Feasibility of the Engager™ aortic transcatheter valve system using a flexible over-the-wire design

OBJECTIVES The aim was to investigate the safety and feasibility of the redesigned Engager™ transcatheter aortic valve implantation (TAVI) system. METHODS Transapical aortic valve implantation with the Engager™ valve prosthesis was intended in 11 patients, and performed in 10. Endpoints were defined according to the valve academic research consortium recommendations for reporting outcomes of TAVI in clinical trials. RESULTS All 10 patients were implanted successfully. No devicerelated or delivery system complications like coronary obstruction or aortic dissection emerged. One patient (10%) died from non-device-related reasons at post-operative day 23 of multi-organ failure. The invasively measured peak-to-peak gradient after valve implantation was 7.1±3.5mmHg. In 90%, there was no or only trivial (≤grad I) aortic regurgitation due to paravalvular leakage. In 10% of the patients, aortic regurgitation grade I-II was observed. At 30-day follow up, the mean gradient was 15.6±4.9mmHg, and no more than a mild transvalvular and paravalvular aortic regurgitation was seen as assessed by transthoracic echocardiography. CONCLUSIONS Application of the Engager™ TAVI system is safe and feasible. Prosthesis deployment in an anatomically correct position was facilitated by the design of the valve prosthesis and was successful in all patients. No device or delivery-system-related complications emerged. Safety and feasibility endpoints were met. Good results concerning the aortic valve performance after implantation and at 30-day follow up were ascertained. These results encouraged the start of a European Pivotal trial including patients to dat

Transapical aortic valve implantation with a self-expanding anatomically oriented valve

Aims The Medtronic Engager™ aortic valve bioprosthesis is a self-expanding valve with support arms facilitating anatomically correct positioning and axial fixation. Valve leaflets, made of bovine pericardium, are mounted on a Nitinol frame. Here, we report the first in man study with this new implant (Trial Identifier NCT00677638). Methods and results Thirty patients (mean age 83.4 ± 3.8 years; 83% female) with tricuspid aortic valve stenosis were included in the study. Mean logistic EuroSCORE was 23.4 ± 11.9. Mean aortic annulus diameter was 21.8 ± 1.4 mm. For this study, the Engager was available in only one size (23 mm), to fit aortic annuli of 19-23 mm. Standard transapical valve implantation was performed using predilation of the aortic valve and rapid ventricular pacing during ballon valvuloplasty and most valve deployments. Accurate valve placement was achieved in 29/30 cases (97%). Post-implant peak-to-peak gradient was 13.3 ± 9.3 mmHg. In 80% of the patients, no more than grade I paravalvular leakage was observed, in 13% grades I-II and in 3% grade II. Three patients (10%) required permanent pacemaker implantation for higher-degree or complete atrioventricular block. Four dissections (13%) occurred during positioning of the valve and were treated surgically in three cases. Thirty-day and in-hospital mortality were 20% and 23%, respectively, and 6-month survival was 56.7%. No structural failure occurred for up to 1 year. Conclusion This series established the feasibility of implanting a novel self-expanding transapical aortic valve prosthesis predictably into an anatomically correct position. Observed complications led to complete redesign of the delivery system for upcoming clinical studies with the goal of establishing safety and performanc

Remote Ischemic Preconditioning Neither Improves Survival nor Reduces Myocardial or Kidney Injury in Patients Undergoing Transcatheter Aortic Valve Implantation (TAVI)

BACKGROUND: Peri-interventional myocardial injury occurs frequently during transcatheter aortic valve implantation (TAVI). We assessed the effect of remote ischemic preconditioning (RIPC) on myocardial injury, acute kidney injury (AKIN) and 6-month mortality in patients undergoing TAVI. METHODS: We performed a prospective single-center controlled trial. Sixty-six patients treated with RIPC prior to TAVI were enrolled in the study and were matched to a control group by propensity-score. RIPC was applied to the upper extremity using a conventional tourniquet. Myocardial injury was assessed using high-sensitive troponin-T (hsTnT), and kidney injury was assessed using serum creatinine levels. Data were compared with the Wilcoxon-Rank and McNemar tests. Mortality was analysed with the log-rank test. RESULTS: TAVI led to a significant rise of hsTnT across all patients (p < 0.001). No significant inter-group difference in maximum troponin release or areas-under-the-curve was detected. Medtronic CoreValve and Edwards Sapien valves showed similar peri-interventional troponin kinetics and patients receiving neither valve did benefit from RIPC. AKIN occurred in one RIPC patient and four non-RIPC patients (p = 0.250). No significant difference in 6-month mortality was observed. No adverse events related to RIPC were recorded. CONCLUSION: Our data do not show a beneficial role of RIPC in TAVI patients for cardio- or renoprotection, or improved survival

