Pil-Ki Min

Endovascular therapy combined with immunosuppressive treatment for occlusive arterial disease in patients with Takayasu's arteritis.

Purpose: To evaluate the feasibility and efficacy of endovascular therapy combined with immunosuppression for the treatment of arterial occlusive disease in patients with Takayasus arteritis (TA). Methods: From January 1998 to June 2003, 25 patients (22 women; age 37.8±15.5 years) with TA were treated with angioplasty for symptomatic lesions or with a hemodynamically significant aortic narrowing. The patients with active disease, defined as an increase in inflammatory markers (e.g., erythrocyte sedimentation rate [ESR]), were treated with immunosuppressive agents before intervention. Angioplasty was performed after the ESR had been normalized. Results: In the 25 patients, 58 vascular territories (7 aortic, 9 carotid, 3 vertebral, 11 subclavian, 2 superior mesenteric, 18 renal, 4 iliac, and 4 coronary arteries) were treated with angioplasty only (19 lesions) or with stents (39 lesions). The mean ESR when the vascular lesions were initially diagnosed was 35.6±26.2 mm/h, which fell to 18.5±7.8 mm/h after immunosuppressive therapy. The endovascular procedure was performed successfully in 52 (90%) of 58 lesions. During the mean 23.7±18.4-month follow-up, 9 (17%) treated segments restenosed; 4 were treated with repeat angioplasty. The overall cumulative primary clinical success rate was 82%; secondary clinical success was 90%. Conclusions: Endovascular therapy for stenotic lesions in patients with TA is safe and effective when disease activity is strictly controlled with immunosuppressive treatment.

Impact of Metabolic Syndrome and Its Individual Components on the Presence and Severity of Angiographic Coronary Artery Disease

Purpose Metabolic syndrome (MS) has been reported as a potential risk factor of coronary artery disease (CAD). The aims of this study were to assess whether there was a relationship between MS score and CAD angiographic severity, and to assess the predictive value of individual components of MS for CAD. Materials and Methods We retrospectively enrolled 632 patients who underwent coronary angiography for suspected CAD (394 men, 61.0 ± 10.6 years of age). MS was defined by the National Cholesterol Education Program criteria with the waist criterion modified into a body mass index (BMI) of more than 25 kg/m2. The MS score defined as the number of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD angiographic severity was evaluated with a Gensini scoring system. Results Of the patients, 497 (78.6%) had CAD and 283 (44.8%) were diagnosed with MS. The MS score was significantly related to the Gensini score. High fasting blood glucose (FBG) was the only predictive factor for CAD. A cluster including high FBG, high blood pressure (BP), and low high-density lipoprotein cholesterol (HDL-C) showed the highest CAD risk. Conclusion The MS score correlates with the angiographic severity of CAD. The predictive ability of MS for CAD was carried almost completely by high FBG, and individual traits with high BP and low HDL-C may act synergistically as risk factors for CAD.

Local increase in microparticles from the aspirate of culprit coronary arteries in patients with ST-segment elevation myocardial infarction.

OBJECTIVE It has been reported that the levels of procoagulant microparticles (MPs) are increased in patients with acute coronary syndromes and this may contribute to the formation of intracoronary thrombi. In the current study, we investigated the presence of locally elevated MPs within the culprit coronary arteries of patients with ST-segment elevation myocardial infarction (STEMI). METHODS The study population consisted of 45 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), and 16 control patients. Before and after PCI, blood samples were collected from the femoral artery and from the culprit coronary arteries. In controls, only peripheral blood was obtained. MPs were measured by a solid-phase capture assay using a commercial kit. The cell origins of MPs were determined by antigenic capture with specific antibodies. RESULTS Baseline levels of MPs in patients with STEMI were higher than in controls. Before PCI, the levels of MPs were significantly higher in culprit coronary arteries than in peripheral arteries in STEMI patients (20.7 ± 15.5 vs. 14.6 ± 15.4 nM phosphatidylserine (PS) equivalent, p = 0.027). MPs from the culprit coronary artery were significantly reduced after PCI (20.7 ± 15.5 vs. 14.3 ± 14.9 nM PS equivalent, p = 0.010). Similarly, the locally increased levels of endothelial- and platelet-derived MPs within the culprit coronary arteries were significantly decreased after PCI. CONCLUSION Locally increased levels of MPs in culprit coronary arteries and their significant reduction after successful PCI suggest a potential role in coronary atherothrombosis in the early period of STEMI.

