Indexes of von Willebrand Factor as Biomarkers of Aortic Stenosis Severity (from the Biomarkers of Aortic Stenosis Severity [BASS] Study)

Abstract

We correlated von Willebrand factor activity indices and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n=66 [16 mild, 20 moderate, 30 severe]) and aortic valve replacement (n=21) were assessed with VWF antigen (VWF:Ag), VWF latex agglutination immunoturbidic activity (VWF:Ltx), platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio (VWF:mult ratio), and BNP level after echocardiography. In AS patients, mean gradient correlated with BNP (Spearman r=0.29, P=.02), VWF:Ltx/VWF:Ag (r=–0.41, P<.001), PFA-CADP (r=0.49, P<.001), and VWF:mult ratio (r=–0.76, P<.001). The area under the curve (95% CI) for detection of severe AS was 0.62 (0.48-0.77) by elevated BNP, 0.81 (0.69-0.92) by PFA-CADP closure time, 0.69 (0.55-0.82) by VWF:Ltx/VWF:Ag ratio, and 0.86 (0.76-0.95) by VWF:mult ratio. For VWF:mult ratio, a threshold of 0.15 yielded sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with prolonged PFA-CADP and reduced VWF:Ltx/VWF:Ag. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 AS patients, freedom from death (n=4) or aortic valve replacement (n=22) was associated with PFA-CADP (P=.003), VWF high molecular weight multimers (HMWM) (P=.009), and VWF:Ltx/VWF:Ag (P<.001), but not BNP (P=.32). In severe AS vs aortic valve replacement, PFA-CADP and VWF:mult ratio differed (P<.001), but BNP and VWF:Ltx/VWF:Ag did not. In conclusion, VWF activity indices are associated with AS severity and bleeding, and predictive of cardiovascular outcome.

Von Willebrand factor multimer quantitation for assessment of cardiac lesion severity and bleeding risk

“…We identified patients with cardiac lesions from our multispecialty practice between 2010 and 2016 as previously described 2, 3, 4, 7. The study protocol was approved by the Mayo Foundation Institutional Review Board is registered at clinicaltrials.gov (NCT01334801).…”

“…After written informed consent was obtained the patients provided research blood samples. Patients were asked to complete a bleeding questionnaire (Appendix) modified from the consensus conference on the assessment of von Willebrand disease as previously described 2, 10. For patients with positive bleeding questionnaire responses, further chart review and patient history acquisition were performed to identify clinically significant bleeding, and to determine whether Heyde syndrome (transfusion‐dependent anemia resulting from GI bleeding and endoscopically documented angiodysplasia) was present.…”

“…Subjects with LVADs were assumed to have severe lesions. Assessment of the severity of AS, AR, MR, prosthetic valvular dysfunction, and HOCM have been described previously 2, 3, 4, 7. All echocardiograms were reviewed for accuracy (J.L.B.…”

“…Comparisons between groups of patients were performed with the Wilcoxon rank sum test for continuous variables and Fisher's exact test for categorical variables. The diagnostic utility of VWF‐related tests for detecting moderate or severe cardiac lesions was explored by estimating the area under the receiver operating characteristic (ROC) curve; sensitivity, specificity, positive predictive value and negative predictive value were estimated for predefined cutoff levels when available 2. Odds ratios were calculated via 2 × 2 contingency analysis of categorical variables, defined by presence of clinic outcome (lesions severity or bleeding, respectively) and predefined cutoff of the assay in question.…”

Von Willebrand factor multimers during transcatheter aortic valve replacement—an additional clue for detecting post-procedural aortic regurgitation?

“…The role of AVWD has been investigated in relation to bleeding events associated with continuous flow mechanical circulatory assist devices (14), in some congenital cardiac defects (15), aortic stenosis (16,17), mitral regurgitation (18) and even in some cases of aortic regurgitation.…”