PURPOSE: The objective is to determine safety and efficacy of intramyocardial angiogenic cell precursors (ACPs) injection for cardiomyopathy.
METHODS: Between May 2005 and March 2007, 92 consecutive patients underwent ACPs injection. Forty four were dilated cardiomyopathy (DCM) and 48 were ischemic cardiomyopathy (ICM). Mean age was 58.6 ± 12.5 years. The ACPs are isolated and cultured from the patient's own blood. ACPs expressed CD34, CD133, KDR, Tie-2, CD144, von Willebrand factor, CD31Bright. The number of cells prior to injection was 24.2 ± 17.1 million cells. Cells were injected into all areas of left ventricle in DCM and were injected into non-viable myocardium and hypokinetic segments in ICM. Combined coronary artery surgery and ACPs injection were performed in 37.5% of ICM.
RESULTS: There was no new ventricular arrhythmia. 30-day mortality rate was 4.5 % (2/44) and 4.2% (2/48) in DCM and ICM, respectively. NYHA class improved from 2.9±0.7 to 1.9±0.9 at 223.2±133.5 days (P<0.001) in DCM and improved from 2.9±0.6 to 2.0±0.8 at 236.4±139.7 days (P<0.001) in ICM. LVEF increased from 25.0±8.1% to 29.5±11.8% at 154.9±113.5 days (P=0.02) in DCM and increased from 24.5±7.3% to 31.1±11.1% at 180.8±111.8 days (P<0.001) in ICM. There was no significant difference in changes of LVEF between combined coronary surgery plus ACPs injection (+6.3±9.7 points percent) and ACPs injection alone (+6.7±4.1 points percent) in ICM. Quality of life postoperatively evaluated at 3 months has significantly improved for physical function and general health domains (P = 0.047 and < 0.001, respectively) in DCM. For ICM, role-physical and general heath domains (P = 0.048 and 0.012, respectively) were improved after the procedure. Myocardial infarction area had decreased by 20±16% at a 5± 2 month follow up in ICM.
CONCLUSION: Intramyocardial ACPs injection is feasible and safe in both DCM and ICM. The NYHA, quality of life and ejection fraction had significantly improved in both DCM and ICM.
CLINICAL IMPLICATIONS: Large-scale placebo-controlled studies are needed to confirm that use of intramyocardial ACPs injection in cardiomyopathy is efficacious.
DISCLOSURE: Permyos Ruengsakulrach, No Financial Disclosure Information; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The “Angiogenic Cell Precursors (ACPs)” developed by TheraVitae Co. Ltd. The ACPs are obtained from the patient own blood therefore no immunological concerned. The multipotent progenitor cells are isolated from the peripheral blood, rich in CD45, CD31Bright, CD34+,CD45-/Dim and CD34Bright cells. The cells at a concentration of 1.5-3.0 x 106 cells/ml are then cultured with vascular endothelial growth factor (VEGF, R&D Systems, Minneapolis, MN, USA) and 5 IU/ml heparin (Kamada, Beit-Kama, Israel). The final product “Angiogenic Cell Precursors” expressed CD34, CD133, KDR, Tie-2, CD144, von Willebrand factor, CD31Bright, concomitant binding of Ulex-Lectin and uptake of acetylated low density lipoprotein (Ac-LDL), secreted interleukin-8, vascular endothelial growth factor and angiogenin and formed tube-like structures in vitro.