Enabling Technologies for Cell-Based Clinical Translation REVIVE Trial: RetrogradeDelivery of Autologous Bone Marrow in Patients With Heart Failure

Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patientswith either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). Thiswas a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjectswere randomized to the ischemicBMACgroupand6 to the ischemic control group. Similarly, 24 subjectswere randomized to thenonischemicBMACgroupand6 to thenonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receivingBMACdemonstrated significant improvement comparedwithbaseline, from25.1%at screening to 31.1% at 12months (p = .007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p = .035). Theend-systolic diameterdecreased significantly in thenonischemicBMACgroup from55.6 to50.9mm (p = .020). Retrograde BMACdelivery is safe. All patients receiving BMACexperienced improvements in left ventricularejection fraction, butonly thosewithNIHFshowed improvements in left ventricular endsystolic diameter andB-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1021–1027