Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

Moderate to severe ischemic mitral regurgitation: More data to guide the choice. Why not consider the use of subvalvular repair?

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Implantation of a poly-L-lactide GCSF-functionalized scaffold in a model of chronic myocardial infarction

A previously developed poly-l-lactide scaffold releasing granulocyte colony-stimulating factor (PLLA/GCSF) was tested in a rabbit chronic model of myocardial infarction (MI) as a ventricular patch. Control groups were constituted by healthy, chronic MI and nonfunctionalized PLLA scaffold. PLLA-based electrospun scaffold efficiently integrated into a chronic infarcted myocardium. Functionalization of the biopolymer with GCSF led to increased fibroblast-like vimentin-positive cellular colonization and reduced inflammatory cell infiltration within the micrometric fiber mesh in comparison to nonfunctionalized scaffold; PLLA/GCSF polymer induced an angiogenetic process with a statistically significant increase in the number of neovessels compared to the nonfunctionalized scaffold; PLLA/GCSF implanted at the infarcted zone induced a reorganization of the ECM architecture leading to connective tissue deposition and scar remodeling. These findings were coupled with a reduction in end-systolic and end-diastolic volumes, indicating a preventive effect of the scaffold on ventricular dilation, and an improvement in cardiac performance

Finite Element Analysis Investigate Pulmonary Autograft Root and Leaflet Stresses to Understand Late Durability of Ross Operation

Ross operation might be a valid option for congenital and acquired left ventricular outflow tract disease in selected cases. As the pulmonary autograft is a living substitute for the aortic root that bioinspired the Ross operation, we have created an experimental animal model in which the vital capacity of the pulmonary autograft (PA) has been studied during physiological growth. The present study aims to determine any increased stresses in PA root and leaflet compared to the similar components of the native aorta. An animal model and a mathematical analysis using finite element analysis have been used for the purpose of this manuscript. The results of this study advance our understanding of the relative benefits of pulmonary autograft for the management of severe aortic valve disease. However, it launches a warning about the importance of the choice of the length of the conduits as mechanical deformation, and, therefore, potential failure, increases with the length of the segment subjected to stress. Understanding PA root and leaflet stresses is the first step toward understanding PA durability and the regions prone to dilatation, ultimately to refine the best implant technique

Impaired Flow-Mediated Dilation and Risk of Restenosis in Patients Undergoing Coronary Stent Implantation

Background— Impaired endothelial function is a key event in the atherosclerosis process and predicts future cardiovascular events in subjects with and without coronary artery disease (CAD). We performed the first prospective study evaluating whether early measurement of brachial artery endothelium-dependent dilation (flow-mediated dilation [FMD]) after coronary stenting could predict occurrence of in-stent-restenosis. Methods and Results— The study population included 136 patients with single-vessel CAD undergoing percutaneous coronary intervention (PCI) with stenting and at least 6 months of follow-up. All patients underwent ultrasound detection of brachial artery reactivity 30 days after PCI; FMD was investigated before and after 5 minutes of occlusion of the brachial artery, and nitroglycerin-mediated dilation was investigated before and after administration of sublingual nitrates. Clinical in-stent restenosis was demonstrated in 20 patients (15%), whereas 116 patients (85%) remained free of signs or symptoms of recurrent ischemia. FMD was significantly impaired in patients with restenosis versus those without restenosis (percent diameter variation 4.6±5.8% versus 9.5±6.6%, P =0.002); moreover, 4% of patients with FMD ≥7% (median value) developed in-stent restenosis versus 28% of those with FMD <7% ( P =0.0001). On multivariate analysis, FMD was the strongest predictor of restenosis (OR 4.5, 95% CI 2.4 to 12.0); conversely, nitroglycerin-mediated dilation did not independently predict the risk of restenosis (OR 2.4, 95% CI 0.8 to 6.3). Conclusions— This is the first prospective study indicating that impaired FMD independently predicts occurrence of in-stent restenosis in patients undergoing PCI. Early evaluation of endothelial function after stenting may represent a useful screening tool to stratify patients according to future risk of restenosis

Statin pretreatment and risk of in-hospital atrial fibrillation among patients undergoing cardiac surgery: a collaborative meta-analysis of 11 randomized controlled trials

Aims Statin pretreatment in patients undergoing cardiac surgery is understood to prevent postoperative atrial fibrillation (AF). However, this is based on observational and limited randomized trial evidence, resulting in uncertainty about any genuine anti-arrhythmic benefits of these agents in this setting.We therefore aimed to quantify precisely the association between statin pretreatment and postoperative AF among patients undergoing cardiac surgery. Methods and results A detailed search of MEDLINE and PubMed databases (1st January 1996 to 31st July 2012)was conducted, followed by a review of the reference lists of published studies and correspondence with trial investigators to obtain individual– participant data for meta-analysis. Evidence was combined across prospective, randomized clinical trials that compared the risk of postoperative AF among individuals randomized to statin pretreatment or placebo/control medication before elective cardiac surgery. Postoperative AF was defined as episodes of AF lasting ≥5 min. Overall, 1105 participants from 11 trials were included; of them, 552 received statin therapy preoperatively. Postoperative AF occurred in 19% of these participants when compared with 36% of those not treated with statins (odds ratio 0.41, 95% confidence interval 0.31–0.54, P , 0.00001, using a random-effects model). Atrial fibrillation prevention by statin pretreatmentwas consistent across different subgroups. Conclusion Short-term statin pretreatment may reduce the risk of postoperative AF among patients undergoing cardiac surgery

Pathophysiology of Ischaemic Mitral Valve Prolapse: A Review of the Evidence and Implications for Surgical Treatment

Ischaemic mitral prolapse (IMP) is a pathologic entity encountered in about one-third of patients undergoing surgery for ischaemic mitral regurgitation. IMP is generally the result of a papillary muscle injury consequent to myocardial infarction, but the recent literature is progressively unveiling a more complex pathogenesis. The mechanisms underlying its development are the impairment of one or more components of the mitral apparatus, which comprises the annulus, chordae tendineae, papillary muscle, and left ventricular wall. IMP is not only a disorder of valvular function but also entails coexistent aspects of a geometric disturbance of the mitral valve configuration and of the left ventricular function and dimension. A correct understanding of all these aspects is crucial to guide and tailor the correct therapeutic strategy to be adopted. Localisation of prolapse and anatomic features of the prolapsed leaflets and the subvalvular apparatus should be carefully evaluated as also constituting the major determinants defining patient outcomes. This review will summarise our current understanding of the pathophysiology of and clinical evidence on IMP, with a particular focus on surgical treatment