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Background: Although exercise stress electrocardiography (ECG) is a popular tool for detecting coronary artery disease (CAD), the induced ST-depression without coronary artery stenosis (FST) remains a challenge for accurate diagnosis. Exercise-induced ST depression is related to poor prognosis even in non-obstructive disease; however, its determinants have not been fully defined. We sought to investigate whether ventriculo-vascular interactional indexes such as arterial stiffness index, exercise hemodynamic parameters and echocardiographic left ventricular (LV) functional parameters were related to FST. Methods: In the current study, 609 participants who underwent both supine bicycle exercise echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement without exercise-induced regional wall motion abnormalities (RWMA) were analyzed. Referral reasons for stress test were CAD detection or evaluation of patency of previous revascularization. Stepwise graded supine bicycle exercise was performed with simultaneous ECG recording and echocardiography after full conventional resting echocardiography. The FST was defined as newly developed >1 mm ST depression without RWMA during exercise. Results: The median age of the study participants was 65 (59.0-70.5) years, and 222 (37%) patients were women. Among them, 103 (17%) patients showed FST during the exercise or recovery phase. The prevalence of FST did not differ between sexes. Older age, higher pulmonary arterial systolic pressure (PASP), left atrial volume index, baPWV and ankle brachial index at rest and hypertensive response, higher heart rate and rate-pressure product at peak exercise were significantly associated with FST. In multivariate analysis, higher peak heart rate, PASP, and baPWV were independently related to FST. Conclusions: Stress-induced RWMA in addition to ECG should be evaluated to detect CAD in patients with higher baPWV and PASP. FST might be linked to subclinical myocardial ischemia through arterial stiffness and diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated.Methods: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated.Results: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (β = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex.Conclusions: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women. [ABSTRACT FROM AUTHOR]

BACKGROUND: Left atrial (LA) remodeling develops as a result of longstanding pressure overload. However, determinants and clinical outcome of excessive remodeling, so called giant left atrium (GLA), are not clear. METHODS: Clinical characteristics of patients with GLA (antero-posterior diameter higher than 65 mm), including echo-Doppler parameters, and follow-up clinical outcomes from a tertiary referral hospital were investigated. RESULTS: Among 68519 consecutive primary patients who underwent echocardiography over a period of 10 years, data from 163 GLA cases (0.24%) were analyzed. Main causes were significant rheumatic mitral stenosis (n = 58, 36%); other causes comprised significant rheumatic mitral regurgitation (MR; n = 10, 6%), mitral valve (MV) prolapse or congenital mitral valvular disease (MVD) (n = 20, 12%), and functional MR (n = 25, 15%). However, mild rheumatic MV disease (n = 4, 3%) or left ventricular (LV) systolic or diastolic dysfunction without significant MR (n = 46, 28%) were also causes of GLA. During median follow-up of 22 months, 42 cases (26%) underwent composite events. MV surgery was related to lower rate of composite events. In multivariate analysis, MV surgery, elevated pulmonary arterial systolic pressure, and increased LA volume index were independent predictors of future events (p < 0.05) regardless of underlying diseases or history of MV surgery. CONCLUSION: Although rheumatic MVD with atrial fibrillation is the main contributor to GLA, longstanding atrial fibrillation with LV dysfunction but without MVD also could be related to GLA. Even in GLA state, accurate measurement of LA volume is crucial for risk stratification for future events, regardless of underlying disease. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is common in patients with heart failure (HF) and worsens their prognosis. Vulnerability to changes in loading is an important factor in the development of AF and is strongly influenced by ventricular stiffness and ventriculo-arterial interaction. The aim of this study was to investigate predictors of AF development in patients with HF.Methods: We studied 349 patients with stable HF. The following parameters of ventricular stiffness and ventriculo-arterial interaction were derived from echo-Doppler measurements: left ventricular (LV) diastolic elastance (Ed), effective arterial elastance (Ea), LV end-systolic elastance (Ees) and ventricular-vascular coupling index (VVI).Results: AF occurred in 57 (16.3%) patients over a median follow up of 30.3 months. Echo-Doppler-derived parameters of ventricular stiffness and ventriculo-arterial interaction were closely associated with HF severity. Ed was independently associated with AF after adjustment for age, hypertension, diabetes mellitus, and left atrial volume index (hazard ratio [HR] 5.49, p = 0.018). Ea and VVI were also associated with new-onset AF (HR 1.66, p = 0.027, and HR 1.06, p = 0.001, respectively).Conclusions: Echo-Doppler indexes of ventricular stiffness are closely associated with HF severity. LV diastolic elastance (Ed) is the strongest predictor of new-onset AF in HF patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Home blood pressure (HBP) measurements are known as an important adjunct to office blood pressure (OBP) measurements in clinical practice. But little is known about the relationship between HBP and subclinical target organ damage (TOD) other than left ventricular hypertrophy (LVH). So we investigated the relationship of HBP measurements with subclinical TOD in untreated hypertensive patients. Methods: We measured ambulatory blood pressure (ABP), HBP and OBP of 93 untreated hypertensive patients (men: 60 and women: 33, mean age, 49±13 years). The ABP was recorded for 24 hours, HBP was measured for one week, and OBP was measured at least in two visits. All BP measurements were taken using automatic BP measuring device. The parameters indicating subclinical TOD were the left-ventricular mass index (LVMI) by transthoracic echocardiography, urinary albumin excretion rate (AER), brachial ankle pulse-wave velocity (PWV), and carotid intima-media thickness (IMT). Results: The LVMI was significantly correlated with systolic HBP and 24 hours systolic ABP but not with OBP The AER, PWV and IMT were also significantly correlated with systolic HBP and 24 hours systolic ABP In a binary logistic regression analysis, systolic HBP 24 hours systolic and diastolic ABP were the predictors of LVMI, AER and PWV (all p<0.05). Conclusion: Our data suggest that HBP is as good as ABP monitoring and superior to OBP measurements in regard to their association with subclinical TOD. Therefore, HBP measurements give valuable information on the subclinical TOD in hypertensive patients in addition to ABP monitoring. [ABSTRACT FROM AUTHOR]

Background: Dynamic left ventricular (LV) outflow tract (LVOT) obstruction (DLVOTO) is not infrequently observed in older individuals without overt hypertrophic cardiomyopathy (HCM). We sought to investigate associated geometric changes and then evaluate their clinical characteristics. Methods: A total of 168 patients with DLVOTO, which was defined as a trans-LVOT peak pressure gradient (PG) higher than 30 mmHg at rest or provoked by Valsalva maneuver (latent LVOTO) without fixed stenosis, were studied. Patients with classical HCM, acute myocardial infarction, stress induced cardiomyopathy or unstable hemodynamics which potentially induce transient-DLVOTO were excluded. Results: Their mean age was 71 ± 11 years and 98 (58%) patients were women. Patients were classified as pure sigmoid septum (n = 14) if they have basal septal bulging but diastolic thickness less than 15 mm, sigmoid septum with basal septal hypertrophy for a thickness ≥15 mm (n = 85), prominent papillary muscle (PM) (n = 20) defined by visually large PMs which occluded the LV cavity during systole or 1/2 LVESD, or as having a small LV cavity with concentric remodelling or hypertrophy (n = 49). The prominent PM group was younger, had a higher S’ and lower E/e’ than other groups. In all groups, a higher peak trans-LVOT PG was related (p < 0.10) to higher E/e’, systolic blood pressure, relative wall thickness, and pulmonary arterial systolic pressure. In multivariate analysis, resting trans-LVOT PG correlated to pulmonary arterial pressure (ß = 0.226, p = 0.019) after adjustment for systolic blood pressure, relative wall thickness, and E/e’. Conclusions: DLVOTO develops from various reasons, and patients with prominent PMs have distinct characteristics. We suggest to use DLVOTO-relieving medication might reduce pulmonary pressure in this group of patients. [ABSTRACT FROM AUTHOR]

Background We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI). Methods Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured. Results Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r = -0.57, p < 0.001), regional wall motion score index (r = 0.52, p = 0.001), and global longitudinal strain (r = 0.56, p < 0.001). The diastolic functional indices significantly correlated with age (r = -0.64, p < 0.001), LV twist (r = -0.39, p = 0.02), average non-infarcted myocardial circumferential strain (r = -0.52, p = 0.001), and LV end-diastolic wall stress index (r = -0.47, p = 0.003 with e') but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury. Conclusions In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function. [ABSTRACT FROM AUTHOR]

Background: It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD. Methods: The study enrolled 363 consecutive patients (196 men, 62 ± 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score. Results: Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0-1, 2, 3, 4-5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM. Conclusions: In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM. [ABSTRACT FROM AUTHOR]

Background: Post-contrast T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequence has been introduced as a promising means to assess an expansion of the extra-cellular space. However, T1 value in the myocardium can be affected by scanning time after bolus contrast injection. In this study, we investigated the changes of the T1 values according to multiple slicing over scanning time at 15 minutes after contrast injection and usefulness of blood T1 correction. Methods: Eighteen reperfused acute myocardial infarction (AMI) patients, 13 cardiomyopathy patients and 8 healthy volunteers underwent cardiovascular magnetic resonance with 15 minute-post contrast MOLLI to generate T1 maps. In 10 cardiomyopathy cases, pre- and post-contrast MOLLI techniques were performed to generate extracellular volume fraction (Ve). Six slices of T1 maps according to the left ventricular (LV) short axis, from apex to base, were consecutively obtained. Each T1 value was measured in the whole myocardium, infarcted myocardium, non-infarcted myocardium and LV blood cavity. Results: The mean T1 value of infarcted myocardium was significantly lower than that of non-infarcted myocardium (425.4±68.1 ms vs. 540.5±88.0 ms, respectively, p< 0.001). T1 values of non-infarcted myocardium increased significantly from apex to base (from 523.1±99.5 ms to 561.1±81.1 ms, p=0.001), and were accompanied by a similar increase in blood T1 value in LV cavity (from 442.1±120.7 ms to 456.8±97.5 ms, p<0.001) over time. This phenomenon was applied to both left anterior descending (LAD) territory (from 545.1±74.5 ms to 575.7±84.0 ms, p<0.001) and non-LAD territory AMI cases (from 501.2±124.5 ms to 549.5±81.3 ms, p<0.001). It was similarly applied to cardiomyopathy patients and healthy volunteers. After the myocardial T1 values, however, were adjusted by the blood T1 values, they were consistent throughout the slices from apex to base (from 1.17±0.18 to 1.25±0.13, p>0.05). The Ve did not show significant differences from apical to basal slices. Conclusion: Post-contrast myocardial T1 corrected by blood T1 or Ve, provide more stable measurement of degree of fibrosis in non-infarcted myocardium in short- axis multiple slicing. [ABSTRACT FROM AUTHOR]

Background: Fixed-dose combination drugs may enhance blood pressure (BP) goal attainment through complementary effects and reduced side effects, which leads to better compliance. Objective: This study aimed to evaluate the efficacy and safety profiles of once-daily combination amlodipine /losartan versus losartan. Methods: This was an 8-week, double-blind, multicenter, randomized phase III study conducted in out-patient hospital clinics. Korean patients with essential hypertension inadequately controlled on losartan 100 mg were administered amlodipine /losartan 5 mg /100 mg combination versus losartan 100 mg. The main outcome measures were changes in sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP) and BP response rate from baseline values, which were assessed after 4 and 8 weeks of treatment. Safety and tolerability were also assessed. Results: At week 8, both groups achieved significant reductions from baseline in DBP (11.7 ± 7.0 and 3.2 ± 7.9 mm Hg), which was significantly greater in the amlodipine /losartan 5 mg /100 mg combination (n = 70) group (p< 0.0001). Additionally, the amlodipine /losartan 5 mg /100 mg combination group achieved significantly greater reductions in SBP at week 8 and in SBP and DBP at week 4 compared with the losartan 100 mg (n= 72) group (all p < 0.0001). Response rates were significantly higher in the amlodipine /losartan 5mg /100 mg group versus the losartan 100 mg group (81.4% vs 63.9 % at week 4, p < 0.0192; 90.0% vs 66.7 % at week 8, p< 0.001). Both treatments were generally well tolerated. Conclusion: Switching to a fixed-dose combination therapy of amlodipine /losartan 5 mg /100 mg was associated with significantly greater reductions in BP and superior achievement of BP goals compared with a maintenance dose of losartan 100 mg in Korean patients with essential hypertension inadequately controlled on losartan 100 mg. Clinical Trial Registration: Registered at Clinicaltrials.gov as NCT00940680. [ABSTRACT FROM AUTHOR]

Background: Fixed-dose combination drugs may enhance blood pressure (BP) goal attainment through complementary effects and reduced side effects, which leads to better compliance. Objective: This study aimed to evaluate the efficacy and safety profiles of once-daily combination amlodipine /losartan versus losartan. Methods: This was an 8-week, double-blind, multicenter, randomized phase III study conducted in out-patient hospital clinics. Korean patients with essential hypertension inadequately controlled on losartan 100 mg were administered amlodipine /losartan 5 mg /100 mg combination versus losartan 100 mg. The main outcome measures were changes in sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP) and BP response rate from baseline values, which were assessed after 4 and 8 weeks of treatment. Safety and tolerability were also assessed. Results: At week 8, both groups achieved significant reductions from baseline in DBP (11.7 ± 7.0 and 3.2 ± 7.9 mm Hg), which was significantly greater in the amlodipine /losartan 5 mg /100 mg combination (n = 70) group (p< 0.0001). Additionally, the amlodipine /losartan 5 mg /100 mg combination group achieved significantly greater reductions in SBP at week 8 and in SBP and DBP at week 4 compared with the losartan 100 mg (n= 72) group (all p < 0.0001). Response rates were significantly higher in the amlodipine /losartan 5mg /100 mg group versus the losartan 100 mg group (81.4% vs 63.9 % at week 4, p < 0.0192; 90.0% vs 66.7 % at week 8, p< 0.001). Both treatments were generally well tolerated. Conclusion: Switching to a fixed-dose combination therapy of amlodipine /losartan 5 mg /100 mg was associated with significantly greater reductions in BP and superior achievement of BP goals compared with a maintenance dose of losartan 100 mg in Korean patients with essential hypertension inadequately controlled on losartan 100 mg. Clinical Trial Registration: Registered at Clinicaltrials.gov as NCT00940680. [ABSTRACT FROM AUTHOR]

Background: Despite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients. Objective: The aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension. Methods: This was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18--75 years with essential hypertension. At screening, patients received placebo for 2--4 weeks. Eligible patients (n = 320) were randomized to one of eight treatment groups: amlodipine 5mg or 10 mg, losartan 50mg or 100 mg, amlodipine camsylate/losartan 5mg/50 mg, 5mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg. Main Outcome Measures: The assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events. Results: The reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100mg versus amlodipine 10 mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant. Conclusion: Combination amlodipine camsylate/losartan (5 mg/50 mg, 5mg/100mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension. Clinical Trial Registration: Registered at clinicaltrials.gov: NCT00942344. [ABSTRACT FROM AUTHOR]

Objectives: Vasovagal syncope (VVS) has been believed to occur when mechanoreceptors are discharged by vigorous ventricular contraction. However, previous investigators have reported divergent observations regarding the presence of left ventricular (LV) hypercontractility in VVS. Because the autonomic nervous system can be promptly activated after certain stimuli, we postulated that instantaneously increased LV contractility at the time of venous pooling may trigger the disregulated vasovagal reaction in VVS. Methods: Forty-seven patients (31 males, mean age 41 ± 18 years) with unexplained syncope were enrolled. Echocardiography was performed during the head-up tilt test (HUTT) as follows: baseline, passive tilting (0 and 20 min), and tilting with isoproterenol administration (5 and 10 min). Patients were divided into 2 groups according to the results of the HUTT; group 1 (n = 12) had a positive result and group 2 had a negative response. Results: LV ejection fraction (LVEF), determined immediately after tilting, increased in group 1, whereas LVEF decreased in group 2 (p = 0.032). Although left atrial and LV volumes decreased similarly during the test, group 1 showed a progressive reduction in LVEF, while LVEF progressively increased in group 2 (p = 0.007). Conclusion: Patients with HUTT-induced VVS presented LV hypercontractions immediately after tilting and a subsequent decrease in LV contractility. An instantaneous activation of the sympathetic nervous system at the time of venous pooling may trigger an early disregulated vasovagal reflex via an increase in LV contractility in VVS. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background:Prasugrel is a third generation thienopyridine that is more potent, rapid in onset, and consistent in inhibition of platelets than clopidogrel. However, early prasugrel dose-ranging studies and the subsequent phase 3 TRITON-TIMI 38 trial were conducted primarily in Caucasian populations.Objectives:The current clinical study is designed to confirm superior inhibition of platelet aggregation with prasugrel versus clopidogrel in the treatment of Asian subjects with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).Research design and methods:This is a phase 3, randomized, double-blind, multi-dose, four-arm parallel, multinational clinical trial. East and Southeast Asian patients (N  715) with moderate- to high-risk ACS undergoing PCI will be randomized to one of three prasugrel dosing regimens (60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD) or clopidogrel (300 mg LD/75 mg MD) for 90 days.Main outcome measures:The primary endpoint is inhibition of platelet aggregation measured by the point-of-care Accumetrics VerifyNow P2Y12 device, and the primary analysis will be performed in a hierarchical manner for descending doses of prasugrel. Additional key endpoints include major adverse cardiovascular events, non-coronary artery bypass-graft (CABG) surgery-related TIMI bleeding, and genetic analyses of cytochrome P450 polymorphisms.Conclusions:This study is a phase 3, multi-dose, pharmacodynamic comparison of prasugrel versus clopidogrel in Asian patients with ACS undergoing PCI. It is the first study designed to investigate prasugrel therapy specifically in Asian ACS subjects, and will inform which doses of prasugrel are effective and safe for patients of Asian ethnicity. [ABSTRACT FROM AUTHOR]

