Comparison of Transendocardial and Intracoronary CD34 ⁺ Cell Transplantation in Patients With Nonischemic Dilated Cardiomyopathy

Abstract

A fter an acute myocardial injury, recruitment of stem cells may significantly influence the repair process. Studies have shown that serum stromal-derived factor-1 (SDF-1) levels rise significantly after an acute myocardial infarction, which increases homing of stem cells to the damaged tissue. 1 In contrast, in patients with chronic heart failure, local homing signals may be less intense. This difference is especially pronounced in patients with nonischemic dilated cardiomyopathy (DCM), which involves significant downregulation of several homing factors, including SDF-1 2 . The importance of homing is especially prominent when considering stem cell therapy in patients with heart failure.3 In a recent study of patients with nonischemic DCM, we demonstrated that the response to intracoronary CD34 + cell therapy is dependent on the degree of myocardial cell retention. 4 These findings suggest that the efficacy of intracoronary cell therapy may be limited by the number of cells retained in the myocardium.Compared with intracoronary delivery, intramyocardial (IM) cell delivery is consistently associated with higher myocardial cell retention rates in both early and late phases after acute myocardial infarction. 5,6 In preclinical models of ischemic heart failure, IM injection of higher doses of bone marrow mononuclear cells was associated with incremental benefit, 7 and late cardiac functional recovery was more prominent in Background-In an open-label blinded study, we compared intracoronary and transendocardial CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy. Methods and Results-Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34 + cell delivery. In both groups, CD34 + cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34 + cells was also comparable (105±31×10 6 in the transendocardial group versus 103±27×10 6 in the intracoronary group, P=0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2±4.8%) than in the intracoronary group (4.4±1.2%, P<0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1±4.3%) than in the intracoronary group (+4.2±2.3%, P=0.03). The same pattern was observed...

Imaging Cardiac Stem Cell Transplantation Using Radionuclide Labeling Techniques: Clinical Applications and Future Directions

“…When direct intramuscular/ subendocardial injection of stem cells is used under the guidance of electrophysiological lv mapping, using noGa ® xP Cardiac navigation system (Biologics delivery systems, irwindale, Ca), significantly higher stem cell retention rates are achieved (up to approximately 10%). 26 our findings confirm those from preclinical models that directly compared different methods of stem cell delivery, showing the direct intramuscular route to be superior.…”

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CD34+ Cell Transplantation Improves Right Ventricular Function in Patients with Nonischemic Dilated Cardiomyopathy

“…Disease progression in DCM affects both ventricles, and right ventricular (RV) dysfunction represents an important adverse prognostic factor 2, 3. Although several clinical trials have demonstrated that left ventricular dysfunction in DCM can be partially reversed by cell therapy 4, 5, 6, 7, no study to date investigated the effects of this approach on RV. Thus, the aim of the present study was to investigate the effects of transendocardial CD34 + cell therapy on RV function in patients with DCM.…”