Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery stenting in Korean patients with atrial fibrillation.

There are limited data on the optimal antithrombotic therapy for patients with atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203 patients (62.6 % men, mean age 68.3 ± 10.1 years) between 2003 and 2012, and recorded clinical and demographic characteristics of the patients. Clinical follow-up included major adverse cardiac and cerebrovascular events (MACCE) (cardiac death, myocardial infarction, target lesion revascularization, and stroke), stent thrombosis, and bleeding. The most commonly associated comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and congestive heart failure (26.6 %). Sixty-three percent of patients had stroke risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37 patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel, warfarin; Group II). The mean follow-up period was 42.0 ± 29.0 months. The mean international normalized ratio (INR) in group II was 1.83 ± 0.41. The total MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P = 0.028) were higher in the group I. Major and any bleeding, however, did not differ between the two groups. In multivariate analysis, no warfarin therapy (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin therapy was associated with a lower risk of MACCE (P = 0.024). In patients with AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy without increased bleeding, which might be related to tighter control with a lower INR value.

Exendin-4 protects against sulfonylurea-induced ß-cell apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from ß-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by ß-cell exhaustion and apoptosis. ER stress induced by Ca(2+) depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in ß-cells after the induction of oxidative and ER stress. In this study, we examined the anti-apoptotic action of a GLP-1 analogue in ß-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca(2+) concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca(2+) replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced ß-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.

Exendin-4 Protects Against Sulfonylurea-Induced ß-Cell Apoptosis.

Sulfonylurea is one of the commonly used anti-diabetic drugs that stimulate insulin secretion from ß-cells. Despite their glucose lowering effects in type 2 diabetes mellitus, long-term treatment brought on secondary failure characterized by ß-cell exhaustion and apoptosis. ER stress induced by Ca2+ depletion in endoplasmic reticulum (ER) is speculated be one of the causes of secondary failure, but it remains unclear. Glucagon like peptide-1 (GLP-1) has anti-apoptotic effects in ß-cells after the induction of oxidative and ER stress. In this study, we examined the antiapoptotic action of a GLP-1 analogue in ß-cell lines and islets against ER stress induced by chronic treatment of sulfonylurea. HIT-T15 and dispersed islet cells were exposed to glibenclamide for 48 h, and apoptosis was evaluated using Annexin/PI flow cytometry. Expression of the ER stress-related molecules and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2/3 was determined by real-time PCR and western blot analysis. Chronic exposure to glibenclamide increased apoptosis by depletion of ER Ca2+ concentration through reduced expression of SERCA 2/3. Pretreatment with Exendin-4 had an anti-apoptotic role through ER stress modulation and ER Ca2+ replenishing by SERCA restoration. These findings will further the understanding of one cause of glibenclamide-induced ß-cell loss and therapeutic availability of GLP-1-based drugs in secondary failure by sulfonylurea during treatment of diabetes.

Association between renal dysfunction and the mixed plaque of coronary artery on computed tomographic angiography.

Coronary artery plaque is related to development of coronary artery disease (CAD), and chronic kidney disease is associated with CAD. However, the association of renal dysfunction (RD) with coronary artery plaque characteristics has not been fully elucidated. We evaluated the association between RD and coronary artery plaque characteristics in patients with suspected CAD, who underwent multislice computed tomographic angiography (CTA). A total of 918 patients were classified into 4 groups: group with no plaque (NP) (48.9%), group with calcified plaque (CP) (16.0%), group with noncalcified plaque (NCP) (22.4%), and group with mixed plaque (MP) (12.7%). NCP is considered as rupture-prone soft plaque, and CP as more stable lesion. The mean of estimated glomerular filtration rate (eGFR) was 82.5 ± 15.4 mL/min/1.73 m(2), and the prevalence of RD (defined as eGFR < 60 mL/min/1.73 m(2)) was 6.3%. The prevalence of RD was 3.3% in the NP group, 10.2% in the CP group, 5.3% in the NCP group, and 14.5% in the MP group (P < 0.001 by ANOVA tests). The adjusted odds ratio for RD was 3.38 (95% confidence interval, 1.27-9.04) for the MP group, compared with the NP group. The presence of RD showed an independent association with the MP counts (r = 0.155, P < 0.001); however, there was no association between RD and other plaque characteristics. In conclusion, RD is associated with MP rather than CP or NCP, compared with NP, which may reflect one of the developmental processes of CAD in patients with RD.

