Combined delivery of bone marrow-derived mononuclear cells in chronic ischemic heart disease: rationale and study design

Abstract

Background: Treatment with bone marrow-derived mononuclear cells (BM-MNC) may improve left ventricular (LV) function in patients with chronic ischemic heart disease (IHD). Delivery method of the cell product may be crucial for efficacy.

Hypothesis: We aimed to demonstrate that the combination of intramyocardial and intracoronary injection of BM-MNC is safe and improves LV function in patients with chronic IHD.

Methods: After a safety/feasibility phase of 10 patients, 54 patients will be randomly assigned in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive either exclusively intramyocardial injection or a combination of intramyocardial and intracoronary injection of autologous BM-MNC. Left ventricular function as well as scar size, transmural extension, and regional wall-motion score will be assessed by cardiac magnetic resonance imaging studies at baseline and after 6 months. The primary endpoint is the change in global LV ejection fraction by cardiac magnetic resonance from 6 months to baseline.

Results: The results, it is hoped, will have important clinical impact and provide essential information to improve the design of future regenerative-medicine protocols in cardiology.

Conclusions: As cell delivery may play an important role in chronic IHD, we aim to demonstrate feasibility and efficacy of a combined cell-delivery approach in patients with decreased LV function.

Trial registration: ClinicalTrials.gov NCT01666132.

Figure 1

Flow chart of the study design. Abbreviations: BM‐MNC, bone marrow–derived mononuclear cells; CCS, Canadian Cardiovascular Society; EF, ejection fraction; i.c., intracoronary; NYHA, New York Heart Association; STEMI, ST‐segment elevated myocardial infarction.

Figure 2

Example of a unipolar voltage map including injection points. In this patient without any overt ischemia at cardiac magnetic resonance. The target zone for intramyocardial injection was defined as mainly the border zone of scar, represented by red and denoting myocardium with low unipolar voltage. Blue and violet represent myocardium with normal voltage, corresponding to viable tissue. Yellow/green denotes myocardium with a unipolar voltage between 5 mV and 8 mV, corresponding to viable but ischemic tissue. The brown points denote the effective injection points, trying to target the border zone of the extensive anterolateral scar and avoiding the apical regions.