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Eur Heart J. 2017 Mar 1;38(9):648-660. doi: 10.1093/eurheartj/ehw543.

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

Author information

1
Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
2
Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA.
3
Momentum Research, Inc, Durham, NC, USA.
4
National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece.
5
University Hospital Center Bezanijska Kosa, Belgrade, Serbia.
6
Cardiology Clinic, Clinical Centre of Serbia, Medical School, University of Belgrade, Belgrade, Serbia.
7
Semmelweis University Heart and Vascular Center, Budapest, Hungary.
8
Jagiellonian University Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.
9
Third Division of Cardiology, Medical University of Silesia, Katowice, Poland.
10
Gottsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary.
11
Heart Institute, University of Pécs, Pécs, Hungary.
12
Department of Cardiology, Barzilai Medical Center, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
13
Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
14
Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia.
15
Department of Cardiology, University of Debrecen, Debrecen, Hungary.
16
University of Belgrade School of Medicine, Belgrade University Medical Center, Belgrade, Serbia.
17
Clinic of Emergency Medicine, Military Medical Academy, School of Medicine, University of Defense, Belgrade, Serbia.
18
Clinical Center Kragujevac, Kragujevac, Serbia.
19
Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria.
20
Department of Cardiology, Galilee Medical Center, Nahariya, Israel.
21
Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
22
Heart Institute, Hillel Yaffe Medical Center, Hadera, Rappaport School of Medicine, Haifa, Israel, Technion.
23
Department of Cardiology Medical University of Lodz, Lodz, Poland.
24
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
25
Medical Centre, Hungarian Defense Forces, Budapest, Hungary.
26
Department of Cardiology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
27
Department of Cardiology, Universite Catholique de Louvain, CHU UcL Namur, Yvoir, Belgium.
28
Department of Cardiology, AZ Glorieux, Ronse, Belgium.
29
Cardiocentro Ticino, Lugano, Switzerland.
30
Department of Cardiology, Hospital Clínico San Carlos, Madrid, Spain.
31
Hospital Universitari Germans Trias I Pujol, Universitat Autònoma, Barcelona, Spain.
32
Hospital Clinico Universitario Virgen de la Victoria, Malaga, Spain.
33
Department of Cardiology, University of Verona, Italy.
34
Department of Cardiology, Medical University of Gdansk, Gdansk, Poland.
35
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
36
School of Medicine, University of California San Francisco and Section of Cardiology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
37
Duke Clinical Research Institute and Duke Medicine, Durham, NC, USA.
38
Cedars Sinai Heart Institute, Los Angeles, CA, USA.
39
Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Spedali Civili, Brescia, Italy.
40
Mount Sinai School of Medicine, New York, NY, USA.
41
Celyad, Mont Saint Guibert, Belgium.
42
Departments of Clinical Research and Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Cary, NC, USA.
43
The Lambe Institute for Translational Medicine and Curam, National University of Ireland Galway and Saolta University Healthcare Group, Galway, Ireland.

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 200-370 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.

KEYWORDS:

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

PMID:
28025189
PMCID:
PMC5381596
DOI:
10.1093/eurheartj/ehw543
[Indexed for MEDLINE]
Free PMC Article

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