Comparison of the effect of preinterventional arterial remodeling on intimal hyperplasia after implantation of a sirolimus- or paclitaxel-eluting stent.

BACKGROUND: We compared the effect of arterial remodeling on intimal hyperplasia (IH) after the implantation of a sirolimus-eluting stent (SES) and a paclitaxel-eluting stent (PES). METHODS: The study population consisted of patients with positive or intermediate remodeling and negative remodeling. RESULTS: Sixty-nine patients had positive or intermediate remodeling and 107 patients had negative remodeling. At follow-up, late loss was significantly larger (0.58 +/- 0.65 vs. 0.38 +/- 0.55 mm; p = 0.026) in the patients with positive or intermediate remodeling. The IH volume (22.6 +/- 26.2 vs. 12.4 +/- 17.4 mm(3); p = 0.002) and the percent IH (12.9 +/- 14.8 vs. 7.0 +/- 9.6%; p = 0.002) were significantly higher in the patients with positive or intermediate remodeling. Compared to negative remodeling, the IH volume was higher in the PES patients with positive or intermediate remodeling, but this difference was not noted in the SES patients. Multiple-regression analysis revealed that arterial remodeling was a significant independent variable for predicting IH volume in the PES patients (p = 0.018). A positive correlation was found between the remodeling index and the IH volume in the PES patients (r = 0.234, p = 0.028), but not in the SES patients. CONCLUSIONS: This prospective observational intravascular ultrasound study showed that drug-eluting stents may have a different effect on reducing IH accumulation in lesions with preinterventional positive remodeling characteristics which may be related to the different properties of the drug and delivery platform.

Exendin-4 protects oxidative stress-induced ß-cell apoptosis through reduced JNK and GSK3ß activity.

Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of ß-cell mass through ß-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of ß-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from ß-cell and differentiation to ß-cell from progenitor cells. Also, it probably has an antiapoptotic effect on ß-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in ß-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 µM H(2)O(2) for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of ß-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3ß activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in ß-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect ß-cell apoptosis by blocking the JNK and GSK3ß mediated apoptotic pathway.

Identification of peptides that selectively bind to myoglobin by biopanning of phage displayed-peptide library.

Biopanning of phage displayed-peptide library was performed against myoglobin, a marker for the early assessment of acute myocardial infarction (AMI), to identify peptides that selectively bind to myoglobin. Using myoglobin-conjugated magnetic beads, phages that bound to myoglobin were collected and amplified for the next round of screening. A 148-fold enrichment of phage titer was observed after five rounds of screening relative to the first round. After phage binding ELISA, three phage clones were selected (3R1, 3R7 and 3R10) and the inserted peptides were chemically synthesized. The analysis of binding affinity showed that the 3R7 (CPSTLGASC) peptide had higher binding affinity (Kd=57 nM) than did the 3R1 (CNLSSSWIC) and 3R10 (CVPRLSAPC) peptide (Kd=125 nM and 293 nM, respectively). Cross binding activity to other proteins, such as bovine serum albumin, troponin I, and creatine kinase-MB, was minimal. In a peptide-antibody sandwich ELISA, the selected peptides efficiently captured myoglobin. Moreover, the concentrations of myoglobin in serum samples measured by a peptide-peptide sandwich assay were comparable to those measured by a commercial antibody-based kit. These results indicate that the identified peptides can be used for the detection of myoglobin and may be a cost effective alternative to antibodies.

Comparison of edge vascular response after sirolimus- and paclitaxel-eluting stent implantation.

