Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding

Bleeding complications are a bane of continuous flow left ventricular assist devices (cfLVAD); gastrointestinal bleeding (GIB) from arteriovenous malformation (AVM) predominating. We hypothesized that shear stress disrupts vascular endothelium altering angiogenesis and contributing to bleeding. We p...

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Main Authors: Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ, Louise L. Dunn, BSc(Hons), PhD, Hunter Eckford, BMedSci, David Connor, BMedSci(Hons), PhD, Desiree Robson, RN, Peter S. Macdonald, MBBS, FRACP, MD, PhD, Christopher S. Hayward, MD, FRACP
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:JHLT Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S295013342400082X
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author Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ
Louise L. Dunn, BSc(Hons), PhD
Hunter Eckford, BMedSci
David Connor, BMedSci(Hons), PhD
Desiree Robson, RN
Peter S. Macdonald, MBBS, FRACP, MD, PhD
Christopher S. Hayward, MD, FRACP
author_facet Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ
Louise L. Dunn, BSc(Hons), PhD
Hunter Eckford, BMedSci
David Connor, BMedSci(Hons), PhD
Desiree Robson, RN
Peter S. Macdonald, MBBS, FRACP, MD, PhD
Christopher S. Hayward, MD, FRACP
author_sort Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ
collection DOAJ
description Bleeding complications are a bane of continuous flow left ventricular assist devices (cfLVAD); gastrointestinal bleeding (GIB) from arteriovenous malformation (AVM) predominating. We hypothesized that shear stress disrupts vascular endothelium altering angiogenesis and contributing to bleeding. We profiled markers of endothelial dysfunction (soluble thrombomodulin [sTM]) and angiogenesis (angiopoietin-1 [Ang-1], angiopoietin-2 [Ang-2]) in 21 patients implanted with a centrifugal cfLVAD. Bleeding episodes were documented in 11 patients, 8 had GIB, 4 of whom had AVMs. We observed a dynamic change in sTM and Ang-2/Ang-1 ratio following cfLVAD support (p = 0.030 and p = 0.025, respectively). Bleeding patients had higher sTM and Ang-2/Ang-1 ratios than patients with no bleeding (p = 0.04 and p = 0.06, respectively). At D180, patients with AVMs had significantly higher Ang-2/Ang-1 ratios vs patients without proven AVMs (p = 0.006). We conclude that bleeding in cfLVAD-supported patients is associated with alteration in endothelial/vascular homeostasis, possibly contributing to AVM formation.
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spelling doaj-art-ccfcaaed3a6e4364b1119944b6badeb32025-08-20T02:12:46ZengElsevierJHLT Open2950-13342024-11-01610013310.1016/j.jhlto.2024.100133Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleedingKavitha Muthiah, MBChB, PhD, FRACP, FCSANZ0Louise L. Dunn, BSc(Hons), PhD1Hunter Eckford, BMedSci2David Connor, BMedSci(Hons), PhD3Desiree Robson, RN4Peter S. Macdonald, MBBS, FRACP, MD, PhD5Christopher S. Hayward, MD, FRACP6Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute, Sydney, Australia; Corresponding author: Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ, Heart and Lung Transplant Unit, St Vincent’s Hospital, 390 Victoria Street, Sydney, NSW 2010, Australia.Victor Chang Cardiac Research Institute, Sydney, AustraliaHeart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, AustraliaSt. Vincent's Centre For Applied Medical Research, Sydney, Australia; Department of Hematology, St. Vincent's Hospital, Sydney, Sydney, AustraliaHeart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, AustraliaHeart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute, Sydney, AustraliaHeart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute, Sydney, AustraliaBleeding complications are a bane of continuous flow left ventricular assist devices (cfLVAD); gastrointestinal bleeding (GIB) from arteriovenous malformation (AVM) predominating. We hypothesized that shear stress disrupts vascular endothelium altering angiogenesis and contributing to bleeding. We profiled markers of endothelial dysfunction (soluble thrombomodulin [sTM]) and angiogenesis (angiopoietin-1 [Ang-1], angiopoietin-2 [Ang-2]) in 21 patients implanted with a centrifugal cfLVAD. Bleeding episodes were documented in 11 patients, 8 had GIB, 4 of whom had AVMs. We observed a dynamic change in sTM and Ang-2/Ang-1 ratio following cfLVAD support (p = 0.030 and p = 0.025, respectively). Bleeding patients had higher sTM and Ang-2/Ang-1 ratios than patients with no bleeding (p = 0.04 and p = 0.06, respectively). At D180, patients with AVMs had significantly higher Ang-2/Ang-1 ratios vs patients without proven AVMs (p = 0.006). We conclude that bleeding in cfLVAD-supported patients is associated with alteration in endothelial/vascular homeostasis, possibly contributing to AVM formation.http://www.sciencedirect.com/science/article/pii/S295013342400082Xleft ventricular assist devicemechanical circulatory supportgastrointestinal bleedingarteriovenous malformationangiogenesis
spellingShingle Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ
Louise L. Dunn, BSc(Hons), PhD
Hunter Eckford, BMedSci
David Connor, BMedSci(Hons), PhD
Desiree Robson, RN
Peter S. Macdonald, MBBS, FRACP, MD, PhD
Christopher S. Hayward, MD, FRACP
Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
JHLT Open
left ventricular assist device
mechanical circulatory support
gastrointestinal bleeding
arteriovenous malformation
angiogenesis
title Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
title_full Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
title_fullStr Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
title_full_unstemmed Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
title_short Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
title_sort higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device supported patients associated with arteriovenous malformation and nonsurgical bleeding
topic left ventricular assist device
mechanical circulatory support
gastrointestinal bleeding
arteriovenous malformation
angiogenesis
url http://www.sciencedirect.com/science/article/pii/S295013342400082X
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