Safford, Robert E.

Aortic stenosis (AS) requires repeat assessments to optimally time intervention. The utility of laboratory tests to complement clinical and hemodynamic assessments has not been established. We assessed clinical, echocardiographic, and laboratory data in 76 patients with AS or heart valve replacement (HVR), age 77 years, 37% women. Laboratory assessments included von Willebrand factor (VWF) antigen, activity, (Act/Ag, normal > 0.8), VWF multimer distribution (abnormal=loss of highest molecular weight multimers=Mult+), brain natriuretic peptide (BNP, abnormal > 155 pg/ml=BNP+), and platelet function analyzer 100 collagen-ADP closure time (PFA, normal < 121 seconds). Table: Coefficients of correlation, r, and F statistic. Chi-square, and probability. Correlation of BNP to mean gradient in patients with GFR>60 remained poor, r=0.29, while for PFA r = 0.65. Median (IQR) for PFA and BNP for mild, moderate, and severe AS and HVR are shown below. VWF multimers were abnormal in 3/14 mild AS, 6/14 moderate AS, 22/25 severe AS and 4/23 HVR patients. The severity of AS was most strongly associated with VWF multimer abnormality and prolonged PFA closure time, weakly with BNP, and not with VWF Act/Ag. Conclusion: Among various laboratory measures, PFA and VWF multimers are strongly associated with AS severity, and may merit assessment as complementary diagnostic and prognostic biomarkers in AS.

Abstract Introduction: Recent reports have utilized von Willebrand factor (VWF) multimerquantitation in the assessment of native cardiac lesions and prosthetic valve dysfunction. However there is no standardized method for quantitation. We compared 3 methods of assessment which utilized a normal plasma control. Methods: We analyzed 476 samples and their control plasma from 395 patients including normal subjects, patients with aortic stenosis, hypertrophic cardiomyopathy, mitral or aortic regurgitation, normal and abnormal left cardiac valve prostheses, and left ventricular assist device therapy (LVAD). VWF multimers were assessed as normal or abnormal, or as normalized (patient / normal plasma) VWF multimerratios of gel bands >15/2-15 (NMR 15) or gel bands > 10/2-10 (NMR 10). We tested whether one technique was more strongly associated with hemodynamic severity of the cardiac lesion, with a history of acquired bleeding, and compared the results to a separate test of VWF function, platelet function analyzer 15 00 (PFA). Results: Two hundred seventeen patient samples reflected normal or mildly abnormal hemodynamics, 111 moderate, and 113 severely abnormal hemodynamics. Abnormal multimers were present in only 19% of samples with normal or mildly abnormal hemodynamics compared to 79% abnormal in the presence of moderate to severe hemodynamic abnormality. The distinction between moderate and severe hemodynamic abnormality was less striking, 65% versus 88% (figure, left). Quantitative NMR values declined with increasing cardiac lesion severity (figure, middle). The two quantitative multimermethods showed similar relationships to lesion severity by ANOVA, r=0.40 (NMR 15) versus r=0.36 (NMR 10), and by Spearman correlation, r=0.68 for NMR 15, and r=0.66 for NMR 10, and PFA results were comparable (all p< 0.001). Bleeding rates were associated with NMR 15, 10 and PFA (Mann-Whitney p<0.001, figure, right). Conclusion: The dichotomous normal / abnormal VWF multimer method appears to distinguish ≥ moderate hemodynamic disruption, whereas there is a continuous relationship between hemodynamic severity and quantitative multimer methods, which may be clinically useful in circumstances in which clinical estimation of lesion severity is challenging, such as with dysfunctional prosthetic valves. Progressive loss of VWF multimersappears to be associated with bleeding, suggesting that quantitative measures may provide incremental value over the dichotomous normal / abnormal designation. Figure Figure. Disclosures Blackshear: Baxalta, Inc: Consultancy, Research Funding.

Background: Although angina is a chronic disease, most clinical trials evaluating antiangi nal therapy are of a few weeks or months in duration. Methods and Results: To evaluate the effects of nicardipine, a second-generation dihydro pyridine calcium channel blocker, as long-term therapy, patients with chronic stable angina were treated for 1 year with open-label nicardipine. Anginal symptoms were controlled with 20 mg tid in 24%, 30 mg tid in 34%, and 40 mg tid in 42%. Of 72 patients completing the 1-year trial, only 14 (19%) had required the addition of long-acting nitrates for control of symptoms. The remaining 57 patients, who had anginal symptoms controlled with nicar dipine alone, were continued into the 3-week, double-blind period and were randomized to continue their usual dose of nicardipine or placebo. Throughout the 1-year, open-label treatment period, the number of anginal episodes and exercise parameters of angina were significantly reduced with nicardipine. Conclusions: During the double-blind period, the patients who continued on nicardipine had significantly greater exercise time and time to onset of angina than patients who were randomized to placebo. The exercise parameters in the patients randomized to placebo were improved over baseline after 1 year of therapy; however, the improvement with nicar dipine was significantly greater.