Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure

• Published in: Circulation (New York, N.Y.) N.Y.), 2003-05, Vol.107 (18), p.2294-2302
• Main Authors: PERIN, Emerson C, DOHMANN, Hans F. R, SILVA, Guilherme V, BELEM, Luciano, VIVACQUA, Ricardo, RANGEL, Fernando O. D, ESPORCATTE, Roberto, GENG, Yong J, VAUGHN, William K, ASSAD, Joao A. R, MESQUITA, Evandro T, WILLERSON, James T, BOROJEVIC, Radovan, SILVA, Suzana A, SOUSA, Andre L. S, MESQUITA, Claudio T, ROSSI, Maria I. D, CARVALHO, Antonio C, DUTRA, Helio S, DOHMANN, Hans J. F
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Applied cell therapy and gene therapy; Biological and medical sciences; Bone Marrow Transplantation; Cardiac Catheterization; Coronary Angiography; Coronary Circulation; Endocardium; Female; Follow-Up Studies; Heart Failure - diagnosis; Heart Failure - therapy; Humans; Injections; Male; Medical sciences; Middle Aged; Myocardial Ischemia - diagnosis; Myocardial Ischemia - therapy; Neovascularization, Physiologic; Stem Cell Transplantation - adverse effects; Tomography, Emission-Computed, Single-Photon; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous; Ventricular Function, Left
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000070596.30552.8b

This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage > or =6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (P=0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P=0.003) and a reduction in end-systolic volume (P=0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (P