AUTHOR=Gowdak Luís Henrique Wolff , Schettert Isolmar Tadeu , Rochitte Carlos Eduardo , de Carvalho Leonardo P. , Vieira Marcelo Luiz Campos , Dallan Luís Alberto Oliveira , de Oliveira Sérgio Almeida , César Luiz Antonio Machado , Brito José Oscar Reis , Guarita-Souza Luiz César , de Carvalho Antonio Carlos Campos , Krieger Jose Eduardo 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1040188

DOI=10.3389/fcvm.2023.1040188

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD).</p></sec><sec><title>Objective</title><p>We 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).</p></sec><sec><title>Methods</title><p>In 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 (<italic>n</italic> = 77) or placebo (<italic>n</italic> = 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.</p></sec><sec><title>Results</title><p>The reduction in global SIMI after CABG was comparable (<italic>p</italic> = 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 (<italic>p</italic> = 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) (<italic>p</italic> = 0.34) and all-cause mortality (<italic>p</italic> = 0.08) did not differ between groups 1 month post intervention.</p></sec><sec><title>Conclusion</title><p>We 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.</p></sec><sec><title>Clinical trial registration</title><p><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/</ext-link>, identifier NCT01727063</p></sec>