Reduction in thrombogenic activity and thrombocytopenia after transcatheter aortic valve implantation - The ATTRACTIVE-TTAS study

Abstract

Introduction: Bleeding complications after transcatheter aortic valve implantation (TAVI) is a major problem in clinical practice. However, there is few information on thrombogenicity after TAVI. The aim of this study was to establish a monitoring of total thrombogenicity in perioperative TAVI using the Total Thrombus-formation Analysis System (T-TAS), a microchip-based flow chamber system for analysis of thrombus formation under flow condition.

Methods: Twenty-three patients with severe aortic stenosis who underwent TAVI between August 2017 and March 2018 at Kumamoto university hospital were enrolled. After exclusion, data of 21 patients were analyzed. Blood samples were obtained before, 2, 7, and 30 days after TAVI. Thrombogenicity were assessed by the T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip. We also measured platelet count, high-molecular-weight von Willebrand factor (HMW-vWF) multimers, and plasma thrombopoietin. Computational fluid dynamics (CFD) analysis was performed to calculate the wall shear stress (WSS).

Results: The AR10-AUC30 levels and platelet counts were significantly lower at 2 days post-TAVI, and then increased gradually. HMW-vWF multimers, and plasma thrombopoietin, were significantly higher at 2 days post-TAVI, compared with before TAVI. CFD analysis showed that WSS of the aortic valve and posterior ascending aortic wall were significantly lower after TAVI than before-TAVI. Multivariate analysis identified max velocity measured by echocardiography, platelet count, and D-dimer as significant determinants of AR10-AUC30, representing total thrombogenicity.

Conclusions: Although HMW-vWF multimers improved earlier after TAVI, total thrombogenic activity evaluated by T-TAS remained relatively low followed by improvement in thrombogenic activity at 30 days after TAVI.Clinical Trial Registration: https://ichgcp.net/clinical-trials-registry/NCT03248232" title="See in ClinicalTrials.gov">NCT03248232.

Keywords: Severe aortic stenosis; Thrombocytopenia; Thrombogenicity; Transcatheter aortic valve implantation.

Figures

Graphical abstract

Fig. 1

Effects of TAVI on AR10-AUC30, vWF HMW multimers, plasma thrombopoietin, and platelet count. In these box-and-whisker plots, lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; and the upper and lower bars outside the boxes represent maximum and minimum values within 1.5 times the interquartile range from the 75th and 25th percentile, respectively. *p < 0.01, Bonferroni's multiple comparison test. †p < 0.05, Bonferroni's multiple comparison test. AR10-AUC30 = area under the curve for the first 30 min for the atheroma chip tested at flow rate of 10 μL/min, vWF = von Willebrand factor, HMW = high molecular weight, TAVI = transcatheter aortic valve implantation.

Fig. 2

Effects of TAVI on results of CFD analysis in patients with severe AS. Clinical characteristics (age, sex), pressure gradient measured by echocardiography, and transcatheter heart valve (THV). CFD analysis showed flow velocity on the view from the front of the ascending aorta, and wall shear stress on the view from the back of the ascending aorta and on the view of aortic base from the left ventricular in pre- and post-TAVI. CFD = computational fluid dynamics, AS = aortic valve stenosis, TAVI = transcatheter aortic valve implantation.

Fig. S1

Scatter plots of AR10-AUC30, vWF HMW multimers, platelet count, and echocardiographic parameters. Relationship between AR10-AUC30 levels measured by T-TAS, relative ratio of vWF HMW multimers, platelet count, and pressure gradient in AS patients before TAVI. AR10‐AUC30 = area under the curve for the first 30 min for the atheroma chip tested at flow rate of 10 μL/min, T-TAS = total thrombus formation analysis system, vWF = von Willebrand factor, HMW = high molecular weight, AS = aortic valve stenosis, TAVI = transcatheter aortic valve implantation, PG = pressure gradient.

Fig. S2

Effects of TAVI on WSS analyzed by CFD. In these box-and-whisker plots, lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; and the upper and lower bars outside the boxes represent maximum and minimum values within 1.5 times the interquartile range from the 75th and 25th percentile, respectively. WSS = wall shear stress, CFD = computational fluid dynamics, TAVI = transcatheter aortic valve implantation, AV = aortic valve, AO = ascending aorta.

Fig. S3

Effects of TAVI on echocardiographic parameters. In these box-and-whisker plots, lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; and the upper and lower bars outside the boxes represent maximum and minimum values within 1.5 times the interquartile range from the 75th and 25th percentile, respectively. V = velocity, PG = pressure gradient, TAVI = transcatheter aortic valve implantation.