Distribution of Cardiac Stem Cells in the Human Heart

Introduction. The existence of human cardiac stem cells (hCSC) and their regenerative capacity are not fully defined. The aim of this study was to identify and analyse the distribution of hCSCs by flow cytometry (FCM). Methods. Tissue samples from the left ventricle (LV) and the appendages of the right atrium (RA) and left atrium (LA) were taken during cardiac surgery. Mononuclear cells (MNCs) were isolated, labelled for the stem-cell-marker c-kit and hematopoietic-lineage markers and analysed by FCM. Results. HCSCs could be isolated from the RA, LA, and LV without significant quantitative difference between both atria (A) (RA 4.80 ± 1.76% versus LA 4.99 ± 1.69% of isolated MNCs, P = 0.922). The number of hCSCs was significantly higher in both atria compared to the left ventricle (A 4.90 ± 1.29% versus LV 0.62 ± 0.14% of isolated MNCs, P = 0.035). Conclusion. The atria contain a higher concentration of hCSC than the left ventricle. HCSCs located in the atria could serve as an endogenous source for heart regeneration

The Leipzig Prospective Vascular Ultrasound Registry in Radial Artery Catheterization Impact of Sheath Size on Vascular Complications

ObjectivesThis study investigated the impact of sheath size on the rate of radial artery occlusions (RAO) (primary objective) and other access site complications (hemorrhage, pseudoaneurysm, arteriovenous fistula) as secondary objectives after transradial coronary catheterization.BackgroundThe number of vascular access complications in the published data ranges from 5% to 38% after transradial catheterization.MethodsBetween November 2009 and August 2010, 455 patients 65.3 ± 10.9 years of age (62.2% male) with transradial access with 5-F (n = 153) or 6-F (n = 302) arterial sheaths were prospectively recruited. Duplex sonography was obtained in each patient before discharge. Patients with symptomatic RAO were treated with low-molecular-weight heparin (LMWH), and a follow-up was performed.ResultsThe incidence of access site complications was 14.4% with 5-F sheaths compared with 33.1% with 6-F sheaths (p < 0.001). Radial artery occlusion occurred in 13.7% with 5-F sheaths compared with 30.5% with 6-F sheaths (p < 0.001). There was no difference between groups with regard to hemorrhage, pseudoaneurysms, or arteriovenous fistulas. Female sex, larger sheath size, peripheral arterial occlusive disease, and younger age independently predicted RAO in multivariate analysis. In total, 42.5% of patients with RAO were immediately symptomatic; another 7% became symptomatic within a mean of 4 days. Of patients with RAO, 59% were treated with LMWH. The recanalization rates were significantly higher in patients receiving LMWH compared with conventional therapy (55.6% vs. 13.5%, p < 0.001) after a mean of 14 days.ConclusionsThe incidence of RAO by vascular ultrasound was higher than expected from previous data, especially in patients who underwent the procedure with larger sheaths

Final 3-year clinical outcomes following transcatheter aortic valve implantation with a supra-annular self-expanding repositionable valve in a real-world setting: Results from the multicenter FORWARD study.

OBJECTIVES The Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3-year clinical follow up of the FORWARD study. BACKGROUND Transcatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long-term clinical outcome data with the Evolut R platform are scarce. METHODS FORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart-Team assessment. TAVR was attempted in 1039 patients. RESULTS Mean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all-cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all-cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all-cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low. CONCLUSIONS The Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve-related adverse events were low

Impact of Rosuvastatin Treatment on HDL-Induced PKC- β

Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function

Baseline and exercise predictors of VO2peak in systolic heart failure patients : Results from SMARTEX-HF

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by American College of Sports Medicine in Medicine & Science in Sports & Exercise on 04/11/2019.Available online: https://journals.lww.com/acsm-msse/FullText/2020/04000/Baseline_and_Exercise_Predictors_of_V_O2peak_in.5.aspxacceptedVersio

Exercise Training Prevents Diaphragm Contractile Dysfunction in Heart Failure

Purpose: Patient studies have demonstrated the efficacy of exercise training in attenuating respiratory muscle weakness in chronic heart failure (HF), yet direct assessment of muscle fiber contractile function together with data on the underlying intracellular mechanisms remains elusive. The present study, therefore, used a mouse model of HF to assess whether exercise training could prevent diaphragm contractile fiber dysfunction by potentially mediating the complex interplay between intracellular oxidative stress and proteolysis. Methods: Mice underwent sham operation (n = 10) or a ligation of the left coronary artery and were randomized to sedentary HF (n = 10) or HF with aerobic exercise training (HF + AET; n = 10). Ten weeks later, echocardiography and histological analyses confirmed HF. Results: In vitro diaphragm fiber bundles demonstrated contractile dysfunction in sedentary HF compared with sham mice that was prevented by AET, with maximal force 21.0 ± 0.7 versus 26.7 ± 1.4 and 25.4 ± 1.4 N·cm−2, respectively (P < 0.05). Xanthine oxidase enzyme activity and MuRF1 protein expression, markers of oxidative stress and protein degradation, were ~20% and ~70% higher in sedentary HF compared with sham mice (P < 0.05) but were not different when compared with the HF + AET group. Oxidative modifications to numerous contractile proteins (i.e., actin and creatine kinase) and markers of proteolysis (i.e., proteasome and calpain activity) were elevated in sedentary HF compared with HF + AET mice (P < 0.05); however, these indices were not significantly different between sedentary HF and sham mice. Antioxidative enzyme activities were also not different between groups. Conclusion: Our findings demonstrate that AET can protect against diaphragm contractile fiber dysfunction induced by HF, but it remains unclear whether alterations in oxidative stress and/or protein degradation are primarily responsible