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Background To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. Methods This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19–70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. Results Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P P Conclusions The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. Trial registration NCT03156842, Registered 17 May 2017

PURPOSE We investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS This was a multicenter randomized, double-blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. FINDINGS Baseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (-45.7±18.6%) than in the E10 group (-16.7±14.7%, p

Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02–1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30–1.69, P

Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02-1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30-1.69, P .001), and 66% (hazard ratio = 1.66, 95% confidence interval = 1.26-2.18, P .001) in the DM only, proteinuria only, and DM with proteinuria groups, respectively (P for trend .001). Degree of proteinuria in diabetic patients was associated with a significantly higher rate of incident AF in dose dependent manner. Thus, assessing proteinuria by a simple urine dipstick test could provide a useful adjunct to risk assessment for AF in elderly population with DM.

Background: Despite advances in reperfusion times, patients presenting with acute myocardial infarction carry an unacceptably high rate of mortality and morbidity. Mechanical unloading of the left ventricle (LV) has been suggested to reduce infarct size after acute myocardial infarction. Although prior studies have investigated LV unloading during ischemia with a delay in reperfusion, little is known about the optimal timing for LV unloading in the setting of acute myocardial infarction. Methods: Studies were conducted in 17 adult Yorkshire swine weighing 67±5 kg. A coronary balloon was inflated in the mid left anterior descending for 60 minutes to induce a myocardial infarction. The coronary balloon was then deflated for 120 minutes (reperfusion). The animals were stratified into 3 groups: group 1 (control, reperfusion with no LV unloading, n=5), group 2 (LV unloading during ischemia with delayed reperfusion, n=6), and group 3 (simultaneous LV unloading and reperfusion, n=6). Staining the hearts with Evans blue and 2,3,5-triphenyltetrazolium chloride was used to identify the area at risk and the infarct area respectively. Infarct percent size was defined as the area of infarcted myocardium divided by the area at risk. Results: Of the 3 groups, group 3 demonstrated significantly smaller infarct percent size compared with controls (54.7±20.3% versus 22.2±13.4%; P =0.03). Comparison between group 1 and group 2 did not reveal significant difference (54.7±20.3% versus 43.3±24.6%; P =0.19). Conclusions: In our large animal experimental model, simultaneous reperfusion and mechanical LV unloading yielded the smallest infarct size compared with no LV unloading or LV unloading with delayed reperfusion. In the context of prior studies showing benefit to unloading before reperfusion, these findings raise questions about how this strategy may be translated to humans.

The Korean chronic total occlusion (CTO) registry was collected prospectively from 26 cardiovascular centers since May 2007. The aim of this study is to investigate the impact of a successful staged percutaneous coronary intervention (PCI) of CTO lesions in acute myocardial infarction (AMI) patients on clinical outcomes.Among 2813 patients who underwent a staged PCI because of CTO lesions, 422 (15%) patients underwent primary PCI because of AMI. Among 422 patients, successful staged CTO-PCI was performed in 76%. The clinical outcomes were compared between the successful CTO-PCI group (n=321) and the failed CTO-PCI group (n=101). To adjust for potential confounders, a propensity score matching (PSM) analysis was carried out using the logistic regression model.After the PSM analysis, two propensity-matched groups (85 pairs, n=170) were generated and the baseline characteristics were balanced. The incidence of total death (P=0.029) and non-ST-segment elevation myocardial infarction (NSTEMI, P=0.043) at 1 year was higher in the failed CTO-PCI group. Multivariate regression showed that successful CTO-PCI was an independent predictor of preventing mortality (hazard ratio, 0.21, P=0.048). In the subgroup analysis, the Kaplan-Meier curve showed that successful CTO-PCI had a lower incidence of total death (log-rank=0.004) and cardiac death (log-rank=0.005) up to 1 year in NSTEMI patients. Cox-proportional analysis showed that successful CTO-PCI was beneficial in patients with NSTEMI, hypertension, and non-left-anterior descending artery lesion for preventing mortality.In this study, a staged successful CTO-PCI in AMI patients was associated with improved 1-year survival in the Korean population.

