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

Autor:	Bartunek J; Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium., Terzic A; Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA., Davison BA; Momentum Research, Inc, Durham, NC, USA., Filippatos GS; National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece., Radovanovic S; University Hospital Center Bezanijska Kosa, Belgrade, Serbia., Beleslin B; Cardiology Clinic, Clinical Centre of Serbia, Medical School, University of Belgrade, Belgrade, Serbia., Merkely B; Semmelweis University Heart and Vascular Center, Budapest, Hungary., Musialek P; Jagiellonian University Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland., Wojakowski W; Third Division of Cardiology, Medical University of Silesia, Katowice, Poland., Andreka P; Gottsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary., Horvath IG; Heart Institute, University of Pécs, Pécs, Hungary., Katz A; Department of Cardiology, Barzilai Medical Center, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Dolatabadi D; Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium., El Nakadi B; Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium., Arandjelovic A; Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia., Edes I; Department of Cardiology, University of Debrecen, Debrecen, Hungary., Seferovic PM; University of Belgrade School of Medicine, Belgrade University Medical Center, Belgrade, Serbia., Obradovic S; Clinic of Emergency Medicine, Military Medical Academy, School of Medicine, University of Defense, Belgrade, Serbia., Vanderheyden M; Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium., Jagic N; Clinical Center Kragujevac, Kragujevac, Serbia., Petrov I; Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria., Atar S; Department of Cardiology, Galilee Medical Center, Nahariya, Israel.; Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel., Halabi M; Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel., Gelev VL; Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria., Shochat MK; Heart Institute, Hillel Yaffe Medical Center, Hadera, Rappaport School of Medicine, Haifa, Israel, Technion., Kasprzak JD; Department of Cardiology Medical University of Lodz, Lodz, Poland., Sanz-Ruiz R; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Heyndrickx GR; Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium., Nyolczas N; Medical Centre, Hungarian Defense Forces, Budapest, Hungary., Legrand V; Department of Cardiology, Centre Hospitalier Universitaire de Liège, Liège, Belgium., Guédès A; Department of Cardiology, Universite Catholique de Louvain, CHU UcL Namur, Yvoir, Belgium., Heyse A; Department of Cardiology, AZ Glorieux, Ronse, Belgium., Moccetti T; Cardiocentro Ticino, Lugano, Switzerland., Fernandez-Aviles F; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Jimenez-Quevedo P; Department of Cardiology, Hospital Clínico San Carlos, Madrid, Spain., Bayes-Genis A; Hospital Universitari Germans Trias I Pujol, Universitat Autònoma, Barcelona, Spain., Hernandez-Garcia JM; Hospital Clinico Universitario Virgen de la Victoria, Malaga, Spain., Ribichini F; Department of Cardiology, University of Verona, Italy., Gruchala M; Department of Cardiology, Medical University of Gdansk, Gdansk, Poland., Waldman SA; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA., Teerlink JR; School of Medicine, University of California San Francisco and Section of Cardiology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA., Gersh BJ; Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA., Povsic TJ; Duke Clinical Research Institute and Duke Medicine, Durham, NC, USA., Henry TD; Cedars Sinai Heart Institute, Los Angeles, CA, USA., Metra M; Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Spedali Civili, Brescia, Italy., Hajjar RJ; Mount Sinai School of Medicine, New York, NY, USA., Tendera M; Third Division of Cardiology, Medical University of Silesia, Katowice, Poland., Behfar A; Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA., Alexandre B; Celyad, Mont Saint Guibert, Belgium., Seron A; Celyad, Mont Saint Guibert, Belgium., Stough WG; Departments of Clinical Research and Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Cary, NC, USA., Sherman W; Celyad, Mont Saint Guibert, Belgium., Cotter G; Momentum Research, Inc, Durham, NC, USA., Wijns W; 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.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2017 Mar 01; Vol. 38 (9), pp. 648-660.
DOI:	10.1093/eurheartj/ehw543
Abstrakt:	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. (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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