Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Parikh RV

PROVIDER: S-EPMC6377829 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Parikh Rushi V RV Khush Kiran K Pargaonkar Vedant S VS Luikart Helen H Grimm David D Yu Michelle M Okada Kozo K Honda Yasuhiro Y Yeung Alan C AC Valantine Hannah H Fearon William F WF

Journal of cardiac failure 20181210 2

<h4>Background</h4>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.<h4>Methods and results</h4>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 ...[more]

PMID: 30543947

Similar Datasets

Project description:Endothelium-enriched microRNAs (miRs) are involved in the development of cardiac allograft vasculopathy (CAV). Recently, serum-derived miR-126-3p and -5p, known endothelial microRNAs with a crucial function in angiogenesis and re-endothelialization, provided additional predictive power for cardiac allograft vasculopathy in addition to clinical predictors. However, their myocardial expression in and relationship with CAV are still unknown. Our study aim was to investigate the expression of endomyocardial microRNA-126-3p and microRNA-126-5p levels in heart transplant recipients and their relationship with allograft vasculopathy.MethodsWe studied 39 heart transplant recipients, 21 with proven allograft vasculopathy (CAV+) and 18 without allograft vasculopathy (CAV-) with serial coronary angiograms. Additionally, 8 patients with end-stage native coronary artery disease (CAD) were added to the study to investigate disease specificity of the microRNA signature. The mRNA levels of miR-126-3p and miR-126-5p were determined by qRT-PCR in the right ventricular endomyocardial biopsies obtained at baseline and during routine follow-up.ResultsMiR-126-3p levels were significantly lower in the CAV+ group compared to the CAV- group at follow-up, while miR-126-5p levels were unaltered. This was in stark contrast to native CAD patients in whom miR-126-3p and -5p levels were significantly higher. qPCR levels of miR-126 targets are differentially regulated in CAV versus ischemic cardiomyopathy and are influenced by the administration of immunosuppressive agents in endothelial cells.ConclusionsOur data provide evidence for a distinct microRNA signature in heart transplantation patients with allograft vasculopathy. In contrast to CAD patients, lower miR-126-3p levels coincide with the development of cardiac allograft vasculopathy. Further studies in a larger patient population are warranted to determine if the serial measurement of myocardial microRNA-126 products could help in risk assessment and early detection of CAV.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets