Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial

Abstract

Aims: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability.

Methods and results: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed.

Conclusion: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy.

Clinical trial registration information: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1

Patient enrolment and outcomes. PCI: percutaneous coronary intervention; LVEF: left ventricular ejection fraction; SPECT: single-photon-emission computed tomography; RNA: radionuclide angiography; MRI: magnetic resonance imaging; FU: follow-up.

Figure 2

SPECT myocardial viability at baseline and 3 months after myocardial infarction. (A) Cardiac polar map example of myocardial viability improvement using SPECT from baseline to 3 months. Baseline evaluation revealed a large viability defect in the ventricular septum from the apex to the base. Evaluation, after 3 months, showed an improvement in myocardial viability of the septum from the apex to the base segments. (B) percentage of patients in the control and BMC groups with an increase of ≥2/17 viable segments. (C) Increase in viable segment number/patient (median with interquartile ranges). *Adjusted for diabetes and time to revascularization (≤12 or >12 h).

Figure 3

Multivariate logistic regression analysis for improvement of at least 2 non-viable segments becoming viable (n = 77). OR: Odds ratio; CI: Confidence interval; p: p-value.

Figure 4

Evaluation of left ventricular ejection fraction (LVEF) and scar extent at baseline and 3 months. (A) LVEF evaluated by radionuclide angiography. (B) LVEF evaluated by MRI. (C) Regional wall motion score index (WMSI) on cardiac MRI. (D) Scar extent evaluated by MRI.