P100Angiotensin II receptor blockers in modulation of transforming growth factor-b cardiac effects in mitral valve prolapse

Abstract

Purpose: The inhibition by angiotensin II receptor blockers (ARB) the transforming growth factor-b (TGF-b) induced extracellular matrix production has been shown recently in cultured valvular interstitial cells obtained from patients with mitral valve prolapse (MVP) undergoing mitral valve repair. Our aim was to evaluate the effect of ARB therapy on TGF-b serum level and possible impact on valve myxomatous degeneration and left ventricular (LV) systolic dysfunction in MVP patients. Methods: A total of 233 asymptomatic patients (mean age: 53.8±12.9) with severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our retrospective, non-randomized, single-center study between 2009 and 2011. Concentrations of TGF-b1 and b2 in serum were determined by enzyme-linked immunosorbent assay (Bender MedSystems). Standard echocardiography extended with speckle-tracking echocardiography was performed in all patients (EchoPAC'08, GE). Results: According to the case reports only 43 (18.5%) patients received losartan or telmisartan (study group). Majority of the patients (190, 81.5%) did not receive any ARBs (control group). There were no significant differences between groups in age, other medical treatment (β-blockers, diuretics), heart rate and blood pressure. Mitral regurgitation had the similar effective regurgitant orifice area (0.38±0.12 vs. 0.40±0.14 sm2; p=0.38) and volume (69.5±9.8 vs. 72.3±8.6 ml; p=0.08) by PISA in both groups. TGF-b1 level was significantly higher in subjects without ARB therapy (55.9±70.7 ng/ml) than in ARB group (16.1±32.9 ng/ml; p=0.0003), as well TGF-b2 (7.6±0.5 vs. 2.2±1.5 ng/ml; p<0.0001). Subjects in control group had significantly longer (anterior leaflet: 28.6±3.5 vs. 23.4±3.1 mm, p<0.0001; posterior leaflet: 15.2±2.6 vs. 13.8±2.9 mm, p=0.002) and thicker (AL: 4,2±1,1 vs. 3,5±1,4 mm, p=0.0004; PL: 5,0±1,3 vs. 3,7±0,82 mm, p<0.0001) mitral valve leaflets (echocardiographic signs of myxomatous degeneration) than in ARB group. Despite the lack of difference in LV ejection fraction (62.2±9.6 vs. 60.2±10.3 %; p=0.11), systolic longitudinal strain (-15.5±2.6% vs. -13.6±2.2%; p<0.0001) and SR (-1.16±0.16 s-1 vs. -0.91±0.12 s-1; p<0.0001) values were significantly higher in the ARB group. Conclusions: Patients with MVP and significant MR may benefit in valve myxomatous degeneration and LV systolic function from ARB therapy, probably due to its ability to inhibit TGF- β signalling.