104 Latent obstruction elicits a rapid proteolysis of von Willebrand factor in patients with hypertrophic cardiomyopathy. A rest and exercise echocardiographic study

Abstract

Latent obstruction in hypertrophic cardiomyopathy (HCM) have clinical and prognostic consequences. Baseline obstruction impairs hemostatic properties of von Willebrand factor (VWF) in HCM. We sought to assess the acute effect of exercise-induced obstruction on VWF in patients with latent obstruction, and the determinants of obstruction and VWF impairment. A comprehensive echocardiography was performed at rest and during exercise in 32 patients with HCM. Sixteen patients (44±16 years) with latent obstruction (baseline peak gradient < 30 mmHg and exercise peak gradient≥30 mmHg) were matched with 16 patients without obstruction. Maximal peak gradient was recorded; the type and duration of obstruction during exercise were characterized by an obstruction score. Blood was sampled before and after exercise. Baseline median [25-75 th percentiles] peak gradient was 8[6-11] mmHg, and rose up to 32[17-104] mmHg with exercise. Baseline predictors of exercise-induced obstruction (R_ of the model 0.66) were incomplete SAM (r=0.76, p<0.0001) and mitral S velocity (r=0.34, p=0.004). At rest, VWF function was modestly impaired in patients with latent obstruction. VWF-collagen binding activity to antigen ratio (VWF:CB/Ag) and the percentage of high molecular weight multimers of VWF (%HMWM) did not change after exercise in the non obstructive group but were lowered in patients with latent obstruction (both p=0.003). Incomplete SAM at rest was the strongest independent predictor of%HMWM drop (r=-0.70, p<0.0001). %HMWM after exercise tightly correlated with exercise peak gradient (r=-0.78, p<0.0001) and the persistence of obstruction during recovery (r=-0.67, p=0.005). Incomplete SAM and mitral S velocity at rest are the main predictors of latent obstruction in HCM. Latent obstruction elicits a rapid cleavage of the largest multimers of VWF which is related to the peak gradient but also to the persistence of obstruction during recovery.