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JAMA. 2019 Mar 26;321(12):1176-1186. doi: 10.1001/jama.2019.2341.

Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.

Author information

1
Peter Munk Cardiac Centre, Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
2
Division of Cardiac Surgery, University of Toronto, Toronto, Ontario, Canada.
3
Department of Cardiac Surgery, University of Michigan, Ann Arbor.
4
International Center for Health Outcomes and Innovation Research, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
5
Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
6
Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.
7
Division of Cardiothoracic Surgery, University of Utah School of Medicine, Salt Lake City.
8
Thoracic & Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio.
9
Department of Surgery, University of Virginia, Charlottesville.
10
Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota.
11
Department of Cardiac Surgery, Québec City Heart and Lung Institute, Québec City, Québec, Canada.
12
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
13
Icahn School of Medicine at Mount Sinai, New York, New York.
14
Department of Cardiothoracic Surgery, Montefiore Medical Center/Albert Einstein College of Medicine, New York, New York.
15
Division of Cardiology, Massachusetts General Hospital, Boston.
16
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
17
Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina.

Abstract

Importance:

Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery.

Objective:

To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant.

Design, Setting, and Participants:

A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018.

Interventions:

Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53).

Main Outcomes and Measures:

The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival.

Results:

Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68).

Conclusions and Relevance:

Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support.

Trial Registration:

clinicaltrials.gov Identifier: NCT02362646.

PMID:
30912838
PMCID:
PMC6439694
[Available on 2019-09-26]
DOI:
10.1001/jama.2019.2341
[Indexed for MEDLINE]

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