MicroRNA‐365 Inhibits the Proliferation of Vascular Smooth Muscle Cells by Targeting Cyclin D1

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of disease progression in atherosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. MicroRNAs (miR) have been reported to act as important gene regulators and play essential roles in the proliferation and migration of VSMCs in a cardiovascular disease. However, the roles and mechanisms of miRs in VSMCs and neointimal formation are far from being fully understood. In this study, cell cycle‐specific cyclin D1 was found to be a potential target of miR‐365 by direct binding. Through an in vitro experiment, we showed that exogenous miR‐365 overexpression reduced VSMC proliferation and proliferating cell nuclear antigen (PCNA) expression, while miR‐365 was observed to block G1/S transition in platelet‐derived growth factor‐bb (PDGF‐bb)‐induced VSMCs. In addition, the proliferation of VSMCs by various stimuli, including PDGF‐bb, angiotensin II (Ang II), and serum, led to the downregulation of miR‐365 expression levels. The expression of miR‐365 was confirmed in balloon‐injured carotid arteries. Taken together, our results suggest an anti‐proliferative role for miR‐365 in VSMC proliferation, at least partly via modulating the expression of cyclin D1. Therefore, miR‐365 may influence neointimal formation in atherosclerosis patients. J. Cell. Biochem. 115: 1752–1761, 2014.

Incidence and natural history of coronary artery aneurysm developing after drug-eluting stent implantation.

AIMS There is a growing concern about the occurrence of coronary artery aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term course. We assessed the occurrence and the factors affecting the long-term outcome of DES-associated CAA. METHODS AND RESULTS We analyzed 3,612 consecutive patients (4,419 lesions) who underwent follow-up angiography after DES implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient) were detected at follow-up, and the mean elapsed time from DES implantation to CAA diagnosis was 414 ± 213 days. Angiographically, CAAs developed almost exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions), and lesion length was significantly greater in patients with CAA than without CAA (26.9 ± 9.03 vs 23.1 ± 7.14 mm; P = .004). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin only without clopidogrel. CONCLUSION Although CAAs rarely develop after DES implantation and show mostly favorable clinical courses, long-term maintenance of clopidogrel therapy might be required to minimize occurrence of adverse clinical events resulting from stent thrombosis.

Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy

Advanced glycation endproducts (AGEs) have been reported to play a role in neointimal formation and increase the rate of in-stent restenosis (ISR) in the diabetic coronary artery disease patients treated with stents, but the potential pathogenic mechanisms of AGEs in vascular smooth muscle cell proliferation remain unclear. We sought to determine the AGEs related pathobiological mechanism of diabetic vasculopathy. Rat aortic smooth muscle cell (RAoSMC) culture was done with different concentrations of AGEs and proliferation was assessed. Immunohistochemistry for receptor of AGEs (RAGE) was performed with human carotid atheroma. Western blotting was performed to assess the activation of MAP kinase system in the cultured RAoSMC. AGEs increased RAoSMC proliferation and were associated with increased phosphorylation of ERK and p38 kinase by time and dose dependent manner. The MAP kinase activity was decreased by RNA interference for RAGE. AGEs stimulation increased reactive oxygen species (ROS) generation in cultured RAoSMC. From this study it is concluded that AGEs played a key role in RAoSMC proliferation via MAP kinase dependent pathways. Activation of vascular smooth muscle cell (VSMC) proliferation by MAP kinase system and increased formation of ROS may be the possible mechanisms of AGEs induced diabetic vasculopathy.

Comparison of sirolimus-eluting stent and paclitaxel-eluting stent for long-term cardiac adverse events in diabetic patients: the Korean Multicenter Angioplasty Team (KOMATE) Registry.

Background: There is some controversy on long‐term cardiac outcomes between sirolimus‐eluting stents (SES) and paclitaxel‐eluting stents (PES) in diabetes mellitus (DM). We compared cardiac adverse events after SES and PES implantation in patients with DM over a period of 3 year. Methods: A total of 634 patients with DM treated with SES (n = 428) or PES (n = 206) were consecutively enrolled in the KOMATE registry from 2003 to 2004. We assessed major adverse cardiac events (MACEs, cardiovascular death, nonfatal myocardial infarction, ischemia driven target vessel revascularization) and stent thrombosis (ST) according to the definitions set by the Academic Research Consortium. Results: Propensity score (PS) analysis was performed to adjust different baseline characteristics. The mean follow‐up duration was 38 ± 8 month (at least 36 month and up to 53 month). The 3‐year MACE rate did not show a significant difference between the two groups [52 (12.1%) in SES vs. 29 (14.1%) in PES, P = 0.496]. The definite and probable ST at 3 year were similar in both SES and PES [12 (2.8%) in SES vs. 7 (3.4%) in PES, P = 0.681]. There were no differences in hazard ratio for MACE and ST between two stents [MACE, crude: 0.844 (0.536–1.330) and adjusted for PS: 0.858 (0.530–1.389); ST, crude: 0.820 (0.323–2.083) and adjusted for PS: 0.960 (0.357–2.587)]. Conclusions: The present study demonstrated that long‐tem cardiac outcomes including ST were not significantly different between SES and PES in patients with DM.

