Higher soluble thrombomodulin and angiogenic markers in continuous flow left ventricular assist device–supported patients associated with arteriovenous malformation and nonsurgical bleeding
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
Affiliations
Kavitha Muthiah, MBChB, PhD, FRACP, FCSANZ
Heart 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.
Louise L. Dunn, BSc(Hons), PhD
Victor Chang Cardiac Research Institute, Sydney, Australia
Hunter Eckford, BMedSci
Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia
David Connor, BMedSci(Hons), PhD
St. Vincent's Centre For Applied Medical Research, Sydney, Australia; Department of Hematology, St. Vincent's Hospital, Sydney, Sydney, Australia
Desiree Robson, RN
Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia
Peter S. Macdonald, MBBS, FRACP, MD, PhD
Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute, Sydney, Australia
Christopher S. Hayward, MD, FRACP
Heart Failure and Transplant Unit, St. Vincent's Hospital, Sydney, Australia; Victor Chang Cardiac Research Institute, Sydney, Australia
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.
