Browsing by Author "El Nakadi, Badih (6603603243)"

Aims Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. Methods and results This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n= 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving> 24 million mesenchymal stem cells (n=315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n=157) or sham procedure (n= 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n= 151 sham). The primary efficacy endpoint was a Finkelstein Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann Whitney estimator 0.54, 95% confidence interval [CI] 0.47 0.61 [value> 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370mL (60% of patients) (Mann Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. Conclusion The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted. © The Author 2016.

Objectives This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure. Background In pre-clinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling. Methods The C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial, a prospective, multicenter, randomized trial, was conducted in patients with heart failure of ischemic origin who received standard of care or standard of care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were performed in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy. Results Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75% and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (from 27.5 ± 1.0% to 34.5 ± 1.1%) versus standard of care alone (from 27.8 ± 2.0% to 28.0 ± 1.8%, p < 0.0001) and was associated with a reduction in left ventricular end-systolic volume (-24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml, p < 0.001). Cell therapy also improved the 6-min walk distance (+62 ± 18 m vs. -15 ± 20 m, p < 0.01) and provided a superior composite clinical score encompassing cardiac parameters in tandem with New York Heart Association functional class, quality of life, physical performance, hospitalization, and event-free survival. Conclusions The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238). © 2013 by the American College of Cardiology Foundation.

IMPORTANCE Outcomes in patients with diabetes after fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) using current-generation drug-eluting stents (DES) compared with coronary artery bypass grafting (CABG) are unknown. OBJECTIVES To investigate the relative treatment effect of PCI vs CABG according to diabetes status with respect to major adverse cardiac and cerebrovascular events (MACCE) at 3 years and to evaluate the impact of the SYNTAX score. DESIGN, SETTING, AND PARTICIPANTS This is a prespecified subgroup analysis of the FAME (Fractional Flow Reserve vs Angiography for Multivessel Evaluation) 3 trial, an investigator-initiated, randomized clinical trial conducted at 48 centers worldwide. The FAME 3 trial enrolled patients with 3-vessel coronary artery disease not involving the left main undergoing coronary revascularization between August 2014 and December 2019. Data analysis was conducted in August 2023. Clinical follow-up was performed at hospital discharge and at 1 month, 6 months, 1 year, 2 years, and 3 years after randomization. INTERVENTION Either FFR-guided PCI with current-generation DES or CABG. MAIN OUTCOMES AND MEASURES The primary end point was MACCE, defined as the composite of all-cause death, myocardial infarction, stroke, or repeat revascularization at 3 years. RESULTS Of 1500 total patients enrolled, mean (SD) patient age was 65.1 (8.4) years, and 265 patients (17.7%) were female. The FAME 3 trial included 428 patients with diabetes (28.5%). Patients with diabetes, especially those receiving insulin, had a higher risk of MACCE at 3 years compared with those without diabetes. Regarding relative treatment effect, the risk of MACCE was higher after FFR-guided PCI compared with CABG in both patients with diabetes (hazard ratio [HR], 1.44; 95% CI, 0.91-2.28; P = .12) and those without diabetes (HR, 1.50; 95% CI, 1.08-2.07; P = .02), with no significant interaction (P for interaction = .94). In patients with a low SYNTAX score (<23), there was no significant difference in MACCE between PCI and CABG, while in patients with an intermediate to high SYNTAX score (≥23), PCI had a higher risk of MACCE than CABG, regardless of diabetes status. CONCLUSIONS AND RELEVANCE In this subgroup analysis of the FAME 3 randomized clinical trial, the relative benefit of CABG compared with FFR-guided PCI was similar among patients with and without diabetes. © 2025 American Medical Association. All rights reserved, including those for text and data mining, AI training, and similar technologies.