Platelet Activation Is Limited during Transcatheter Aortic Valve Implantation in Patients on Aspirin Monotherapy and without per Procedural Clinical Complications

Abstract

Transcatheter aortic valve implantation (TAVI) is an established treatment option for symptomatic patients with severe aortic valve stenosis (AS). During and early after the procedure, both ischemic events (predominantly stroke) and bleedings remain prevalent. The optimal antithrombotic regimen is still debated. Single- versus dual-antiplatelet therapy is associated with a lower rate of severe bleeding, without difference in thrombotic complications. Although platelets have been empirically targeted, little is known on their contribution to these events primarily related to embolization of thrombotic material and tissue-derived debris from the wounded aortic valve and large vessels. The objective of this study was to assess local platelet activation in blood sampled in the ascending aorta immediately before and within minutes postimplantation. A series of 18 patients with AS on monotherapy with aspirin successfully underwent TAVI with the self-expandable Medtronic CoreValve by transfemoral route. No clinical thrombotic complication occurred at 30-day follow-up. Compared with patients with stable coronary artery disease unscathed of AS and similarly treated by low-dose aspirin, AS patients displayed a chronic state of platelet activation before TAVI, assessed in venous blood using various biomarkers. However, per procedure, in aortic blood, no change occurred between the two time points in the plasma levels of serotonin or 12-lipoxgenase products, or membrane exposure of granule markers CD62-P and CD63. Our results suggest that local acute platelet activation is limited during TAVI on monotherapy with aspirin.

Keywords

platelet activation - aortic valve stenosis - transcatheter aortic valve implantation

^* These authors contributed equally to this study.

