Timing for intracoronary administration of bone marrow mononuclear cells after acute ST-elevation myocardial infarction: a pilot study

Rongchong Huang, Kang Yao, Aijun Sun, Juying Qian, Lei Ge, Yiqi Zhang, Yuhong Niu, Keqiang Wang, Yunzeng Zou, Junbo Ge, Rongchong Huang, Kang Yao, Aijun Sun, Juying Qian, Lei Ge, Yiqi Zhang, Yuhong Niu, Keqiang Wang, Yunzeng Zou, Junbo Ge

Abstract

Introduction: Most studies on intracoronary bone marrow mononuclear cell transplantation for acute myocardial infarction involve treatment 3-7 days after primary percutaneous coronary intervention (PCI); however, the optimal timing is unknown. The present study assessed the therapeutic effect at different times after ST-elevation myocardial infarction.

Methods: The present trial was not blinded. A total of 104 patients with a first ST-elevation myocardial infarction and a left ventricular ejection fraction below 50 %, who had PCI of the infarct-related artery, were randomly assigned to receive intracoronary infusion of bone marrow mononuclear cells within 24 hours (group A, n = 27), 3 to 7 days after PCI (group B, n = 26), or 7 to 30 days after PCI (group C, n = 26), or to the control group (n = 25), which received saline infusion performed immediately after emergency PCI. All patients in groups A, B and C received an injection of 15 ml cell suspension containing approximately 4.9 × 10(8) bone marrow mononuclear cells into the infarct-related artery after successful PCI.

Results: Compared to control and group C patients, group A and B patients had a significantly higher absolute increase in left ventricular ejection fraction from baseline to 12 months (change: 3.4 ± 5.7 % in control, 7.9 ± 4.9 % in group A, 6.9 ± 3.9 % in group B, 4.7 ± 3.7 % in group C), a greater decrease in left ventricular end-systolic volumes (change: -6.4 ± 15.9 ml in control, -20.5 ± 13.3 ml in group A, -19.6 ± 11.1 ml in group B, -9.4 ± 16.3 ml in group C), and significantly greater myocardial perfusion (change from baseline: -4.7 ± 5.7 % in control, -7.8 ± 4.5 % in group A, -7.5 ± 2.9 % in group B, -5.0 ± 4.0 % in group C). Group A and B patients had similar beneficial effects on cardiac function (p = 0.163) and left ventricular geometry (left ventricular end-distolic volume: p = 0.685; left ventricular end-systolic volume: p = 0.622) assessed by echocardiography, whereas group C showed similar results to those of the control group. Group B showed more expensive care (p < 0.001) and longer hospital stays during the first month after emergency PCI (p < 0.001) than group A, with a similar improvement after repeat cardiac catheterization following emergency PCI.

Conclusion: Cell therapy in acute myocardial infarction patients that is given within 24 hours is similar to 3-7 days after the primary PCI.

Trial registration: NCT02425358 , registered 30 April 2015.

Figures

Fig. 1
Fig. 1
Flow chart outlining the study protocol. A total of 104 acute myocardial infarction (AMI) patients were enrolled and randomly assigned to four groups in this trial depending on bone marrow mononuclear cell (BMNC) transplantation after primary percutaneous coronary intervention (PCI). Before discharge, the patients underwent echocardiography and single photon emission computed tomography (SPECT) and the data were collected as baseline. At the 6-month follow-up, patients underwent angiography. The SPECT and echocardiography data were recorded at 6 and 12 months. Group A BMNC infusion within 24 hours after PCI; group B BMNC infusion at 3–7 days after PCI; group C BMNC infusion at 7–30 days after PCI; LV, left ventricular; LVEF left ventricular ejection fraction
Fig. 2
Fig. 2
Left ventricular ejection fraction at baseline and at 12 months after myocardial infarction. Left ventricular ejection fraction (LVEF) determined by echocardiography initially and at 12-month follow-up in the four groups. Compared with baseline, global LVEF in the four groups was significantly increased on echocardiography at 12 months. Compared with the control group (CON), the absolute change in LVEF from baseline to 12 months was significantly higher in groups A and B, but not in group C. group A bone marrow mononuclear cell (BMC) infusion within 1 day after percutaneous coronary intervention (PCI); group B BMC infusion at 3–7 days after PCI; group C BMC infusion at 7–30 days after PCI

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