Postoperative high-sensitivity troponin T predicts 1-year mortality and days alive and out of hospital after orthotopic heart transplantation

Abstract

Background: Orthotopic heart transplantation (HTX) is the gold standard to treat end-stage heart failure. Numerous risk stratification tools have been developed in the past years. However, their clinical utility is limited by their poor discriminative ability. High sensitivity troponin T (hsTnT) is the most specific biomarker to detect myocardial cell injury. However, its prognostic relevance after HTX is not fully elucidated. Thus, this study evaluated the predictive value of postoperative hsTnT for 1-year survival and days alive and out of hospital (DAOH) after HTX.

Methods: This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany between 2011 and 2021. The main exposure was hsTnT concentration at 48 h after HTX. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis, logistic regression model and linear regression with adjustment for risk index for mortality prediction after cardiac transplantation (IMPACT) were performed.

Results: Out of 231 patients screened, 212 were included into analysis (mean age 55 ± 11 years, 73% male). One-year mortality was 19.7% (40 patients) and median DAOH was 298 days (229-322). ROC analysis revealed strongest discrimination for mortality by hsTnT at 48 h after HTX [AUC = 0.79 95% CI 0.71-0.87]. According to Youden Index, the cutoff for hsTnT at 48 h and mortality was 1640 ng/l. After adjustment for IMPACT score multivariate logistic and linear regression showed independent associations between hsTnT and mortality/DAOH with odds ratio of 8.10 [95%CI 2.99-21.89] and unstandardized regression coefficient of -1.54 [95%CI -2.02 to -1.06], respectively.

Conclusion: Postoperative hsTnT might be suitable as an early prognostic marker after HTX and is independently associated with 1-year mortality and poor DAOH.

Keywords: Heart failure; Heart transplantation; IMPACT score; Patient-centered outcomes; Risk prediction.

Fig. 1

Postoperative levels of hsTnT of survivors and non-survivors. The graphs depict high-sensitivity troponin (hs-TnT) concentrations for survivors (triangles) and non-survivors (dots) across different time points with corresponding standard errors. Preoperative hs-TnT values did not differ significantly between groups [baseline hsTnT—survivors 165 ± 687 ng/L vs. non-survivors 228 ± 906 ng/L, p = 0.638]. Postoperative values at timepoints 12 h, 24 h, 48 h and 72 h after surgery were significantly higher in non-survivors as compared to survivors [hsTnT 12 h—survivors 5089 ± 5305 ng/L vs. non-survivors 7972 ± 7419 ng/L, p = 0.005; hsTnT 24 h—survivors 3309 ± 2934 ng/L vs. non-survivors 7266 ± 7942 ng/L, p ≤ 0.0001; hsTnT 48 h—survivors 1911 ± 1598 ng/L vs. non-survivors 5115 ± 5196 ng/L, p ≤ 0.0001; hsTnT 72 h—survivors 1363 ± 1565 ng/L vs. non-survivors 3651 ± 4126 ng/L, p ≤ 0.0001]

Fig. 2

Receiver operating characteristic curves of postoperative hsTnT and 1-year mortality. The figure shows the receiver operating characteristics (ROC) curves for association of different hs-TnT sampling time points with 1-year mortality after heart transplantation. The areas under the curves (AUC) are as follows: hsTnT 12 h AUC = 0.66 (CI 0.56–0.75); hsTnT 24 h AUC = 0.74 (CI 0.66–0.82); hsTnT 48 h AUC = 0.79 (CI 0.71–0.87); hsTnT 72 h AUC = 0.77 (CI 0.68–0.86). The numerically strongest discrimination ability is given for hsTnT values at 48 h after heart transplantation

Fig. 3

Receiver operating characteristic curves of two prediction models for 1-year mortality. The figure shows the receiver operating characteristics (ROC) curves of risk prediction models for 1-year mortality. While on its own the IMPACT score has a ROC- a moderate discrimination ability (AUC = 0.65 95% CI 0.56–0.74), adding hsTnT levels at 48 h after heart transplantation to the model improves its performance (AUC = 0.79; CI 0.71–0.87)

Fig. 4

Decision curves for different models of risk prediction after HTX. The figure shows a decision curve analysis for mortality prediction model with IMPACT score (turquoise) and IMPACT score with hsTnT (purple). The x-axis shows the threshold probability for 1-year mortality while the y-axis shows the net benefit of the models. Beyond a threshold of 5% the combined model of IMPACT and hsTnT shows the greatest net benefit. The red line depicts a model in which all patients would be treated and the green line represents a model in which none patient will be treated

Fig. 5

Association of hsTnT levels above cutoff and days alive and out of hospital. The box-plot shows significantly fewer DAOH for patients above the determined cutoff of hs-TnT at 48 h after heart transplantation [hsTnT 48 h—below cutoff 317 (283–328) days vs. above cutoff 278 (14–308) days, p ≤ 0.0001]. Black dots represent individual DAOH values of patients, the upper end of the boxes shows the median while error bars depict interquartile ranges. The hsTnT cutoff was determined by Youden index