P4483Transforming growth factor-beta and arrhythmias in mitral valve prolapse patients

Abstract

Abstract Transforming growth factor-β (TGF-β) is a multifunctional cytokine with fibrogenic properties. Also increased TGF-β signaling contributes to the development of myxomatous changes of the mitral valve (MV). Recent data suggests that TGF-β may play a potentially important role in the heart arrhythmogenesis. Our aim was to evaluate the possible proarrhythmic effects of TGF-β in patients with mitral valve prolapse (MVP) and severe mitral regurgitation (MR) undergoing MV repair. Methods 30 consecutive patients (mean age 53.1±9.4, 47% male) undergoing MV repair for severe MR due to MVP were enrolled in our observational, prospective, single-center study. Immunohistochemical characterization of mitral valve sections was performed with TGF-β1 and TGF-β2 primary antibodies. The levels of TGF-β1 and TGF-β2 in serum were determined by enzyme-linked immunosorbent assay Human Platinum ELISA.Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. Atrial fibrillation, PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results Resected MV leaflets showed the increase ofTGF-β1 and TGF-β2 positive cell count (33% and 38%, respectively). High level of TGF-β1 (>14.75 ng/ml) and/or TGF-β2 (>2.0 ng/ml) was detected in majority (77%) of patients and associated with thickening of posterior leaflet (r=0.67; p=0.016), residual valve prolapse (r=0.68; p=0.007) and recurrent MR (r=0.56; p=0.01), pre- and postoperative left atrial (p<0.001) and end-systolic LV diameter (p<0.001), and negatively with LV ejection fraction (p<0.001). Atrial fibrillation was documented in 20% patients before repair. Postoperative AF occurred in 17% and associates with postoperative left atrial diameter (rs=0.60; p=0.008) and MR degree (rs=0.51; p=0.01). Total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=0.04, Wilcoxon matched pairs test) and 2nd (p=0.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT associates strongly with postoperative end-diastolic LV diameter (rs=0.70; p=0.005), moderate negatively with LV ejection fraction (rs=−0.55; p=0.01). TGF-β2 (but not TGF-β1) serum level were associated with postoperative incidence of atrial fibrillation (p<0.001), but not PVCs or VT. In univariate analysis, postoperative left atrial diameter (p=0.001), residual MR (p=0.003), myxomatous degeneration (p=0.008) and the serum level of TGF-β2 (p=0.001) were identified as risk factors of persistent atrial fibrillation after surgery. Conclusions High level of TGF-β2 is associated with persistent atrial (but not ventricular) arrhythmias in MVP patients after mitral valve repair, possibly through 1) progression of valve myxomatous after reconstructive surgery (via recurrent MR and LA enlargement) and 2) previously shown alteration of the electrophysiological phenotype of cardiac myofibroblasts.