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

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3318-3318 ◽  
Author(s):  
Dong Chen ◽  
Colleen S Thomas ◽  
Joseph L Blackshear
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Valve Replacement ◽  
Logistic Regression Analysis ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand ◽  
Time Velocity Integral ◽  
Valve Area

Abstract Abstract 3318 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. Disclosures: No relevant conflicts of interest to declare.

Changes in von Willebrand factor-cleaving protease (ADAMTS-13) in patients with aortic stenosis undergoing valve replacement or balloon valvuloplasty

2012 ◽  
Vol 108 (07) ◽  
pp. 86-93 ◽  
Author(s):  
Sammy Elmariah ◽  
Louis Aledort ◽  
Jeffrey Dlott ◽  
Paul Stelzer ◽  
Jonathan Halperin ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Von Willebrand Factor ◽  
Multivariable Analysis ◽  
Acquired Von Willebrand Syndrome ◽  
Postoperative Changes ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIt was the objective of this study to determine whether reduced cleavage of von Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a consequence of reduced shear stress or postoperative changes in VWF cleavage protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by acquired von Willebrand disease. Aortic valve replacement (AVR) corrects the associated haematologic abnormalities. We enrolled 114 patients with severe AS scheduled for either balloon aortic valvuloplasty (BAV; n=64) or AVR (n=50). Haematologic assessments of VWF levels and activity and ADAMTS-13 were performed before and 24 hours after valve intervention. The VWF:RCo to VWF:Ag ratio, a surrogate for large VWF multimer activity, increased by 37% (p < 0.0001) after AVR and by 10% (p = 0.0002) after BAV. ADAMTS-13 activity significantly decreased after AVR (579 ± 127 to 468 ± 135 ng/ml; p<0.0001), but not after BAV (484 ± 153 to 529 ± 185 ng/ml; p = 0.10). By multivariable analysis, the change in VWF:RCo ratio after AVR was more strongly associated with the fall in ADAMTS-13 than with reduction of valve gradient; whereas the change in gradient better predicted the rise in VWF:RCo after BAV. In conclusion, both BAV and AVR reverse the haematological abnormalities of the acquired von Willebrand syndrome of AS and ADAMTS-13 levels decrease after AVR. These findings suggest that a portion of the haematologic benefit of AVR may be due to a postoperative decline in ADAMTS-13 rather than solely to relief of AS as previously thought.

A Scoring System to Predict the Likelihood of Acquired Von Willebrand Syndrome (AVWS) in Patients with Cardiovascular Diseases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3377-3377
Author(s):  
Katherine M. Duello ◽  
Thomas S Colleen ◽  
Dong Chen ◽  
Joseph L Blackshear
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Relative Risk ◽  
Logistic Regression Analysis ◽  
Scoring System ◽  
Conflicts Of Interest ◽  
Peak Velocity ◽  
Forward Selection ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand

Abstract Abstract 3377 Background Bleeding from AVWS may occur in aortic stenosis (AS), hypertrophic cardiomyopathy (HCM), mitral regurgitation (MR), and prosthetic valve dysfunction (PVD) due to loss of von Willebrand factor (VWF) high molecular weight multimers caused by shear stress. Traditional laboratory testing for AVWS, including VWF antigen (VWF:Ag) and ristocetin cofactor activity lack sensitivity in this setting, and VWF multimer analysis, a costly and time-consuming test, must be used for confirmative diagnosis. The goal of this study is to develop a clinical and laboratory approach to predict the likelihood of AVWS, and consequently obviate the need for multimer analysis. Methods 160 patients with or without a bleeding history were prospectively enrolled with mild, moderate, or severe AS (n=65), HCM (n=32), MR (n=25), or with heart valve replacement (n=38). These patients were investigated at the time of clinically indicated echocardiography with VWF latex immunoturbidic activity (VWF:Ltx), VWF:Ag, (abnormal versus normal cutoff of VWF:Ltx/VWF:Ag is <0.80) platelet function analyzer 100 collagen ADP (PFA-CADP) and VWF multimer analysis. Single variable logistic regression analysis was performed to estimate clinical or laboratory variables that were strongly associated with the probability of abnormal multimers, including results of echocardiographic peak velocity and PFA-CADP. Associations with abnormal multimers were summarized with estimated relative risk (RR) and 95% CI. A scoring system was then created to evaluate the risk of abnormal multimers among cardiac patients. Results Overall, 50% of patients had abnormal multimers, indicating likely AVWS. The estimated probability of abnormal multimers showed a significant association between peak velocity, PFA-CADP and VWF:Lx/Ag (Table 1). Logistic regression analysis using forward selection identified only peak velocity (p<0.001) and PFA-CADP (p=0.033) as the factors showing the strongest evidence of association with abnormal multimers. VWF:Lx/Ag was no longer significant after adjusting for these two variables. Estimated relative risk of abnormal multimers for values of peak velocity and PFA-CADP were then derived (Table 2). From these relative risks a scoring algorithm was created in order to determine who should be screened for abnormal multimers. A value of 1 was subtracted from each relative risk and rounded to the nearest integer to obtain a score for peak velocity (<3 m/sec=0, 3.0–3.9 m/sec=3, 4.0–4.9 m/sec=5, >5.0 m/sec=7), and for PFA-CADP (≤120 sec=0, 121–180 sec=2, > 180 sec=3). The score from each of the two variables was added to obtain a total score ranging from 0 to 10. The risk score was categorized into four levels, which are 0, 2–3, 5–7, and 8–10, as shown in Table 3. Conclusion Both hemodynamic severity and PFA-CADP testing results could be incorporated into a scoring system to identify potential AVWS due to loss of HMWM in patients with various cardiovascular conditions. Further studies are needed to validate such a scoring system in a separate set of patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 189: ADAMTS13 Activity Predicts Response to Thrombolysis in the Acute Stroke Setting