Background Reduced preprocedural thrombolysis in myocardial infarction (TIMI) flow in patients with ST-segment elevation myocardial infarction (STEMI) is known to be associated with increased mortality. However, clinical implications of reduced preprocedural TIMI flow in patients with non-ST-segment elevation myocardial infarction (NSTEMI) have not been fully elucidated as yet. The aim of the present study was to compare the clinical influence of reduced preprocedural TIMI flows between patients with STEMI and NSTEMI undergoing percutaneous coronary intervention (PCI). Methods From the Korea Acute Myocardial Infarction Registry, a total of 7336 AMI patients with angiographically confirmed reduced preprocedural TIMI flow (TIMI 0/1) during PCI were selected and divided into STEMI (n=4852) and NSTEMI (n=2484) groups. The 12-month composite of total death, nonfatal myocardial infarction, coronary artery bypass graft, and repeated PCI was compared between the two groups. Results After adjustment of baseline confounders by propensity score stratification, the NSTEMI group had lower incidences of major adverse cardiac events than the STEMI group (7.15 vs. 11.19%; hazard ratio: 0.63; 95% confidence interval: 0.47-0.84; P=0.001) at 12 months, which was largely attributable to the lower incidences of total deaths (2.43 vs. 3.99%; P=0.04) and repeated PCI (3.81 vs. 6.41%; P=0.01). Conclusion Among AMI patients with TIMI 0/1, patients with NSTEMI had better outcomes compared with those of patients with STEMI on the basis of the incidences of 12-month outcomes. This could be attributable to lower total death and repeated revascularization in patients with NSTEMI.

Coronary spasm generally occurs in patients with minimal atherosclerotic plaque lesion, and it has a rather favorable prognosis. However, in some cases, coronary spasm may induce myocardial infarction and even sudden cardiac death (SCD). Here, we report a case in which multi-vessel intractable coronary vasospasm suddenly occurred in a diffuse atherosclerotic lesion after percutaneous coronary intervention (PCI) in a patient with aborted SCD. We identified the characteristics of the spasm portion in intravascular ultrasound (IVUS) images and conducted percutaneous cardiopulmonary bypass support-PCI with stenting as treatment. Intima and media thickening and a large attenuated plaque burden with rupture were identified in IVUS images at the obstructive spasm portion.

Limited data exist on the long-term efficacy of extended dual antiplatelet therapy (DAPT) after left main coronary artery (LMCA) bifurcation stenting. This study investigated the long-term clinical outcomes associated with long-term DAPT after LMCA bifurcation stenting. Using data from the multicenter KOMATE and COBIS registries, we analyzed 1,142 patients who received a drug-eluting stent for a LMCA bifurcation lesion and who experienced no adverse events for 12 months after the index procedure. Patients were divided into 2 groups: DAPT >12 months (n = 769) and DAPT ≤12 months (n = 373). The primary end point was major adverse cardiovascular events (MACEs), as a composite of cardiac death, myocardial infarction, stroke, and stent thrombosis, over 5 years of follow-up. We further performed propensity score adjustment for clinical outcomes. DAPT >12 months afforded a lower MACE rate than DAPT ≤12 months (2.3% vs 5.4%, adjusted hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.19 to 0.71; p = 0.003). The use of DAPT for >12 months was an independent predictor of a reduced likelihood of MACEs (HR 0.34; 95% CI 0.17 to 0.67; p = 0.002). A DAPT score ≥2, chronic kidney disease, and age >75 years were significant independent predictors of MACEs. In subgroup analysis, the use of DAPT for >12 months consistently resulted in better clinical outcomes across all subgroups, especially among patients with ACS, compared with the use of DAPT for ≤12 months. In conclusion, an extended duration of DAPT reduces MACE rates after LMCA bifurcation stenting.

