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Objective : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats.Methods : Twenty-eight female Wistar rats (250–300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson’s trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured.Results : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson’s trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p

The purpose of this study was to determine the efficacy of highly concentrated tricalcium phosphate (TCP) biocomposite screws on local bone formation in a rabbit model of osteoporosis induced by bilateral ovariohysterectomy (OHE). Fourteen 24-week-old female New Zealand rabbits (weight, 3-3.5 kg) were divided into two groups: 1) OHE and biodegradable poly(lactic-co-glycolic acid) (PLGA) without s-TCP plate or screw insertion (OHE/BSR) group; and 2) OHE and biocomposite PLGA with highly concentrated s-TCP plate and screw insertion (OHE/HCCP). Both groups underwent bilateral OHE and had two different types of screws and plates inserted at the proximal tibia. Bilateral tibiae were extracted at 25 weeks post-OHE. The extracted tibiae were scanned with ex-vivo micro-computed tomography (micro-CT). Parameters including bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were evaluated after staining the tibial samples with hematoxylin and eosin (H&E) and Masson's trichrome. We then performed pathological assessments. Micro-CT images revealed improved new bone formation near the implant in the OHE/HCCP group with higher values of BMD, BV/TV, and Tb.N but lower values of Tb.Th and Tb.Sp than the OHE/BSR group. Analyses of H&E and Masson's trichrome staining showed better new bone formation around the implant in the OHE/HCCP group than in the OHE/BSR group. The use of highly concentrated TCP biocomposite screw and plate might improve local bone formation and facilitate osteoconductivity in an osteoporotic rabbit model. This article is protected by copyright. All rights reserved.

Background Studies have shown that the concomitant use of a vitamin K antagonist (VKA) and an antiplatelet (APL) drug increased the bleeding risk and was less effective at preventing ischemic events. This study aimed to investigate the control status of international normalized ratio (INR) and the discontinuation rate of a VKA in patients taking VKA plus an APL drug compared with those taking a VKA alone. Methods Data were extracted from the KORean Atrial Fibrillation Investigation II registry, a multicenter noninterventional prospective observational study. Nonvalvular atrial fibrillation (NVAF) patients with CHADS 2 scores ≥ 1 who newly started (within 3 months) a VKA were enrolled and followed up for 1 year. Results A total of 866 NVAF patients (mean age, 67.7 years; 60.3% men) without a bleeding history were divided into the VKA+APL (n = 229) and VKA alone (n = 637) groups. During follow‐up, mean INR level was lower in the VKA+APL group than in the VKA alone group (1.7 ± 0.8 vs 1.9 ± 0.9, P = 0.0005). INR levels were poorly controlled in both groups (66.1% and 64.7%, respectively). Patients in the VKA+APL group more frequently discontinued VKA than patients in the VKA alone group (28.8% vs 24.2%, P = 0.045). Major causes of VKA discontinuation were uncontrolled INR level and patient dissatisfaction or concerns. Conclusions The conditions of NVAF patients were inadequately controlled with VKA with or without an APL. These findings suggest that other antithrombotic treatment options are warranted in NVAF patients to achieve INR control.

Objective The aim of this study was to evaluate the effect for biodegradable screws containing bone morphogenetic protein-2 (BMP-2) in an osteoporotic rat model. Methods Twenty-four female Wistar rat (250–300 g, 12 weeks of age) were randomized into four groups. Three groups underwent bilateral ovariectomy (OVX). Biodegradable screws with or without BMP-2 were inserted in the proximal tibia in two implantation groups. The extracted proximal metaphysis of the tibiae were scanned by exo-vivo micro-computed tomography. Evaluated parameters included bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number, trabecular thickness, and trabecular separation (Tb.Sp). The tibia samples were pathologically evaluated by staining with by Hematoxylin and Eosin, and trichrome. Results Trabecular formation near screw insertion site was evident only in rats receiving BMP-2 screws. BMD and BV/TV significantly differed between controls and the OVX and OVX with screw groups. However, there were no significant differences between control and OVX with screw BMP groups. Tb.Sp significantly differed between control and OVX and OVX with screw groups (p

The cryoballoon was invented to achieve circumferential pulmonary vein isolation more efficiently to compliment the shortcomings of point-by-point ablation by radiofrequency ablation (RFA). Its efficacy and safety were shown to be comparable to those of RFA, and the clinical outcomes have improved with the second-generation cryoballoon. The basic biophysics, implemental techniques, procedural recommendations, clinical outcomes, and complications of the cryoballoon are presented in this practical and systematic review.

