R ight ventricular (RV) function is a major determinant of functional capacity and survival in pulmonary arterial hypertension (PAH) and other types of pulmonary hypertension.1 Although afterload is a prominent determinant for RV systolic function in PAH, there remains significant variability between patients with PAH in the ability of the RV to adapt to pressure overload and pulmonary resistance.2,3 The mechanisms accounting for this variability in RV adaptability to increased pulmonary load and for the transition to RV failure remain elusive. Despite the tremendous attention that left ventricular (LV) failure has received, RV failure has remained understudied at both the preclinical and clinical levels. 3 As a result, RV failure has emerged as an important research priority in the cardiopulmonary research field. Clinical Perspective on p 943Magnetic resonance imaging performed in patients with PAH has shown that the hypertrophied RV is ischemic 5 andBackground-Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, the underlying mechanisms resulting in the failed RV in PAH remain unknown. There is growing evidence that angiogenesis and microRNAs are involved in PAH-associated RV failure. We hypothesized that microRNA-126 (miR-126) downregulation decreases microvessel density and promotes the transition from a compensated to a decompensated RV in PAH. Methods and Results-We studied RV free wall tissues from humans with normal RV (n=17), those with compensated RV hypertrophy (n=8), and patients with PAH with decompensated RV failure (n=14). Compared with RV tissues from patients with compensated RV hypertrophy, patients with decompensated RV failure had decreased miR-126 expression (quantitative reverse transcription-polymerase chain reaction; P<0.01) and capillary density (CD31 + immunofluorescence; P<0.001), whereas left ventricular tissues were not affected. miR-126 downregulation was associated with increased Sprouty-related EVH1 domain-containing protein 1 (SPRED-1), leading to decreased activation of RAF (phosphorylated RAF/RAF) and mitogen-activated protein kinase (MAPK); (phosphorylated MAPK/MAPK), thus inhibiting the vascular endothelial growth factor pathway. In vitro, Matrigel assay showed that miR-126 upregulation increased angiogenesis of primary cultured endothelial cells from patients with decompensated RV failure. Furthermore, in vivo miR-126 upregulation (mimic intravenous injection) improved cardiac vascular density and function of monocrotaline-induced PAH animals. Conclusions-RV failure in PAH is associated with a specific molecular signature within the RV, contributing to a decrease in RV vascular density and promoting the progression to RV failure. More importantly, miR-126 upregulation in the RV improves microvessel density and RV function in experimental PAH. Key Words: hypertension, pulmonary ◼ microRNAs ◼ microvessels ◼ pulmonary heart disease ◼ right ventricular failure © 2015 American Heart Assoc...
Background-When compared to mitral valve replacement (MVR), mitral valve repair (MVRp) is associated with better survival in patients with organic mitral regurgitation (MR). However, there is an important controversy about the type of surgical treatment that should be used in patients with ischemic MR. The objective of this study was to compare the postoperative outcome of MVRp versus MVR in patients with ischemic MR. Methods and Results-Preoperative and operative data of 370 patients with ischemic MR who underwent mitral valve surgery were prospectively collected and retrospectively analyzed. MVRp was performed in 50% of patients (nϭ186) and MVR in 50% (nϭ184). Although operative mortality was significantly lower after MVRp compared to MVR (9.7% versus 17.4%; Pϭ0.03), overall 6-year survival was not statistically different between procedures (73Ϯ4% versus 67Ϯ4%; Pϭ0.17). After adjusting for other risk factors and propensity score, the type of procedure (MVRp versus MVR) did not come out as an independent predictor of either operative (OR, 1.5; 95% CI, 0.7-2.9; Pϭ0.34) or overall mortality (HR, 1.2; 95% CI, 0.7-1.9; Pϭ0.52). Conclusion-As opposed to what has been reported in patients with organic MR, the results of this study suggest thatMVRp is not superior to MVR with regard to operative and overall mortality in patients with ischemic MR. These findings provide support for the realization of a randomized trial comparing these 2 treatment modalities. (Circulation. 2009;120[suppl 1]:S104-S111.)
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