title: Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
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authors.affiliation: Semmelweis University Heart and Vascular Center, Budapest, Hungary.
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authors.affiliation: Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.|The Lambe Institute for Translational Medicine and Curam, National University of Ireland Galway and Saolta University Healthcare Group, Galway, Ireland.
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mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: Cardiopoiesis; Cardiovascular disease; Disease severity; Marker; Precision medicine; Regenerative medicine; Stem cell; Target population