Objective To evaluate the efficacy of biocomposite screws used in ovariectomy (OVX)-induced osteoporotic rats. Methods Twenty-four female Wistar rats (250–300 g, 12 weeks old) were divided into 4 groups: sham group (control), OVX-induced osteoporosis group (OVX), OVX and biodegradable poly(lactic- co -glycolic acid) (PLGA) without tricalcium phosphate (β-TCP) screw insertion group (OVX/BSR), and OVX and biocomposite (PLGA with β-TCP) screw insertion group (OVX/CSR). Three groups underwent bilateral OVX, and of these, 2 groups had 2 different types of screw inserted at the proximal tibia. At 25 weeks after OVX, the bilateral tibias were extracted. The extracted tibiae were scanned by ex vivo micro-computed tomography (CT) and stained with hematoxylin and eosin (H&E) and with Masson's trichrome stain for pathological assessment. Results Compared with the ovariectomized groups, the control group had the highest values for bone mineral density (BMD), bone volume (BV)/total volume (TV), and trabecular number (Tb.N) and the lowest values for trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). In the pairwise comparison among ovariectomized groups, the OVX/CSR group had significantly higher BMD, BV/TV, and Tb.N values than the other 2 groups (OVX and OVX/BSR) and significantly lower Tb.Sp. Micro-CT scans showed clear evidence of new trabecular formation near the screw insertion site in the OVX/CSR group only. Analyses of H&E- and Masson's trichrome–stained sections showed more and thicker trabecular bone around the implant in the OVX/CSR group compared with the OVX and OVX/BSR groups. Conclusions Biocomposite screws can improve local bone quality and facilitate osteoconductivity in an osteoporotic rat model.

Noncompaction of ventricular myocardium, once thought to represent a rare cardiomyopathy, is being diagnosed with increased frequency. It is often accompanied by various congenital heart diseases. Coexisting valvular anomalies are an emerging issue that requires further investigation in patients with noncompaction cardiomyopathy, because they can increase the potential for adverse clinical events. This article describes the case of a 45-year-old male diagnosed with left ventricular noncompaction (LVNC) with a bicuspid aortic valve. Progressive deterioration of cardiac function in this patient could be explained by myocardial fibrosis and accompanying valvular anomalies on cardiac magnetic resonance imaging (MRI). The clinical implications of cardiac MRI in noncompaction cardiomyopathy are discussed based on its ability to depict both morphological and functional features. Considering the potential for coexisting congenital heart disease to declines in cardiac function, patients with LVNC should be comprehensively evaluated for concurrent cardiac anomalies and myocardial fibrosis.

Background Vitamin K antagonist (VKA) to prevent thromboembolism in non-valvular atrial fibrillation (NVAF) patients has limitations such as drug interaction. This study investigated the clinical characteristics of Korean patients treated with VKA for stroke prevention and assessed quality of VKA therapy and treatment satisfaction. Methods We conducted a multicenter, prospective, non-interventional study. Patients with CHADS2 ≥ 1 and treated with VKA (started within the last 3 months) were enrolled from April 2013 to March 2014. Demographic and clinical features including risk factors of stroke and VKA treatment information was collected at baseline. Treatment patterns and international normalized ratio (INR) level were evaluated during follow-up. Time in therapeutic range (TTR) > 60% indicated well-controlled INR. Treatment satisfaction on the VKA use was measured by Treatment Satisfaction Questionnaire for Medication (TSQM) after 3 months of follow-up. Results A total of 877 patients (age, 67; male, 60%) were enrolled and followed up for one year. More than half of patients (56%) had CHADS2 ≥ 2 and 83.6% had CHA2DS2-VASc ≥ 2. A total of 852 patients had one or more INR measurement during their follow-up period. Among those patients, 25.5% discontinued VKA treatment during follow-up. Of all patients, 626 patients (73%) had poor-controlled INR (TTR < 60%) measure. Patients' treatment satisfaction measured with TSQM was 55.6 in global satisfaction domain. Conclusion INR was poorly controlled in Korean NVAF patients treated with VKA. VKA users also showed low treatment satisfaction., Graphical Abstract

