(VP062) IMPACT OF TRANSCATHETER AORTIC VALVE IMPLANTATION ON CIRCULATING VON WILLEBRAND FACTOR IN PATIENTS WITH SEVERE AORTIC STENOSIS

Background: Aortic stenosis (AS) is primarily an age-related condition that results from an inflammatory process that causes calcification of the valve leading to stiffness of leaflets. It is prevalent in 10% of adults in their eighth decade of life. Severe AS can lead to acquired von Willebrand syndrome, characterized by the loss of high molecular weight multimers (HMWM) of von Willebrand factor (VWF) due to AS-induced sheer stress. As HMWM VWF is important for hemostasis, its loss can lead to increased bleeding risk, primarily gastrointestinal bleeding. Surgical aortic valve replacement (SAVR) has been shown to improve the VWF multimer profile but many patients are ineligible for SAVR due to increased operative risk. These patients are referred for the less invasive transcatheter aortic valve implantation (TAVI). However, it is unclear how effective TAVI may be in improving the VWF multimer profile within this patient population. The study aimed to identify differences in VWF multimer profile and function in patients with severe AS before and after TAVI.

METHODS AND RESULTS: Adult patients with severe AS referred for TAVI at our institution were prospectively enrolled in this cohort study. Blood samples were collected from patients at three time points: one day before TAVI, three days post-TAVI, and one-month post-TAVI. Plasma VWF antigen (VWF:Ag), VWF Ristocetin Cofactor (VWF:RCo), VWF propeptide (VWFpp), VWF collagen binding (VWF:CB), and Factor VIII coagulant activity (FVIII:C) were measured using various assays. VWF multimers were visualized using 1.6% sodium dodecyl sulfate agarose gel electrophoresis and densitometry was used to assess VWF multimer profiles.

Twenty participants were recruited for the study. All patients had severe AS (average mean aortic valve gradient of 40.9 ± 9.4 mmHg; aortic valve area of 0.8 ± 0.2 cm2; and DI of 0.21 ± 0.04). Many patients had co-morbidities including hypertension (n =13), diabetes (n = 10), and hyperlipidemia (n=15). The study found that TAVI improved VWF quantity and function in patients with severe AS at three days and one-month post-TAVI compared to baseline (Table 1). Specifically, VWF:Ag, VWF:RCo, and VWF:CB increased significantly three days post-TAVI compared to pre-TAVI (p < 0.05 for all). Most notably, at one-month post-TAVI, HMWM VWF was significantly increased from pre-TAVI levels (p < 0.05).

Conclusion: In conclusion, this study serves as the first efforts to investigate longer-term effects (> 1 week) of TAVI on various VWF quantity and function parameters. The findings suggest long-term improvements in HMWM VWF in severe AS patients undergoing TAVI (Figure 1).