin I greater than 1 ng/ml had higher central venous pressure and pulmonary arterial wedge pressure, lower cardiac index and fractional shortening, and worse wall motion score index than those with troponin I lower than 1 ng/ml (4
). In aiming to establish troponin as a biochemical surrogate for donor cardiac function, the authors of this study noted that within their study group, nine of the 79 potential grafts were not retrieved due to poor function.
Boccheciampe and colleagues bolstered these findings, demonstrating that troponin I values were elevated in potential donors with ejection fractions below 50 percent and with segmental wall motion abnormalities compared with those with better functional parameters (5
). However, this study also followed the recipients' outcomes and found no discernible differences in cardiac function one week after transplantation or, most importantly, in graft survival one year after transplantation between groups with varying troponin I values. Along a similar vein, Vijay and colleagues noted in a small cohort an increased incidence and severity of acute graft rejection in patients receiving hearts from donors with increased troponin T levels (6
). However, a seven-year follow-up study demonstrated no differences in cardiac function or survival among the participants (7
). Finally, when 139 heart donors in the California Transplant Donor Network were divided by pre-procurement troponin I levels (>1.0 ng/ml vs. ≤1.0 ng/ml), 30-day and one-year graft survival rates after transplantation were equal between the two groups (8
However, conflicting evidence that links elevated troponins to poor outcomes exists as well. In Grant and colleagues' series of 19 infant heart donors and 18 infant heart recipients, five of eight grafts from donors with troponin I values greater than 3.2 ng/ml failed, and all grafts from donors with lower troponin I values survived (9
). Troponin levels correlated with arrest time in the donor, and pathologic examination revealed myocardial necrosis suggestive of pre-procurement ischemic damage. In a larger retrospective study of 118 brain dead donors above ten years of age, Potapov and colleagues found that elevations in both donor troponin I and troponin T were associated with early graft failure after transplantation (10
Although somewhat contradictory, these prior studies and ours together demonstrate that elevated donor troponin values present a common and unresolved conundrum in heart procurement. Cardiac troponin I is a highly sensitive and specific biomarker for myocardial damage. It has become essential in the diagnosis of acute myocardial infarction (11
), and its presence is often observed in cases of myocardial stunning, myocardial reperfusion, and acute myocarditis (12
). Serum cardiac troponins also rise with cardiopulmonary resuscitation (13
), cardioversion (15
), and significant blunt trauma (16
). A root cause of elevated troponin levels in potential heart donors that is less well understood, but likely very significant in our pediatric population, is brain death itself. Researchers and clinicians have long observed the occurrence of decreasing cardiac function to varying degrees following brain death in patients (3
) that may often preclude heart procurement. It is thought that impending brain death leads to a catecholamine surge from the stressed sympathetic neuroendocrine system that impairs function in a number of ways. This surge has been observed in human (18
) and animal (20
) studies, and has been linked to poor hemodynamic stability and cardiac function (20
), decreased coronary blood flow (23
), cardiomyocyte damage (24
), as well as increased troponin production and turnover (25
). Whether troponin elevations and impaired function reflect irreversible cardiac damage in potential donors who suffer a non-cardiac arrest remains a point of much debate (3
One must be cautious not to conclude from these retrospective results that an elevated troponin I level is irrelevant in the evaluation of a potential donor heart. While donor troponin I levels did not predict graft survival in this cohort of subjects that went on to transplantation, we do not know what would have happened to the other potential donors with elevated donor troponin I levels that did not go on to transplantation. It is our practice to request further details when an otherwise acceptable donor has an elevated troponin level. Has the reported value been verified? What is the trend in troponin levels? What was the timing of troponin verification with respect to the determination of brain death? Perhaps, as suggested in a recent review of the role of biomarkers in assessment of the potential heart donor, we will soon have additional biomarkers that can be interpreted in combination with troponin levels to better discriminate between acceptable and unacceptable donor hearts (29
The main limitations of this study relate to its retrospective design. This cohort only includes outcome data and troponin values from donor hearts that went on to transplantation. While clinical information including troponin values from donor hearts that are declined is available, by definition there is no transplant outcome information in that situation. Selection bias may certainly be one reason that the outcomes from our donors with the highest recorded troponin values is no different from the rest of the cohort.
Furthermore, the troponin I values provided by UNOS were all performed by the laboratory affiliated with the care of the donor, rather than a central laboratory. The normal and detectable ranges of troponin I may vary by the laboratory in which it is performed as well as the specific assay that is used. In this study, we have compared troponin I levels between graft survival and failure groups as if they were all performed by identical methodologies. We did not have access to the specific methodologies utilized by each laboratory. Whenever possible, however, it is important to assess the normal range and precision in a particular laboratory of the troponin assay used, rather than solely relying on the absolute value of troponin level reported.