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Cardiac stem cells (CSCs) were known to secrete diverse paracrine factors leading to functional improvement and beneficial left ventricular remodeling via activation of the endogenous pro-survival signaling pathway. However, little is known about the paracrine factors secreted by CSCs and their roles in cardiomyocyte survival during hypoxic condition mimicking the post-myocardial infarction environment. We established Sca-1+/CD31- human telomerase reverse transcriptase-immortalized CSCs (Sca-1+/CD31- CSCs(hTERT)), evaluated their stem cell properties, and paracrine potential in cardiomyocyte survival during hypoxia-induced injury. Sca-1+/CD31- CSCs(hTERT) sustained proliferation ability even after long-term culture exceeding 100 population doublings, and represented multi-differentiation potential into cardiomyogenic, endothelial, adipogenic, and osteogenic lineages. Dominant factors secreted from Sca-1+/CD31- CSCs(hTERT) were EGF, TGF-β1, IGF-1, IGF-2, MCP-1, HGF R, and IL-6. Among these, MCP-1 was the most predominant factor in Sca-1+/CD31- CSCs(hTERT) conditioned medium (CM). Sca-1+/CD31- CSCs(hTERT) CM increased survival and reduced apoptosis of HL-1 cardiomyocytes during hypoxic injury. MCP-1 silencing in Sca-1+/CD31- CSCs(hTERT) CM resulted in a significant reduction in cardiomyocyte apoptosis. We demonstrated that Sca-1+/CD31- CSCs(hTERT) exhibited long-term proliferation capacity and multi-differentiation potential. Sca-1+/CD31- CSCs(hTERT) CM protected cardiomyocytes from hypoxic injury partly via MCP-1-dependent mechanism. Thus, they are valuable sources for in vitro and in vivo studies in the cardiovascular field.

Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34- mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.

Results: Decreases from baseline in total cholesterol levels (-22.7±34.3 mg/dL vs. 0.0±34.7mg/dL, p

Background Long-term clinical implications of embryonic stem cell markers such as Oct4 and Nanog have not been investigated in ST-elevation myocardial infarction (STEMI) patients. The aim of this study was to investigate the effects of early peripheral mobilization of stem cells with Oct4 and Nanog gene expression on major adverse cardiovascular events (MACEs) in patients with STEMI during a 4-year follow-up. Methods Peripheral blood mononuclear cells (PBMCs) were isolated on days 0, 1 and 7 from patients with STEMI (n=40) and healthy controls (n=20). The numbers of CD34+, CD117+, CD133+ and c-met+ stem cells were measured by flow-cytometry. Oct4 and Nanog gene expressions were analyzed by real-time PCR. MACEs such as non-fatal MI, death, stroke, target lesion and revascularization were observed. Results MACEs were significantly lower in patients with Oct4 gene expression≥1.13 and Nanog gene expression≥1.20 at admission. The numbers of CD34+, CD117+, CD133+ and c-met+ cells within 7days after STEMI did not show significant differences in patients with or without MACE. Level of anti-inflammatory marker such as IL-10 was significantly higher within 7days following STEMI in patients without MACE. Inflammatory and angiogenic markers such as CRP, IL-6, SCF, SDF-1α, and VEGF did not show significant differences in patients with or without MACE. Conclusion mRNA levels of pluripotent embryonic stem cell markers such as Oct4 and Nanog were significantly higher in STEMI patients without MACEs during a 4-year follow-up. Baseline Oct4 and Nanog gene expression levels could be used as predictors of MACE in STEMI patients.

The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6-73) vs 25 (7.3-105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7-28.2) vs 5.9 (1.8-14.6) μmol/ml, p < 0.05; and 5.8 (2.6-14.4) vs 4.2 (0.7-7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.

A 68-year-old previously healthy man presented with chest discomfort. He was diagnosed with angina pectoris. Chest radiography showed multiple rice-like subcutaneous calcifications (Fig. 1A). The patient confirmed that he had observed these subcutaneous nodules all over his body, which showed no change in number and size for over 10 years (Fig. 2A). He lived in a rural area where pigs are raised and was fond of consuming pork; further, he confirmed having no past history of seizures and tuberculosis. Total serum immunoglobulin E level was 19.1 IU/mL. Blood enzyme-linked immunosorbent assay for Taenia solium was negative for cysticercosis IgG antibodies. Stool examination showed normal results. For evaluation of neurocysticercosis, brain computed tomography scan was performed, and a few dot-like calcified lesions in the brain parenchyma was observed (Fig. 1B). Femur radiography showed numerous oval-shaped calcifications in the thigh soft tissue (Fig. 1C). Analysis of subcutaneous tissue biopsy specimen from the upper left arm showed a well demarcated encapsulated calcific nodule in intramuscular area (Fig. 2B and 2C). On the basis of the above results, we made a final diagnosis of disseminated cysticercosis. However, the patient presented only palpable subcutaneous nodules, and the diagnosis of disseminated cysticercosis was an incidental finding. No antiparasitic therapy was initiated, and the patient showed no complication at 7 months after diagnosis. Figure 1 (A) Chest radiography showing multiple rice-like subcutaneous calcifications. (B) Brain computed tomography showing a few dot-like calcified lesions in the brain parenchyma. (C) Femur radiography showing numerous oval-shaped calcifications in the soft ... Figure 2 (A) Subcutaneous nodules were observed all over his body, but had not changed in number or size for more than 10 years. (B, C) Subcutaneous dystrophic calcification was demonstrated in the subcutaneous tissue biopsy specimen from the upper left arm (B: ...