The long-term prognosis of patients with variant angina presenting with aborted sudden cardiac death (ASCD) is unknown.The purpose of this study was to evaluate the long-term mortality and ventricular tachyarrhythmic events of variant angina with and without ASCD.Between March 1996 and September 2014, 188 patients with variant angina with ASCD and 1,844 patients with variant angina without ASCD were retrospectively enrolled from 13 heart centers in South Korea. The primary endpoint was cardiac death.Predictors of ASCD manifestation included age (odd ratio [OR]: 0.980 by 1 year increase; 95% confidence interval [CI]: 0.96 to 1.00; p = 0.013), hypertension (OR: 0.51; 95% CI: 0.37 to 0.70; p 0.001), hyperlipidemia (OR: 0.38; 95% CI: 0.25 to 0.58; p 0.001), family history of sudden cardiac death (OR: 3.67; 95% CI: 1.27 to 10.6; p = 0.016), multivessel spasm (OR: 2.06; 95% CI: 1.33 to 3.19; p = 0.001), and left anterior descending artery spasm (OR: 1.40; 95% CI: 1.02 to 1.92; p = 0.04). Over a median follow-up of 7.5 years, the incidence of cardiac death was significantly higher in ASCD patients (24.1 per 1,000 patient-years vs. 2.7 per 1,000 patient-years; adjusted hazard ratio [HR]: 7.26; 95% CI: 4.21 to 12.5; p 0.001). Death from any cause also occurred more frequently in ASCD patients (27.5 per 1,000 patient-years vs. 9.6 per 1,000 patient-years; adjusted HR: 3.00; 95% CI: 1.92 to 4.67; p 0.001). The incidence rate of recurrent ventricular tachyarrhythmia in ASCD patients was 32.4 per 1,000 patient-years, and the composite of cardiac death and ventricular tachyarrhythmia was 44.9 per 1,000 patient-years. A total of 24 ASCD patients received implantable cardioverter-defibrillators (ICDs). There was a nonsignificant trend of a lower rate of cardiac death in patients with ICDs than those without ICDs (p = 0.15).The prognosis of patients with variant angina with ASCD was worse than other patients with variant angina. In addition, our findings supported ICDs in these high-risk patients as a secondary prevention because current multiple vasodilator therapy appeared to be less optimal.

Objective Hypothermia can induce ECG J waves. Recent studies suggest that J waves may be associated with ventricular fibrillation (VF) in patients with structurally normal hearts. However, little is known about the ECG features, clinical significance or arrhythmogenic potentials of therapeutic hypothermia (TH)-induced J waves. Methods We analysed ECGs from 240 patients who underwent TH at six major university hospitals in Korea between August 2010 and December 2013. The prevalence, amplitudes and distributions of the J waves and the development of malignant arrhythmia were analysed. Results The average patient body temperature was 33.5±1.0°C during TH. J waves were observed in 98 patients (40.8%). They were newly developed in 91 cases, and pre-existing J waves were augmented in seven patients. J waves during TH were primarily observed in leads II, III, aVF and V 4–6 . The average amplitude of the J waves was 0.239±0.152 mV. There were four VF events during TH. These events occurred in three patients who were finally diagnosed with Brugada syndrome, idiopathic VF or early repolarisation syndrome, respectively, and in one patient with non-cardiac aetiology (asphyxia). Conclusions J waves were recorded in about 40% of the patients who received TH. They were most frequently observed in the inferior limb leads or lateral precordial leads. Life-threatening VF occurred only rarely (1.7%) during TH and were mainly observed in patients with primary arrhythmic disorder. Although a causal relationship between TH-induced J waves and VF remains unknown, administering TH to this potentially susceptible, high-risk population may require careful attention.

Background and objectives Pacemaker (PM) implantation is a well-accepted treatment option for patients with paroxysmal atrial fibrillation (AF) and related tachycardia-bradycardia syndrome (TBS). Data on the long-term clinical outcomes after radiofrequency catheter ablation (RFCA) or PM implantation are sparse. Methods The medical records of 217 patients with TBS were retrospectively assessed. Outcomes in patients who underwent RFCA (n=108, 49.8%) were compared to those with PM implantation (n=109, 50.2%). The clinical outcomes were sinus rhythm maintenance, conversion to persistent AF, additional procedure or crossover, and the composite of cardiovascular hospitalization and death. Results During the follow-up period (mean 3.5±2.0 years), the RFCA group, compared to the PM group, showed better sinus rhythm maintenance (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.15-0.46; p=0.002) and less progression to persistent AF (aHR, 0.20; 95% CI, 0.06-0.63; p=0.006). Additional procedure or crossover did not differ significantly between the groups (aHR, 2.07; 95% CI, 0.71-6.06; p=0.185 and aHR, 0.69; 95% CI, 10.8-2.67; p=0.590, respectively). Most RFCA patients (92.6%) did not require pacemaker implantation during long term follow-up period (>3.5 years). The composite endpoint of cardiovascular rehospitalization and death was not significantly different between the groups (aHR, 0.92; 95% CI, 0.50-1.66; p=0.769). Conclusions RFCA is an effective alternative to PM implantation in patients with TBS. In these patients, successful RF ablation of AF is related to a higher rate of sinus rhythm maintenance compared to PM implantation, and the composite outcome of cardiovascular rehospitalization and death is similar.

