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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.

Publication ,  Journal Article
Yau, TM; Pagani, FD; Mancini, DM; Chang, HL; Lala, A; Woo, YJ; Acker, MA; Selzman, CH; Soltesz, EG; Kern, JA; Maltais, S; Charbonneau, E ...
Published in: JAMA
March 26, 2019

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.

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

March 26, 2019

Volume

321

Issue

12

Start / End Page

1176 / 1186

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Treatment Failure
  • Stroke Volume
  • Prosthesis Failure
  • Myocardium
  • Middle Aged
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Injections
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yau, T. M., Pagani, F. D., Mancini, D. M., Chang, H. L., Lala, A., Woo, Y. J., … Cardiothoracic Surgical Trials Network, . (2019). 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. JAMA, 321(12), 1176–1186. https://doi.org/10.1001/jama.2019.2341
Yau, Terrence M., Francis D. Pagani, Donna M. Mancini, Helena L. Chang, Anuradha Lala, Y Joseph Woo, Michael A. Acker, et al. “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.JAMA 321, no. 12 (March 26, 2019): 1176–86. https://doi.org/10.1001/jama.2019.2341.
Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Selzman CH, Soltesz EG, Kern JA, Maltais S, Charbonneau E, Pan S, Marks ME, Moquete EG, O’Sullivan KL, Taddei-Peters WC, McGowan LK, Green C, Rose EA, Jeffries N, Parides MK, Weisel RD, Miller MA, Hung J, O’Gara PT, Moskowitz AJ, Gelijns AC, Bagiella E, Milano CA, Cardiothoracic Surgical Trials Network. 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. JAMA. 2019 Mar 26;321(12):1176–1186.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

March 26, 2019

Volume

321

Issue

12

Start / End Page

1176 / 1186

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Left
  • Treatment Failure
  • Stroke Volume
  • Prosthesis Failure
  • Myocardium
  • Middle Aged
  • Mesenchymal Stem Cell Transplantation
  • Male
  • Injections
  • Humans