Cell administration routes for heart failure: a comparative re-evaluation of the REGENERATE-DCM and REGENERATE-IHD trials

Aims: Given the logistical issues surrounding intramyocardial cell delivery, we sought to address the efficacy of the simpler, more accessible intracoronary route by re-evaluating REGENERATE-DCM and REGENERATE-IHD (autologous cell therapy trials for heart failure; n = 150). Methods: A retrospective statistical analysis was performed on the trials' combined data. The following end points were evaluated: left ventricular ejection fraction (LVEF), N-terminal pro brain natriuretic peptide concentration (NT-proBNP), New York Heart Association class (NYHA) and quality of life. Results: This demonstrated a new efficacy signal for intracoronary delivery, with significant benefits to: LVEF (3.7%; p = 0.01), NT-proBNP (median -76 pg/ml; p = 0.04), NYHA class (48% patients; p = 0.01) and quality of life (12 +/- 19; p = 0.006). The improvements in LVEF, NYHA and quality of life scores remained significant compared to the control group. Conclusion: The efficacy and logistical simplicity of intracoronary delivery should be taken into consideration for future trials. Plain language summary Trials of cell therapy for heart failure have not clearly identified the best method to deliver the cells to the heart. A small proportion of these studies have used the intracoronary method (which infuses the cells into the heart's arteries) as it was thought to be less effective. However, this is the simplest method and uses widely accessible techniques and equipment. By combining data from two previous heart failure trials, we sought to look for an efficacy signal for the intracoronary method in a larger sample size. We found that the intracoronary route demonstrated improvements in patients' heart function and symptoms. Although it may require a larger number of patients to show efficacy, this signal, alongside the intracoronary route's relative simplicity, should be taken into consideration when future trials of cell therapy for heart failure are planned. Tweetable abstract The efficacy and logistical simplicity of intracoronary delivery should be considered when planning cell therapy trials.