Purpose Although current guidelines recommend the administration of dual antiplatelet therapy (DAPT) for up to 12 months after the implantation of a drug-eluting stent (DES), extended DAPT is frequently used in real-world practice. Materials and Methods From the Korean Multicenter Angioplasty Team registry, we identified a total of 1414 patients who used DAPT for >3 years after DES implantation (extended-DAPT group) and conducted a landmark analysis at 36 months after the index procedure. We evaluated the determinants for and long-term outcomes of extended DAPT and compared the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stent thrombosis, and stroke, between the extended-DAPT group and the guideline-DAPT group [DAPT

Acute myocardial infarction (AMI) is a progressive disease in Korea and active treatment strategies can improve the clinical outcomes. In the CADILLAC trial, anemia on admission was associated strongly with adverse outcomes and increased mortality in AMI. However, it remains controversial whether anemia on admission is an independent poor prognostic factor of long-term clinical outcomes in AMI patients undergoing a percutaneous coronary intervention with a drug-eluting stent in Koreans.A total of 1143 AMI patients undergoing percutaneous coronary intervention with drug-eluting stent at Korea University Guro Hospital between 2005 and 2015 were enrolled. Anemia on admission was defined as hemoglobin levels of less than 13 g/dl in men and less than 12 g/dl in women using the WHO's criteria. Patients were divided into two groups (472 patients with anemia and 671 patients without anemia). The primary endpoint was major adverse cardiac events (MACE) up to 5 years including death, myocardial infarction, and revascularization.To adjust for confounding factors, we carried out a propensity score matching analysis. Two matched groups (300 pairs, n=600 patients) were generated and their baseline characteristics were balanced. During the 5-year clinical follow-up, patients with anemia had a higher incidence of MI [hazard ratio (HR): 2.137, 95% confidence interval (CI): 1.074-4.254], target vessel revascularization (HR: 1.641, 95% CI: 1.004-2.682), and total MACE (HR: 1.427, 95% CI: 1.012-2.614).AMI patients with anemia on admission had higher incidence of MI, target vessel revascularization, and total MACE over the 5-year follow-up.

Background and objectives Extracorporeal membrane oxygenation (ECMO) support is increasingly used in primary percutaneous coronary intervention (PCI) during cardiopulmonary resuscitation (CPR) to treat acute myocardial infarction (AMI) patients who experienced cardiogenic shock. However, to date, there have been no studies on the relationship between clinical outcomes and CPR time in such patients with AMI treated by ECMO-assisted primary PCI. Methods From July 2008 to March 2016, we analyzed data from 42 AMI with cardiogenic shock patients who underwent CPR and were treated by ECMO-assisted primary PCI. The primary outcome was 30-day in-hospital mortality after primary PCI. The predictors of mortality were determined using a Cox proportional hazards model. Results Thirty-day in-hospital mortality was observed for 33 patients (78.6%). The mean CPR time was 37.0±37.3 minutes. The best cut-off CPR time value associated with clinical outcome was calculated to be 12.5 minutes using receiver operating characteristic curve analysis. Multivariate analysis revealed that CPR time of >12.5 minutes was an independent predictor of 30-day mortality (adjusted hazard ratio, 4.71; 95% confidence interval, 1.30-17.406; p=0.018). Conclusions Despite ECMO support, the clinical outcomes of AMI patients with a complication of cardiogenic shock remain poor. Prolonged CPR time is associated with a poor prognosis in patients with AMI treated by ECMO-assisted primary PCI.

This study sought to investigate the long-term clinical effects of stent generation and stent strategy for left main coronary artery (LMCA) bifurcation lesion treatment.Limited data are available to assess long-term clinical outcomes after stenting, including use of current-generation drug-eluting stent (C-DES) for treatment of LMCA bifurcation lesions.A total of 1,353 patients who were recorded in 2 multicenter real-world registries were treated by either early-generation drug-eluting stent (E-DES) (n = 889) or C-DES (n = 464). Primary endpoint was major adverse cardiovascular events (MACE). MACE was defined as a composite of cardiac death or myocardial infarction, stent thrombosis, and target lesion revascularization rates during 3-year follow-up. The authors further performed propensity-score adjustment for clinical outcomes.During 3-year follow-up, the overall MACE rate was 8.7%. Use of a 1-stent strategy resulted in better clinical outcomes than use of a 2-stent strategy (4.7% vs. 18.6%, hazard ratio [HR]: 3.71; 95% confidence interval [CI]: 2.55 to 5.39; p 0.001). Use of C-DES resulted in a lower MACE rate compared with using E-DES (4.6% vs. 10.9%, HR: 0.55; 95% CI: 0.34 to 0.89; p = 0.014), especially for the 2-stent strategy. For patients with C-DES, the presence of chronic kidney disease and pre-intervention side branch diameter stenosis ≥50% were significant independent predictors of MACE.Intervention of LMCA bifurcation lesions using DES implantation demonstrated acceptable long-term clinical outcomes, especially in C-DES patients. Use of a 1-stent strategy resulted in better clinical benefits than using a 2-stent strategy.

Background Hypertension and dyslipidemia are major risk factors of cardiovascular disease (CVD) events. The objective of this study was to evaluate the efficacy and safety of the co-administration of fimasartan and rosuvastatin in patients with hypertension and hypercholesterolemia. Methods We conducted a randomized double-blind and parallel-group trial. Patients who met eligible criteria after 4 weeks of therapeutic life change were randomly assigned to the following groups. 1) co-administration of fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV), 2) fimasartan 120 mg (FMS) alone 3) rosuvastatin 20 mg (RSV) alone. Drugs were administered once daily for 8 weeks. Results Of 140 randomized patients, 135 for whom efficacy data were available were analyzed. After 8 weeks of treatment, the FMS/RSV treatment group showed greater reductions in sitting systolic (siSBP) and diastolic (siDBP) blood pressures than those in the group receiving RSV alone (both p

Limited data exist on the long-term efficacy of extended dual antiplatelet therapy (DAPT) after left main coronary artery (LMCA) bifurcation stenting. This study investigated the long-term clinical outcomes associated with long-term DAPT after LMCA bifurcation stenting. Using data from the

There are limited long-term outcome data comparing BioLinx polymer (B)-zotarolimus-eluting stents (ZES) with phosphorylcholine polymer (P)-ZES. The aim of this study was to compare the efficacy and safety of B-ZES with P-ZES in patients who underwent percutaneous coronary intervention (PCI) during a 3-year follow-up period.One thousand two hundred fifty four patients who underwent PCI with P-ZES (Endeavor [ZES-E] or Endeavor sprint [ZES-S], n = 356) or B-ZES (Endeavor resolute [ZES-R] or Resolute Integrity [ZES-I], n = 889) were enrolled. The primary endpoint was major adverse cardiac events (MACE); the composite of total death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), non-target vessel revascularization (Non-TVR), and the secondary endpoint was stent thrombosis (ST).After PSM, 2 propensity-matched (PSM) groups (275 pairs, n = 550, C-statistic = 0.730) were generated. During the 3-year follow-up period, the cumulative incidence of MACE (hazard ratio [HR], 1.525; 95% confidence interval [CI], 0.920-2.526; P = .101) and ST (HR, 1.248; 95% CI, 0.335-4.4649; P = .741) were similar between P-ZES and B-ZES after PSM. However, TLR rate was significantly higher in ZES-S than ZES-I (11.3% vs 3.8%, log rank P = .029) and TVR rate was higher in ZES-S than ZES-R (14.1% vs 4.8%, log rank P = .025).In this single-center, all-comer registry, despite different polymers, P-ZES, and B-ZES showed comparable safety and efficacy during a 3-year follow-up period after PCI.