Background:Prasugrel is a third generation thienopyridine that is more potent, rapid in onset, and consistent in inhibition of platelets than clopidogrel. However, early prasugrel dose-ranging studies and the subsequent phase 3 TRITON-TIMI 38 trial were conducted primarily in Caucasian populations.Objectives:The current clinical study is designed to confirm superior inhibition of platelet aggregation with prasugrel versus clopidogrel in the treatment of Asian subjects with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).Research design and methods:This is a phase 3, randomized, double-blind, multi-dose, four-arm parallel, multinational clinical trial. East and Southeast Asian patients (N  715) with moderate- to high-risk ACS undergoing PCI will be randomized to one of three prasugrel dosing regimens (60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD) or clopidogrel (300 mg LD/75 mg MD) for 90 days.Main outcome measures:The primary endpoint is inhibition of platelet aggregation measured by the point-of-care Accumetrics VerifyNow P2Y12 device, and the primary analysis will be performed in a hierarchical manner for descending doses of prasugrel. Additional key endpoints include major adverse cardiovascular events, non-coronary artery bypass-graft (CABG) surgery-related TIMI bleeding, and genetic analyses of cytochrome P450 polymorphisms.Conclusions:This study is a phase 3, multi-dose, pharmacodynamic comparison of prasugrel versus clopidogrel in Asian patients with ACS undergoing PCI. It is the first study designed to investigate prasugrel therapy specifically in Asian ACS subjects, and will inform which doses of prasugrel are effective and safe for patients of Asian ethnicity. [ABSTRACT FROM AUTHOR]

Background: There are still controversies about long-term clinical outcomes of sirolimus-eluting stents (SES) versus bare metal stents (BMS) implantation in patients with end-stage renal diseases (ESRD). Objective: To compare long-term outcomes in patients with (ESRD) following SES versus BMS implantation. Methods: Between March 2003 and July 2005, a total of 54 patients (80 lesions) with ESRD undergoing SES implantation [SES-ESRD] were enrolled and compared with 51 patients (54 lesions) with ESRD receiving BMS during the same periods [BMS-ESRD] in the Korean Multicenter Angioplasty Team Registry. The primary outcome was the composite of death, myocardial infarction (MI), or any stent thrombosis (ST) according to the Academic Research Consortium definition during a 3-year follow-up. Results: The cumulative 3-year rate of composite of death, MI, or ST of the SES-ESRD group (24%) was nearly similar with that of the BMS-ESRD group (24%, P = 1.000). The 3-year rates of death (26% vs. 24%, P = 0.824) or MACE (37% vs. 43%, P = 0.331) in the SES-ESRD did not differ significantly from those in the BMS-ESRD. However, the SES-ESRD showed a sustained lower 3-year TVR rate (9%), compared with BMS-ESRD (24%, P = 0.042). The rate of any ST in SES-ESRD was not significantly higher than that in the BMS-ESRD (17% vs. 14%, P = 0.788). There was no significant difference in the rate of late or very late ST between SES-ESRD (15%) versus BMS-ESRD group (10%, P = 0.557). Conclusions: SES did not increase the risks for death, MI, or any ST in patients with ESRD during the long-term follow-up, compared with BMS. [ABSTRACT FROM AUTHOR]