To identify potential downstream targets of Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells, global gene expression profiles in Nanog small interfering RNA (siRNA)-transfected P19 EC stem cells were performed using cDNA, 60-mer, and 30-mer microarray platforms. The putative Nanog target genes identified by Nanog silencing were verified using reverse transcription-polymerase chain reaction after Nanog overexpression. Downregulation of Nanog in P19 cells resulted in reduction of pluripotency markers, such as Fgf4, Klf2, Mtf2, Oct-4, Rex1, Sox1, Yes, and Zfp143, whereas overexpression of Nanog in P19 cells reversely upregulated their expression. However, expressions of pluripotency markers Cripto, germ cell nuclear factor, Sox2, and Zfp57 as well as leukemia inhibitory factor (LIF)/Stat3 pathway molecules LIF, IL6st, and Stat3 were not affected after 48 h transfection with Nanog siRNA or construct. Nanog silencing also downregulated expression of molecules involved in the p53- and cell cycle-signaling pathway (Atf3, Jdp2, Cul3, Hist1hic, and Bcl6), whereas expression of E2f1, Tob1, Lyn, and Smarcc1 was upregulated by Nanog silencing. Expressions of cyclins D1, D2, D3, and E1 as well as cyclin-dependent kinase (Cdk) 1 and Cdk6 were downregulated by Nanog silencing in P19 cells, whereas Nanog overexpression reversely increased their expressions. Taken together, examination of global transcriptional changes after Nanog silencing followed by verification by Nanog overexpression has revealed new molecules involved in the maintenance of self-renewal and in the regulation of the p53- and cell cycle-pathway of P19 cells.

Background Clopidogrel resinate is a resinate complex of (+)-clopidogrel optical isomer, wherein the (+)-clopidogrel isomer binds to a water-soluble cation exchange resin via sulfonic acid groups. It was approved by the Korean Food and Drug Administration on the basis of a Phase I study that demonstrated the bioequivalence of clopidogrel resinate and clopidogrel bisulfate. However, there are no available data regarding efficacy and tolerability in patients with vascular disease. Objective The goal of this study was to investigate the antiplatelet efficacy and tolerability of clopidogrel resinate in patients with coronary heart disease (CHD) or CHD-equivalent risks. Methods This study was a Phase IV, randomized, double-blind, double-dummy, parallel-group, noninferiority trial. We prospectively recruited patients in 10 centers between March 2008 and July 2008. Patients who had documented CHD or CHD-equivalent risks were randomly assigned to 1 of 3 groups: group A, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate placebo; group B, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate (75 mg); or group C, aspirin (100 mg) + clopidogrel bisulfate (75 mg) + clopidogrel resinate placebo. The primary outcome was the percent P2Y 12 inhibition after medication, assessed by using a point-of-care assay. If the 1-sided 90% upper confidence limit for the difference was less than the prespecified delta value (–5.7), clopidogrel resinate would be considered noninferior to clopidogrel bisulfate. The secondary outcome, the prevalence of adverse events (AEs) associated with study medications, was assessed at each visit by direct interview. Results A total of 314 patients (mean [SD] age, 62.2 [9.0] years; male 63.7%; weight, 67.3 [13.6] kg [range, 45–102 kg]; all Asian) were enrolled, and 287 patients finished the study (group A, n=97; group B, n=90; and group C, n=100). Eight patients took no study medications and were excluded from the tolerability and efficacy analyses. Nineteen patients discontinued the study because of protocol violation (n = 15), adverse events (n = 3), or voluntary withdrawal (n = 1) and were excluded from the efficacy analysis. There were no significant differences in baseline clinical characteristics among the groups except for the frequency of a history of CHD (group A, 85.4%; group B, 73.0%; and group C, 88.3%; P = 0.01). Patients treated with either type of clopidogrel showed significant inhibition (mean [SD]) of P2Y 12 (group A, –5.9% [15.1%]; group B, 23.4% [21.9%]; and group C, 19.5% [23.8%]; P 12 did not exceed the predetermined value for inferiority ( P for noninferiority, 0.02; 90% CI, −0.9 to 10.3). In the tolerability analysis, there was no mortality during the study period and no significant differences between groups in the frequency of AEs and serious AEs (AEs: group A, 33.0%; group B, 26.0%; and group C, 23.3% [ P = 0.27]; serious AEs: group A, 1.0%; group B, 3.0%; and group C, 1.0% [ P = 0.42]). One patient in group B underwent coronary stent implantation for treatment of stable angina. Conclusions In this small, selected Asian patient population, differences in the platelet inhibition efficacies of clopidogrel resinate and clopidogrel bisulfate did not exceed the predetermined limits for noninferiority. The differences in tolerability between the 2 drugs did not reach statistical significance. ClinicalTrials.gov identifier: NCT00947843.