Objectives The goal of this study was to evaluate shorter duration (3 months) dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation. Background There have been few published reports of prospective randomized clinical studies comparing the safety and efficacy of shorter duration DAPT after DES implantation. Methods We randomly assigned 2,117 patients with coronary artery stenosis into 2 groups according to DAPT duration and stent type: 3-month DAPT following Endeavor zotarolimus-eluting stent (E-ZES) implantation (E-ZES+3-month DAPT, n = 1,059) versus 12-month DAPT following the other DES implantation (standard therapy, n = 1,058). We hypothesized that the E-ZES+3-month DAPT would be noninferior to the standard therapy for the primary composite endpoint (cardiovascular death, myocardial infarction, stent thrombosis, target\vessel revascularization, or bleeding) at 1 year. Results The primary endpoint occurred in 40 (4.7%) patients assigned to E-ZES+3-month DAPT compared with 41 (4.7%) patients assigned to the standard therapy (difference: 0.0%; 95% confidence interval [CI]: −2.5 to 2.5; p = 0.84; p Conclusions E-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint. (REal Safety and Efficacy of a 3-month dual antiplatelet Therapy following E-ZES implantation [RESET]; NCT01145079 )

Patient initials or identifier number LKT ### Relevant clinical history and physical exam An 82-years-old male suffered chest pain and dyspnea for 6 hours. He has the history of hypertension. Initial his EKG showed ST-segment elevation in II, III, aVF lead and ST-segment depression in other

Aortoiliac occlusive disease (AIOD) affects the systemic vascular resistance and increases the afterload because the left ventricle (LV) must work harder to eject blood into a smaller vascular bed. This study was to determine whether successful revascularization of AIOD is associated with improvement of left ventricular diastolic dysfunction (LVDD). A total of 37 patients with AIOD (34 men and 3 women; age 65.1 ± 7.2 years) were analyzed. The primary endpoint was defined as the change in the mitral E/E′ ratio. There were no significant changes in the E velocity (from 0.7 ± 0.2 to 0.7 ± 0.2 m/s, P-value = .153), A velocity (from 0.8 ± 0.2 to 0.9 ± 0.2 m/s, P-value = .169), LAVI (from 36.1 ± 18.7 to 33.9 ± 15.7 mL/m2, P-value = .176), E/A ratio (from 0.9 ± 0.4 to 0.8 ± 0.2, P-value = .091), and E′ velocity (from 6.5 ± 2.0 to 6.9 ± 2.1 m/s, P-value = .068). However, successful revascularization significantly reduced the E/E′ ratio (from 14.1 ± 5.7 to 11.7 ± 3.3, P-value = .015). Additionally, a significant increase in the A′ velocity (from 9.1 ± 1.9 to 10.0 ± 2.2 m/s, P-value = .029) and a decrease in the LA diameter (from 40.7 ± 6.4 to 38.6 ± 6.6 mm, P-value = .014) were noted. Our results show that a successful revascularization of AIOD was associated with an improved E/E′ ratio.

Previously, antihypertensive treatment in severe aortic stenosis was considered a relative contraindication. However, recent studies have shown that antihypertensive treatment may be safe and even beneficial in terms of reducing the progression of left ventricular pressure overload and even retarding the progression of valvular aortic stenosis. To date, no randomized clinical trials have been performed and no definite treatment guideline exist for the proper antihypertensive regimens. Antihypertensive treatment with β-blockers has generally been avoided in patients with severe aortic stenosis (AS) due to the concerns for inducing left ventricular dysfunction and hemodynamic compromise in the presence of severe outflow tract obstruction. Although it remains unclear whether antihypertensive treatment with a β-blocker is associated with increased risk of cardiovascular events in patients with AS, recent studies have shown that the use of β-blockers may be safe and may even be beneficial. Renin-angiotensin system (RAS) are upregulated in AS and have been shown to be involved in valve calcification and progression in both experimental models and in human trials. As such, theoretically, RAS inhibition would have benefit in retarding the progression of valvular stenosis as well as have benefit in left ventricle remodeling. Recent clinical studies are indeed showing that use of RAS inhibition may be beneficial in patients with AS. Future clinical trials to establish the ideal target blood pressure and antihypertensive regimens in severe AS is essential.