Background: The pathophysiological role and metabolic pathway of Lp(a) have not been clearly defined. An association between Lp(a) and oxidative low-density lipoprotein (LDL) were recently reported. And small dense LDL (sd-LDL) were associated with circulating malondialdehyde-modified LDL. We investigated the relationships between serum Lp(a) level and LDL particle size in coronary artery disease (CAD) patients. Further, we investigated the relationships of sd-LDL and Lp(a) with the extent and severity of CAD. Methods: A total of 490 patients (mean: 60.5 ± 11.5 years old) who underwent coronary angiography to evaluate chest pain were investigated. Patients were classified into two groups, a CAD group (n = 256), who had significant stenosis observed by coronary angiogram, and a control group (n = 234), who had normal, or minimal coronary arteries. CAD severity was measured by Gensini scores. The distribution of the LDL subfraction was analyzed using a Quantimetrix Lipoprint LDL System. Results: The serum Lp(a) concentration was correlated with the fraction of sd-LDL (r = 0.193, p < 0.001) and mean LDL size (r = 0.160, p = 0.003). The Lp(a) level and mean LDL particle size were significantly correlated with a high Gensini score. LDL particle size in the CAD group was smaller than in the control group (26.74 ± 0.64 vs. 26.43 ± 0.93 nm, p < 0.001). The Gensini score was significantly higher in small LDL with high Lp(a) level groups. Conclusion: The positive correlation of the level of Lp(a) and sd-LDL fraction were demonstrated. The mechanism of this association is not clearly defined; we can suggest that it may stem from the individual atherogenic condition that linked to increased oxidative stress. Both increased Lp(a) and sd-LDL fraction were correlated with the severity of CAD. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This study aims to investigate surgical outcomes in patients with Behcet’s disease (BD) and to identify risk factors for the occurrence of postoperative complications. The medical records of 37 patients with newly diagnosed BD were reviewed retrospectively. All patients fulfilled the International Study Group criteria for diagnosis of BD and underwent surgeries after diagnosis. Demographic, clinical, and laboratory data at the time when surgeries were performed were collected and surgical modalities, postoperative complications, and postoperative medical treatments were evaluated. Forty-three surgeries were performed in 37 patients. During mean follow-up duration of 78.2 ± 50.3 months, 14 surgeries (32.6%) were complicated by wound dehiscence, infection, and graft occlusion or failure with the mean lag time of 6.0 ± 4.6 months from surgeries. Cumulative incidence of postoperative complications was 7.7% at 3 months, 25.6% at 6 months, 33.3% at 12 months, and 35.9% at 18 months. Postoperative complications occurred more frequently after surgeries that were performed in patients with positive pathergy test ( P < 0.001) and after vascular surgeries than after nonvascular surgeries ( P < 0.05). Moreover, surgeries that were followed by glucocorticoids with immunosuppressive agents showed a significantly lower postoperative complication rate compared to those that were followed by glucocorticoids alone and those that were not followed by medical treatment ( P < 0.05). Multivariate analysis showed that a positive pathergic reaction ( P < 0.05, hazard ratio = 1.91) at the time of surgery and surgeries that were not followed by treatment with glucocorticoids and immunosuppressive agent ( P < 0.01, hazard ratio = 2.11) was an independent risk factor for the occurrence of postoperative complications. Our findings suggest that the occurrence of postoperative complications can be reduced when postsurgical immunosuppressive treatment was implemented and that the pathergy test can be used as screening methods for occurrence of postoperative complications in patients with BD. [ABSTRACT FROM AUTHOR]

Murine leukemia virus (MLV)-derived vectors are widely used for hematopoietic stem cell (HSC) gene transfer, but lentiviral vectors such as the simian immunodeficiency virus (SIV) may allow higher efficiency transfer and better expression. Recent studies in cell lines have challenged the notion that retroviruses and retroviral vectors integrate randomly into their host genome. Medical applications using these vectors are aimed at HSCs, and thus large-scale comprehensive analysis of MLV and SIV integration in long-term repopulating HSCs is crucial to help develop improved integrating vectors. We studied integration sites in HSCs of rhesus monkeys that had been transplanted 6 mo to 6 y prior with MLV- or SIV-transduced CD34+ cells. Unique MLV (491) and SIV (501) insertions were compared to a set of in silico-generated random integration sites. While MLV integrants were located predominantly around transcription start sites, SIV integrants strongly favored transcription units and gene-dense regions of the genome. These integration patterns suggest different mechanisms for integration as well as distinct safety implications for MLV versus SIV vectors. [ABSTRACT FROM AUTHOR]