Objective Telmisartan is a peroxisome proliferator-activated receptor-γ activator with potent anti-inflammatory and antiatherogenic effects. The authors compared the effects of telmisartan and valsartan on neointima volume, atherosclerosis progression and brachial-ankle pulse wave velocity (baPWV) after stenting in hypertensive type 2 diabetes. Design This was a prospective, randomised, 8-month follow-up study that included patients with significant coronary stenosis who received telmisartan (n=36) or valsartan (n=37). Setting University hospital. Main outcome measures Neointima volume and atherosclerosis progression 10 mm proximal and distal to the stented segment were analysed using repeat intravascular ultrasonography. baPWV and inflammatory markers such as interleukin 6, tumour necrosis factor α, C-reactive protein and adiponectin were compared. Results Neointima volume at 8 months was significantly lower in the telmisartan group than the valsartan group (1.9±1.0 vs 2.6±1.4 mm 3 /1 mm, p=0.007, respectively). Total plaque volumes 10 mm proximal (7.1±1.5 vs 7.8±1.6 mm 3 /1 mm, p=0.032, respectively) and distal (3.5±1.4 vs 4.1±1.3 mm 3 /1 mm, p=0.028, respectively) to the stent were significantly lower in the telmisartan group than the valsartan group at 8 months. The decrease from baseline in baPWV was significantly greater in the telmisartan group than the valsartan group (−52±104 vs 30±113 cm/s, p=0.002, respectively). The increase from baseline in adiponectin levels and the decreases from baseline in interleukin 6 and tumour necrosis factor α levels were significantly greater in the telmisartan group at 8 months. Retinol-binding protein-4, homeostasis model of assessment index, hemoglobin A 1c and low-density lipoprotein cholesterol levels decreased significantly in both groups without differences in changes from baseline between the two groups. Conclusions Telmisartan reduced neointima volume; atherosclerosis progression 10 mm proximal and distal to the stented segment and baPWV independent of blood pressure, glucose and lipid control in hypertensive type 2 diabetes. Clinical trial no NCT00599885 (clinicaltrials.gov.)

Objective— To investigate the mechanistic basis underlying antirestenosis and the antiatherogenic effect of pioglitazone in patients with type 2 diabetes mellitus who were undergoing zotarolimus-eluting stent implantation. Methods and Results— Recent studies highlight the beneficial effect of pioglitazone in attenuating neointimal growth after stent implantation. Patients with coronary artery diseases were randomly assigned to pioglitazone (n=47) or placebo (n=47) after stent implantation. Pioglitazone significantly reduced neointimal hyperplasia within the stented lesion and attenuated total plaque burden in the in-segment regions of the stent, as assessed by intravascular ultrasonography at the 8-month follow-up. These changes were preceded by reduced circulating natural killer (NK) cells, diminished interleukin 6 and monocyte chemoattractant protein-1 levels, and downregulation of chemokine receptor 2 at 2 days after stent implantation; and an elevated interleukin 10 level at 10 days after implantation. Furthermore, the proliferation and migration of vascular smooth muscle cells were inhibited in the presence of pioglitazone-treated patient serum, demonstrating that the antiproliferative effects of pioglitazone occurred concurrently with its antiinflammatory action. Conclusion— Our data present early cellular and immunologic changes by pioglitazone that might have been associated with antirestenotic and antiatherogenic effects in diabetic patients. Inhibiting proinflammatory responses while promoting antiinflammatory circuits, together with an antiproliferative action, may, in part, account for the antirestenotic effect of pioglitazone by altering vascular remodeling processes in the early phase.

Background: Three-year follow-up of major adverse cardiovascular event (MACE) (death, nonfatal myocardial infarction, target lesion revascularization) and the predictors of MACEs in diabetic patients after sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) implantation have not been reported. Methods: Diabetic patients with de novo coronary lesions (169 patients with 190 lesions) were randomly assigned prospectively to either SES or PES. Results: Baseline characteristics were similar between the two groups. The rates of MACEs [5.9% (n = 5) in the SES vs. 9.5% (n = 8) in the PES Group, P = 0.374] and definite stent thrombosis [1.2% (n = 1) in the SES vs. 3.6% (n = 3) in the PES Group, P = 0.368] were similar in the two groups during the three-year follow-up. Multivariate logistic analysis showed that insulin treatment was the only independent predictor of MACE [odds ratio (OR) 8.60, 95% confidence interval (CI) 3.25–22.76, P < 0.001] and target vessel revascularization (TVR) (OR 9.50, 95% CI 3.07–29.44, P < 0.001) during the three-year follow-up. Conclusions: The rates of MACEs, TVR, and stent thrombosis during the three-year follow-up were similar in the SES and PES Groups. Insulin treatment was a main predictor of MACEs and TVR during the three-year follow-up after either SES or PES implantation. © 2009 Wiley-Liss, Inc.

