Influence of Hypoxia Inducible Factor-1α of Endothelial Progenitor Cells on Left Ventricular Function in Experimental Myocardial Infarction

Based on the promotion of myocardial activity via endothelial progenitor cells (EPCs) subsequent to acute myocardial infarction (AMI), our research was designed to explore the influence of excessive HIF-1α expression in expanded EPCs (eEPCs) on promotion of the activity of left ventricle subsequent to MI. Isolation of EPCs from cord blood was performed before transduction with the help of retroviral vector with or without HIF-1α expression. Transplantation was performed subsequent to ligation of the left anterior descending coronary artery in mice. Ejection fraction (EF) of left ventricle was promoted via transplantation after 2 weeks. Excessive HIF-1α expression enhanced EF of left ventricle and decreased the extent of MI. It was revealed via functional studies that excessive HIF-1α expression enhanced proliferation of EPCs triggered by low oxygen concentration and suppressed cell death in the region of infarction. Moreover, markers of endothelium CD31, VEGF, and eNOS were upregulated. Transplantation of eEPCs with excessive HIF-1α expression in AMI can promote myocardial activities by increasing differentiation, generation of vessels, proliferation of eEPCs, and suppressing cell death. The above findings propose that regulation of EPCs via HIF-1α enhances the activity as well as mobilization of EPCs, indicating that reinforcement of expression of HIF-1α is beneficial for coronary heart disease.

Left Ventricular Mechanics Differ in Subtypes of Aortic Stenosis Following Transcatheter Aortic Valve Replacement

BackgroundLeft ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). We hypothesized that there would be differences in myocardial mechanics, measured by global longitudinal strain (GLS) recovery in patients with four subtypes of severe AS after transcatheter aortic valve replacement (TAVR), stratified based upon flow and gradient.MethodsWe retrospectively evaluated 204 patients with severe AS who underwent TAVR and were followed post-TAVR at our institution for clinical outcomes. Speckle-tracking transthoracic echocardiography was performed pre- and post-TAVR. Patients were classified as: (1) normal-flow and high-gradient, (2) normal-flow and high-gradient with reduced LV ejection fraction (LVEF), (3) classical low-flow and low-gradient, or (4) paradoxical low-flow and low-gradient.ResultsBoth GLS (−13.9 ± 4.3 to −14.8 ± 4.3, P < 0.0001) and LVEF (55 ± 15 to 57 ± 14%, P = 0.0001) improved immediately post-TAVR. Patients with low-flow AS had similar improvements in LVEF (+2.6 ± 9%) and aortic valve mean gradient (−23.95 ± 8.34 mmHg) as patients with normal-flow AS. GLS was significantly improved in patients with normal-flow (−0.93 ± 3.10, P = 0.0004) compared to low-flow AS. Across all types of AS, improvement in GLS was associated with a survival benefit, with GLS recovery in alive patients (mean GLS improvement of −1.07 ± 3.10, P < 0.0001).ConclusionsLV mechanics are abnormal in all patients with subtypes of severe AS and improve immediately post-TAVR. Recovery of GLS was associated with a survival benefit. Patients with both types of low-flow AS showed significantly improved, but still impaired, GLS post-TAVR, suggesting underlying myopathy that does not correct post-TAVR.

Left ventricle reverse remodeling in chronic aortic regurgitation patients with dilated ventricle after aortic valve replacement

Background Aortic valve replacement (AVR) for chronic aortic regurgitation (AR) with a severe dilated left ventricle and dysfunction leads to left ventricle remodeling. But there are rarely reports on the left ventricle reverse remodeling (LVRR) after AVR. This study aimed to investigate the LVRR and outcomes in chronic AR patients with severe dilated left ventricle and dysfunction after AVR. Methods We retrospectively analyzed the clinical datum of chronic aortic regurgitation patients who underwent isolated AVR. The LVRR was defined as an increase in left ventricular ejection fraction (LVEF) at least 10 points or a follow-up LVEF ≥ 50%, and a decrease in the indexed left ventricular end-diastolic diameter of at least 10%, or an indexed left ventricular end-diastolic diameter ≤ 33 mm/m2. The changes in echocardiographic parameters after AVR, survival analysis, the predictors of major adverse cardiac events (MACE), the association between LVRR and MACE were analyzed. Results Sixty-nine patients with severe dilated left ventricle and dysfunction underwent isolated AVR. LV remodeling in 54 patients and no LV remodeling in 15 patients at 6–12 months follow-up. The preoperative left ventricular dimensions and volumes were larger, and the EF was lower in the LV no remodeling group than those in the LV remodeling group (all p < 0.05). The adverse LVRR was the predictor for MACE at follow-up. The mean follow-up period was 47.29 months (range 6 to 173 months). The rate of freedom from MACE was 94.44% at 5 years and 92.59% at 10 years in the remodeling group, 60% at 5 years, and 46.67% at 10 years in the no remodeling group. Conclusions The left ventricle remodeling after AVR was the important predictor for MACE. LV no remodeling may not be associated with benefits from AVR for chronic aortic regurgitation patients with severe dilated LV and dysfunction.

Left ventricular mass regression, all-cause and cardiovascular mortality in chronic kidney disease: a meta-analysis

Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.