Jooeun Kang1, David M Zhang1, David J Restle1, Faouzi Kallel2, Michael A Acker1, Pavan Atluri1, Carlo R Bartoli3. 1. Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa. 2. Thoratec Corporation, Pleasanton, Calif. 3. Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa. Electronic address: carlo.bartoli@uphs.upenn.edu.
Abstract
BACKGROUND: Nonsurgical bleeding is a frequent complication of continuous-flow left ventricular assist device (LVAD) support. Abnormal von Willebrand factor (vWF) metabolism plays a major role. However, the relationship between LVAD speed and vWF degradation is unknown. Recent evidence has demonstrated that supraphysiologic shear stress from continuous-flow LVADs accelerates vWF degradation and causes an acquired vWF deficiency and bleeding. To manage LVAD-associated bleeding, it has been proposed that reduced LVAD speed may decrease shear stress and thereby reduce pathologic vWF metabolism. However, there are little published data to support this clinical practice. We tested the hypothesis that reduced continuous-flow LVAD speed decreases vWF degradation. METHODS: Whole blood was collected from patients before and after the implantation of a HeartMate II continuous-flow LVAD (n = 10) to quantify in vivo vWF degradation. In parallel, to evaluate the relationship between LVAD rpm and vWF degradation, whole blood was collected from human donors (n = 30). Single-donor units of blood circulated in an ex vivo HeartMate II mock circulatory loop for 12 hours at 11,400, 10,000, or 8600 rpm (n = 10/each rpm group). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblot analysis. Paired Student t tests were performed within each group. ANOVA with Tukey post hoc test was performed across groups. RESULTS: In patients, LVAD support reduced large vWF multimers and significantly (P < .05) increased vWF degradation fragments. The profile of vWF degradation was nearly identical between LVAD patients and blood circulated in the LVAD mock circulatory loop. At 11,400, 10,000, and 8600 rpm, decreased large vWF multimers and significantly increased vWF degradation fragments were noted. vWF degradation fragments were not statistically different across the 3 rpm groups or versus LVAD patients, which suggested that LVAD rpm did not influence vWF degradation. CONCLUSIONS: Reduced LVAD speed (within the clinical operational range) did not significantly decrease vWF degradation in a mock circulatory loop with human blood. During bleeding events, reduced LVAD speed, itself, may not diminish vWF degradation.
BACKGROUND: Nonsurgical bleeding is a frequent complication of continuous-flow left ventricular assist device (LVAD) support. Abnormal von Willebrand factor (vWF) metabolism plays a major role. However, the relationship between LVAD speed and vWF degradation is unknown. Recent evidence has demonstrated that supraphysiologic shear stress from continuous-flow LVADs accelerates vWF degradation and causes an acquired vWF deficiency and bleeding. To manage LVAD-associated bleeding, it has been proposed that reduced LVAD speed may decrease shear stress and thereby reduce pathologic vWF metabolism. However, there are little published data to support this clinical practice. We tested the hypothesis that reduced continuous-flow LVAD speed decreases vWF degradation. METHODS: Whole blood was collected from patients before and after the implantation of a HeartMate II continuous-flow LVAD (n = 10) to quantify in vivo vWF degradation. In parallel, to evaluate the relationship between LVAD rpm and vWF degradation, whole blood was collected from human donors (n = 30). Single-donor units of blood circulated in an ex vivo HeartMate II mock circulatory loop for 12 hours at 11,400, 10,000, or 8600 rpm (n = 10/each rpm group). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblot analysis. Paired Student t tests were performed within each group. ANOVA with Tukey post hoc test was performed across groups. RESULTS: In patients, LVAD support reduced large vWF multimers and significantly (P < .05) increased vWF degradation fragments. The profile of vWF degradation was nearly identical between LVAD patients and blood circulated in the LVAD mock circulatory loop. At 11,400, 10,000, and 8600 rpm, decreased large vWF multimers and significantly increased vWF degradation fragments were noted. vWF degradation fragments were not statistically different across the 3 rpm groups or versus LVAD patients, which suggested that LVAD rpm did not influence vWF degradation. CONCLUSIONS: Reduced LVAD speed (within the clinical operational range) did not significantly decrease vWF degradation in a mock circulatory loop with human blood. During bleeding events, reduced LVAD speed, itself, may not diminish vWF degradation.
Authors: Lorenzo Valerio; Jawaad Sheriff; Phat L Tran; William Brengle; Alberto Redaelli; Gianfranco B Fiore; Federico Pappalardo; Danny Bluestein; Marvin J Slepian Journal: Thromb Res Date: 2017-12-05 Impact factor: 3.944
Authors: Carlo R Bartoli; Samson Hennessy-Strahs; Jeff Gohean; Maryann Villeda; Erik Larson; Raul Longoria; Mark Kurusz; Michael A Acker; Richard Smalling Journal: Ann Thorac Surg Date: 2018-12-23 Impact factor: 5.102
Authors: Davor Milicic; Binyamin Ben Avraham; Ovidiu Chioncel; Yaron D Barac; Eva Goncalvesova; Avishai Grupper; Johann Altenberger; Maria Frigeiro; Arsen Ristic; Nicolaas De Jonge; Steven Tsui; Jacob Lavee; Giuseppe Rosano; Marisa Generosa Crespo-Leiro; Andrew J S Coats; Petar Seferovic; Frank Ruschitzka; Marco Metra; Stefan Anker; Gerasimos Filippatos; Stamatis Adamopoulos; Miriam Abuhazira; Jeremy Elliston; Israel Gotsman; Righab Hamdan; Yoav Hammer; Tal Hasin; Lorrena Hill; Osnat Itzhaki Ben Zadok; Wilfried Mullens; Sanemn Nalbantgil; Massimo Francesco Piepoli; Piotr Ponikowski; Luciano Potena; Arjang Ruhparwar; Aviv Shaul; Laurens F Tops; Stephan Winnik; Tiny Jaarsma; Finn Gustafsson; Tuvia Ben Gal Journal: ESC Heart Fail Date: 2021-09-14