The presence of an occluded culprit artery or collaterals in non-ST-segment elevation myocardial infarction (NSTEMI) is relatively common; however, limited data are available regarding their clinical significance. The aim of the current study was to determine the clinical characteristics of occluded culprit arteries and coronary collaterals in patients with NSTEMI and their impact on patient outcomes. A total of 345 patients diagnosed with NSTEMI via coronary angiography between February 2006 and May 2013 were evaluated in the present study. Patient demographics, procedural characteristics and clinical outcomes of patients were analyzed according to the presence of an occluded culprit artery and coronary collaterals. A total of 78 (22.6%) and 166 patients (48.1%) exhibited an occluded artery and coronary collaterals, respectively. The left anterior descending artery is a more common location of culprit arteries in patients with NSTEMI with patent artery (NSTEMIPA) and distal parts of the artery are more common location of culprit arteries in patients with NSTEMI with occluded arteries (NSTEMIOA). Patients with NSTEMIOA exhibited higher peak creatine kinase-MB (CKMB) and troponin-I levels compared with patients that had NSTEMIPA. The presence of coronary collaterals is associated with a lower mean left ventricular ejection fraction, higher regional wall motion score index and extensive coronary artery disease. However, the clinical outcomes of patients with collaterals did not differ, irrespective of the presence of an occluded culprit artery or coronary collaterals. In the current study, ~25% of patients with NSTEMI had an occluded culprit coronary artery whereas 50% of patients with NSTEMI had coronary collaterals. The presence of an occluded artery and/or coronary collaterals did not affect clinical outcomes. Further studies are required to evaluate the long-term prognostic impact of an occluded artery and collaterals.

A 67-year-old man with a DDD pacemaker for complete atrioventricular block had dyspnea with cardiomegaly on a chest radiogram. Additionally, he had atrial fibrillation, which was well controlled with a class Ic antiarrhythmic agent. He had chronic kidney disease; therefore, uremic pericardial effusion was highly suspected, and pericardiostomy was performed. During surgery, the pacemaker mode was temporarily set to DOO to avoid electrical interference. After surgery, dyspnea was relieved, but it recurred 2 days later without aggravated pericardial effusion. An electrocardiogram showed wide QRS tachycardia at 150 beats per minute. What is the mechanism?

This study investigated the efficacy of adult adipose tissue-derived stem cells in restoring bone using an osteoporotic rat model. Thirty-six female Wistar rats (250–300 g, 12 weeks) were randomized into three equal groups: SHAM group (sham-operated), ovariectomy-induced (OVX) group and OVX with stem cell injection group (OVX with stem). Femur extraction and blood sampling were performed at 5, 6, 7 and 8 weeks. The proximal femoral metaphysis was scanned by micro-CT and evaluated for changes in various histomorphometric parameters. β-catenin expression was determined using H&E and immunohistochemistry. Bone metabolism was assessed using measurements of C-telopeptide of collagen type I (CTX), osteocalcin, and bone alkaline phosphatase (BALP). There was a trend for an increase in the bone mineral density (BMD), bone volume/trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the OVX with stem group as compared with the OVX group, and decrease in the OVX with stem group as compared with SHAM group. The trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) of the OVX group were increased compared with those values in the SHAM and OVX with stem group. BALP levels were higher in the OVX group as compared with that in the other two groups and osteocalcin levels were highest in the SHAM group and slightly increased in the OVX with stem group as compared with the OVX group. This study may help us gain an understanding of the role of MSCs in the pathophysiology and treatment of osteoporosis.

This study aimed to investigate whether stem cell transplantation in acute stage is safe, and determined the relationship between the treatment effects and the degree of intervertebral disc degeneration. IVD rat model was created by needle aspiration. Thirty rats were divided into 5 groups as follow: normal (disc without injury), sham (only disc injury without injection), Day 3 (cell injection at 3 day after disc degeneration), Day 7 (cell injection at 7 day after disc degeneration), and Day 14 (cell injection at 14 day after disc degeneration). Magnetic resonance imaging (MRI) and histological evaluation were performed 4 times, 2 weeks after the degeneration was induced and 2, 4, and 6 weeks after cell transplantation at the level of 3 discs. We also evaluated the expression of the disc regeneration markers, such as aggrecan, collagen II, and SOX-9, by western blotting. Day 3 and Day 7 groups showed significantly lesser reduction of the disc height and better restoration of the MRI signal intensity of the intervertebral disc. In hematoxylin and eosin staining of annulus fibrosus, Day 3 and Day 7 groups showed a better grading than Day 14 group did, according to the Nishimura and Mochida grading system. The results of the western blotting revealed patterns similar to the radiologic findings. We revealed that transplanted ADMSCs promote the regeneration of the nucleus pulposus and extracellular matrix. Additionally, we demonstrated that regenerative stem cell therapy is more effective when applied at relatively early stages of degeneration.

