Cell therapy fails to improve cardiac recovery in advanced HF
CHICAGO — Among patients with advanced HF designated for left ventricular assist device therapy, mesenchymal precursor cells did not improve cardiac recovery, but there was a signal of benefit in ischemic HF, according to the results of the LVAD MPC-II trial.
Francis D. Pagani, MD, PhD, surgical director of the Adult Heart Transplant Program and program director for the Center for Circulatory Support at the University of Michigan Medical School, and colleagues evaluated whether immunomodulation from mesenchymal precursor cells could augment cardiac recovery and reduce adverse events in patients with advanced HF (ischemic or nonischemic) who were scheduled for LVAD implantation.
The researchers randomly assigned 159 patients (mean age, 56 years; 89% men) on a 2:1 basis to an intramyocardial injection of mesenchymal precursor cells (Mesoblast) or a sham procedure. Mean LV ejection fraction was 17.3% in the cell group and 16.2% in the control group.
The primary efficacy endpoint was successful temporary wean (at least 30 minutes) from full to minimal LVAD support at 2, 4 and 6 months. The primary safety endpoint was intervention-related adverse events, including infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction and immune sensitization.
According to the researchers, the mean proportion of successful temporary weans was 61% in the cell group and 58% in the control group (RR = 1.08; 95% CI, 0.83-1.41).
Pagani said the posterior probability of mesenchymal precursor cells increasing likelihood of successful weaning was 69%, which was below the prespecified threshold of 80%.
However, he said, in an exploratory subgroup analysis, among patients with ischemic HF, the wean rate ratio favored the mesenchymal precursor cell therapy group (RR = 1.55; 95% CI, 1.01-2.36), whereas among patients with nonischemic HF, there was no difference (RR = 0.82; 95% CI, 0.58-1.14; P for interaction = .02).
The results did not vary by indication for LVAD (destination therapy vs. bridge to transplant).
There were no safety-related stopping events in either group, and allosensitization to class I human leukocyte antigens was higher in the cell group (26% vs. 9.4%; between-group difference, 16.5 percentage points; 95% CI, 5-28), according to the researchers.
At 1 year, time to transplant did not differ between the groups (P = .31), nor did survival (HR = 0.89; 95% CI, 0.38-2.11), Pagani said.
Mucosal bleeding was lower at 6 months in the cell group (3.8 per 100 patient-months vs. 15.9 per 100 patient-months; P < .001), he said.
“Mesenchymal precursor cells did not increase the rate of cardiac recovery in LVAD-supported patients. However, in an exploratory subgroup analysis, there was a positive signal in ischemic HF,” Pagani said. “This may affect patient selection in future cardiac recovery trials. There was a clinically meaningful decrease in rate of mucosal bleeding. If this is substantiated in future trials, it may lead to a new therapeutic approach.” – by Erik Swain
Pagani FD, et al. LBS.06 - Late Breaking Science in Coronary Revascularization. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Disclosure: Mesoblast provided the mesenchymal precursor cells and cryoprotective media for the study at no cost. Pagani reports no relevant financial disclosures.