Predictors of Acquired Von Willebrand Syndrome in Patients with Aortic Stenosis,

Abstract

Abstract 3318▪▪This icon denotes a clinically relevant abstract Background:Acquired von Willebrand syndrome (AVWS) due to loss of high molecular weight multimers (HMWM), is a frequent cause of bleeding in aortic stenosis (AS), and is reversed by valve replacement. The goal of this study was to explore predictors of AVWS in patients with AS. Methods:A total of 91 patients (59 men, median age 79 years) with AS (n=64) or heart valve replacement (n=27) were included. We recorded peripheral blood count, vital signs, mean gradient (MG), peak velocity (peak vel), aortic valve time velocity integral (AV-TVI), aortic valve area (AVA) and valve area index (AVAi), time velocity integral ratio (TVI ratio), VWF antigen (VWF:Ag), VWF activity by latex immunoturbidity assay (VWF:Lx), VWF multimer analysis, closure times of platelet function analyzer ADP and epinephrine cartridges (PFA-CADP and –CEPI). HMWM losses were graded as normal, mild or severe when compared to HMWM analyses of pooled plasma samples from normal donors. Potential predictors of HMWM loss were explored using logistic regression analysis. Results:Of the 91 patients, 42 (46%) had loss of HMWM (23 mild and 19 severe). In single variable logistic regression analysis, AVWS was associated with a low AVA (<1.0 cm2; OR=5.08, P<0.001), and low AVAi (<0.60 cm2/m2; OR=5.54, P<0.001), low TVI ratio (<0.25; OR=10.80, P<0.001), prolonged PFA-CADP (≥121 sec; OR=6.76, P<0.001), and low VWF:Lx/Ag (≤0.8; OR=8.06, P=0.008). Moderate peak vel (3–4 m/sec) and high peak vel (>4 m/sec) were associated with loss of HMWM (OR[vs. <3 m/sec]=5.80 and 37.70 respectively, P<0.001) as were moderate MG (25–40 mmHg) and high MG (>40 mmHg), (OR [vs. <25mmHg]=4.50 and 32.50 respectively, P<0.001). In exploratory multivariable analysis, mean gradient remained one of the strongest predictor of loss of HMWM. The estimated sensitivity of MG (≥25mmHg) in diagnosing AVWS was 83% (35/42, 95% CI: 69%-93%) and estimated specificity was 71% (35/49, 95% CI: 57%-83%). Considering the very strong correlation with mean gradient, we also considered the diagnostic utility of peak vel. Peak vel≥ 3 m/sec had a sensitivity of 89% (38/42, 95% CI: 77%-97%) and a specificity of 59% (29/49, 95% CI: 44%-73%) in detecting loss of HMWM. Conclusion:Our data suggest that mean gradient (>25 mmHg) and peak vel (≥ 3 m/sec), both derived from the Doppler aortic valve velocity envelope, are accurate predictors for AS-AVWS, and should be incorporated into algorithmic approaches to laboratory screening for AVWS.Table:Predictors of AS-AVWS (N=91)Single variable analysisMultivariable analysis1VariableOR (95% CI)p-valueOR (95% CI)p-valueGender (male)0.79 (0.33–1.87)0.590.61 (0.20–1.82)0.37Age (years)1.20 (0.84–1.78)0.340.96 (0.62–1.54)0.86Patient type (AS vs. valve replacement)12.48 (3.86–56.47)<0.0013.03 (0.65–16.69)0.17Aortic stenosis symptoms1.58 (0.67–3.73)0.300.27 (0.05–1.01)0.076Current use of coumadin0.14 (0.04–0.39)<0.0010.23 (0.06–0.83)0.031Current use of aspirin1.35 (0.58–3.19)0.491.29 (0.44–3.88)0.64GFR (60 vs. <60)1.96 (0.80–5.05)0.152.25 (0.71–7.73)0.18Atrial fibrillation0.56 (0.22–1.36)0.210.86 (0.27–2.73)0.80Left ventricular hypertrophy2.02 (0.80–5.21)0.141.17 (0.34–3.89)0.80Heart rate (10 bpm increase)1.30 (0.92–1.90)0.151.15 (0.75–1.77)0.52Systolic blood pressure ≥(140 mmHg2.41 (0.99–6.04)0.0523.41 (1.06–12.39)0.047Platelet (100 unit increase)2.12 (1.02–4.77)0.0533.83 (1.53–10.85)0.006Hemoglobin (1 unit increase)0.95 (0.72–1.24)0.691.08 (0.76–1.55)0.67Mean Gradient<0.001<0.001<25 mmHg1.00 (reference)1.00 (reference)25–40 mmHg4.50 (1.36–15.77)4.50 (1.36–15.77)>40 mmHg32.50 (9.47–140.35)32.50 (9.47–140.35)Peak velocity(m/sec)<0.001NA<3 m/sec1.00 (reference)3–4 m/sec5.80 (1.70–23.70)>4 m/sec37.70 (10.15–179.37)Aortic valve area <1.0 cm 25.08 (2.09–13.06)<0.001NAAortic TVI (10 cm increase)1.73 (1.41–2.21)<0.001NATVI Ratio<0.25210.80 (4.08–31.91<0.001NAAortic valve area index<0.60 cm25.54 (2.30–14.09)<0.001NAvWF: Lx/Ag = 0.8) 28.06 (1.99–54.58)0.009NAPFA collagen ADP closure time ≥ 121 sec6.76 (2.72–18.04)<0.001NA- Odds ratios (ORs), 95% confidence intervals (CIs), and corresponding p-values result from logistic regression analysis.2Variable was not included in multivariable analyses due to strong collinearity with mean gradient.1Multivariable models are adjusted for mean gradient. Disclosures:No relevant conflicts of interest to declare.