This study was to evaluate the longitudinal and radial function of the left- and right-side ventricular septum (Ls and Rs) in patients with acute anterior myocardial infarction (AMI) by tissue Doppler imaging.Thirty patients with anterior ST-elevation AMI and revascularization and 20 age-matched normal subjects were enrolled as controls. The longitudinal and radial systolic tissue velocity (TV), strain rate (SR) and strain (ɛ) of both Ls and Rs were assessed.In normal, there were no significant differences of longitudinal TV, SR and ɛ between the Ls and Rs. The radial TV was same directed, but larger in Ls than Rs (P0.001). The radial SR and ɛ were positive values of Ls and negative values of Rs, but the degrees were similar in both sides. In AMI, longitudinal and radial TV were significantly decreased in both sides. However, longitudinal and radial SR and ɛ were significantly decreased in Ls only (P0.001 in all). Fourteen patients with AMI who showed no functional recovery had more reduced radial ɛ of Ls (3.9 ± 1.5% vs. 5.5 ± 2.1%, P = 0.02), but not longitudinal ɛ of Ls than the other 16 patients with recovery.This study showed the ventricular septum can be functionally differentiated the Ls from the Rs, which can be well demonstrated by SR imaging. The impairment of radial rather than longitudinal function of the Ls was related to no functional recovery.

Cilostazol, a phosphodiesterase III inhibitor, is known to have anti-proliferative activity. We investigated the effects of cilostazol 200 mg, in addition to aspirin 100 mg and clopidogrel 75 mg, on carotid intima-media thickness (IMT) progression during a 2-year follow-up period in patients with acute coronary syndrome (ACS) requiring stent implantation. Patients with ACS (n = 130) were randomly assigned to the cilostazol group (n = 64) or the control group (n = 66). Longitudinal images of left and right carotid IMT were measured at baseline, at 6, 12, and 24 months using a 10-MHz linear vascular probe. The primary endpoint was to compare the changes in maximum carotid IMT at 2 years. Other parameters such as inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and adiponectin] and bleeding risk were also compared. The carotid IMT showed no significant progression from baseline in the cilostazol group compared to significant progression in the control group at 12 months (0.78 ± 0.38 and 0.85 ± 0.41 mm, p = 0.034, respectively) and 24 months (0.82 ± 0.41 and 0.96 ± 0.39 mm, p = 0.022, respectively). Major bleeding (p = 1.00), minor bleeding (p = 0.68), and total bleeding rates (p = 0.74) were similar between the two groups during the 2-year follow-up. Decreases from baseline in IL-6 (−2.79 ± 2.83 and −2.14 ± 3.36 pg/ml, p = 0.010, respectively) and TNF-α (−2.81 ± 1.97 and −2.21 ± 2.68 pg/ml, p = 0.029, respectively) were significantly greater in the cilostazol group than the control group during the follow-up. Cilostazol treatment, with greater anti-inflammatory effect, inhibited the progression of carotid IMT without increasing the risk of bleeding in patients with ACS during the 2-year follow-up.

The effects of red ginseng extract on circulating angiogenic cell mobilization and improvement of microvascular integrity were evaluated in ST-elevation acute myocardial infarction (AMI) patients during 8-month follow-up. AMI patients (n = 50) were randomly assigned to the red ginseng group (3 g/day, n = 25) or the placebo group (n = 25) after coronary stenting. Coronary flow reserve (CFR) was measured at baseline and at 8 months with an intracoronary Doppler wire. Serial changes in the absolute numbers of circulating angiogenic cells such as CD34(+) , CXCR4(+) , CD117(+) , CD133(+) and C-met(+) were measured at baseline, 1 day, 5 days and at 8 months. CFR were similar between the two groups at baseline, and CFR was significantly higher in the red ginseng group than in the placebo group (2.80 ± 0.91 and 2.56 ± 0.77, p0.05, respectively) after 8 months of red ginseng administration. The absolute numbers of circulating CD34(+) , CXCR4(+) and CD117(+) cells were significantly higher in the red ginseng group at 1 and 5 days after stenting. Significant positive correlations were found between the numbers of circulating angiogenic cells at day 1 and the changes from baseline in CFR for CD34(+) , CXCR4(+) , CD117(+) and C-met(+) cells. Red ginseng extract increased CD34(+) , CXCR4(+) and CD117(+) circulating angiogenic cell mobilization and decreased inflammation in AMI patients, thereby improving CFR during the 8-month follow-up.

