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Continuous-flow left ventricular assist devices (LVADs) cause an acquired von Willebrand factor (VWF) deficiency and bleeding. Models to risk-stratify for bleeding are urgently needed. We developed a model of continuous-flow LVAD bleeding risk from patient-specific severity of VWF degradation. In a prospective, longitudinal cohort study, paired blood samples were obtained from patients (n = 67) with a continuous-flow LVAD before and during support. After 640 ± 395 days, patients were categorized as all-cause bleeders, gastrointestinal (GI) bleeders, or nonbleeders. VWF multimers and VWF clotting function were evaluated to determine bleeding risk. Of 67 patients, 34 (51%) experienced bleeding, 26 (39%) experienced GI bleeding, and 33 (49%) did not bleed. In all patients, LVAD support significantly reduced high-molecular-weight VWF multimers (P <.001). Bleeders exhibited greater loss of high-molecular-weight VWF multimers (mean ± standard deviation, –10 ± 5% vs –7 ± 4%, P =.008) and reduced VWF clotting function versus nonbleeders (median [interquartile range], –12% [–31% to 4%] vs 0% [–9 to 26%], P =.01). A combined metric of VWF multimers and VWF function generated the All-Cause Bleeding Risk Score, which stratified bleeders versus nonbleeders (86 ± 56% vs 41 ± 48%, P <.001) with a positive predictive value of 86% (95% confidence interval, 66%-95%) and diagnostic odds ratio of 11 (95% confidence interval, 2.9-44). A separate GI Bleeding Risk Score stratified GI bleeders versus nonbleeders (202 ± 114 vs 120 ± 86, P =.003) with a positive predictive value of 88% (64%-97%) and diagnostic odds ratio of 18 (3.1-140). The severity of loss of VWF multimers and VWF clotting function generated Bleeding Risk Scores with high predictive value for LVAD-associated bleeding. This model may guide personalized antithrombotic therapy and patient surveillance. [Display omitted] [ABSTRACT FROM AUTHOR]

Continuous-flow left ventricular assist devices (LVADs) cause degradation of von Willebrand factor (VWF) multimers and bleeding. Multiple techniques exist to characterize VWF deficiency. However, a standard methodology has not been established in LVAD patients. Toward this goal, we evaluated 4 methods to quantify VWF multimers. We collected paired blood samples from patients (n = 48) before and after 1 week of LVAD support. After 652 ± 59 days of support, patients were classified as bleeders (≥1 bleeding episode) or nonbleeders. VWF multimers were resolved with electrophoresis and immunoblotting, the gold-standard to evaluate VWF multimers. We evaluated 4 quantification methods. Each method demonstrated significant VWF degradation during LVAD support vs a paired, pre-LVAD sample (method 1, VWF length: 48 of 48 patients, –10% ± 1%, P <.0001; method 2, VWF density: 40 of 48, –34% (interquartile range, –46% to -8%), P <.0001; method 3, pre-LVAD to LVAD ratio: 46 of 48, 17 ± 5: 10 ± 1, P <.0001; method 4, LVAD/pre-LVAD index: 46 of 48, 57% (interquartile range, 50% to 73%), P <.0001). Bleeding occurred in 27 of 48 patients. Method 1 demonstrated significantly fewer VWF multimers in bleeders compared with nonbleeders (–11% ± 1% vs –8% ± 1%; P =.01). Other methods did not demonstrate this potentially important clinical relationship. A standardized methodology is needed to quantify VWF multimer degradation with mechanical circulatory support devices. Novel method 1 successfully quantified the patient-specific change in VWF multimer length during LVAD support and demonstrated a difference in VWF multimers between bleeders and nonbleeders. Adoption of consensus methodology will assist to standardize patient-specific bleeding risk, inform anticoagulation and antiplatelet therapy, and evaluate LVAD hemocompatibility. [ABSTRACT FROM AUTHOR]