BACKGROUND: To compare the edges vascular response, we analyzed the intravascular ultrasound (IVUS) parameters after implantation of the sirolimus-eluting stent (SES) or the paclitaxel-eluting stent (PES). METHODS: Two hundred-two angina patients (123 men; 61.5 ± 9.2 years of age, SES: n = 91, PES: n=111) were enrolled. Both edge segments of the stent were analyzed. The change (Δ) of each parameter at follow-up was calculated. RESULTS: The edge restenosis rate was higher in the PES group. However, the Δ Vessel, Δ Plaque and Δ Lumen volume at 5mm edge segments were not different between the two groups except the Δ Plaque volume at the distal segment, higher in the PES than the SES group (6.6 ± 15.7 vs. 1.0 ± 13.1mm(3), P=.016). In the PES group, lumen area at the both 1mm edge segments decreased because of plaque progression (proximal, 1.9 ± 1.5 to 2.2 ± 2.0mm(2), P=.095; distal, 0.6 ± 1.1 to 1.0 ± 1.4mm(2), P=.018) with negative remodeling (proximal, 9.9 ± 2.4 to 9.4 ± 2.6mm(2), P=.004; distal, 7.6 ± 2.4 to 7.2 ± 2.4mm(2), P=.052). Conversely, lumen area at these segments increased due to plaque regression (proximal, 3.2 ± 1.8 to 2.1 ± 1.6mm(2), P=.000; distal, 1.5 ± 1.4 to 0.9 ± 1.3mm(2), P=.000) even though there was negative remodeling in the SES group (proximal, 10.1 ± 2.4 to 9.6 ± 2.3mm(2), P=.019; distal, 7.8 ± 2.3 to 7.5 ± 2.3mm(2), P=.074). The Δ Plaque and Δ Lumen area at the both 1mm edge segments were more prominent in the PES group. CONCLUSIONS: Compared to SES, PES was associated with luminal reduction accompanied by plaque progression with negative remodeling at edge segments.

Predictors of edge stenosis after paclitaxel-eluting stent implantation.

BACKGROUND: Although edge stenosis (ES) is a main limitation of drug-eluting stents, the predictors for ES are not well known. We evaluated the predictors for ES after paclitaxel-eluting stent implantation. METHODS: One hundred and eleven angina patients (64 men; 62.2±8.4 years of age) were divided into ES (n=9) and non-ES groups (n=102). The clinical findings, procedural factors, and intravascular ultrasound (IVUS) parameters were analyzed. RESULTS: Although clinical characteristics were not different between groups, diabetes mellitus (DM) was more common in the ES group (P=0.002). The vessel, plaque, and lumen areas of the lesions were not different between groups; however, the vessel area of the proximal and distal reference artery was smaller in the ES group. Lesions with positive remodeling were more common in the ES group (P=0.015). On the basis of univariate analysis, predictors of ES included DM, lesions with positive remodeling, IVUS parameters, and procedural factors. After adjusting for clinical findings, angiographic factors, and IVUS parameters, the presence of DM [odds ratio (OR): 9.20; 95% confidence interval (CI): 1.40-60.62, P=0.021] and lesions with positive remodeling (OR: 5.93; 95% CI: 1.13-31.02, P=0.035) were independent predictors of ES. The lumen area in the distal 1 mm reference segment was a protective factor for ES (OR: 0.05; 95% CI: 0.00-0.74, P=0.029). CONCLUSION: The risk of ES after paclitaxel-eluting stent implantation was higher in patients who had DM and lesions with positive remodeling. Of the IVUS parameters, the lumen area in the distal 1 mm reference segment was a protective factor against ES.

Impact of arterial remodeling on high sensitive C-reactive protein after a DES implantation.

The inflammatory response after percutaneous coronary intervention (PCI) with stent between coronary lesions with positive (PR) and negative remodeling (NR) might be different. In 68 patients, the changes of the hs-CRP from baseline to 24 h after PCI and the intimal hyperplasia (IH) volume at follow up were significantly higher in the PR. A positive correlation was noted between the changes of the hs-CRP from baseline to each stage (24 h and 72 h) and the IH volume. This prospective study showed that an increased IH in lesions with PR after PCI might be associated with an increased inflammatory response.

Coronary artery perforation following implantation of a drug-eluting stent rescued by deployment of a covered stent in symptomatic myocardial bridging.

We successfully rescued a patient whose coronary artery perforated following implantation of a drug-eluting stent (DES), by deploying a stent-graft in symptomatic myocardial bridging. Our case demonstrated that coronary perforation could be handled without difficulty when perforated myocardial bridging is confined to the interventricular groove.

Combined open and endovascular repair for aortic arch pathology.

