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Title: Differential Effects of Progenitor Cell Populations on Left Ventricular Remodeling and Myocardial Neovascularization After Myocardial Infarction
Topic: General Cardiology Date Posted: 6/4/2010 Author(s): Dubois C, Liu X, Claus P, et al. Citation: J Am Coll Cardiol 2010;55:2232-2243. Clinical Trial: No Study Question: What is the effect of late-outgrowth endothelial progenitor cells (EPCs) versus mesenchymal stem cells (MSCs) on left ventricular (LV) recovery following myocardial infarction (MI) in pigs? Methods: In a blinded, randomized study, autologous late-outgrowth EPCs (n = 10, 34 ± 22 x 106 CD29-31-positive, capable of tube formation), allogeneic green fluorescent peptide-labeled MSCs (n = 11, 10 ± 2 x 106 CD29-44-90-positive, capable of adipogenic and osteogenic differentiation), or vehicle (CON) (n = 12) were infused in the circumflex artery 1 week after acute MI. Systolic function (ejection fraction), LV end-diastolic and end-systolic volumes, and infarct size were assessed with magnetic resonance imaging at 1 week and 7 weeks. Cell engraftment and vascular density were evaluated on postmortem sections. Results: Recovery of LV ejection fraction from 1 to 7 weeks was similar between groups, but LV remodeling markedly differed with a greater increase of LV end-systolic volume in MSC and CON (+11 ± ml/m2 and +7 ± 8 ml/m2 vs. -3 ± 11 ml/m2 in EPC, respectively, p = 0.04), and a similar trend was noted for LV end-diastolic volume (p = 0.09). After EPC, infarct size decreased more in segments with >50% infarct transmurality (p = 0.02 vs. MSC and CON) and was associated with a greater vascular density (p = 0.01). Late outgrowth EPCs secrete higher levels of the pro-angiogenic placental growth factor (733 [277-1,214] pg/106 vs. 59 [34-88] pg/106 cells in MSC, p = 0.03) and incorporate in neovessels in vivo. Conclusions: Infusion of late-outgrowth EPCs after acute MI improves MI remodeling via enhanced neovascularization, but does not mediate cardiomyogenesis. Perspective: Most preclinical and clinical studies using cell-based therapies for MI have failed to show meaningful improvement in LV function. Replacement of infarcted myocardium with functional cardiomyocytes does not appear to occur with the cell-based strategies used to date. However, minor effects on LV remodeling may occur, especially in the setting of large MIs, due to ill-defined paracrine effects. Similarly, the current study shows only minor effects on LV remodeling with EPCs, but does show that late outgrowth EPCs can incorporate into neovessels and promote their growth. These pro-angiogenic effects may be potentially useful in the chronic setting in patients with refractory ischemic vascular disease. Daniel T. Eitzman, M.D., F.A.C.C. Title: Characterization of the Arrhythmogenic Substrate in Ischemic and Nonischemic Cardiomyopathy: Implications for Catheter Ablation of Hemodynamically Unstable Ventricular Tachycardia Topic: Arrhythmias Date Posted: 6/4/2010 Author(s): Nakahara S, Tung R, Ramirez RJ, et al. Citation: J Am Coll Cardiol 2010;55:2355-2365. Clinical Trial: No Study Question: How useful are late potentials (LPs) for guiding radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in patients with nonischemic cardiomyopathy (NICM) versus ischemic cardiomyopathy (ICM)? Methods: Thirty-three patients (mean age 64 years, mean ejection fraction 24%) underwent detailed electroanatomical mapping and catheter ablation of VT. Sixteen patients had NICM and 17 patients had ICM. Endocardial mapping was performed in all patients and epicardial mapping was performed in 58%. Very late potentials (vLPs) were defined as LPs occurring >100 ms after the end of the QRS. Catheter ablation was guided by pace mapping and LPs within and around dense scars. Results: There were fewer endocardial LPs in patients with NICM (median 9.5/patient) than in patients with ICM (median 32/patient). Epicardial LPs were equally prevalent in NICM and ICM, but epicardial vLPs were less prevalent in NICM (median 4.5/patient vs. 29/patient). The acute success rate of RFCA was 44% in patients with NICM compared to 82% in patients with ICM, and efficacy at a mean of 15 months of follow-up was 50% compared to 82% in the two groups, respectively. Conclusions: LPs are not as useful for identifying VT ablation sites in NICM as in ICM. Perspective: LPs are generated by slow or delayed conduction in surviving myocardial fibers surrounded by fibrosis. These myocardial fibers often are the substrate for scar-related VT. Compared to ICM, scars in NICM are less confluent and less often endocardial. The findings of this study demonstrate that a VT mapping strategy guided by identification of LPs is much less likely to be feasible in NICM than in ICM. Fred Morady, M.D., F.A.C.C. |