TY - JOUR
TI - Cardiopoietic cell therapy for advanced ischaemic heart failure: Results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial
AU - Bartunek, J.
AU - Terzic, A.
AU - Davison, B.A.
AU - Filippatos, G.S.
AU - Radovanovic, S.
AU - Beleslin, B.
AU - Merkely, B.
AU - Musialek, P.
AU - Wojakowski, W.
AU - Andreka, P.
AU - Horvath, I.G.
AU - Katz, A.
AU - Dolatabadi, D.
AU - El Nakadi, B.
AU - Arandjelovic, A.
AU - Edes, I.
AU - Seferovic, P.M.
AU - Obradovic, S.
AU - Vanderheyden, M.
AU - Jagic, N.
AU - Petrov, I.
AU - Atar, S.
AU - Halabi, M.
AU - Gelev, V.L.
AU - Shochat, M.K.
AU - Kasprzak, J.D.
AU - Sanz-Ruiz, R.
AU - Heyndrickx, G.R.
AU - Nyolczas, N.
AU - Legrand, V.
AU - Guédès, A.
AU - Heyse, A.
AU - Moccetti, T.
AU - Fernandez-Aviles, F.
AU - Jimenez-Quevedo, P.
AU - Bayes-Genis, A.
AU - Hernandez-Garcia, J.M.
AU - Ribichini, F.
AU - Gruchala, M.
AU - Waldman, S.A.
AU - Teerlink, J.R.
AU - Gersh, B.J.
AU - Povsic, T.J.
AU - Henry, T.D.
AU - Metra, M.
AU - Hajjar, R.J.
AU - Tendera, M.
AU - Behfar, A.
AU - Alexandre, B.
AU - Seron, A.
AU - Stough, W.G.
AU - Sherman, W.
AU - Cotter, G.
AU - Wijns, W.
JO - EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
PY - 2017
VL - 38
TODO - 9
SP - 648-660
PB - Oxford University Press
SN - null
TODO - 10.1093/eurheartj/ehw543
TODO - acetylsalicylic acid;  alpha adrenergic receptor blocking agent;  antivitamin K;  beta adrenergic receptor blocking agent;  creatine kinase MB;  dipeptidyl carboxypeptidase inhibitor;  hydroxymethylglutaryl coenzyme A reductase inhibitor;  loop diuretic agent;  troponin T, adult;  aorta coarctation;  aphasia;  Article;  ascending aorta surgery;  bone marrow cell;  cardiac resynchronization therapy;  cardiopoietic cell therapy;  cardiovascular mortality;  cell therapy;  clinical outcome;  controlled study;  double blind procedure;  female;  follow up;  heart failure;  heart left bundle branch block;  heart left ventricle enddiastolic volume;  heart left ventricle endsystolic volume;  heart muscle ischemia;  heart tamponade;  heart transplantation;  heart ventricle tachycardia;  human;  ischemic heart disease;  major clinical study;  male;  mesenchymal stem cell;  middle aged;  multicenter study;  New York Heart Association class;  pericardial effusion;  priority journal;  prospective study;  randomized controlled trial;  sham procedure;  stem cell expansion;  sudden cardiac death;  transient ischemic attack;  aged;  clinical trial;  heart failure;  heart muscle ischemia;  procedures;  treatment outcome;  young adult, Adult;  Aged;  Double-Blind Method;  Female;  Heart Failure;  Humans;  Male;  Mesenchymal Stem Cell Transplantation;  Middle Aged;  Myocardial Ischemia;  Prospective Studies;  Treatment Outcome;  Young Adult
TODO - 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. © The Author 2016.
ER -