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (≤170 U/ml) (19.6%) (p

We sought to determine whether insulin resistance (IR) is related to arterial stiffness in nondiabetic hypertensive patients, independent of metabolic status and gender. IR has been associated with increased arterial stiffness in patients with diabetes. In nondiabetic hypertensive patients, the correlation between IR and arterial stiffness has yet to be investigated. We enrolled 284 nondiabetic patients who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment including homeostatic model assessment (HOMA) IR index and pulse wave velocity (PWV). The HOMA IR index is used as a marker of IR, and brachial to ankle PWV (baPWV) was used as a marker of arterial stiffness. Of the 284 study subjects, 121 were classified as having metabolic syndrome. The patients with metabolic syndrome were older than the non-metabolic syndrome patients (55.4+/-10.7 vs. 52.1+/-11.6 years, p=0.013), but there was no gender difference between the two groups. The average baPWV was significantly higher in the patients with metabolic syndrome (1,506+/-235 vs. 1,435+/-211 cm/s, p=0.009). The HOMA index was independently associated with an increase in arterial stiffness (r=0.548, p

Extracorporeal Membrane Oxygenation (ECMO) is an increasingly used supportive measurement for patients with Acute coronary syndrome (ACS) complicated by cardiogenic shock. Despite its increasing use, clinical outcomes still remain very poor. We investigated the clinical features and predictors of 1

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

Importance Use of intravascular ultrasound (IVUS) promotes better clinical outcomes for coronary intervention in complex coronary lesions. However, randomized data demonstrating the clinical usefulness of IVUS are limited for lesions treated with drug-eluting stents. Objective To determine whether the long-term clinical outcomes with IVUS-guided drug-eluting stent implantation are superior to those with angiography-guided implantation in patients with long coronary lesions. Design, Setting, and Participants The Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions (IVUS-XPL) randomized, multicenter trial was conducted in 1400 patients with long coronary lesions (implanted stent ≥28 mm in length) between October 2010 and July 2014 at 20 centers in Korea. Interventions Patients were randomly assigned to receive IVUS-guided (n = 700) or angiography-guided (n = 700) everolimus-eluting stent implantation. Main Outcomes and Measures Primary outcome measure was the composite of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction, or ischemia-driven target lesion revascularization at 1 year, analyzed by intention-to-treat. Results One-year follow-up was complete in 1323 patients (94.5%). Major adverse cardiac events at 1 year occurred in 19 patients (2.9%) undergoing IVUS-guided and in 39 patients (5.8%) undergoing angiography-guided stent implantation (absolute difference, −2.97% [95% CI, −5.14% to −0.79%]) (hazard ratio [HR], 0.48 [95% CI, 0.28 to 0.83], P = .007). The difference was driven by a lower risk of ischemia-driven target lesion revascularization in patients undergoing IVUS-guided (17 [2.5%]) compared with angiography-guided (33 [5.0%]) stent implantation (HR, 0.51 [95% CI, 0.28 to 0.91], P = .02). Cardiac death and target lesion–related myocardial infarction were not significantly different between the 2 groups. For cardiac death, there were 3 patients (0.4%) in the IVUS-guided group and 5 patients (0.7%) in the angiography-guided group (HR, 0.60 [95% CI, 0.14 to 2.52], P = .48). Target lesion–related myocardial infarction occurred in 1 patient (0.1%) in the angiography-guided stent implantation group ( P = .32). Conclusions and Relevance Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at 1 year. These differences were primarily due to lower risk of target lesion revascularization. Trial Registration clinicaltrials.gov Identifier:NCT01308281

Treatments of choice for cardiac implantable electronic device (CIED) infections are the removal of the entire CIED system, control of infection, and new device implantation. Occasionally, a complete CIED removal can not be performed for several reasons, such as very old age, severe comobidity, limited life expectancy, or refusal by a patient. We encountered a male patient who developed traumatic CIED infection five years after cardioverter-defibrillator implantation. An intravenous electrode could not be removed by a simple transvenous extraction procedure, and he refused surgical removal of the remnant electrode. After control of local infection, the tips of the electrode were separated and buried between muscles, and the wound was closed with a local flap. CIED infection did not recur for 12 months even without relying on long-term antimicrobial treatment.