BACKGROUND AND OBJECTIVES: We describe our experience with combined open and endovascular repair in patients who have aortic arch pathology. SUBJECTS AND METHODS: This study is a retrospective analysis of 7 patients who underwent combined open and endovascular repair for aortic arch pathology. Medical records and radiographic information were reviewed. RESULTS: A total of 7 consecutive patients (5 men, 71.4%) underwent thoracic stent graft implantation. The mean age was 59.9±16.7 years. The indication for endovascular repair was aneurysmal degeneration in 5 patients, and rupture or impending rupture in 2 patients. In all 7 cases, supra-aortic transposition of the great vessels was performed successfully. Stent graft implantation was achieved in all cases. Surgical exposure of the access vessel was necessary in 2 patients. A total of 9 stent grafts were implanted (3 stent grafts in one patient). The Seal thoracic and the Valiant endovascular stent graft were implanted in 6 patients and 1 patient, respectively. There were no post-procedure deaths or neurologic complications. In 2 patients, bleeding and injury of access vessel were noted after the procedure. Postoperative endoleak was noted in 1 patient. One patient died at 10 months after the procedure due to a newly developed ascending aortic dissection. No patients required secondary intervention during the follow-up period. The aortic diameter decreased in 4 patients. In 3 patients, including 1 patient with endoleak, there was no change in aortic diameter. CONCLUSION: Our experience suggests that combined open and endovascular repair for aortic arch pathology is safe and effective, with few complications.

Echocardiographic assessments of left atrial strain and volume in healthy patients and patients with mitral valvular heart disease by tissue Doppler imaging and 3-dimensional echocardiography.

BACKGROUND AND OBJECTIVES: The purpose of the current study was to assess left atrial (LA) physiology in relation to associations between LA volume change and regional tissue velocities and strains, and to extend this information to patients with mitral stenosis (MS) or mitral regurgitation (MR). SUBJECTS AND METHODS: Twenty-two healthy persons, 22 patients with moderate-to-severe MS, and 22 patients with moderate-to-severe MR were studied. Tissue velocities, strains, and time-volume curves of the LA were acquired using tissue Doppler imaging and 3-dimensional echocardiography. RESULTS: In healthy controls, the maximal LA volume was negatively correlated with the posterior wall longitudinal systolic strain (r=-0.45, p=0.03). The time-to-maximal LA volume was positively correlated with the time-to-posterior wall longitudinal peak strain (r=0.46, p=0.03) and the time-to-circumferential peak strain (r=0.59, p=0.004). The LA active emptying fraction (LAactEF) was positively correlated with the posterior wall longitudinal peak systolic and late diastolic tissue velocities. In patients with MS, the maximal LA volume was negatively correlated with the posterior wall radial peak systolic velocity and the longitudinal late diastolic velocity. In patients with MS, the LAactEF had an additional positive correlation with the anterior wall longitudinal and circumferential systolic velocities, whereas the patients with MR had an additional positive correlation between the LAactEF and the lateral wall longitudinal peak strain as compared with the healthy cantrols. CONCLUSION: LA longitudinal and circumferential deformations are more related than radial deformation to determining LA volume and function. The LA of patients with MS revealed a greater pathologic physiology than those of patients with MR.

Left anterior descending coronary artery myocardial bridging detected by 64-multidetector computed tomography.

A 59-year-old female came to the clinic to evaluate an operation risk of knee joint arthritis. She has history of hypertension for 6 years. She complained of dyspnea on exercise before. Radionuclide imaging demonstrated large moderate perfusion defect in anterior, anteroseptal, and anterolateral regions with significant reversibility. ECG gated 64-multidetector computed tomography demonstrated the middle third of the left anterior descending coronary artery myocardial bridging. The length of tunneled artery was 23 mm and the depth of tunneled artery was 3 mm. Coronary angiogram confirmed the middle third of the left anterior descending coronary artery myocardial bridging. Multidetector computed tomography is a reliable and noninvasive tool for diagnosing coronary myocardial bridging.

Simultaneous subacute stent thrombosis after implantation of sirolimus-eluting stent and bare-metal stent.

Simultaneous multivessel stent thrombosis is a rare, but can cause catastrophic clinical results. We report a case occurred ST simultaneously in DES and BMS. Our case demonstrated that the use of multiple stents, irrespective of stent type, in multiple coronary artery lesions should be undertaken with great attention in the patient who has multiple adverse clinical predictors such as AMI.