The aim of this study was to evaluate comparative clinical outcomes of discordant electrocardiographic (ECG) and echocardiographic (Echo) findings compared with concordant findings during treadmill exercise echocardiography in patients with chest pain and no history of coronary artery disease (CAD).A total of 1725 consecutive patients who underwent treadmill echocardiography with chest pain and no history of CAD were screened. The patients were classified into 4 groups: ECG-/Echo- (negative ECG and Echo), ECG+/Echo- (positive ECG and negative Echo), ECG-/Echo+, and ECG+/Echo+. Concomitant CAD was determined using coronary angiography or coronary computed tomography. Major adverse cardiac events (MACEs) were defined as a composite of coronary revascularization, acute myocardial infarction, and death.MACEs were similar between ECG-/Echo- and ECG+/Echo- groups. Compared with ECG+/Echo- group, ECG-/Echo+ group had more MACEs (adjusted hazard ratio [HR] adjusted by clinical risk factors [95% confidence interval {CI}], 3.57 [1.75-7.29], P < .001). Compared with ECG+/Echo+ group, ECG-/Echo+ group had lower prevalence of concomitant CAD and fewer MACEs (HR, 0.49 [0.29-0.81], P = .006).Positive exercise Echo alone during treadmill exercise echocardiography had worse clinical outcomes than positive ECG alone, and the latter had similar outcomes to both negative ECG and Echo. Positive exercise Echo alone also had better clinical outcomes than both positive ECG and Echo. Therefore, exercise Echo findings might be superior for predicting clinical outcomes compared with exercise ECG findings. Additional consideration of ECG findings on positive exercise Echo will also facilitate better prediction of clinical outcomes.

Background This study evaluated whether blunted autonomic activity as measured by heart rate recovery (HRR) was associated with increased arterial stiffness, especially increased exercise-induced arterial stiffness, in normotensive patients without overt atherosclerosis. Methods One hundred fifty-four normotensive patients without overt atherosclerosis who had undergone a treadmill exercise test were consecutively enrolled. HRR was measured at one minute after exercise. Brachial-ankle pulse wave velocity (baPWV) at rest was measured, and carotid arterial stiffness indices at rest (CSI at rest) and after exercise (CSI after exercise) were assessed. Results Patients with slow HRR were older and tended to be male, and they had diabetes, higher resting and peak systolic blood pressures, higher resting heart rate, lower peak heart rate, lower metabolic equivalents, increased baPWV, and increased CSIs at rest and after exercise. HRR was inversely associated with baPWV and CSI after exercise when established cardiovascular risk factors were adjusted as confounding factors, and HRR was associated with CSI after exercise when resting systolic blood pressure and metabolic equivalent of tasks on cardiovascular risk factors were added as confounding factors. Conclusions Sympathovagal imbalance demonstrated by slow HRR was associated with increased arterial stiffness and, above all, was closely associated with exercise-induced arterial stiffness in normotensive patients without overt atherosclerosis. This phenomenon might have been observed because blunt carotid arterial vasomotion following exercise results from autonomic dysfunction as well as vascular endothelial dysfunction.

Background: Elderly persons are rapidly increasing in Korea. Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality in this age group. In this research, we evaluated the clinical characteristics of the elderly patients presenting chest pain. Methods: A total of 471 patients who visited cardiovascular center of Kyung Hee University Hospital at Gangdong for chest pain were reviewed and divided by three groups, via age; under 40, from 40 to 69 and over 70 years old. Results: The number of patients over 70 years was 142 (30.1%). The proportion of patients diagnosed as having significant, multivessel coronary diseases was higher than that of younger patients (p=0.0002). The rate of atypical chest discomfort presenting as a cardiac symptom was not higher than in the middle-aged group (4.8% vs. 2.1%, p=0.255). Conclusion: In elderly patients, the proportion of female patients and significant multivessel diseases were more common than younger patients.

