%0 Journal Article
%A Bartunek, Jozef
%A Terzic, Andre
%A Davison, Beth A
%A Filippatos, Gerasimos S
%A Radovanovic, Slavica
%A Beleslin, Branko
%A Merkely, Bela
%A Musialek, Piotr
%A Wojakowski, Wojciech
%A Andreka, Peter
%A Horvath, Ivan G
%A Katz, Amos
%A Dolatabadi, Dariouch
%A El Nakadi, Badih
%A Arandjelovic, Aleksandra
%A Edes, Istvan
%A Seferovic, Petar M
%A Obradovic, Slobodan
%A Vanderheyden, Marc
%A Jagic, Nikola
%A Petrov, Ivo
%A Atar, Shaul
%A Halabi, Majdi
%A Gelev, Valeri L
%A Shochat, Michael K
%A Kasprzak, Jaroslaw D
%A Sanz-Ruiz, Ricardo
%A Heyndrickx, Guy R
%A Nyolczas, Noémi
%A Legrand, Victor
%A Guédès, Antoine
%A Heyse, Alex
%A Moccetti, Tiziano
%A Fernandez-Aviles, Francisco
%A Jimenez-Quevedo, Pilar
%A Bayes-Genis, Antoni
%A Hernandez-Garcia, Jose Maria
%A Ribichini, Flavio
%A Gruchala, Marcin
%A Waldman, Scott A
%A Teerlink, John R
%A Gersh, Bernard J
%A Povsic, Thomas J
%A Henry, Timothy D
%A Metra, Marco
%A Hajjar, Roger J
%A Tendera, Michal
%A Behfar, Atta
%A Alexandre, Bertrand
%A Seron, Aymeric
%A Stough, Wendy Gattis
%A Sherman, Warren
%A Cotter, Gad
%A Wijns, William
%A CHART Program
%T Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
%D 2017
%U http://hdl.handle.net/10668/10715
%X 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. 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. 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.
%K Cardiopoiesis
%K Cardiovascular disease
%K Disease severity
%K Marker
%K Precision medicine
%K Regenerative medicine
%K Stem cell
%K Target population
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