TY - JOUR
T1 - Cardiopoietic cell therapy for advanced ischaemic heart failure
T2 - Results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial
AU - Bartunek, Jozef
AU - Terzic, Andre
AU - Davison, Beth A.
AU - Filippatos, Gerasimos S.
AU - Radovanovic, Slavica
AU - Beleslin, Branko
AU - Merkely, Bela
AU - Musialek, Piotr
AU - Wojakowski, Wojciech
AU - Andreka, Peter
AU - Horvath, Ivan G.
AU - Katz, Amos
AU - Dolatabadi, Dariouch
AU - El Nakadi, Badih
AU - Arandjelovic, Aleksandra
AU - Edes, Istvan
AU - Seferovic, Petar M.
AU - Obradovic, Slobodan
AU - Vanderheyden, Marc
AU - Jagic, Nikola
AU - Petrov, Ivo
AU - Atar, Shaul
AU - Halabi, Majdi
AU - Gelev, Valeri L.
AU - Shochat, Michael K.
AU - Kasprzak, Jaroslaw D.
AU - Sanz-Ruiz, Ricardo
AU - Heyndrickx, Guy R.
AU - Nyolczas, Noemi
AU - Legrand, Victor
AU - Guédès, Antoine
AU - Heyse, Alex
AU - Moccetti, Tiziano
AU - Fernandez-Aviles, Francisco
AU - Jimenez-Quevedo, Pilar
AU - Bayes-Genis, Antoni
AU - Hernandez-Garcia, Jose Maria
AU - Ribichini, Flavio
AU - Gruchala, Marcin
AU - Waldman, Scott A.
AU - Teerlink, John R.
AU - Gersh, Bernard J.
AU - Povsic, Thomas J.
AU - Henry, Timothy D.
AU - Metra, Marco
AU - Hajjar, Roger J.
AU - Tendera, Michal
AU - Behfar, Atta
AU - Alexandre, Bertrand
AU - Seron, Aymeric
AU - Stough, Wendy Gattis
AU - Sherman, Warren
AU - Cotter, Gad
AU - Wijns, William
N1 - Publisher Copyright:
© The Author 2016.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - Cardiopoiesis
KW - Cardiovascular disease
KW - Disease severity
KW - Marker
KW - Precision medicine
KW - Regenerative medicine
KW - Stem cell
KW - Target population
UR - https://www.scopus.com/pages/publications/85016214953
U2 - 10.1093/eurheartj/ehw543
DO - 10.1093/eurheartj/ehw543
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C2 - 28025189
AN - SCOPUS:85016214953
SN - 0195-668X
VL - 38
SP - 648
EP - 660
JO - European Heart Journal
JF - European Heart Journal
IS - 9
ER -
SDG 3 Good Health and Well-being