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Background: Hypertrophic obstructive cardiomyopathy submits blood to conditions of high shear stress. High shear stress impairs von Willebrand factor (VWF) and promotes abnormal bleeding in aortic stenosis. We sought to evaluate VWF impairment and its relationships to baseline or exercise obstruction in hypertrophic cardiomyopathy (HCM).
Methods And Results: Outflow obstruction was evaluated by rest and exercise echocardiography in 62 patients with HCM (age 44+/-16 years, 40 males). HCM was considered obstructive in 28 patients with rest or exercise peak gradient >or=30 mm Hg. Blood was sampled to assess VWF. History of bleeding was recorded. Baseline median (25th to 75th percentile) peak gradient was 11 (5-62) mm Hg. Shear-induced platelet adhesion was impaired in patients with obstructive HCM. The ratio of VWF-collagen-binding activity to antigen and the percentage of high-molecular-weight multimers of VWF were lower in patients with obstructive HCM than in those with nonobstructive HCM (0.49 [0.43 to 0.59] versus 0.82 [0.73 to 1.03] and 5.0% [3.9% to 7.2%] versus 11.7% [10.8% to 12.5%], respectively; both P<0.0001). Platelet adhesion time, VWF-collagen-binding activity-to-antigen ratio, and the percentage of high-molecular-weight multimers correlated closely and independently with peak gradient (r=0.81, r=-0.68, and r=-0.89, respectively; all P<0.0001). According to receiver operating characteristic curves, a peak gradient threshold of 15 mm Hg at rest and 35 mm Hg during exercise was sufficient to impair VWF. Conversely, VWF function tended to improve with a decrease in peak gradient. Obstructive HCM patients had a trend toward abnormal spontaneous bleeding.
Conclusions: In obstructive HCM, VWF impairment is frequent and is closely and independently related to the magnitude of outflow obstruction. A resting peak gradient of 15 mm Hg is sufficient to impair VWF. VWF abnormalities might favor abnormal bleeding in this setting.
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| http://dx.doi.org/10.1161/CIRCULATIONAHA.108.786681 | DOI Listing |
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