• References

• 1 Thonghong T, De Backer O, Søndergaard L. Comprehensive update on the new indications for transcatheter aortic valve replacement in the latest 2017 European guidelines for the management of valvular heart disease. Open Heart 2018; 5 (01) e000753
• 2 Gaede L, Blumenstein J, Liebetrau C. , et al. Outcome after transvascular transcatheter aortic valve implantation in 2016. Eur Heart J 2018; 39 (08) 667-675
• 3 Nijenhuis VJ, Bennaghmouch N, van Kuijk JP, Capodanno D, ten Berg JM. Antithrombotic treatment in patients undergoing transcatheter aortic valve implantation (TAVI). Thromb Haemost 2015; 113 (04) 674-685
• 4 Puri R, Altisent OA, Campelo-Parada F, del Trigo M, Regueiro A, Rodés-Cabau J. Balancing the risks of thrombosis and bleeding following transcatheter aortic valve implantation: current state-of-evidence. Curr Pharm Des 2016; 22 (13) 1904-1910
• 5 Erdoes G, Basciani R, Huber C. , et al. Transcranial Doppler-detected cerebral embolic load during transcatheter aortic valve implantation. Eur J Cardiothorac Surg 2012; 41 (04) 778-783 , discussion 783–784
• 6 Van Mieghem NM, El Faquir N, Rahhab Z. , et al. Incidence and predictors of debris embolizing to the brain during transcatheter aortic valve implantation. JACC Cardiovasc Interv 2015; 8 (05) 718-724
• 7 Gandhi S, Schwalm J-DR, Velianou JL, Natarajan MK, Farkouh ME. Comparison of dual-antiplatelet therapy to mono-antiplatelet therapy after transcatheter aortic valve implantation: systematic review and meta-analysis. Can J Cardiol 2015; 31 (06) 775-784
• 8 Vahanian A, Alfieri O, Andreotti F. , et al; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012; 33 (19) 2451-2496
• 9 Nishimura RA, Otto CM, Bonow RO. , et al; ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129 (23) e521-e643
• 10 Tchetche D, Dumonteil N, Sauguet A. , et al. Thirty-day outcome and vascular complications after transarterial aortic valve implantation using both Edwards Sapien and Medtronic CoreValve bioprostheses in a mixed population. EuroIntervention 2010; 5 (06) 659-665
• 11 Leon MB, Piazza N, Nikolsky E. , et al. Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J 2011; 32 (02) 205-217
• 12 Le Faouder P, Baillif V, Spreadbury I. , et al. LC-MS/MS method for rapid and concomitant quantification of pro-inflammatory and pro-resolving polyunsaturated fatty acid metabolites. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 932: 123-133
• 13 Xiao Z, Théroux P. Platelet activation with unfractionated heparin at therapeutic concentrations and comparisons with a low-molecular-weight heparin and with a direct thrombin inhibitor. Circulation 1998; 97 (03) 251-256
• 14 Natorska J, Bykowska K, Hlawaty M, Marek G, Sadowski J, Undas A. Increased thrombin generation and platelet activation are associated with deficiency in high molecular weight multimers of von Willebrand factor in patients with moderate-to-severe aortic stenosis. Heart 2011; 97 (24) 2023-2028
• 15 Wurster T, Tegtmeyer R, Borst O. , et al. Platelet expression of stromal cell-derived factor-1 is associated with the degree of valvular aortic stenosis. PLoS One 2014; 9 (05) e97405
• 16 Lukito P, Wong A, Jing J. , et al. Mechanical circulatory support is associated with loss of platelet receptors glycoprotein Ibα and glycoprotein VI. J Thromb Haemost 2016; 14 (11) 2253-2260
• 17 Motovska Z, Odvodyova D, Karpisek M. , et al. Platelet-derived chemokines, PF-4 and RANTES, are significantly increased in hemodynamically significant degenerative aortic stenosis. Int J Cardiol 2011; 152 (02) 273-275
• 18 Rouzaud-Laborde C, Delmas C, Pizzinat N. , et al. Platelet activation and arterial peripheral serotonin turnover in cardiac remodeling associated to aortic stenosis. Am J Hematol 2015; 90 (01) 15-19
• 19 Diehl P, Nagy F, Sossong V. , et al. Increased levels of circulating microparticles in patients with severe aortic valve stenosis. Thromb Haemost 2008; 99 (04) 711-719
• 20 Jung C, Lichtenauer M, Figulla HR. , et al. Microparticles in patients undergoing transcatheter aortic valve implantation (TAVI). Heart Vessels 2017; 32 (04) 458-466
• 21 Marchini JF, Miyakawa AA, Tarasoutchi F, Krieger JE, Lemos P, Croce K. Endothelial, platelet, and macrophage microparticle levels do not change acutely following transcatheter aortic valve replacement. J Negat Results Biomed 2016; 15: 7
• 22 Badr Eslam R, Gremmel T, Schneller A. , et al. High levels of platelet-monocyte aggregates after valve replacement for aortic stenosis: relation to soluble P-selectin and P-selectin glycoprotein ligand-1 genes. Thromb Res 2012; 129 (04) 453-458
• 23 O'Donnell VB, Murphy RC, Watson SP. Platelet lipidomics: modern day perspective on lipid discovery and characterization in platelets. Circ Res 2014; 114 (07) 1185-1203
• 24 Maskrey BH, Rushworth GF, Law MH. , et al. 12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition. J Inflamm (Lond) 2014; 11 (01) 33
• 25 Chen Z, Mondal NK, Zheng S. , et al. High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets 2019; 30 (01) 112-119
• 26 Panzer S, Badr Eslam R, Schneller A. , et al. Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis. Thromb Haemost 2010; 103 (02) 408-414
• 27 Van Belle E, Rauch A, Vincentelli A. , et al. Von Willebrand factor as a biological sensor of blood flow to monitor percutaneous aortic valve interventions. Circ Res 2015; 116 (07) 1193-1201
• 28 Takahashi N, Tanabe K, Yoshitomi H. , et al. Impairment of platelet retention rate in patients with severe aortic valve stenosis. J Cardiol 2013; 62 (03) 171-175
• 29 Fateh-Moghadam S, Voesch S, Htun P. , et al. Platelet activation is less enhanced in the new balloon expandable Edwards Sapien 3 valve compared to its predecessor model (Edwards Sapien XT). Thromb Haemost 2016; 115 (01) 109-116
• 30 Maes F, Stabile E, Ussia GP. , et al. Meta-analysis comparing single versus dual antiplatelet therapy following transcatheter aortic valve implantation. Am J Cardiol 2018; 122 (02) 310-315
• 31 Gross L, Jochheim D, Nitschke T. , et al. Platelet reactivity and early outcomes after transfemoral aortic valve implantation. Thromb Haemost 2018; 118 (10) 1832-1838
• 32 Nijenhuis VJ, Ten Berg JM, Hengstenberg C. , et al. Usefulness of clopidogrel loading in patients who underwent transcatheter aortic valve implantation (from the BRAVO-3 Randomized Trial). Am J Cardiol 2019; 123 (09) 1494-1500