Safety and Feasibility of Intramyocardial Versus Intracoronary Delivery of Autologous Cell Therapy in Advanced Heart Failure: The REGENERATE-IHD Pilot Study

Abstract

Aim: This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. Methods & results: The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. Conclusion: Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.

Keywords::

• autologous bone marrow-derived stem/progenitor cells
• chronic ischemic heart failure
• granulocyte-colony stimulating factor
• intracoronary delivery
• intramyocardial delivery

Acknowledgements

The authors would like to acknowledge contribution of the following members of the trial team: C Davies, M Flather, D Hipperson, A Kapur, C Knight, T Koh, M Preston, S Minger, L Roberts, A Timmis and M Westwood.

Financial & competing interests disclosure

This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research. This work was funded by unrestricted grants from Heart Cells Foundation, Barts & The London Charity, Chugai Pharma UK and Cordis Corporation. C Yeo is currently funded by the Medical Research Council (PhD studentship). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research. This work was funded by unrestricted grants from Heart Cells Foundation, Barts & The London Charity, Chugai Pharma UK and Cordis Corporation. C Yeo is currently funded by the Medical Research Council (PhD studentship). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.