Cardiopoietic cell therapy for advanced ischaemic heart failure: Results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Jozef Bartunek, Andre Terzic, Beth A. Davison, Gerasimos S. Filippatos, Slavica Radovanovic, Branko Beleslin, Bela Merkely, Piotr Musialek, Wojciech Wojakowski, Peter Andreka, Ivan G. Horvath, Amos Katz, Dariouch Dolatabadi, Badih El Nakadi, Aleksandra Arandjelovic, Istvan Edes, Petar M. Seferovic, Slobodan Obradovic, Marc Vanderheyden, Nikola JagicIvo Petrov, Shaul Atar, Majdi Halabi, Valeri L. Gelev, Michael K. Shochat, Jaroslaw D. Kasprzak, Ricardo Sanz-Ruiz, Guy R. Heyndrickx, Noemi Nyolczas, Victor Legrand, Antoine Guédès, Alex Heyse, Tiziano Moccetti, Francisco Fernandez-Aviles, Pilar Jimenez-Quevedo, Antoni Bayes-Genis, Jose Maria Hernandez-Garcia, Flavio Ribichini, Marcin Gruchala, Scott A. Waldman, John R. Teerlink, Bernard J. Gersh, Thomas J. Povsic, Timothy D. Henry, Marco Metra, Roger J. Hajjar, Michal Tendera, Atta Behfar, Bertrand Alexandre, Aymeric Seron, Wendy Gattis Stough, Warren Sherman, Gad Cotter, William Wijns

Research output: Contribution to journalArticle

87 Scopus citations

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 200-370mL (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.

Original languageEnglish (US)
Pages (from-to)648-660
Number of pages13
JournalEuropean heart journal
Volume38
Issue number9
DOIs
StatePublished - Mar 1 2017

Keywords

  • Cardiopoiesis
  • Cardiovascular disease
  • Disease severity
  • Marker
  • Precision medicine
  • Regenerative medicine
  • Stem cell
  • Target population

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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