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.

Background—Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results—This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P0.001 and P0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P0.001 for adiponectin, P0.029 for QUICKI by ANOVA). Conclusions—Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients. (Circulation. 2004; 110:3687-3692.)

C-reactive protein (CRP) has been known to be associated with vascular inflammation and hypertension. Pulse wave velocity (PWV) increases according to the degree of the arterial stiffness in hypertension patients. Therefore, PWV may be correlated with CRP levels in treated hypertensive patients, irrespective of medication. We sought to determine whether there is a correlation between hsCRP and arterial stiffness in non-diabetic treated hypertensive patients, independent of cardiovascular risk factor. This study consisted of 424 non-diabetic patients at least 45-years-old who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment of C-reactive protein levels and pulse wave velocity (PWV). Heart to femoral PWV (hfPWV) and brachial to ankle PWV (baPWV) were used as a marker of arterial stiffness. Subjects were categorized according to tertiles of hsCRP level [Group 1: first tertile (0.20-0.46 mg/L), Group 2: second tertile (0.47-1.15 mg/L), Group 3: third tertile (1.17-9.71 mg/L)]. Group 1 consisted of 141 patients (mean age 58+/-8 years), Group 2 had 142 patients (mean age 60+/-9 years) and Group 3 had 141 patients (mean age 61+/-8 years). The hfPWV and baPWV increased significantly along with the hsCRP level. Group 1, Group 2 and Group 3 demonstrated hfPWV and baPWV of 965+/-199 and 1438+/-246, 975+/-174 and 1487+/-258 and 1043+/-215 and 1566+/-252 cm/s, respectively (p

Background Non-dippers are known to carry a high risk of cardiovascular complications due to higher cumulative 24-h pressure load over time. In this study, we hypothesized that non-dippers would be associated with adverse cardiac remodeling and left ventricular (LV) dysfunction in treated hypertensive patients. Materials and methods A total of 150 outpatients treated with antihypertensive drugs for at least 1 year were enrolled. The patients were classified as non-dippers if their daytime ambulatory systolic and diastolic BP did not decrease by at least 10% during the night. LV diastolic function was assessed by measuring mitral inflow velocity ( E ), early diastolic mitral annulus tissue velocity ( E ′) and LV systolic function was assessed by measuring systolic tissue velocity ( S ′), longitudinal systolic strain and strain rate. Results The Cornell voltage product, LA volume index and LV mass index was significantly higher in non-dippers. Early diastolic mitral annulus tissue velocity ( E ′) was lower and E / E ′ was higher in non-dippers suggestive of diastolic dysfunction. Systolic tissue velocity ( S ′), systolic strain and strain rate were significantly lower in non-dippers suggestive of systolic dysfunction. The non-dipper status, controlled for age, sex and LV mass index showed significant correlation with E ′ ( β =−0.203, P =0.002), E / E ′ ( β =0.354, P S ′ ( β =−0.231, P =0.002), strain ( β =−0.162, P =0.040) and strain rate ( β =−0.186, P =0.015). Conclusions This study showed the non-dippers in treated hypertensive patients were associated with adverse cardiac remodeling and early LV dysfunction. Further studies to demonstrate the long term prognostic significance of this finding is warranted.