Continuous-flow left ventricular assist devices (LVADs) cause blood trauma that includes von Willebrand factor degradation, platelet activation, and subclinical hemolysis. Blood trauma contributes to bleeding, thrombosis, and stroke, which cause significant morbidity and mortality. The TORVAD (Windmill Cardiovascular Systems, Inc, Austin, TX) is a first-of-its kind, toroidal-flow LVAD designed to minimize blood trauma. We tested the hypothesis that the TORVAD causes less blood trauma than the HeartMate II (Abbott Laboratories, Pleasanton, CA) LVAD. Whole human blood was circulated for 6 hours in ex vivo circulatory loops with a HeartMate II (n = 8; 10,000 rpm, 70 ± 6 mm Hg, 4.0 ± 0.1 L/min) or TORVAD (n = 6; 144 rpm, 72 ± 0.0 mm Hg, 4.3 ± 0.0 L/min). von Willebrand factor degradation was quantified with electrophoresis and immunoblotting. Platelet activation was quantified by cluster of differentiation (CD) 41/61 enzyme-linked immunosorbent assay (ELISA). Hemolysis was quantified by plasma free hemoglobin ELISA. The TORVAD caused significantly less degradation of high-molecular-weight von Willebrand factor multimers (−10% ± 1% vs −21% ± 1%, p < 0.0001), accumulation of low-molecular-weight von Willebrand factor multimers (22% ± 2% vs 45% ± 2%, p < 0.0001), and accumulation of von Willebrand factor degradation fragments (7% ± 1% vs 25% ± 6%, p < 0.05) than the HeartMate II. The TORVAD did not activate platelets, whereas the HeartMate II caused significant platelet activation (CD 41/61: 645 ± 20 ng/mL vs 1,581 ± 150 ng/mL, p < 0.001; normal human CD 41/61, 593 ng/mL; range, 400 to 800 ng/mL). Similarly, the TORVAD caused minimal hemolysis, whereas the HeartMate II caused significant hemolysis (plasma free hemoglobin: 11 ± 2 vs 109 ± 10 mg/dL, p < 0.0001; normal human plasma free hemoglobin <4 mg/dL). The TORVAD design, with markedly lower shear stress and pulsatile flow, caused significantly less blood trauma than the HeartMate II. LVADs with reduced blood trauma are likely to improve clinical outcomes and expand LVAD therapy into patients with less advanced heart failure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastrointestinal bleeding from angiodysplasia is a major problem in continuous-flow left ventricular assist device (LVAD) patients. LVAD shear stress causes pathologic degradation of VWF (von Willebrand factor). A mechanistic relationship between VWF degradation and angiodysplasia has not been explored. We tested 2 novel hypotheses: (1) clinical hypothesis: VWF fragments are elevated in LVAD patients that develop angiodysplasia and (2) in vitro hypothesis: VWF fragments generated during LVAD support alter angiogenesis, which may contribute to angiodysplasia. METHODS AND RESULTS: Clinical study: Paired blood samples were collected from continuous-flow LVAD patients (n=35). VWF was quantified with immunoblotting. In vitro experiments: (1) To investigate whether LVAD support alters angiogenesis, human endothelial cells were cultured with LVAD patient plasma (n=11). To investigate mechanism, endothelial cells were cultured with VWF fragments produced by exposing human VWF and ADAMTS-13 (VWF protease) to LVAD-like shear stress (175 dyne/cm2, n=8). Clinical study results: In all patients (n=35, mean support 666±430 days), LVAD support degraded highmolecular- weight VWF multimers (P<0.0001) into low-molecular-weight VWF multimers (P<0.0001) and VWF fragments (P<0.0001). In patients with gastrointestinal bleeding from angiodysplasia (n=7), VWF fragments were elevated (P=0.02) versus nonbleeders. In contrast, in patients with gastrointestinal bleeding without angiodysplasia, VWF fragments were not elevated versus nonbleeders (P=0.96). In vitro experiments results: LVAD patient plasma caused abnormal angiogenesis with reduced tubule length (P=0.04) and migration (P=0.05). Similarly, endothelial cells grown with VWF degradation fragments exhibited reduced tubule length (P<0.001) and migration (P=0.01). CONCLUSIONS: LVAD patients who bled from angiodysplasia had higher levels of VWF fragments than nonbleeders and gastrointestinal bleeders without angiodysplasia. VWF fragments caused abnormal angiogenesis in vitro. These findings suggest that VWF fragments may be a mechanistic link between LVAD support, abnormal angiogenesis, angiodysplasia, and gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Background Recent data suggest that hemolysis contributes to left ventricular assist device (LVAD) thrombosis, but the mechanism is unknown. In a clinical study, we measured plasma free hemoglobin (pfHgb) and the incidence of LVAD thrombosis. In an in vitro