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

IMPORTANCE Left ventricular assist device ( LVAD) therapy improvesmyocardial 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 pointwas 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 thatMPCs increased the likelihood of successfulweaning was 69%; belowthe predefined threshold for success. The mean proportion of successful temporaryweaning from LVADsupport over 6 monthswas 61% in theMPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P =.55). Nopatient experienced a primary safety end point. Of 10prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortalitywas not significantly different between theMPC 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 seriousadverseeventswasnotsignificantly different between groups(70.9vs78.7per 100 patient months; difference, -7.89; 95% CI, -39.95 to 24.17; P =.63) norwas the rate of readmissions (0.68 vs0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to0.27; 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.