Additional improvement in regional myocardial ischemia after intracardiac injection of bone marrow cells during CABG surgery

Abstract

BackgroundPost-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD).ObjectiveWe evaluated whether autologous bone marrow-derived cells (BMC) contribute to additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG).MethodsIn a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (n = 77) or placebo (n = 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG.ResultsThe reduction in global SIMI after CABG was comparable (p = 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (p = 0.047). Baseline regional SIMI values were comparable [18.5 (16.2–21.0) vs. 18.5 (16.5–20.7)] and reached the lowest values at 1 month [9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85)] for BMC and placebo groups, respectively. The ischemia’s improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (p = 0.34) and all-cause mortality (p = 0.08) did not differ between groups 1 month post intervention.ConclusionWe provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT01727063

Intramyocardial Stem Cell Transplantation during Coronary Artery Bypass Surgery Safely Improves Cardiac Function: Meta-Analysis of 20 Randomized Clinical Trials

“…A summary of the stem cell mechanisms in improving outcomes is illustrated in Figure 19, below. [3,9,21,26,27]. This in turn supports myocardial tissue and vasculature repair [3,9,21,26,27].…”

“…[3,9,21,26,27]. This in turn supports myocardial tissue and vasculature repair [3,9,21,26,27]. The transplanted stem cells also release cytokines that exert paracrine effects [3,[25][26][27][30][31][32].…”

“…The mechanism by which intramyocardial stem cell transplantation improves cardiac function outcomes in patients who underwent CABG can be seen through several different mechanisms, but each is connected to and supports other mechanisms. Like other cell-based therapies, IMSC transplantation also works primarily by the effect of secreted cytokines [ 3 , 9 , 10 , 18 , 19 , 21 , 25 , 26 , 27 , 30 , 31 , 32 ]. There are three main mechanisms of action of IMSC in ischemic cardiac tissue.…”

“…First, by the direct effect of injected stem cells, which are multipotent stem cells that can differentiate to other cells [ 26 , 27 ]. The injected stem cells are thought to differentiate into cardiomyocytes and endothelial cells that can improve cardiac tissue regeneration and, later, function [ 3 , 9 , 21 , 26 , 27 ]. But this true myocardial regeneration via differentiating stem cells is still inconclusive [ 8 , 30 , 31 ].…”

“…Figure11. Forest plot of total death incidence difference between ISMC and control group[3,4,10,11,[18][19][20][21][25][26][27][28][29][30][31][32].…”