A Sensitive Cardiac Troponin I Assay to Screen for Acute Rejection in Heart Transplant Patients
Background—A noninvasive biomarker which could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies (EMB). We assessed the performance metrics of a novel highly sensitive (hs) cardiac troponin I (cTnI) assay for this purpose.
Methods and Results—Stored serum samples were retrospectively matched to EMB in 98 cardiac transplant recipients who survived ≥ 3 months post-transplant. AR was defined as ISHLT grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain etiology leading to treatment for presumed rejection. cTnI was measured with a hs assay (Abbott Diagnostics). Cross-sectional analyses determined the association of cTnI concentrations with rejection and ISHLT grade; and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had at least one rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median 57.1 vs. 10.2 ng/L, p < 0.0001), and increased in a graded manner with higher biopsy scores (ptrend < 0.0001). The c-statistic to discriminate AR was 0.82 (95% CI 0.76-0.88). Using a cut-point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%.
Conclusions—A hs-cTnI assay appears useful to "rule out" AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a hs-cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance.
- Received May 15, 2013.
- Accepted March 24, 2014.