study, we examined biophysical relationships between shear stress, pfHgb and von Willebrand factor (vWF) metabolism toward understanding mechanisms of LVAD thrombosis. Methods In the clinical study, blood samples were obtained from continuous-flow LVAD patients (n = 30). Plasma free hemoglobin was measured via enzyme-linked immunosorbent assay. Plasma lactate dehydrogenase (LDH) was measured with a fluorimetric assay. In the in vitro study, to investigate mechanism, human plasma (n = 10) was exposed to LVAD-like shear stress (175 dyne/cm 2 ) with and without free hemoglobin (30 mg/dL). ADAMTS-13 (the vWF protease) activity was quantified with Förster resonance energy transfer. vWF size was quantified with immunoblotting. vWF clotting function was quantified with an enzyme-linked immunosorbent assay. Results In the clinical study, LVAD support caused subclinical hemolysis. In all patients, LDH increased significantly from 213 ± 9 U/L to 366 ± 31 U/L at 10 days of support ( p < 0.0001) and remained significantly elevated at 280 ± 18 U/L at 1 month of support ( p < 0.01). In 21 patients that did not develop LVAD thrombosis, pfHgb increased early but decreased over time (pre-LVAD: 5.2 ± 0.8 mg/dL; 1 week: 19.8 ± 4.4 mg/dL, p < 0.01; 3 months: 9.3 ± 2.2 mg/dL, p = 0.07). In 9 patients that developed LVAD thrombosis, pfHgb was significantly elevated versus patients without thrombosis before ( p < 0.001) and after 3 months ( p < 0.05) of support (pre-LVAD: 20.2 ± 6.3 mg/dL; 1 week: 17.3 ± 3.7 mg/dL; 3 months: 21.5 ± 7.8 mg/dL). Similarly, after 3 months, patients that did not develop LVAD thrombosis had an LDH of 271 ± 28 U/L, whereas patients that later developed LVAD thrombosis had a significantly higher LDH of 625 ± 210 U/L ( p = 0.02). In the in vitro study, shear stress degraded vWF similarly to an LVAD. Free hemoglobin inhibited ADAMTS-13 activity during shear stress (633 ± 27 ng/mL to 565 ± 24 ng/mL; p < 0.001). vWF was thereby protected from degradation, 4 vWF fragments decreased significantly ( p ≤ 0.05), and vWF clotting function increased (1.15 ± 0.09 U/mL to 1.29 ± 0.09 U/mL, p = 0.06). Conclusions These are the first data to demonstrate mechanistic relationships between subclinical hemolysis and a procoagulant state during continuous-flow LVAD support. Patients with high pfHgb and LDH were more likely to develop LVAD thrombosis. In vitro experiments demonstrated that free hemoglobin inhibited ADAMTS-13, protected vWF from degradation, increased vWF clotting function, and created a procoagulant state. As such, pfHgb may be a clinical target to prevent LVAD thrombosis. [ABSTRACT FROM AUTHOR]

Background Supraphysiologic shear stress from continuous-flow left ventricular assist devices (LVADs) accelerates von Willebrand factor (vWF) degradation and predisposes patients to nonsurgical bleeding. It is unknown whether unique design characteristics of LVADs differentially affect vWF degradation. We tested the hypothesis that the centrifugal-flow EVAHEART (Evaheart, Houston, TX) left ventricular assist system (LVAS), which was designed to minimize shear stress (low operational revolutions per minute [rpm], larger flow gaps, low shear stress, flat H-Q curve), reduced vWF degradation versus the axial-flow HeartMate II (Thoratec, Pleasanton, CA) LVAD. Methods Whole human blood was obtained from volunteer donors (n = 22). Blood was circulated for 12 hours in mock circulatory loops through a HeartMate II (n = 10; 11,400 rpm, 6.3 ± 0.8 L/min, 76 ± 2 mm Hg) or an EVAHEART LVAS (n = 12; 2,300 rpm, 5.7 ± 0.1 L/min, 80 ± 1 mm Hg). vWF degradation was characterized with electrophoresis and immunoblotting for large vWF multimers and 11 vWF degradation fragments. Results The HeartMate II eliminated large vWF multimers and significantly ( p < 0.05) increased 10 of 11 vWF degradation fragments at 6 and 12 hours. The increase was approximately 2.0-fold at 6 hours and 2.2-fold at 12 hours. In contrast, the EVAHEART LVAS modestly reduced large vWF multimers and significantly increased 5 of 11 and 8 of 11 vWF degradation fragments at 6 and 12 hours, respectively. The increase was approximately 1.5-fold at 6 hours and 1.7-fold at 12 hours. The EVAHEART LVAS caused significantly less degradation ( p < 0.01) than the HeartMate II of the 140 kDa vWF fragment (cleavage product of ADAMTS-13, the vWF protease). Conclusions The EVAHEART LVAS caused significantly less vWF degradation than the HeartMate II in a mock circulatory loop with whole human blood. LVAD design features may minimize vWF degradation. These data may inform the design and operation of next-generation LVADs to minimize blood trauma. [ABSTRACT FROM AUTHOR]

