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Gastrointestinal angiodysplasia is associated with significant gastrointestinal bleeding in patients with continuous left ventricular assist devices.

ABSTRACT: Patients with a continuous-flow left ventricular assist device (LVAD) have a 65 % incidence of bleeding events within the first year. The majority of gastrointestinal bleeding (GIB) is from gastrointestinal angiodyplasia (GIAD). The primary aim of the study was to determine whether GIAD was associated with a higher rate of significant bleeding, an increased number of bleeding events per year, and a higher rate of transfusion compared to non-GIAD sources.This retrospective cohort study included 118 individuals who received a LVAD at a tertiary medical center from 2006 through 2014. Patients were subdivided into GIB and non-GIB for comparison of patient demographics, comorbid conditions, and laboratory data. GIB was further divided into sources of GIB, GIAD, obscure, or non-GIAD to establish severity of bleeding, rate of re-bleeding, and transfusion rate.GIAD is associated with an increased number of bleeding events compared to non-GIAD sources of GIB (2.07 vs 1.23, P = 0.01) and a higher number of bleeding events per year (0.806 vs. 0.455 P = 0.001). GIAD compared to non-GIAD sources of GIB was associated with an increased incidence of major bleeding (100 % vs 60 %, P = 0.006) and increased rates of transfusion (8.8 vs 2.95 units, P = 0.0004). Cox Regression analysis between non-GIB and GIAD demonstrated increased risk with age (P = 0.001), history of chronic kidney disease (P = 0.005), and length of stay after LVAD implantation of more than 45 days (P = 0.04). History of hypertension (P = 0.045), diabetes mellitus (P = 0.016), and male gender was associated with decreased risk (P = 0.04).Patients with a continuous-flow LVAD who develop a GIB secondary to GIAD have a higher rate of major bleeding, multiple bleeding events, and require more transfusions to achieve stabilization compared to patients who do not have GIAD.

SUBMITTER: Cochrane J

PROVIDER: S-EPMC4798933 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other

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Project description:BackgroundNonsurgical bleeding is the most common adverse event in patients with continuous-flow left ventricular assist devices (LVADs) and is caused by arteriovenous malformations. We hypothesized that deregulation of an angiogenic factor, angiopoietin-2 (Ang-2), in patients with LVADs leads to increased angiogenesis and higher nonsurgical bleeding.MethodsAng-2 and thrombin levels were measured by ELISA and Western blotting, respectively, in blood samples from 101 patients with heart failure, LVAD, or orthotopic heart transplantation. Ang-2 expression in endothelial biopsy was quantified by immunofluorescence. Angiogenesis was determined by in vitro tube formation from serum from each patient with or without Ang-2-blocking antibody. Ang-2 gene expression was measured by reverse transcription-polymerase chain reaction in endothelial cells incubated with plasma from each patient with or without the thrombin receptor blocker vorapaxar.ResultsCompared with patients with heart failure or those with orthotopic heart transplantation, serum levels and endothelial expression of Ang-2 were higher in LVAD patients (P=0.001 and P<0.001, respectively). This corresponded to an increased angiogenic potential of serum from patients with LVADs (P<0.001), which was normalized with Ang-2 blockade. Furthermore, plasma from LVAD patients contained higher amounts of thrombin (P=0.003), which was associated with activation of the contact coagulation system. Plasma from LVAD patients induced more Ang-2 gene expression in endothelial cells (P<0.001), which was reduced with thrombin receptor blockade (P=0.013). LVAD patients with Ang-2 levels above the mean (12.32 ng/mL) had more nonsurgical bleeding events compared with patients with Ang-2 levels below the mean (P=0.003).ConclusionsOur findings indicate that thrombin-induced Ang-2 expression in LVAD patients leads to increased angiogenesis in vitro and may be associated with higher nonsurgical bleeding events. Ang-2 therefore may contribute to arteriovenous malformation formation and subsequent bleeding in LVAD patients.

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Gastrointestinal angiodysplasia is associated with significant gastrointestinal bleeding in patients with continuous left ventricular assist devices.

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