Stem-cell therapy in ST-segment elevation myocardial infarction with reduced ejection fraction: A multicenter, double-blind randomized trial

Abstract

Background: Left ventricular ejection fraction (LVEF) is a major determinant of long-term prognosis after ST-segment elevation myocardial infarction (STEMI). STEMI patients with reduced LVEF have a poor prognosis, despite successful reperfusion and the use of renin-angiotensin-aldosterone inhibitors.

Hypothesis: Intracoronary infusion of bone marrow-derived mononuclear cells (BMMC) may improve LVEF in STEMI patients successfully reperfused.

Methods: The main inclusion criteria for this double-blind, randomized, multicenter study were patient age 30 to 80 years, LVEF ≤50%, successful angioplasty of infarct-related artery, and regional dysfunction in the infarct-related area analyzed before cell injection. Cardiac magnetic resonance imaging was used to assess LVEF, left ventricular volumes, and infarct size at 7 to 9 days and 6 months post-myocardial infarction.

Results: One hundred and twenty-one patients were included (66 patients in the BMMC group and 55 patients in the placebo group). The primary endpoint, mean LVEF, was similar between both groups at baseline (44.63% ± 10.74% vs 42.23% ± 10.33%; P = 0.21) and at 6 months (44.74% ± 12.95 % vs 43.50 ± 12.43%; P = 0.59). The groups were also similar regarding the difference between baseline and 6 months (0.11% ± 8.5% vs 1.27% ± 8.93%; P = 0.46). Other parameters of left ventricular remodeling, such as systolic and diastolic volumes, as well as infarct size, were also similar between groups.

Conclusions: In this randomized, multicenter, double-blind trial, BMMC intracoronary infusion did not improve left ventricular remodeling or decrease infarct size.

Keywords: Acute Coronary Syndrome; Cardiomyopathy; Ischemic Heart Disease; Myocardial Infarction; Stem Cell Therapy.

Figure 1

Trial profile. Abbreviations: BMT, bone marrow transplantation; EF, ejection fraction; LTFU, lost to follow‐up; MRI, magnetic resonance imaging; PCI, percutaneous coronary intervention

Figure 2

Difference in MRI results between baseline and 6 months. P values for the difference between the stem‐cell and placebo groups are >0.05 for all indicators. Abbreviations: MRI, magnetic resonance imaging

Figure 3

Forest plot showing the ORs for the proportion of patients with ΔLVEF above the median of 2% between treated and placebo group across prespecified subgroups. Interaction with statin and DAPT was not analyzed because of the very small number of patients not taking these drugs. Δ = LVEF at 6 months minus LVEF at baseline. Abbreviations: AMI, acute myocardial infarction; CI, confidence interval; DAPT, dual antiplatelet therapy; LVEF, left ventricular ejection fraction; OR, odds ratio