To evaluate the relationship between strain rate (SR) imaging and coronary flow reserve (CFR) in assessing viability of akinetic myocardium after acute myocardial infarction (MI).Forty patients with acute first ST-elevation MI were analyzed. SR imaging and CFR by intracoronary flow measurement were obtained on the same day, 3~5 days after primary percutaneous coronary intervention. Viability of the akinetic myocardium was determined on 6-week echocardiography.Systolic SR (SRs, -0.42 ± 0.10 vs. -0.35 ± 0.11 per second, P = 0.03), early diastolic SR (SRe, 0.68 ± 0.31 vs. 0.41 ± 0.22 per second, P = 0.003), and systolic strain (Ss, -5.9 ± 3.4 vs. -2.5 ± 4.0%, P = 0.04) were greater in akinetic, but viable myocardium of 21 patients than in akinetic and nonviable myocardium of 19 patients. CFR was also higher in patients with akinetic, but viable myocardium (2.0 ± 0.5 vs. 1.5 ± 0.5, P0.001). SRs, SRe, and Ss were significantly related to CFR (r =-0.50, r = 0.58, r =-0.56, respectively, all P ≤ 0.001) and SRe was most related to CFR (P0.001). The sensitivity and specificity to predict myocardial viability were 85.7% and 68.4% for CFR (cutoff = 1.75), and 90.5% and 57.9% for SRe (cutoff = 0.37 per second), respectively.The degree of myocardial deformation determined by SR imaging was related to the degree of microvascular integrity determined by CFR, and can be used as a noninvasive method to predict myocardial viability after acute MI.

Adipose-derived stem cells (ASCs) are readily available from autologous adipose tissue and have been demonstrated to provide significant potential for tissue rescue from, or repair of, damage in multiple animal models. These include models of myocardial infarction, heart failure, hind limb ischemia, and inflammatory conditions. Early clinical studies have now extended testing of the effects of ASC into patients. This review highlights some of the key reports underlining the potential of ASCs, focusing particularly on diseases involving the cardiovascular system, vascular growth, and tissue repair.Clinical applications of ASCs have begun to show early safety results and promising possibility of efficacy in patients with a range of diseases, including acute myocardial infarction, peripheral vascular disease, and soft and bony tissue defects including cranial bone loss, Crohn's-related fistula, and skin wounds. These effects are importantly based on the secretion of trophic and survival factors by these cells and by their participations in the growth and remodeling of blood vessels. These results suggest that ASCs could be a valuable therapeutic option in vascular growth and tissue repair in various clinical settings.ASCs may ultimately represent a valuable therapeutic option in tissue rescue and repair based on their ready availability, proangiogenesis and antiapoptotic factor secretion, immunomodulatory effects, and capacity for multilineage differentiation and ready expansion.

The aims of this study were to assess the sequential changes of left ventricular (LV) systolic and diastolic synchronicity in patients with acute myocardial infarction (AMI) and to assess their relation with LV recovery and remodeling. Forty-patients with acute ST-elevation MI were examined within 2days, 6weeks and 6months after primary coronary intervention. Fifteen-age matched subjects were enrolled for normal control. The time from the onset of QRS complex to peak systolic velocity (Ts) and to peak early diastolic velocity (Te) were measured on color-coded tissue Doppler imaging. To assess LV synchronicity, SDs of Ts (Ts-SD) and Te (Te-SD) of all 12 segments were calculated (within 2days, at 6weeks and 6months; SD1, SD2 and SD3, respectively). LV recovery was defined as the improvement of wall motion at least more than two segments at 6 weeks. In all AMI patients, the wall motion score index was 1.72±0.27 and LV ejection fraction was 45.9±9.9%. The Ts-SD1 was higher in AMI patients than in controls (45.4±13.5 vs 29.4±13.3ms, p

Background: With the introduction of drug-eluting stents (DES), the angiographic rates of restenosis have reduced dramatically but less prominently in diabetic patients. We compared the effects of sirolimus-eluting stents (SES) versus paclitaxel-eluting stents (PES) on 6-month angiographic and clinical outcomes in Korean diabetic patients. Method: Diabetic patients with de novo coronary lesions (169 patients with 190 lesions) were randomly assigned to either SES or PES in six different cardiovascular centers from April 2005 to January 2006. Patients with vessel size >2.0 mm and ≤2 vessel diseases requiring ≤2 DES implantation were included in the study. Results: Baseline clinical and angiographic characteristics were similar between the two groups. At 6-month follow-up, the late lumen loss (0.26 ± 0.76 in the SES group vs. 0.39 ± 0.92 mm in the PES group, P = 0.356) and the rate of binary restenosis (2.8%[n = 2] in the SES group vs. 6.9%[n = 5] in the PES group, P = 0.441) showed no significant differences. Rates of death (1.2%[n = 1] in the SES group vs. 1.2%[n = 1] in the PES group, P = 1.000), myocardial infarction (1.2%[n = 1] in the SES group vs. 1.2%[n = 1] in the PES group, P = 1.000), and target lesion revascularization (2.4%[n = 2] in the SES group vs. 4.8%[n = 4] in the PES group, P = 0.443) were similar in both groups during 6 months of follow-up. Conclusion: The use of either SES or PES demonstrated similar 6-month angiographic and clinical outcomes in Korean diabetic patients with coronary artery disease.