Background: Prompt diagnosis and management of atrial tachyarrhythmias (ATAs) during catheter ablation of atrial fibrillation (AF) is still challenging. Methods and Results: In 88 patients undergoing catheter ablation of AF, 128 regular ATAs were induced or converted from AF. The coronary sinus activation time (CSAT) around the mitral annulus (MA) was measured as the difference in activation time between the most proximal and distal poles of the coronary sinus (CS) electrodes. Entrainment pacing was performed around the MA, roof area, or cavotricuspid isthmus (CTI) depending on the CSAT result. Mechanisms of tachycardias included macro-reentry around the MA (perimitral atrial flutter [PM-AFL], n=63), roof-dependent AFL (Roof-AFL, n=14), CTI-dependent AFL (CTI-AFL, n=25), and atrial tachycardia (AT, n=26). When the CSAT was ≥45ms, the MA activation sequence was sequential, either proximal to distal or distal to proximal. When the CSAT was

The preferred treatment for patients with ST elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PCI). However, not all patients improve or maintain heart function following primary PCI, and certain patients may experience decreased heart function. The present study investigated factors associated with left ventricular (LV) dysfunction, and improvement or deterioration of LV ejection fraction (LVEF) at follow-up echocardiography following successful primary PCI. The clinical outcomes following primary PCI were also investigated. The present study assessed 4,044 patients who underwent primary PCI following a diagnosis of STEMI between January 2008 and March 2012. A total of 1,736 patients who underwent echocardiography between 30 days and 1 year after STEMI and PCI, and who had completed clinical follow-up, were included in the present study. A total of 243 patients (14.0%) demonstrated LV dysfunction at follow-up echocardiography. Multivariate analysis revealed that LV dysfunction (≤40%) at index STEMI, LVEF at index admission, renal insufficiency (creatinine ≥1.4 mg/dl), peak creatine kinase (CK) and peak CK MB isoenzyme (CKMB) were independent predictors of LV dysfunction at follow-up. Independent predictors for the deterioration of LVEF at follow-up were dyslipidemia, LVEF at index admission, LVEF ≤40% at index admission, peak CK and peak troponin-I. Furthermore, being male, having no history of coronary artery disease, pre-thrombolysis in myocardial infarction (TIMI) flow, LVEF at index admission, LVEF ≤40% at index admission, peak CKMB and peak troponin I were independent predictors of LVEF improvement at follow-up. One-year major adverse cardiac events were significantly increased in the LV dysfunction group compared with patients who did not exhibit LV dysfunction according to Cox regression analysis (13.6 vs. 20.4%; P=0.017). Therefore, the present study may provide valuable prognostic information for clinicians to advise patients who experience LV dysfunction despite having undergone successful primary PCI. Additional management is required in patients with these high-risk features following STEMI.

Background: In typical atrioventricular nodal reentrant tachycardia, radiofrequency (RF) ablation of the slow pathway (SP) is known to change the effective refractory period of the fast pathway (ERPFP) after successful RF ablation of the SP. The purpose of this study was to ascertain the mechanism of the ERPFP changes after SP ablation by comparing the results of both cryo- and RF ablation. Methods and Results: A total of 112 patients were enrolled prospectively and their electrophysiological properties analyzed before and after successful SP ablation. Patients were grouped into cryoablation (n=54) and RF ablation (n=58) groups and each group was subdivided into complete ablation (CG) and modification (MG) based on the presence of the SP after successful ablation. CG was performed in 64 patients: 30 by cryoablation and 34 by RF ablation. In patients who underwent complete SP ablation, the ERPFP was shortened significantly after cryoablation (375±74 vs. 281±39ms, P

Catheter ablation (CA) is reported to improve left ventricular (LV) function in patients with atrial fibrillation (AF). This study compared the effects of CA and antiarrhythmic drug treatment (AT) on LV remodeling and other echocardiography parameters in AF. We performed a non-randomized prospective study involving 72 drug-resistant AF patients who were treated with either CA (n = 42) or who declined CA and continued on AT (n = 30). Baseline and follow-up (mean 20.7 ± 7.5 months) echocardiography was performed in all patients. The maintenance of sinus rhythm was determined based on clinical interview, electrocardiography, and 24-h Holter and event recording. There were no significant differences between the two groups in regard to demographic features, blood pressure, and medication. CA was superior to AT with respect to sinus rhythm maintenance, LV ejection fraction, left atrium (LA) diameter, and LA volume index. In addition, CA resulted in decreases in the LV mass [from 190.5 ± 36.1 to 179.3 ± 32.4 g (p = 0.02)] and the LV mass index [from 104.2 ± 20.5 to 98.2 ± 18.3 g/m2 (p = 0.03)]. No parameter improved in AT patients. These improved echocardiographic parameters were observed in both groups with maintained sinus rhythm. Reverse LV remodeling after CA may include a reduction in the LV mass index, which appears to be associated with sinus rhythm maintenance.

We report a case of 68-yr-old male who died from brain injuries following an episode of prolonged hypoglycemia. While exploring controversies surrounding magnetic resonance imaging (MRI) findings indicating the bad prognosis in patients with hypoglycemia-induced brain injuries, we here discuss interesting diffusion-MRI of hypoglycemic brain injuries and their prognostic importance focusing on laminar necrosis of the cerebral cortex.