A 34-year-old woman was admitted to the hospital because of recently aggravated right heart failure without angina for 5 months. When she was 25 years old, patch repair with Polytetrafluoroethylene (PTFE) was performed for the secondum type of atrial septal defect (ASD) with moderate pulmonary hypertension. The chest PA, echocardiography and cardiac catheterization at current admission revealed Eisenmenger syndrome without intracardiac shunt. Chest CT scan with contrast revealed markedly dilated pulmonary trunk, both pulmonary arteries and concave disfigurement of the left side of the ascending aorta suggesting extrinsic compression, as well as total occlusion of the ostium of the left main coronary artery that was retrogradly filled with collateral circulation from the right coronary artery. The coronary angiography showed normal right coronary artery and the collaterals that come out from the conus branch to the mid-left anterior descending artery (LAD) and that from distal right coronary artery to the left circumflex artery (LCX) and to the distal LAD, respectively. On aortography, the left main coronary artery was not visualized with no stump, suggestive of total occlusion of the ostium of the left main coronary artery. From our experience, it is possible to say that the occlusion of the ostium of the left main coronary can be induced by the dilated pulmonary artery trunk due to ASD with pulmonary hypertension and that, if the ASD closure was too late, the narrowing or obstruction of the left coronary artery could not be resolved even after operation owing to irreversible pulmonary hypertension.

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.

Drug-eluting stents (DES) dramatically reduce the rate of restenosis and the need for repeat revascularization. Despite these promising results, stent thrombosis seems to occur more frequently with DES and often seems to be associated with premature discontinuation of antiplatelet agents. We experienced a case of recurrent stent thrombosis with separate lesions. Recurrent stent thrombosis is a very rare event, and simultaneous stent thrombosis is also rare. Here, we report a case of recurrently developing stent thrombosis involving separate lesions. (Korean J Med 2013;84:567-571)

Diagnosing and selecting an appropriate treatment strategy for left main coronary artery (LMCA) obstruction is very important. Although this disease is not frequently encountered, it can cause severe hemodynamic deterioration resulting in a less favorable prognosis without a suitable management approach. Another aspect of LMCA that we must not overlook is coronary artery spasm, which can be an infrequent but important cause of acute coronary syndrome. Although it is rare, LMCA can cause critical complications. In this study, we report the case of a 35-year-old female who was admitted to the hospital with a diagnosis of acute myocardial infarction with ST-segment elevation in the aVR lead caused by a left main coronary spasm that was examined on intravascular ultrasound.

Chest trauma can lead to various cardiac complications ranging from simple arrhythmias to myocardial rupture. A variety of injuries to the coronary arteries, including laceration, thrombosis, intimal dissection, arteriovenous fistula and pseudoaneurysm formation following blunt trauma have been rarely reported. We report a very unusual case of distal embolization of left ventricular thrombus due to blunt chest trauma-induced coronary artery occlusion.

Small dense LDL (sd-LDL) has recently emerged as an important coronary artery disease (CAD) risk factor. This study was performed to investigate how LDL particle size is related to CAD and acute coronary syndrome (ACS). Blood samples were collected from 504 patients that underwent coronary angiography to evaluate chest pain. The LDL particle size of these samples was measured. The mean LDL particle size was smaller in patients with angiographically proven CAD than in the controls (26.41 ± 0.95 vs 26.73 ± 0.64 nm, p < 0.001), and was negatively correlated with the Framingham risk score (r = -0.121, p = 0.007). Patients with more extensive CAD had smaller LDL particles. LDL particle size was also smaller in patients with acute coronary syndrome as compared to non-ACS patients (26.09 ± 1.42 vs 26.54 ± 0.63 nm, p = 0.011). These results suggest that sd-LDL is independently associated with the incidence and extent of CAD, and can be a risk factor for the development of ACS in the Korean population.

Antiarrhythmic agents may increase capture threshold, but this is rarely of clinical significance. Flecainide acetate, a class IC agent, is reported to have a significant effect on the myocardial capture threshold. In this presentation, we report the case of a 72-year-old male, with a previously implanted VVI pacemaker due to sick sinus syndrome, who was treated with flecainide acetate for paroxysmal atrial arrhythmia control. During the fifteenth day of treatment, an abrupt rise in the ventricular capture threshold with ventricular pacing failure was noted. The capture threshold decreased two days after discontinuation of flecainide acetate.

Objectives This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an “all-comer” group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention. Background DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated. Methods Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization. Results Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706 [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs. 72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p Conclusions After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.