Objectives Bleeding is an important source of morbidity in patients with a left ventricular assist device. Evidence suggests a major role for von Willebrand factor. However, limited data exist to explain the mechanism(s) of von Willebrand factor degradation during left ventricular assist device support. We investigated whether left ventricular assist device--related shear stress and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13, the von Willebrand factor protease) altered von Willebrand factor metabolism. Methods Whole blood was collected from patients (n = 8) with a left ventricular assist device. von Willebrand factor multimers and degradation fragments were characterized with electrophoresis and immunoblotting. To investigate mechanisms, an in vitro model was developed to generate the supraphysiologic shear stress of a continuous-flow left ventricular assist device. Normal human blood (n = 8) was cycled in a laboratory vortexer (~2400 rpm, shear stress ~175 dyne/cm², 4 hours) to reproduce the pathologic degradation of von Willebrand factor that occurs during left ventricular assist device support. To investigate the specific mechanistic roles of shear stress and ADAMTS-13 in von Willebrand factor degradation, purified von Willebrand factor protein ± ADAMTS-13 protease were exposed to supraphysiologic shear stress in the vortexer. von Willebrand factor multimers and 11 von Willebrand factor degradation fragments were characterized with electrophoresis and immunoblotting. Results Left ventricular assist device support reduced large von Willebrand factor multimers and significantly increased 10/11 von Willebrand factor degradation fragments (P < .05). Normal human blood exposed to supraphysiologic shear stress in the vortexer demonstrated the same profile of von Willebrand factor degradation fragments as in a patient with a left ventricular assist device. Supraphysiologic shear stress alone caused modest mechanical demolition of large von Willebrand factor multimers into smaller multimers but did not greatly generate von Willebrand factor fragments. In the presence of supraphysiologic shear stress, ADAMTS-13 completely eliminated large von Willebrand factor multimers and generated statistically significant amounts of 11/11 von Willebrand factor degradation fragments (P < .05). The profile of von Willebrand factor fragments generated was identical to the profile that was observed in vivo in patients with a left ventricular assist device. Conclusions Supraphysiologic shear stress alone causes physical demolition of large von Willebrand factor multimers into smaller von Willebrand factor multimers. In the setting of supraphysiologic shear stress, ADAMTS-13 cleaves large von Willebrand factor multimers into von Willebrand factor degradation fragments. ADAMTS-13 may be a therapeutic target to reduce von Willebrand factor degradation and bleeding complications in patients with a left ventricular assist device. [ABSTRACT FROM AUTHOR]

Objectives: Less invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System (Abiomed, Inc, Danvers, Mass) is a volume-displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces nonphysiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods: In calves (n = 23; 80-100 kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery was studied. Histologic and molecular assays evaluated architectural changes. Quantitative real-time polymerase chain reaction evaluated gene expression of matrix metalloproteinase (MMP)-2, MMP-9, and connective tissue growth factor. In vitro carotid arterial-ring studies evaluated physiologic responses. Results: During Symphony support, carotid arterial pressure was 200/15 mm Hg. Antegrade flow increased significantly (P < .05) from 1.40 ± 0.32 to 4.29 ± 0.33 