Rationale and design of a prospective, randomised study of retrograde application of bone marrow aspirate concentrate (BMAC) through coronary sinus in patients with congestive heart failure of ischemic etiology (the RETRO study)

Abstract

Background: Heart failure (HF) is a major chronic illness and results in high morbidity and mortality. The most frequent cause of HF with reduced ejection fraction (HFREF) is coronary artery disease (CAD). Although revascularisation of ischemic myocardium lead to improvements in myocardial contractility and systolic function, it cannnot restore the viability of the already necrotic myocardium.

Methods/design: The aim of our prospective randomised study is to assess the efficacy of the retrograde application of non-selected bone marrow autologous cells concentrate (BMAC) in patients with HFREF of ischemic aetiology. The evaluated preparation is concentrated BMAC, obtained using Harvest SmartPReP2 (Harvest Technologies, Plymouth, MA, USA). The study population will be a total of 40 patients with established CAD, systolic dysfunction with LV EF of ≤40% and HF in the NYHA class 3. Patients have been on standard HF therapy for 3 months and in a stabilised state for at least 1 month, before enrolling in the clinical study. Patients will be randomised 1:1 to either retrograde BMAC administration via coronary sinus or standard HF therapy. The primary end-points (left ventricular end-systolic and end-diastolic diameters [LVESd/EDd] and volumes [LVESV/EDV] and left ventricular ejection fraction [LV EF]) will be assessed by magnetic resonance imaging. The follow-up period will be 12 month.

Discussion: The application of bone marrow stem cells into affected areas of the myocardium seems to be a promising treatment of ischemic cardiomyopathy. The Harvest BMAC contains the entire population of nuclear cells from bone marrow aspirates together with platelets. The presence of both platelets and additional granulocytes can have a positive effect on the neovascularisation potential of the resulting concentrate. Our assumption is that retrograde administration on non-selected BMAC via coronary sinus, due to the content of platelets and growth factors, might improve left ventricular function and parameters compared to standard HF therapy. Furthermore, it will be associated with improved exercise tolerance in the six-minute corridor walk test and an improvement in the life quality of patients without increasing the incidence of severe ventricular arrythmias.

Trial registration: (ClinicalTrials.gov; https://ichgcp.net/clinical-trials-registry/NCT03372954" title="See in ClinicalTrials.gov">NCT03372954).

Conflict of interest statement

Ethics approval and consent to participate

The study protocol complied with the Declaration of Helsinki and was approved by the Ethics Committee of University Hospital Ostrava, Czech Republic.

Written informed consent to participate will be obtained from each patient before enrollment in the study.

The study was registered at Consent for publication

Written informed consent to publish will be obtained from each patient before enrollment in the study.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

CONSORT study flow diagram