Prognostic Impact of High-Molecular-Weight von Willebrand Factor Multimer Ratio in Classical Low-Flow Low-Gradient Aortic Stenosis

High-molecular-weight (HMW) von Willebrand factor (VWF) multimer deficiency occurs in classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) due to shear force induced proteolysis. The prognostic value of HMW VWF mul timer deficiency is unknown. Therefore, we sought to evaluate the impact of HMW VWF multimer deficiency on clinical out come. Methods: In this prospective research study, a total of 83 patients with classical LF/LG AS were included. All patients underwent dobutamine stress echocardiography to distinguish true-severe (TS) from pseudo-severe (PS) classical LF/LG AS. HMW VWF multimer ratio was calculated using densitometric Western blot band quantification. The primary endpoint was all cause mortality. Results: Mean age was 79 ± 9 years, and TS classical LF/LG AS was diagnosed in 73% (n=61)andPSclassical LF/LG AS in 27% (n = 22) of all patients. Forty-six patients underwent aortic valve replacement (AVR) and 37 were treated Received: November 22, 2023 Accepted: May 22, 2024 Published online: June 24, 2024 conservatively.Duringameanfollow-upof27±17months,47 deaths occurred. Major bleeding complications after AVR (10/46; 22%) were more commonin patients with HMW VWF multimer ratio <1 (8/17; 47%) in comparison to patients with a normal multimer pattern (2/29; 7%) at baseline (p = 0.003). In a mul tivariable Cox regression analysis, HMW VWF multimer defi ciency was a predictor of all-cause mortality (HR: 3.02 [95% CI: 1.31–6.96], p = 0.009) in the entire cohort. This association was driven by higher mortality rates in the AVR group (multivariable adjusted HR: 9.4; 95% CI 2.0–43.4, p= 0.004). Conclusions: This is the first study to demonstrate the predictive value of HMW VWF multimer ratio for risk stratification in patients with classical LF/ LG AS. HMW VWF multimer deficiency was associated with an increased risk of all-cause mortality and major bleeding com plications after AVR