Background: Recent data suggest that the pathogenesis of vascular inflammation and thrombosis involves CD40 ligand (CD40L), which is mostly derived from platelets. Previous studies have demonstrated that platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS). However, in patients with MS, the plasma level of soluble CD40L has never been investigated.
Methods and results: Seventeen patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty were studied (group 1, 11 patients in permanent atrial fibrillation and 6 patients in sinus rhythm). Solid-phase, sandwich enzyme-linked immunosorbent assay determined the plasma levels of soluble CD40L in the femoral vein and artery, and right and left atria before valvuloplasty, and those in the peripheral venous blood obtained 10 min after valvuloplasty, and at the 4-week follow-up after valvuloplasty. The Doppler pressure half-time method was used to calculate the mitral valve area. Additionally, plasma concentrations of soluble CD40L in the peripheral venous blood obtained from 17 control patients were measured (including nine healthy volunteers in sinus rhythm [group 2] and eight patients in permanent lone atrial fibrillation [group 3]). Plasma levels of soluble CD40L were significantly elevated in group 1 patients (437.6 ± 370.2 pg/mL) [mean ± SD] compared with group 2 (203.8 ± 218.0 pg/mL) and group 3 patients (173.5 ± 105.0 pg/mL) [p < 0.05]. The area of mitral valve increased significantly after valvuloplasty (1.10 ± 0.20 cm2 vs 1.47 ± 0.29 cm2, p < 0.0001). The mean left atrial pressure fell significantly and immediately after valvuloplasty (22.8 ± 4.9 mm Hg vs 17.6 ± 5.5 mm Hg, p = 0.0004). The peripheral venous plasma levels of soluble CD40L obtained before valvuloplasty significantly fell after valvuloplasty (before, 437.6 ± 370.2 pg/mL; vs 10 min after, 215.4 ± 113.9 pg/mL; vs 4 weeks after, 217.5 ± 111.9 pg/mL; p < 0.02).
Conclusions: Patients with moderate-to-severe MS had higher venous plasma levels of soluble CD40L than healthy volunteers or patients with lone atrial fibrillation. Additionally, the elevated venous plasma levels of soluble CD40L fell significantly following valvuloplasty.