Background This study evaluated the inflammatory reaction at the site of overlapping drug-eluting stents (DES) in a porcine model of in-stent restenosis. Methods and Results Twenty bare metal stents (BMS) (group I; n=10), 20 sirolimus-eluting stents (SES) (group II: n=10), 20 paclitaxel-eluting stent (PES) (group III: n=10), and 10 PES and 10 SES (group IV: n=10) were overlapped in the left anterior descending coronary arteries of 40 pigs. Follow-up coronary angiography and histopathology were performed at 4 weeks after stenting. For the overlapped segments, the minimal luminal diameter at 4 weeks was smaller in group I than in the other groups (1.78±0.13 mm, 2.79±0.09 mm, 2.90±0.04 mm, 2.80±0.07 mm, respectively; p

Background: Circulating bone marrow-derived stem cells are capable of homing to sites of myocardial infarction and endothelial disruption, thereby restoring myocardial function and microvascular integrity after acute myocardial infarction. We compared the effects of atorvastatin 10 mg versus 40 mg in follow-up clinical events and in restoring coronary flow reserve (CFR) during the 8 months follow-up in patients with acute myocardial infarction. Methods: CFR, which is reflective of the integrity of coronary microvasculature, was measured by using intracoronary Doppler wire in 102 consecutive patients with acute myocardial infarction 5 days after the successful primary coronary intervention with sirolimus-eluting stents. Stented patients were randomly assigned to either atorvastatin 10 mg (ATOR10, n=52) or atorvastatin 40 mg (ATOR40, n=50). All patients received aspirin and clopidogrel. Clinical events such as death, myocardial infarction, and target lesion revascularization (TLR) were compared during the 8-month follow-up. Results: CFR increased significantly in both groups during the 8 months follow-up (1.9 ± 0.6 at baseline vs. 2.6 ± 0.7 at follow-up in the ATOR10, p Conclusion: The increases from baseline in CFR, CD34+ cells and CXCR4+ cells were significantly greater in the ATOR40 Group compared with the ATOR10 Group. However, the improvement in left ventricular systolic function and the rate of clinical events revealed no significant differences between the 2 groups.

We compared the effects of telmisartan and valsartan on late lumen loss and inflammatory markers after sirolimus-eluting stent implantation in hypertensive patients. This was a prospective, randomized, single-blinded, 8-month follow-up study that included hypertensive patients with significant coronary artery stenosis treated with telmisartan (n=79) or valsartan (n=80). Risk factors such as diabetes, hyperlipidemia, smoking, and obesity were similar between groups. After 8 months of follow-up, only the telmisartan group showed significant decreases in interleukin-6 and tumor necrosis factor-alpha. The decreases from baseline level in total cholesterol and low-density lipoprotein cholesterol concentrations were significantly greater in the telmisartan group. The increase in adiponectin concentrations from baseline measurements was significantly greater in the telmisartan group than in the valsartan group (1.9+/-2.7 vs 0.4+/-2.0 microg/ml, respectively, p0.05). Moreover, late lumen loss was significantly lower in the telmisartan group than in the valsartan group (0.1+/-0.4 vs 0.3+/-0.5 mm, respectively, p=0.001). Major adverse cardiac events were similar between groups. In conclusion, compared with valsartan, telmisartan was associated with a significant decrease in late lumen loss and inflammatory markers after sirolimus-eluting stent implantation in hypertensive patients with significant coronary narrowing.

Introduction: To assess the relationship between visceral fat (VF) and coronary artery calcium (CAC), we performed visceral fat scan and coronary CT angiography (CCTA) in metabolic syndrome (MetS) ...

