Abstract 17665: Complementary Role of Von Willebrand Factor Indices to Brain Natriuretic Peptide in Hypertrophic Cardiomyopathy

Abstract

Introduction: In hypertrophic cardiomyopathy (HCM), brain natriuretic peptide (BNP) has been weakly associated with septal thickness, diastolic function parameters, resting left ventricular outflow tract gradient ([[Unable to Display Character: ∆]]P), and more strongly associated with prognosis. Von Willebrand factor activity is known to be altered in HCM, and acquired bleeding may occur in up to ¼ of patients. Hypothesis: We hypothesized that indices of von Willebrand factor (VWF) activity would be more strongly related to [[Unable to Display Character: ∆]]P than BNP. Methods: We compared BNP and three independent measures of VWF function to echo/Doppler parameters in 84 HCM patients. Results: In obstructive (resting [[Unable to Display Character: ∆]]P ≥30 mm Hg), n-58 versus labile HCM (resting [[Unable to Display Character: ∆]]P <30 mm Hg, Valsalva [[Unable to Display Character: ∆]]P ≥30 mm Hg), n=28, VWF multimers were abnormal in 90% versus 52% (p=0.0005), VWF activity to antigen ratio was markedly lower, 0.76±0.09 vs 0.89±0.16, p<0.0001, and PFA markedly prolonged, 207±75 versus 129±61 seconds (p<0.0001), while BNP was moderately higher, 331±273 versus176±163 pg/ml, p=0.007. BNP correlated (Spearman rho, ρ), most strongly with echocardiographic E/e’ (ρ=0.51, p<0.001) and left atrial volume (ρ=0.34, p=0.003) but not peak gradient, [[Unable to Display Character: ∆]]P, (ρ=0.13, NS), while BNP normalized for age and gender was weakly associated with [[Unable to Display Character: ∆]]P, ρ=0.26,p=0.02 and powerfully associated with septal thickness (ρ=0.50, p<0.001), and left ventricular mass index (ρ=0.43, p<0.001). In contrast, quantitative VWF activity measures correlated strongly with [[Unable to Display Character: ∆]]P, VWF activity/antigen (ρ=-0.59, p<0.0001), and PFA (ρ=0.51, p<0.0001). In HCM patients with bleeding (n=31), VWF antigen level was higher than in those without bleeding suggesting that the combination of elevated total VWF antigen and absent high molecular weight multimers may be involved in the causation of bleeding. Conclusion: Our data suggest that BNP elevations are associated most strongly with E/e’, left atrial volume, septal thickness, and left ventricular mass, while VWF activity indices more strongly reflect [[Unable to Display Character: ∆]]P, and may thus have a complementary role in assessing therapeutic responses and prognosis. Loss of high molecular weight VWF multimers and elevated total VWF antigen concentration may be a novel marker of bleeding risk from acquired von Willebrand syndrome in HCM.