Early Inflammatory Predictors of Post-Transplant Major Adverse Cardiac Events

Abstract

<h3>Purpose</h3> To determine whether adding inflammatory markers to an established atherothrombotic (AT) model improves prediction of major adverse cardiac events (MACE) following heart transplantation. <h3>Methods and Materials</h3> Inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) and AT markers (myocardial fibrin, loss of vascular antithrombin and tissue plasminogen activator, arterial endothelial intercellular adhesion molecule-1 expression) were measured in serial serum and heart biopsy samples of 172 patients followed prospectively for 8.9±5.0 years for MACE (myocardial infarction, percutaneous cardiac interventions, coronary artery bypass graft, implantable cardiac defibrillator, cardiac death/retransplantation). Multivariate stepwise logistic regression models were estimated using AT markers obtained from (1) the first post-transplant biopsy only (median: 9 days), or (2) all biopsies obtained within 3 months. The additional predictive value of adding inflammatory markers (IL-6 and CRP) was evaluated by inclusion into the established AT model. Final models were adjusted for covariates (eg., recipient sex) and cross-validated in 200 bootstrapped samples drawn with replacement from the original sample. <h3>Results</h3> Most AT markers univariately predicted MACE at 5- and 10-years; however, in multivariate models (Table 1), antithrombin and fibrin were the only significant (p<0.005) predictors. Table 1 shows that adding IL-6, but not CRP, to the best AT model improves discriminatory power (as indicated by the change in the ROC value). <h3>Conclusions</h3> Loss of antithrombin and presence of fibrin as early as 9 days post-transplant are significant predictors of future MACE. Adding IL-6, but not CRP, improves the AT model.