Left Atrial Strain Assessed by Speckle Tracking Imaging Is Related to New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting

BACKGROUND Left atrial (LA) dysfunction was recently proposed as an important factor in the development of postoperative atrial fibrillation (POAF). LA strain analysis by 2-dimensional (2D) speckle tracking imaging is emerging as a new tool to evaluate LA function. We aimed to evaluate the correlation of LA dysfunction assessed by 2D speckle tracking imaging with the occurrence of POAF after coronary artery bypass grafting (CABG). METHODS In this study, 53 patients (mean age 66 ± 9 years) undergoing elective isolated CABG were enrolled. Conventional transthoracic echocardiography and 2D speckle tracking strain analysis were performed before surgery. POAF was detected with continuous electrocardiography monitoring throughout hospitalization (mean duration 17 ± 10 days). RESULTS POAF occurred in 13 of 53 patients (24%). Patients with POAF were significantly older than patients with normal sinus rhythm after surgery (71 ± 5 vs 64 ± 10 years, P = 0.026). Compared with patients with normal sinus rhythm, patients with POAF had a significantly larger LA volume index (32.6 ± 5.1 vs 27.3 ± 7.2 mL/m(2), P = 0.018), lower value of LA global strain (25.4 ± 10.4 vs 36.8 ± 7.6%, P = 0.001), and strain rate (1.2 ± 0.6 vs 1.6 ± 0.8 seconds, P = 0.024). By multivariate logistic regression analysis, only LA global strain (odds ratio, 1.12; 95% confidence interval, 1.00-1.24; P = 0.040) was an independent predictor of POAF after CABG. CONCLUSIONS Preoperative LA global strain measured by 2D speckle tracking strain analysis is associated with the development of POAF after CABG.

Successful endovascular treatment of iatrogenic coronary artery dissection extending into the entire ascending aorta

Iatrogenic acute dissection of the ascending aorta during percutaneous coronary intervention occurs rarely. Localized aortic dissections may be treated by sealing the entry with a coronary stent. However, extensive dissections may require a surgical intervention. A case of iatrogenic coronary dissection with extensive propagation into the ascending aorta during angioplasty of the right coronary artery is presented. The aortic dissection was successfully treated by stenting at the right coronary artery ostium. Follow-up computed tomography and coronary angiography showed complete resolution of aortic dissection.

Clopidogrel pretreatment before primary percutaneous coronary stenting in patients with acute ST-segment elevation myocardial infarction: comparison of high loading dose (600 mg) versus low loading dose (300 mg)

BackgroundAggressive platelet inhibition is crucial to reduce myocardial injury and early cardiac events after coronary intervention. As compared with the conventional 300-mg dose, pretreatment with a 600-mg loading dose of clopidogrel significantly reduced periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI). We investigated that the advantage of the 600-mg dose in inhibiting platelet aggregation more rapidly than the 300-mg dose may actually have special value for acute ST-segment elevation MI patients. MethodsA total of 171 patients with ST-segment elevation MI underwent primary PCI. A 600-mg (n=73) or 300-mg (n=98) loading regimen of clopidogrel was given before the procedure. We did a follow-up of all patients clinically for 30 days after coronary intervention. The primary endpoint was the 30-day occurrence of death, MI, urgent revascularization, or stroke. ResultsThe primary endpoint occurred in 1.4% (1 of 73) of patients in the high dose versus 11.2% (11 of 98) of those in the conventional loading dose group (P=0.013). Death, recurrent MI, urgent revascularization, and stroke were lower in patients treated with the high dose of clopidogrel compared with conventional dose. Safety endpoints were similar in the two groups. ConclusionPretreatment with a 600-mg loading dose of clopidogrel before the procedure is safe and, as compared with the conventional 300-mg dose, significantly reduces recurrent MI and urgent revascularization in patients with primary PCI.