Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
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 200-370 mL (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.
Bartunek, J; Terzic, A; Davison, BA; Filippatos, GS; Radovanovic, S; Beleslin, B; Merkely, B; Musialek, P; Wojakowski, W; Andreka, P; Horvath, IG; Katz, A; Dolatabadi, D; El Nakadi, B; Arandjelovic, A; Edes, I; Seferovic, PM; Obradovic, S; Vanderheyden, M; Jagic, N; Petrov, I; Atar, S; Halabi, M; Gelev, VL; Shochat, MK; Kasprzak, JD; Sanz-Ruiz, R; Heyndrickx, GR; Nyolczas, N; Legrand, V; Guédès, A; Heyse, A; Moccetti, T; Fernandez-Aviles, F; Jimenez-Quevedo, P; Bayes-Genis, A; Hernandez-Garcia, JM; Ribichini, F; Gruchala, M; Waldman, SA; Teerlink, JR; Gersh, BJ; Povsic, TJ; Henry, TD; Metra, M; Hajjar, RJ; Tendera, M; Behfar, A; Alexandre, B; Seron, A; Stough, WG; Sherman, W; Cotter, G; Wijns, W; CHART Program,
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