Background Atrial tachyarrhythmias (ATA) frequently develop during catheter ablation of atrial fibrillation (AF), but the mechanism of ATA during combined pulmonary vein isolation (PVI) and complex fractionated electrogram-guided ablation (CFEA) has not been reported. Methods and results This study involved 105 patients with symptomatic, drug-refractory AF. After PVI, CFEA was performed in the left/right atrium if AF remained inducible in paroxysmal AF (PAF) or persisted in persistent AF (PeAF). For the 70 PAF patients, PVI alone rendered AF non-inducible in 29 patients (41.4%), and converted inducible AF into inducible atrial flutter (AFl) in 10 patients (14.3%). For the remaining 31 PAF patients, additional CFEA rendered AF non-inducible in 11 patients (15.7%), whereas only AFl was inducible in 11 patients (15.7%). For 35 PeAF patients, PVI and CFEA converted AF into sinus rhythm in 2 (5.7%) and into AFl in 21 (60.0%) patients, while AF persisted in 12 patients (34.3%). The mechanism of ATA was focal (20/114, 17.5%), roof-dependent (20/114, 17.5%), peri-mitral (33/114, 28.9%), cavotricuspid isthmus-dependent (34/114, 29.8%) AFl or unknown (7/114, 6.1%). Successful ablation was achieved in 93/114 (81.6%) tachycardias. Conclusions The major mechanism of ATA during the combined approach of PVI and CFEA is macroreentry around large anatomic obstacles such as the pulmonary vein or the mitral or tricuspid annuli.

This is a case of full-blown Takayasu's arteritis in a young woman complicated with recurrent strokes, which was diagnosed late, after echocardiographic examination identifying concentric left ventricular hypertrophy of unknown cause and falsely normal blood pressure due to arterial stenoses in all four limbs. Herein we describe this interesting and instructive case with a short review of literature.

We report a case of Takotsubo cardiomyopathy, which involved the right ventricle at first presentation and demonstrated involvement of the left ventricle during recurrence. The patient was admitted to Kyung Hee University Hospital due to a left hip fracture, which was considered a result of physical stress. Complete recovery was confirmed by echocardiography prior to recurrence. The cause of the second event was surgery for the left hip fracture. Recurrence of Takotsubo cardiomyopathy at various cardiac locations provides evidence against the existing hypotheses that variants of Takotsubo cardiomyopathy are associated with anatomically different distributions of cardiac adrenergic receptors, the degree of stimulation by sympathetic activity and different susceptibilities to such sympathetic stimulation.

The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified cerebral artery disease. Some clinical factors such as age, hypertension, and osteoporotic hip fracture, smoking history and anti-osteoporosis drug use were associated with cerebral artery disease.

Pheochromocytoma is a rare cause of cardiogenic shock. Clinical management is directed at reducing the heart rate while maintaining blood pressure. However, medical treatment is often unsuccessful because of the high endogenous catecholamine level and low cardiac output. Percutaneous cardiopulmonary bypass system is a circulatory device that allows for safer use of heart-rate-reducing agents, which is advantageous when used early in the course of the cardiogenic shock induced by pheochromocytoma. (Circ J 2009; 73: 1753-1755)

Objective Electrocardiographic markers identifying malignant forms of early repolarisation (ER) from ER of normal variants are of prime clinical importance. We compared the ECG parameters of ER patterns in patients with early repolarisation syndrome (ERS) proximate to the ventricular fibrillation (VF) episodes, remote from the events and those with normal controls with ER. Design A retrospective, case-control study. Setting University hospital. Patients This study included 12 patients with ERS and 36 age-matched, gender-matched controls with ER. Main outcome measures Dynamic change of J-wave. Results The highest amplitude of J-wave, sum of the J-wave amplitudes or the number of leads with ER showed a dramatic change during the perievent period. J-wave amplitudes (2.0±1.3 vs 4.0±1.7, p=0.004) and the number of leads with ER (3.3±1.7 vs 5.3±2.0, p=0.021) were significantly higher around the time of VF. In particular, the characteristic morphology of ‘giant’ (wide, >80 ms) J-waves were observed during the perievent period in 5/12 patients with ERS. However, there were no significant differences in the electrocardiographic parameters of ER pattern remote from VF events between the patients with ERS and normal control subjects with ER. Conclusions Although the extent of and amplitude of J-wave or ST segment elevation (STE) increased significantly around VF episodes, the electrocardiographic parameters of ER remote from VF episodes were not significantly different from those of normal controls. The narrow time window of these ECG changes limits early detection of ER patients at risk of developing VF or sudden cardiac death.

