Left ventricular-aortic angle is associated with platelet reactivity in patients with aortic stenosis

The impact of aortic stenosis on platelet reactivity is unclear. Previous studies reported contradicting results. The reason for this is unknown. It is known that flow alterations enhance platelet reactivity. A steep left ventricular-aortic angle (LV-AO-angle) is associated with turbulent flow in the aorta ascendens. Therefore, in this study, we hypothesized that LV-AO-angle is associated with platelet reactivity in patients with severe aortic stenosis. We included 289 patients with severe aortic stenosis and performed cardiac computertomography to assess the LV-AO-angle. Platelet function was evaluated by light transmission aggregometry. Platelet reactivity was higher in patients with a steep LV-AO-angle (ADP: <160°: 66.99% ± 20.72% vs. ≥160°: 60.66% ± 19.85%, P = 0.009; collagen: <160°: 78.67% ± 13.19% vs. ≥160°: 73.85% ± 14.44%, P = 0.003). Using Spearman correlation, ADP and collagen-induced aggregation was associated with LV-AO-angle (ADP: r = −0.19, P = 0.0009, R2 = 0.022; collagen: r = −0.21, P = 0.0004, R2 = 0.027). Apart from platelet reactivity, body weight, history of myocardial infarction and other factors were associated with steep LV-AO-angle. However, multivariate cox-regression (including body weight, comorbidities, history of MI and cardiac surgery, kidney function and laboratory parameters) revealed that LV-AO angle was a robust predictor of ADP and collagen-induced platelet aggregation. Steep LV-AO-angle is associated with enhanced platelet reactivity in patients with aortic stenosis. This could be the reason of contradicting results regarding platelet function in patients with aortic stenosis in previous studies. In addition, enhanced platelet reactivity in steep LV-AO-angle aortic stenosis patients might be a promising target in pathogenesis of aortic stenosis.

[1]  D. Miličić,et al.  Transcatheter aortic valve implantation induces transient drop in platelet reactivity. , 2021, Journal of cardiovascular pharmacology.

[2]  T. Hohlfeld,et al.  Impact of Transcatheter Aortic Valve Implantation on Thrombin Generation and Platelet Function , 2021, Thrombosis and Haemostasis.

[3]  Y. Bossé,et al.  Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis , 2019, European heart journal.

[4]  P. Buszman,et al.  Peri-procedural hemostasis disorders in surgical and transcatheter aortic valve implantation , 2019, Postepy w kardiologii interwencyjnej = Advances in interventional cardiology.

[5]  W. Lam,et al.  Platelet Mechanotransduction. , 2018, Annual review of biomedical engineering.

[6]  T. McCaffrey,et al.  Predictors of high on-aspirin platelet reactivity in elderly patients with coronary artery disease , 2017, Clinical interventions in aging.

[7]  J. Chambers,et al.  Comparison of Frequency of Ischemic Cardiovascular Events in Patients With Aortic Stenosis With Versus Without Asymmetric Septal Hypertrophy (from the SEAS Trial). , 2017, The American journal of cardiology.

[8]  M. Chatterjee,et al.  Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14 , 2017, Cellular Physiology and Biochemistry.

[9]  Sheldon Goldberg,et al.  Aortic Stenosis: Pathophysiology, Diagnosis, and Therapy. , 2017, The American journal of medicine.

[10]  G. Kim,et al.  The influence of the aortic valve angle on the hemodynamic features of the thoracic aorta , 2016, Scientific Reports.

[11]  R. Kornowski,et al.  Platelet reactivity in patients undergoing transcatheter aortic valve implantation , 2016, Journal of Thrombosis and Thrombolysis.

[12]  G. Vartholomatos,et al.  Platelet activation after endovascular repair of abdominal aortic aneurysm , 2016, Vascular.

[13]  C. Otto,et al.  Calcific aortic stenosis , 2016, Nature Reviews Disease Primers.

[14]  M. Gąsior,et al.  Heyde syndrome: gastrointestinal bleeding and aortic stenosis , 2016, Canadian Medical Association Journal.

[15]  T. Hohlfeld,et al.  Antiplatelet effects of aspirin in chronic kidney disease patients , 2016, Journal of thrombosis and haemostasis : JTH.

[16]  R. Storey,et al.  The role of platelets in inflammation , 2015, Thrombosis and Haemostasis.

[17]  S. Watson,et al.  The role of platelets in the recruitment of leukocytes during vascular disease , 2015, Platelets.

[18]  M. Mack,et al.  5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial , 2015, The Lancet.

[19]  Kirk B Hansen,et al.  Mechanical platelet activation potential in abdominal aortic aneurysms. , 2015, Journal of biomechanical engineering.

[20]  B. Payrastre,et al.  Platelet activation and arterial peripheral serotonin turnover in cardiac remodeling associated to aortic stenosis , 2015, American journal of hematology.

[21]  B. Coller,et al.  Association Between Shear Stress and Platelet-Derived Transforming Growth Factor-&bgr;1 Release and Activation in Animal Models of Aortic Valve Stenosis , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[22]  Deepak L. Bhatt,et al.  Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. , 2013, Journal of the American College of Cardiology.

[23]  C. Gohlke-Bärwolf,et al.  Natural history of mild and of moderate aortic stenosis-new insights from a large prospective European study. , 2013, Current problems in cardiology.

[24]  Deepak L. Bhatt,et al.  Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. , 2010, Journal of the American College of Cardiology.

[25]  W. Schmid,et al.  Estimation of platelet function under high shear conditions to assist a rapid diagnosis of Heyde Syndrome , 2008, Platelets.

[26]  G. Davı̀,et al.  Platelet activation in obese women: role of inflammation and oxidant stress. , 2002, JAMA.

[27]  C M Otto,et al.  Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. , 1997, Circulation.

[28]  J. Reilly,et al.  Shear stress and platelet function: a therapeutic challenge? , 1995, The Lancet.

[29]  J. Schapiro,et al.  Platelet hyperreactivity and prognosis in survivors of myocardial infarction. , 1990, The New England journal of medicine.

[30]  P. Stein,et al.  Evaluation of platelet reactivity in patients with valvular heart disease. , 1983, Journal of the American College of Cardiology.

[31]  Tanaka The role of , 2000, Journal of insect physiology.

[32]  P. Elwood,et al.  Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. , 1991, Circulation.