Abstract
Antecedents Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Aim Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. Methods 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction < 50%, or heart failure not due to an acute rejection. Results 51 patients (53%) presented CAV at evaluation; 21 of them had CV events. Hs-cTnT (56 ± 45 versus 20 ± 18 ng/L; p = 0.04) and sAXL concentrations (98 ± 51 versus 26 ± 26 ng/L; p = 0.01) were significantly higher in patients with CV events. Hs-cTnT (HR 1.03; 95% CI 1.015–1.042, p = 0.0001) and sAXL (HR 1.01; 95% CI 1.001–1.019, p = 0.02) were independent predictors of CV events. A hs-cTnT concentration < 21 ng/L, detected by AUC ROC, predicted the absence of CV events with a predictive value of 91%; sAXL did not add more predictive value to hs-cTnT. Survival free of CV events was 92% in patients with hs-cTnT < 21 ng/L and 57% in those with hs-cTnT > 21 ng/L (p < 0.001). Conclusion Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.
Highlights
Despite the improvement of long-term (>1 year) survival after heart transplantation (HTx), several clinical conditions such as neoplasms, graft failure, infections, and cardiac allograft vasculopathy (CAV) limit it [1, 2]
HR: hazard ratio; CI: confidence interval; high-sensitivity cardiac troponin T (hs-cTnT): cardiac troponin T measured with high-sensitivity methods; soluble form of AXL (sAXL): soluble form of the AXL receptor; HTx: heart transplantation
The current study analyzed the prognostic value of two biomarkers of cardiomyocyte lesion and endothelial dysfunction, hs-cTnT and sAXL, respectively, to predict severe CV events in long-term surviving patients (42 ± 15 months) after HTx
Summary
Despite the improvement of long-term (>1 year) survival after heart transplantation (HTx), several clinical conditions such as neoplasms, graft failure, infections, and cardiac allograft vasculopathy (CAV) limit it [1, 2]. CAV is the most important cause of cardiovascular (CV) adverse events during follow-up of HTx. CAV is initiated by immunologic and inflammatory phenomena causing endothelial dysfunction and damage. Endothelial damage leads to intimal growth of the coronary epi- and endocardial vessels [3]. CAV is often clinically silent and symptoms can only appear in its advanced stages as acute heart failure (HF) or sudden death. CAV has been associated with adverse outcomes, the progression of the disease is variable, making uncertain the prediction of the associated CV events.
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