Refer to the page 457-468 Transradial coronary angiogram was initially attempted with 8-10 F catheter in 1948,1) and transradial stent implantation was successfully performed in 1993.2) Transradial access (TRA) became widely used, and the proportion of radial approach during percutaneous coronary intervention (PCI) increased from 1.18% in 2007 to 16.07% in 2012.3) The transfemoral approach (TFA) has been widely used because of the huge arterial accessibility, with added advantages of reduced procedure time, catheter selection without major restrictions on the thickness, and faster learning of procedure as compared with the TRA. However, TFA was significantly associated with vascular complications, such as increasing transfusion rate, retroperitoneal hemorrhage, morbidities, and mortality.4),5) Several studies which compared TRA with TFA demonstrated that transradial coronary angiography and angioplasty are safe, feasible, and effective with similar results, if not superior, to those of the TFA.6),7),8) In contrast to the TFA, the rate of major vascular complications was negligible using the TRA.9) Meta-analysis comparing TRA with TFA showed a major reduction in complications associated with bleeding when compared with TFA, and a major reduction in transfusion rates as well as improved outcome of death or myocardial infarction.10),11) However, TRA had some complications which include radial artery perforation, evulsion, pseudoaneurysm formation, non-occlusive radial artery injury, radial artery occlusion, and higher procedural duration and radiation exposure.12) Many countries and races have reported a trend towards TRA, but there is only limited information regarding these trends in the Korean population. Youn et al.13) have reported a large prospective registry showing the current practice of coronary angiogram (CAG) and PCI using radial access in Korea. Also, in this issue of the Korean Circulation Journal, they have summarized the current practice of CAG and PCI using radial access. As per the Korean Transradial Intervention Prospective Registry, this study13) showed that TRA was 82.4% in the initial access site for PCI, which was a surprising number when compared with only 16.1% for TRA PCI in the United States in 2012.3) Although the adoption of TRA has rapidly increased, some centers still prefer TFA especially during primary PCI, because not all centers and operators in Korea are specialized for radial procedures. Considering this, the value of 82.4% could be interpreted to reflect an over-estimated value rather than the actual percentage in Korea, since 20 participating centers in this registry have been performing TRA for many years and have a high volume of TRA PCI. It is the limitation of this study that the TRA data conducted only by high volume centers may not be completely extrapolated to all PCI centers in Korea. The rate of access site crossover, bleeding, and major vascular complications in overall subjects, was similar with other major studies.7),8),14) TRA needed a learning curve for the proficiency and training for specific skills. The fact that the rate of access site crossover increased to 8.1% of the subjects undergoing PCI and decreased to 4.8% of the subjects undergoing primary PCI, reflected that TRA needed experience and confidence for TRA PCI. When TRA failed, crossover to TFA required additional cost, patient inconvenience, longer procedural time, and reperfusion delays. The radial-to-femoral crossover rate of TRA in primary PCI, from the study of radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL), was 7%.8) A reasonable recommendation is that interventional cardiologists should not start performing transradial primary PCI until their procedure success rates are comparable between their elective radial and femoral PCI procedures, and their radial-to-femoral crossover rate is ≤7%. Considering this, a crossover rate of 4.8% in this study was an outstanding result compared to the RIVAL study. Moreover, in this study,13) the rate of bleeding after primary PCI was lower than that of the RIVAL study, and the rate of major vascular complications was also very low. Considering the low complication rates, primary PCI was safely and reasonably performed via TRA in 20 participating centers in Korea. Furthermore, for patients with acute coronary syndrome in the Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox (MATRIX) study, TRA PCI not only reduced bleeding, but also reduced mortality.7) However, we need to keep in mind that experienced interventional cardiologists who performed at least 75 TRA PCI within the past year, and who performed more than 50% of their PCI via radial artery, participated in the MATRIX trial.7) It is clear from the available evidence that radial access CAG and PCI not only improve clinical outcomes and reduce cost, but also have no adverse effects on arm or hand functions. These data will provide evidence for achieving consensus on radial access CAG and PCI in the Korean population, and will encourage radial access to be the default strategy for PCI.

We present a case of a 52-year-old woman with iatrogenic stent deformation occurred after deployment of the left main (LM) stent due to the unintentional undermining of the proximal part of the LM stent with subsequent balloon dilatation. We tried to crush the deformed part of the LM stent against the left coronary cusp by pushing it with a guiding catheter.

To identify parameters influencing the likelihood of restenosis after implantation of drug-eluting stents (DES) in patients with diabetes.Stented patients (n = 840) with DES were retrospectively reviewed for inclusion in the study from the Multicenter PCI Database Registry. From this database, 211 (25.1%) of 840 patients with six-month angiographic follow up had diabetes. Predictors of coronary restenosis were identified with univariate and multivariate logistic regression analyses.Restenosis occurred in 92 of 629 (14.6%) patients without diabetes and in 44 (20.9%) of 211 patients with diabetes (p0.001). Multivariate parameters for predicting restenosis in the diabetic group were current smoking (odds ratio (OR) 1.923, 95% confidence interval (CI) 1.055 to 4.725, p = 0.036), higher C reactive protein concentration (OR 1.031, 95% CI 1.011 to 1.075, p = 0.043), use of the paclitaxel-eluting stent (OR 2.638, 95% CI 1.338 to 5.200, p = 0.005), longer stent length (OR 1.065, 95% CI 1.021 to 1.119, p = 0.033), smaller reference diameter before DES implantation (OR 0.501, 95% CI 0.110 to 0.965, p = 0.040), smaller reference diameter (OR 0.455, 95% CI 0.120 to 0.814, p = 0.026) and minimum lumen diameter (OR 0.447, 95% CI 0.068 to 0.876, p = 0.039) after DES implantation.Even with the introduction of DES, diabetes remains a significant predictor of coronary restenosis, especially in cases of a small baseline vessel size, small vessel size after percutaneous coronary intervention, longer stent length, use of the paclitaxel-eluting stent, current smoking and high C reactive protein concentration.

