Exercise stress testing enhances blood coagulation and impairs fibrinolysis in asymptomatic aortic valve stenosis

Abstract

Background: Increased thrombin formation and fibrin deposition on the valves were observed in patients with severe aortic valve stenosis (AS). Exercise enhances blood coagulation and fibrinolysis in healthy subjects, but its haemostatic effects in AS are unknown. We sought to investigate how stress echocardiography alters blood coagulation and fibrinolysis in AS patients free of significant atherosclerotic vascular disease.

Methods: We studied 32 consecutive asymptomatic moderate-to-severe AS patients and 32 age- and sex-matched controls. We measured peak thrombin generated using calibrated automated thrombogram, clot lysis time (CLT), and fibrinolytic markers at four time points, i.e. at rest, at peak exercise, and 1h and 24h after a symptom-limited exercise test.

Results: We observed that peak thrombin generated rose at peak exercise to 25% higher value in the patients than in controls (p<0.001) and reached its highest level 24h from exercise in AS patients while it decreased post-exercise in controls. Baseline CLT was 13% longer in AS patients (p=0.006) and associated with thrombin activatable fibrinolysis inhibitor (TAFI) activity (r=0.69, p<0.001), antiplasmin (r=0.47, p=0.007), and plasminogen (r=-0.55, p=0.001). In AS, CLT remained unaltered at peak exercise, while it decreased in controls, yielding the intergroup difference of 28% (p<0.001). Twenty-four hours after exercise CLT became 15% longer in AS patients (p<0.001). This hypofibrinolytic effect followed a similar pattern observed for TAFI activity.

Conclusions: Asymptomatic moderate-to-severe AS patients respond to exercise with more pronounced and prolonged increase in thrombin generation, together with impaired fibrinolysis as compared to controls. Repeated episodes of exercise-induced prothrombotic state in AS might contribute to the progression of this disease.

Keywords: Aortic valve stenosis; Exercise; Fibrinolysis; Thrombin potential.