Abstract 17120: Association of Endotoxemia and Endothelin-1 With Development of Cardiac Allograft Vasculopathy After Heart Transplantation

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A17120-A17120
• Main Authors: Braghieri, Lorenzo, Bohn, Bruno, Mondellini, Giulio, Javaid, Azka, Kim, Andrea J, Onat, Hatice D, Latif, Farhana, Farr, Maryjane, Sayer, Gabriel T, Uriel, Nir, Takeda, Koji, Naka, Yoshifumi, Demmer, Ryan, Colombo, Paolo C, Yuzefpolskaya, Melana
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.17120

IntroductionCardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplant (HT). Inflammation is a known cardiovascular risk factor, with gut derived endotoxemia potentially instigating this process, leading to endothelial damage. Our prior work showed that elevation of biomarkers of inflammation (endothelin-1 (ET-1)) and endotoxemia (lipopolysaccharide (LPS)) persists after HT. We investigated the association of LPS and ET-1 with subsequent development of CAV. MethodsPts who met the following criteria were includedi) blood sampling ≥6 mo post-HT; ii) no evidence of CAV at the time of sampling. Pts were followed up to 2.3y after sampling. Cox-PH was used to regress freedom from CAV on LPS and ET-1 (≤ vs >median), time from HT to sampling (≤ vs >1y), interaction among variables. Results33 HT pts enrolled, mean age 57±11y; 70% male; median time post-HT 1.96(0.5-3.7)y. 17(52%) pts developed CAV at 0.7(0.6-1)y following blood collection. Baseline characteristics of pts who developed CAV vs not were similar, except for longer median time post-HT in pts who developed CAV2.4(0.7-5.3) vs 1.05(0.5-2.7)y, p=0.1. Median LPS and ET-1 for the entire cohort were 0.34(0.28-0.45) EU/ml and 1.83(1.26-2.72) pg/ml. Pts with >median LPS or ET-1 values trended towards higher risk of developing CAVHR 1.79(0.66, 4.85), p=0.3 (Fig.1A); HR 2.05(0.71, 5.92), p=0.2 (Fig.1B). No association was observed between time post-HT and CAVHR=0.87 comparing ≤ vs. >1y, p=0.8. Pts with both >median LPS and ET-1 levels (n=7) were at significantly higher risk of CAVHR 2.96(1.06, 8.27), p=0.039, compared to others (Fig.1C). When examining pts sampled within the first year of HT (N=14), pts with >median LPS (N=5) were at particularly increased risk of CAVHR 9.71(0.97, 96.9), p=0.05, while pts with >median ET-1 were not. ConclusionsElevated LPS and ET-1 synergistically associate with increased CAV risk post-HT. Further studies are warranted to validate these findings.