The aim of this study was to assess the effects of percutaneous coronary intervention with drug-eluting stents (DESs) versus minimally invasive direct coronary artery bypass (MIDCAB) surgery in the management of patients with proximal left anterior descending (LAD) coronary artery stenosis. Until recent years, despite the advantages of percutaneous transluminal coronary angioplasty (PTCA) with bare metal stent implantation, such as shorter hospital stays and recovery time, MIDCAB showed better results with regard to the need for repeated intervention in the target vessel than PTCA with proximal LAD lesions. Symptomatic patients (n = 189) were randomly assigned to DES group (n = 119) and MIDCAB group (n = 70). Patients with an isolated high-grade lesion (stenosis of > or = 70% of the luminal diameter) in the proximal LAD coronary artery (from the ostium to the first diagonal branch) were included in this study. During the 6-month follow-up period, 1.7% (n = 2) in the DES group needed repeated revascularization procedures for target lesion revascularization compared with 5.9% (n = 4) in the MIDCAB group (P = 0.196). The rates of death and myocardial infarction were similar in both groups [DES 0.0% (n = 0) vs. MIDCAB 2.9% (n = 2), P = 0.135; DES 1.7% (n = 2) vs. MIDCAB 2.9% (n = 2), P = 0.627; respectively] during 6 months of follow-up. In-hospital length of stay was significantly shorter in the DES group compared with the MIDCAB group (5.8 +/- 2.1 days vs. 8.9 +/- 2.6 days; P = 0.001). DES implantation and MIDCAB surgery showed similar rates of myocardial infarction, the need for repeated revascularization, and death during 6 months of follow-up. However, DES implantation resulted in lower average number of hospital stays and similar postoperative complications.

Ventricular Tachycardia and Restitution. Introduction: Action potential duration restitution (APDR) plays a role in initiation and maintenance of ventricular tachycardia (VT)/ventricular fibrillation (VF). We hypothesizedthat the steeply sloped APDR and its spatial heterogeneity contribute to VT/VF inducibility in patients with ventricular arrhythmia. Method and Results: After programmed ventricular stimulation (PVS) for evaluation of clinically documented VT, patients (n = 20,15 male, age 52.5 ′ 9.5 years) were divided into two groups: inducible sustained VT/VF (IVT, n = 10) and noninducible VT/VF (NVT, n = 10). Data were compared with the corresponding results obtained from normal controls (C, n = 10). Right ventricular (RV) monophasic action potential duration at 90% repolarization (APD 9 0 ) and ventricular effective refractory period (VERP) in the right ventricular apex (RVA) and right ventricular outflow tract (RVOT) were determined. APDR was acquired by scanning diastole with premature ventricular beats during a pacing cycle length of 600 msec (S1-S2) in all patients and by rapid pacing at the cycle lengths that induced APD alternans in three patients. Maximal slopes (Smax) of the APDR curves and ΔAPD 9 0 (APD 9 0 at S2 400 ms - APD 9 0 at the shortest S2) were measured. VERP and APD 9 0 at each RV site did not differ among the three groups. Smax obtained by S1-S2 (1.6 ′ 0.6) did not differ from Smax obtained by rapid pacing (1.2 ′ 0.7), with a significant correlation noted between these values (r = 0.92, P < 0.01). The IVT group had a higher spatial dispersion of Smax (Smax at RVOT - Smax at RVA) compared to the C group (P < 0.05), with no difference between the NVT group and the IVT or C groups. The IVT group had a higher spatial dispersion of ΔAPD 9 0 compared to the NVT and C groups (P < 0.01, respectively). Smax at the RVOT (2.7 ′ 1.9) was steeper than that at the RVA (1.9 ′ 1.2, P < 0.05). Inducibility of sustained VT/VF was greater at the RVOT (83.3%) than at the RVA (50.0%, P < 0.05). Conclusion: In patients with ventricular arrhythmia, VT/VF is highly inducible under conditions of greater spatial dispersion of ventricular refractoriness and APDR.

We describe a case in which a polytetrafluoroethylene (PTFE)-covered stent was implanted to treat impending rupture of a coronary artery pseudoaneurysm related to a chest stab wound. In this case, transthoracic echocardiography was used to verify the characteristics of the pseudoaneurysm, and we concluded that a PTFE-covered stent may prevent rupture in post-traumatic pseudoaneurysm.