• Terrence M Yau, Francis D Pagani, Donna M Mancini, Helena L Chang, Anuradha Lala, Woo Y Joseph YJ Department of Cardiothoracic Surgery, Stanford University, Stanford, California., Michael A Acker, Craig H Selzman, Edward G Soltesz, John A Kern, Simon Maltais, Eric Charbonneau, Stephanie Pan, Mary E Marks, Ellen G Moquete, Karen L O'Sullivan, Wendy C Taddei-Peters, Lydia K McGowan, China Green, Eric A Rose, Neal Jeffries, Michael K Parides, Richard D Weisel, Marissa A Miller, Judy Hung, Patrick T O'Gara, Alan J Moskowitz, Annetine C Gelijns, Emilia Bagiella, Carmelo A Milano, and Cardiothoracic Surgical Trials Network.
• Peter Munk Cardiac Centre, Division of Cardiovascular Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
• JAMA. 2019 Mar 26; 321 (12): 1176-1186.

ImportanceLeft 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.ObjectiveTo assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant.Design, Setting, And ParticipantsA 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.InterventionsIntramyocardial 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 MeasuresThe 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.ResultsOf 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 RelevanceAmong 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 Registrationclinicaltrials.gov Identifier: NCT02362646.

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