Impaired fibrinolysis in degenerative mitral and aortic valve stenosis

Abstract

Valvular heart disease is associated with an increased thromboembolic risk. Impaired fibrinolysis was reported in severe aortic stenosis (AS). Little is known about fibrinolysis in mitral stenosis (MS). We sought to compare fibrinolysis impairment in AS and MS. We studied 121 individuals scheduled for elective aortic valve (AV) or mitral valve (MV) surgery for AS (n = 76) or MS (n = 45), in order to compare fibrinolysis impairment. Fibrinolytic capacity was assessed by determination of clot lysis time (t_50%) and fibrinolysis inhibitors, including plasma plasminogen activator inhibitor-1 (PAI-1) antigen (PAI-1:Ag) and activity, thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity. Prolonged t_50% (+ 29%), elevated TAFI activity (+ 12%), TAFI:Ag (+ 21%), and PAI-1:Ag (+ 84%) were observed in patients with MS, compared with those with AS. t_50% Correlated with mean and maximal MV gradients (r = 0.43, p < 0.0001 and r = 0.39, p < 0.0001, respectively), but not with AV gradients. Mean and maximal MV gradients correlated with TAFI activity and PAI:Ag. Patients with permanent atrial fibrillation (AF; 35 with MS and 5 with AS) had longer t_50% (by 22%, p = 0.0002) and higher PAI-1:Ag (by 74%, p < 0.0001) than the remainder. In the whole group, postoperative drainage volumes correlated inversely with PAI-1:Ag (r = - 0.22, p = 0.02). MS is associated with more pronounced impairment of global fibrinolytic capacity than AS at the stage of surgical intervention, which is in part driven by AF. Our findings suggest that hypofibrinolysis might be implicated in the progression of MS and its thromboembolic complications.

Keywords: Aortic stenosis; Cardiac surgery; Fibrin; Fibrinolysis; Mitral stenosis; PAI-1; TAFI.