Search

Objectives: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes., Methods: Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population., Results: FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found., Conclusions: BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction and Objectives: At present, surgery is the only recommended effective treatment for severe aortic stenosis. However, the surgical risk is increased when left ventricular dysfunction is present. The aim of this study was to identify predictors of postoperative and long-term mortality and functional improvement after valve replacement in patients with severe aortic stenosis and left ventricular dysfunction., Methods: Between 1996 and 2008, 635 consecutive patients with severe aortic stenosis underwent surgery. Early postoperative mortality in the 82 with an ejection fraction <40% was 19.5%. The following independent predictors of early postoperative mortality were identified: female sex (odds ratio [OR]=2.60; 95% confidence interval [CI], 2.20-89.0; P=.004), mild mitral regurgitation (OR=2.38; 95% CI, 1.40-80.0; P=.020) and coronary artery disease (OR=2.09; 95% CI, 1.26-51.0; P=.027)., Results: During the mean follow-up period of 42.59+/-40.83 months, overall mortality was 18.8% and cardiovascular mortality was 11.3%. The only factor associated with increased mortality during follow-up was a low postoperative cardiac output (OR=4.40; 95% CI, 1.20-15.5; P=.02). In total, 70.5% showed early improvement in ventricular function, the predictors of which were: no improvement following a previous myocardial infarction (P=.04), no revascularized coronary lesions (P=.04), and a low aortic valve pressure gradient (P=.02). Functional class improved significantly during follow-up in 93.4% of patients., Conclusions: Despite considerable early postoperative mortality in patients with aortic stenosis and left ventricular dysfunction, over the long term there was evidence of better survival coupled to improved ventricular function and functional class.

The NADPH oxidases are a key family of ROS (reactive oxygen species)-producing enzymes which may differentially contribute to cardiac pathophysiology. Animal studies show uncertain results regarding the regulation of cardiac Nox4 by pressure overload and no data are available on human myocardial Nox4. In the present study, we evaluated Nox4 expression and its relationship with myocardial remodelling and LV (left ventricular) function in patients with severe AS (aortic valve stenosis). Endomyocardial biopsies from 34 patients with AS were obtained during aortic valve replacement surgery. LV morphology and function were assessed by echocardiography. Myocardial samples from subjects deceased of non-CVDs (cardiovascular diseases) were analysed as controls. Nox4 localization was evaluated by immunohistochemistry and quantified by Western blot. Myocardial capillary density, fibrosis and cardiomyocyte dimensions and apoptosis were assessed histologically to evaluate myocardial remodelling. Nox4 was present in samples from all subjects and expressed in cardiomyocytes, VSMCs (vascular smooth muscle cells), endothelium and fibroblasts. Nox4 levels were reduced 5-fold in AS patients compared with controls (P<0.01). Nox4 levels directly correlated with cardiomyocyte cross-sectional area (r =0.299, P<0.05) and diameter (r =0.406, P<0.05) and capillary density (r =0.389, P<0.05), and inversely with cardiomyocyte apoptosis (r =-0.316, P<0.05) in AS patients. In addition, Nox4 levels correlated with echocardiographic parameters (LV ejection fraction: r =0.353, P<0.05; midwall fractional shortening: r =0.355, P<0.05; deceleration time: r =-0.345, P<0.05) in AS patients. Nox4 is expressed in human myocardium and reduced in AS patients. The observed associations of Nox4 with cardiomyocyte parameters and capillary density in AS patients suggest a potential role of Nox4 deficiency in the myocardial remodelling present in the human pressure-overloaded heart. [ABSTRACT FROM AUTHOR]