Association of Endothelin-1 With Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation

JOURNAL OF CARDIAC FAILURE

卷:25

Article

Parikh, Rushi V.¹  Khush, Kiran²  Pargaonkar, Vedant S.²  Luikart, Helen²  Grimm, David²  Yu, Michelle²  Okada, Kozo²  Honda, Yasuhiro²  Yeung, Alan C.²  Valantine, Hannah²  Fearon, William F.² 

[1] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA

[2] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA

关键词: Endothelin-1;    heart transplantation;    cardiac allograft vasculopathy;    mortality;   

DOI  :  10.1016/j.cardfail.2018.12.001

来源: Elsevier

【 摘 要 】

Background: Endothelin-1 (ET-1) has been implicated in the development of post heart transplantation (HT) cardiac allograft vasculopathy (CAV), but has not been well studied in humans. Methods and Results: In 90 HT patients, plasma ET-1 was measured within 8 weeks after HT (baseline) via a competitive enzyme-linked immunosorbent assay. Three-dimensional volumetric intravascular ultrasound of the left anterior descending artery was performed at baseline and at 1 year. Accelerated CAV (lumen volume loss) was defined with the 75th percentile as a cutoff. Patients were followed beyond the first year after HT for late death or retransplantation. A receiver operating characteristic (ROC) curve demonstrated that a baseline ET-1 concentration of 1.75 pg/mL provided the best accuracy for diagnosis of accelerated CAV at 1 year (area under the ROC curve 0.69, 95% confidence interval [CI] 0.57-0.82; P = .007). In multivariate logistic regression, a higher baseline ET-1 concentration was independently associated with accelerated CAV (odds ratio [OR] 2.13, 95% CI 1.15-3.94; P = .01); this relationship persisted when ET-1 was dichotomized at 1.75 pg/mL (OR 4.88, 95% CI 1.69-14.10; P = .003). Eighteen deaths occurred during a median follow-up period of 3.99 (interquartile range 2.51-9.95) years. Treated as a continuous variable, baseline ET-1 was not associated with late mortality in multivariate Cox regression (hazard ratio [HR] 1.22, 95% CI 0.72-2.05; P = .44). However, ET-1 >1.75 pg/mL conferred a significantly lower cumulative event-free survival on Kaplan-Meier analysis (P = .047) and was independently associated with late mortality (HR 2.94, 95% CI 1.12-7.72; P = .02). Conclusions: Elevated ET-1 early after HT is an independent predictor of accelerated CAV and late mortality, suggesting that ET-1 has durable prognostic value in the HT arena.

【 授权许可】

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