Beneficial effects of reconstituted high-density lipoprotein (rHDL) on circulating CD34+ cells in patients after an acute coronary syndrome

Background: High-density lipoproteins (HDL) favorably affect endothelial progenitor cells (EPC). Circulating progenitor cell level and function are impaired in patients with acute coronary syndrome (ACS). This study investigates the short-term effects of reconstituted HDL (rHDL) on circulating progenitor cells in patients with ACS. Methods and Findings: The study population consisted of 33 patients with recent ACS: 20 patients from the ERASE trial (randomized to receive 4 weekly intravenous infusions of CSL-111 40 mg/kg or placebo) and 13 additional patients recruited as controls using the same enrolment criteria. Blood was collected from 16 rHDL (CSL-111)-treated patients and 17 controls at baseline and at 6–7 weeks (i.e. 2–3 weeks after the fourth infusion of CSL-111 in ERASE). CD34+ and CD34+/kinase insert domain receptor (KDR+) progenitor cell counts were analyzed by flow cytometry. We found preserved CD34+ cell counts in CSL-111-treated subjects at follow-up (change of 1.6%), while the number of CD34+ cells was reduced (-32.9%) in controls (p = 0.017 between groups). The level of circulating SDF-1 (stromal cell-derived factor-1), a chemokine involved in progenitor cell recruitment, increased significantly (change of 21.5%) in controls, while it remained unchanged in CSL-111-treated patients (p = 0.031 between groups). In vitro exposure to CSL-111 of early EPC isolated from healthy volunteers significantly increased CD34+ cells, reduced early EPC apoptosis and enhanced their migration capacity towards SDF-1. Conclusions: The relative increase in circulating CD34+ cells and the low SDF-1 levels observed following rHDL infusions in ACS patients point towards a role of rHDL in cardiovascular repair mechanisms

The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral Access The Campeau Radial Paradox

AbstractObjectivesThe purpose of this study was to assess whether the benefits conferred by radial access (RA) at an individual level are offset by a proportionally greater incidence of vascular access site complications (VASC) at a population level when femoral access (FA) is performed.BackgroundThe recent widespread adoption of RA for cardiac catheterization has been associated with increased rates of VASCs when FA is attempted.MethodsLogistic regression was used to calculate the adjusted VASC rate in a contemporary cohort of consecutive patients (2006 to 2008) where both RA and FA were used, and compared it with the adjusted VASC rate observed in a historical control cohort (1996 to 1998) where only FA was used. We calculated the adjusted attributable risk to estimate the proportion of VASC attributable to the introduction of RA in FA patients of the contemporary cohort.ResultsA total of 17,059 patients were included. At a population level, the VASC rate was higher in the overall contemporary cohort compared with the historical cohort (adjusted rates: 2.91% vs. 1.98%; odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.17 to 1.89; p = 0.001). In the contemporary cohort, RA patients experienced fewer VASC than FA patients (adjusted rates: 1.44% vs. 4.19%; OR: 0.33, 95% CI: 0.23 to 0.48; p < 0.001). We observed a higher VASC rate in FA patients in the contemporary cohort compared with the historical cohort (adjusted rates: 4.19% vs. 1.98%; OR: 2.16, 95% CI: 1.67 to 2.81; p < 0.001). This finding was consistent for both diagnostic and therapeutic catheterizations separately. The proportion of VASCs attributable to RA in the contemporary FA patients was estimated at 52.7%.ConclusionsIn a contemporary population where both RA and FA were used, the safety benefit associated with RA is offset by a paradoxical increase in VASCs among FA patients. The existence of this radial paradox should be taken into consideration, especially among trainees and default radial operators

Bicuspid aortic valve stenosis: from pathophysiological mechanism, imaging diagnosis, to clinical treatment methods

Bicuspid aortic valve (BAV) is the most frequent congenital anomaly and has a natural evolution toward aortic regurgitation or stenosis due to the asymmetrical valve function associated with an evolutive ascending aortopathy. Several BAV classifications exist describing the presence and number of raphe, amount and location of calcium, and the symmetry of the functional cusps. The impact of BAV morphology on transcatheter aortic valve implantation (TAVI) outcomes still remains little investigated. Pivotal randomized trials comparing TAVI with surgery have excluded BAV until yet. However, data from registries and observational studies including highly selected patients have shown promising results of TAVI in BAV. With this review, we aimed at describing anatomical and pathophysiological characteristics of BAV, discussing the main aspects to assess diagnostic imaging modalities, and giving an overview of TAVI outcomes and technical considerations specific to BAV morphology

Novel Humanized Biosimulator to Predict Coronary Obstruction in High-Risk Valve-in-Valve Procedures

We developed humanized biosimulator to predict the risk of coronary obstruction among high-risk patients undergoing valve-in-valve (ViV) procedures. In this case, based on unchanged instantaneous wave-free ratio values measured during a ViV simulation session, the procedure was performed safely in the patient the day afterward, without coronary artery issues and with good hemodynamic results. (Level of Difficulty: Advanced.

<i>In vitro</i> exposure of circulating progenitor cells to CSL-111.

<p>Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors (n = 7) and plated on fibronectin-coated plates in the absence or presence of CSL-111 (1 mg/mL) from day 0 to day 4 (D0-4), 4 to 7 (D4-7) or 0 to 7 (D0-7). After 7 days of culture, adherent cells were harvested and analyzed by flow cytometry. (A) All adherent cells were quantified by flow cytometry using cell counting beads for enumeration. (B) CSL-111 treatment increases the total number of CD34⁺ cells when added to cell culture media at D0-4 and D0-7; CD34⁺ cells were quantified by flow cytometry. (C) CSL-111 treatment reduces basal apoptosis in eEPCs when added to cell culture media at D0-4 and D0-7. Apoptosis was measured by flow cytometry using Annexin V labeling. Each box plot shows the median, the interquartile range, the maximum and the minimum of the relative change. * indicates p < 0.05 between groups from Wilcoxon signed-rank tests.</p

Decreased levels of serum stromal cell-derived factor-1 (SDF-1) in patients with acute coronary syndrome following treatment with reconstituted high-density lipoprotein (rHDL) compared to controls.

<p>Relative changes from baseline in serum SDF-1 in the control group and in the rHDL-treated group. Each box plot shows the median, the interquartile range, the maximum and the minimum. p < 0.05 between groups from Mann-Whitney test.</p