Cardiopoietic cell therapy for advanced ischaemic heart failure : results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial
Bartunek, Jozef (Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium)
Terzic, Andre (Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA)
Davison, Beth A. (Momentum Research, Inc, Durham, NC, USA)
Filippatos, Gerasimos S. (University General Hospital Attikon (Haidari, Grècia))
Radovanovic, Slavica (University Hospital Center Bezanijska Kosa, Belgrade, Serbia)
Beleslin, Branko (University of Belgrade. Cardiology Clinic)
Merkely, Bela (Semmelweis University. Heart and Vascular Center)
Musialek, Piotr (Jagiellonian University Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland)
Wojakowski, Wojciech (Third Division of Cardiology, Medical University of Silesia, Katowice, Poland)
Andreka, Peter (Gottsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary)
Horvath, Ivan G. (Heart Institute, University of Pécs, Pécs, Hungary)
Katz, Amos (Department of Cardiology, Barzilai Medical Center, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel)
Dolatabadi, Dariouch (Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium)
El Nakadi, Badih (Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium)
Arandjelovic, Aleksandra (Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia)
Edes, Istvan (Department of Cardiology, University of Debrecen, Debrecen, Hungary)
Seferovic, Petar M. (University of Belgrade School of Medicine, Belgrade University Medical Center, Belgrade, Serbia)
Obradovic, Slobodan (Clinic of Emergency Medicine, Military Medical Academy, School of Medicine, University of Defense, Belgrade, Serbia)
Vanderheyden, Marc (Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium)
Jagic, Nikola (Clinical Center Kragujevac, Kragujevac, Serbia)
Petrov, Ivo (Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria)
Atar, Shaul (Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel)
Halabi, Majdi (Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel)
Gelev, Valeri L. (Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria)
Shochat, Michael K. (Heart Institute, Hillel Yaffe Medical Center, Hadera, Rappaport School of Medicine, Haifa, Israel, Technion)
Kasprzak, Jaroslaw D. (Medical University of Lodz)
Sanz-Ruiz, Ricardo (Hospital General Universitario Gregorio Marañón)
Heyndrickx, Guy R. (Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium)
Nyolczas, Noémi (Medical Centre, Hungarian Defense Forces, Budapest, Hungary)
Legrand, Victor (Department of Cardiology, Centre Hospitalier Universitaire de Liège, Liège, Belgium)
Guédès, Antoine (Department of Cardiology, Universite Catholique de Louvain, CHU UcL Namur, Yvoir, Belgium)
Heyse, Alex (Department of Cardiology, AZ Glorieux, Ronse, Belgium)
Moccetti, Tiziano (Cardiocentro Ticino, Lugano, Switzerland)
Fernandez Aviles, Francesc (Hospital General Universitario Gregorio Marañón)
Jimenez-Quevedo, Pilar (Hospital Clínico San Carlos (Madrid))
Bayés-Genís, Antoni (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Hernandez-Garcia, Jose Maria (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Ribichini, Flavio (Department of Cardiology, University of Verona, Italy)
Gruchala, Marcin (Department of Cardiology, Medical University of Gdansk, Gdansk, Poland)
Waldman, Scott A. (Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA)
Teerlink, John R. (School of Medicine, University of California San Francisco and Section of Cardiology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA)
Gersh, Bernard J. (Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA)
Povsic, Thomas J. (Duke Clinical Research Institute and Duke Medicine, Durham, NC, USA)
Henry, Timothy D. (Cedars Sinai Heart Institute (Los Angeles, Estats Units d'Amèrica))
Metra, Marco (Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Spedali Civili, Brescia, Italy)
Hajjar, Roger J. (Mount Sinai School of Medicine, New York, NY, USA)
Tendera, Michal (Third Division of Cardiology, Medical University of Silesia, Katowice, Poland)
Behfar, Atta (Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA)
Alexandre, Bertrand (Celyad, Mont Saint Guibert, Belgium)
Seron, Aymeric (Celyad, Mont Saint Guibert, Belgium)
Stough, Wendy Gattis (Departments of Clinical Research and Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Cary, NC, USA)
Sherman, Warren (Celyad, Mont Saint Guibert, Belgium)
Cotter, Gad (Momentum Research, Inc, Durham, NC, USA)
Wijns, William (The Lambe Institute for Translational Medicine and Curam, National University of Ireland Galway and Saolta University Healthcare Group, Galway, Ireland)
Universitat Autònoma de Barcelona

Data:	2016
Resum:	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. 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. 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.
Nota:	Altres ajuts: This work was supported by Celyad, SA (Mont-Saint-Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Regenerative medicine ; Cardiopoiesis ; Cardiovascular disease ; Stem cell ; Target population ; Disease severity ; Marker ; Precision medicine
Publicat a:	European heart journal, Vol. 38 (december 2016) , p. 648-660, ISSN 1522-9645

DOI: 10.1093/eurheartj/ehw543
PMID: 28025189

14 p, 657.9 KB

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