Objective: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. Methods and Results:

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...

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Aim To evaluate the effect of once‐weekly subcutaneous semaglutide 1.0 mg on the late digestive period of gastric emptying (GE) after ingestion of a standardized solid test meal by using technetium scintigraphy, the reference method for this purpose. Methods We conducted a single‐blind, placebo‐controlled trial in 20 obese women with polycystic ovary syndrome (PCOS; mean [range] age 35 [32.3‐40.8] years, body mass index 37 [30.7‐39.8] kg/m2) randomized to subcutaneous semaglutide 1.0 mg once weekly or placebo for 12 weeks. GE was assessed after ingestion of [99mTc] colloid in a pancake labelled with radiopharmaceutical by scintigraphy using sequential static imaging and dynamic acquisition at baseline and at Week 13. Estimation of GE was obtained by repeated imaging of remaining [99mTc] activity at fixed time intervals over the course of 4 hours after ingestion. Results From baseline to the study end, semaglutide increased the estimated retention of gastric contents by 3.5% at 1 hour, 25.5% at 2 hours, 38.0% at 3 hours and 30.0% at 4 hours after ingestion of the radioactively labelled solid meal. Four hours after ingestion, semaglutide retained 37% of solid meal in the stomach compared to no gastric retention in the placebo group (P = 0.002). Time taken for half the radiolabelled meal to empty from the stomach was significantly longer in the semaglutide group than the placebo group (171 vs. 118 min; P < 0.001). Conclusion Semaglutide markedly delayed 4‐hour GE in women with PCOS and obesity.