title: Reduced continuous-flow left ventricular assist device speed does not decrease von Willebrand factor degradation.
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.
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Jooeun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: David M
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: David J
authors.initials: DJ
authors.lastname: Restle
authors.affiliation: Thoratec Corporation, Pleasanton, Calif.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Kallel
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Acker
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Pavan
authors.initials: P
authors.lastname: Atluri
authors.affiliation: Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa. Electronic address: carlo.bartoli@uphs.upenn.edu.
authors.forename: Carlo R
authors.initials: CR
authors.lastname: Bartoli
mesh_terms: D000328:Adult; D000368:Aged; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D013314:Stress, Mechanical; D014842:von Willebrand Diseases / Q000097:blood* / Q000209:etiology; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D014841:von Willebrand Factor
keywords: bleeding; heart failure; left ventricular assist device; mechanical circulatory support; shear stress; von Willebrand factor