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Alejandro Bustamante ◽  
Victor Llombart ◽  
Cristina Boada ◽  
Anna Penalba ◽  
Alba Simats ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Acute Stroke ◽  
Logistic Regression Analysis ◽  
Arterial Occlusion ◽  
Adamts13 Activity ◽  
Stroke Patients ◽  
Vessel Patency ◽  
A Disintegrin And Metalloproteinase ◽  
Von Willebrand

INTRODUCTION: Biological markers predicting tPA response in acute stroke could be used for dose adjustments or early selection of patients for endovascular procedures. ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) inactivates Von Willebrand Factor by cleaving it, and its deficiency may generate prothrombotic diseases such as thrombotic thrombocytopenic purpura. We aimed to analyze ADAMTS13 activity in acute stroke patients and its relation to vessel patency among those treated with intravenous tPA. METHODS: Acute ischemic stroke patients (n=104) with documented arterial occlusion by transcranial Doppler (TCD), who received tPA within the first 4.5 hours after symptoms onset were recruited and compared with 38 age-matched healthy subjects. Samples were collected at baseline, before thrombolytic treatment, and ADAMTS13 activity was measured by ELISA and expressed as %. A temporal profile of ADAMTS13 activity was determined at 24 hours and 3 months in a subset of 10 patients. Recanalization was assessed 2 hours after tPA bolus by TCD, using thrombolysis in brain ischemia (TIBI) flow grading system. Logistic regression analysis was conducted to determine independent predictors of 2-hour recanalization in patients with proximal arterial occlusions. RESULTS: ADAMTS13 activity was consistently lower in stroke patients than in healthy controls (p<0.001), and remained lower at 24 hours and 3 months. For those patients who presented arterial recanalization at 2 hours, higher baseline ADAMTS13 activity (p=0.032) was noted. In logistic regression analysis from 72 patients with proximal MCA occlusion, ADAMTS13 activity >74.72% was an independent predictor of recanalization [OR=5.148 (1.463-18.111), p=0.011], together with early ischemic signs at baseline neuroimaging [OR=0.065 (0.006-0.712), p=0.025] and OCSP classification (TACI vs. PACI) [OR=0.072 (0.011-0.45), p=0.005]. CONCLUSIONS: In stroke patients treated with tPA, ADAMTS13 activity may be used to monitor the treatment as well as to make decisions regarding more aggressive reperfusion therapies when the absence of a response to intravenous tPA is anticipated.

scholarly journals Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001720
Author(s):  
Edda Bahlmann ◽  
Eigir Einarsen ◽  
Dana Cramariuc ◽  
Helga Midtbø ◽  
Costantino Mancusi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Aortic Stenosis ◽  
Logistic Regression Analysis ◽  
Myocardial Dysfunction ◽  
Smoothing Splines ◽  
Left Ventricular ◽  
Energetic Efficiency ◽  
Generalised Additive Model ◽  
Cox Regression Analysis

ObjectivesIn hypertension, low myocardial energetic efficiency (MEEi) has been documented as an integrated marker of metabolic and left ventricular (LV) myocardial dysfunction. We tested the predictive performance of MEEi in initially asymptomatic aortic stenosis (AS) patients free from diabetes and known cardiovascular disease.MethodsData from 1703 patients with mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study followed for 4.3 years was used. MEE was calculated from Doppler stroke volume/([heart rate/60]) and indexed to LV mass (MEEi). The threshold value for MEEi associated with increased mortality was identified in generalised additive model with smoothing splines. Covariables of MEEi were identified in logistic regression analysis. Outcome was assessed in Cox regression analysis and reported as HR and 95% CI.ResultsMEEi <0.34 mL/s per gram was associated with increased cardiovascular mortality (n=80) (HR 2.53 (95% CI 1.50 to 4.28)) and all-cause mortality (n=155) (HR 1.74 (95% CI 1.20 to 2.52)) (both p<0.01). The association was independent of confounders of low MEEI (<0.34 mL/s per gram) identified in multivariable logistic regression analysis, including more severe AS, higher body mass index, lower LV midwall shortening and ejection fraction and presence of hypertension. Comparison of the Cox models with and without MEEi among the covariables demonstrated that MEEi significantly improved the prognostic yield (both p<0.01).ConclusionsIn patients with initially asymptomatic AS, low MEEi was associated with clustering of cardiometabolic risk factors, lower LV myocardial function and subsequent increased mortality during 4.3 years follow-up, independent of known prognosticators.Trial registration numberNCT00092677.

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