Ontology highlight
ABSTRACT: 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.
SUBMITTER: Bartunek J
PROVIDER: S-EPMC5381596 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
Bartunek Jozef J Terzic Andre A Davison Beth A BA Filippatos Gerasimos S GS Radovanovic Slavica S Beleslin Branko B Merkely Bela B Musialek Piotr P Wojakowski Wojciech W Andreka Peter P Horvath Ivan G IG Katz Amos A Dolatabadi Dariouch D El Nakadi Badih B Arandjelovic Aleksandra A Edes Istvan I Seferovic Petar M PM Obradovic Slobodan S Vanderheyden Marc M Jagic Nikola N Petrov Ivo I Atar Shaul S Halabi Majdi M Gelev Valeri L VL Shochat Michael K MK Kasprzak Jaroslaw D JD Sanz-Ruiz Ricardo R Heyndrickx Guy R GR Nyolczas Noémi N Legrand Victor V Guédès Antoine A Heyse Alex A Moccetti Tiziano T Fernandez-Aviles Francisco F Jimenez-Quevedo Pilar P Bayes-Genis Antoni A Hernandez-Garcia Jose Maria JM Ribichini Flavio F Gruchala Marcin M Waldman Scott A SA Teerlink John R JR Gersh Bernard J BJ Povsic Thomas J TJ Henry Timothy D TD Metra Marco M Hajjar Roger J RJ Tendera Michal M Behfar Atta A Alexandre Bertrand B Seron Aymeric A Stough Wendy Gattis WG Sherman Warren W Cotter Gad G Wijns William W
European heart journal 20170301 9
<h4>Aims</h4>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.<h4>Methods and results</h4>This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-di ...[more]