L/min. Flow during native cardiac diastole reversed completely from 0.25 ± 0.05 to −4.15 ± 0.38 L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia than in control carotid arteries. MMP-9 gene expression decreased significantly, connective tissue growth factor gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial-independent contraction decreased significantly, whereas endothelial-dependent relaxation increased modestly. Conclusions: Assisted circulation with a left ventricular assist device triggered arterial remodeling that allowed a peripheral artery to accommodate the altered hemodynamics of a novel partial-support pump. Further delineation of remodeling pathways may be of significance for the emerging field of partial circulatory support. [Copyright &y& Elsevier]

Background: Counterpulsation with an intra-aortic balloon pump (IABP) has not achieved the same success or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. Methods: In Yorkshire piglets (n = 19; weight, 13.0 ± 0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with micro-spheres. Results: Despite significant suprasystolic diastolic augmentation and aflerload reduction at heart rates of 105 ± 3 beats per minute, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. Conclusions: Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted. [ABSTRACT FROM AUTHOR]

Objective: Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for yon Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support. Methods: In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤ 2 weeks of support, platelet aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay. Results: During support, statistically significant (P < .05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly. Conclusions: Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the vWF-platelet aggregation pathway. Additional delineation of these pathways may improve management of left ventricular assist device-associated bleeding. [ABSTRACT FROM AUTHOR]

Objective: An ectopic coronary artery that courses between the aortic root and the pulmonary trunk may lead to sudden cardiac death, especially in athletes. It has been speculated that during exercise, compression of the coronary artery between the great vessels may impair coronary blood flow and produce myocardial ischemia and fatal arrhythmia. However, this hypothesis cannot be tested in humans, and little experimental data exist to explain this phenomenon. To this end, in a calf with an anomalous left coronary artery that coursed from the right sinus of Valsalva between the great vessels, we assessed for myocardial ischemia during pharmacologically induced tachycardia and hypertension. Methods: We identified a juvenile male calf (103 kg) with an anomalous left coronary artery from the right sinus of Valsalva that coursed between the great vessels. Via thoracotomy, the animal was instrumented for hemodynamic measurements. Intravenous dobutamine increased heart rate and myocardial metabolic demands. Intravenous phenylephrine produced arterial hypertension and increased myocardial metabolic demands. Fluorescent-labeled microspheres were used to map regional myocardial blood flow, and hemodynamics were recorded during each condition. Masson’s trichrome staining for fibrosis, wheat-germ agglutinin staining for myocyte size, terminal deoxynucleotidyl transferase dUTP nick end-label staining for apoptosis, and isolectin-B4 staining for capillary density were performed. Results: For the first time, empiric data documented that an ectopic coronary artery produced myocardial ischemia during elevated myocardial metabolic demands. Left coronary artery resistance increased in a cardiac cycle–dependent pattern that was consistent with systolic compression between the great vessels. Increased cardiac fibrosis, myocyte hypertrophy, cardiac apoptosis, and capillary density indicated that regional ischemic, inflammatory-mediated myocardial remodeling was present. Conclusions: These findings confirm the proposed mechanism of sudden death and support early surgical repair of coronary arteries that course between the aortic root and the pulmonary trunk. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]