Early risk stratification is crucial for appropriate management using invasive strategies in non-ST elevation myocardial infarction (NSTEMI), and electrocardiography (ECG) has been widely used for risk stratification. However, ECG findings in NSTEMI vary, and there is a need to define the clinical characteristics and outcomes according to ECG. We analyzed the admission ECGs of 345 NSTEMI patients who underwent coronary angiography from 2006 to 2013. Demographics, procedural characteristics, and clinical outcomes were analyzed. The ST-segment depression, T-wave inversion, and no ECG change groups included 114, 90, and 141 patients, respectively. The ST-segment depression group trended toward older, nonsmoking, and female, with a lower body mass index (BMI) and a higher incidence of comorbidities, than the no ECG change group. The ST-segment depression group also had a higher Killip class, a lower left ventricular ejection fraction, a higher regional wall motion score index (RWMSI), and 3-vessel coronary artery disease angiographically, than the no ECG change group. Patients with T-wave inversion trended toward older, female, lower BMI, less smoking, lower creatine kinase MB, and more left anterior descending (LAD) artery involvement, than the no ECG change group. In clinical outcomes, the ST-segment depression group had a higher mortality rate at 30 days and 12 months after the index procedure than the no ECG change group, whereas the T-wave inversion group showed similar clinical outcomes. Patients with ST-segment depression have a greater burden of comorbidities with risk factors and worse clinical outcomes, whereas patients with T-wave inversion have an intermediate number of risk factors but similar outcomes, compared with the no ECG change group. Further study is necessary to evaluate the prognostic impact of the baseline ECG on admission.

Objective Recent studies have shown encouraging progress toward the use of autogenic and allogenic mesenchymal stem cells (MSCs) to arrest, or even lead to partial regeneration in, intervertebral disc (IVD) degeneration. However, this technology is still in its infancy, and further development is required. The aim of this study was to analyze whether rat adipose-derived mesenchymal stem cells (ADMSC) can differentiate towards IVD-like cells after treatment with transforming growth factor β3 (TGF-β3) in vitro. We also performed quantitative analysis of gene expression for ADMSC only, ADMSCs treated with TGF-β3, and co-cultured ADMSCs treated with TGF-β3. Methods ADMSCs were sub-cultured to homogeneity and used in fluorocytometry assays for CD11, CD45, and CD90/Thy1. ADMSCs were differentiated in spheroid culture towards the chondrogenic lineage by the presence of TGF-β3, dexamethasone, and ascorbate. We also co-cultured pure ADMSCs and nucleus pulposus cells in 24-well plates, and performed immunohistochemical staining, western blotting, and RT-PCR for quantitativeanalysis of gene expression. Results Results of fluorocytometry were positive for CD90/Thy1 and negative for CD11 and CD45. TGF-β3-mediated induction of ADMSCs led to the expression of the differentiation markers of intervertebral disc-like cells, such as aggrecan, collagen II, and sox-9. Co-cultured ADMSCs treated with TGF-β3 showed higher expression of differentiation markers and greater extracellular matrix production compared with ADMSCs treated with TGF-β3 alone. Conclusion ADMSC treated with TGF-β3 may be an attractive source for regeneration therapy in degenerative IVD. These findings may also help elucidate the pathologic mechanism of MSC therapy in the degeneration of IVD in vivo.

BACKGROUND This study was conducted to determine the early cardiac valvular changes in young male ankylosing spondylitis (AS) patients. METHODS A total of 70 AS patients on treatment without clinical cardiac symptoms were divided into group I (< 10 years, n = 50) and group II (≥ 10 years, n = 20) depending on their disease duration after first diagnosis. Twenty-five healthy volunteers were selected as control subjects. All the subjects underwent transthoracic and transesophageal echocardiography, electrocardiography, and rheumatologic evaluation for AS patients. RESULTS The thickness of both the aortic and mitral valve was more increased in AS patients than in controls. Aortic valve thickness over 1.3 mm could predict AS with a sensitivity of 73% and specificity of 76%. The prevalence of aortic valve thickening was higher in the AS group compared to the controls. The prevalence of aortic and mitral regurgitation was very low and there was no difference between the controls and the patients. The aortic valve thickening was related to longer disease duration, high blood pressure, disease activity and inflammatory markers. CONCLUSION Thickening of the aortic and mitral valve was observed without regurgitation in male AS patients early in the course of their disease without clinical cardiac manifestations. This subclinical change of aorto-mitral valve in early AS should be considered and followed up to determine its prognostic implication and evolution.

Background Because adipose-tissue-derived stromal cell (ADSC) is readily accessible and abundant in stem cell, ADSC may be a better candidate for cell therapy and tissue engineering. This study investigated the potential of ADSC implantation to restore disc in a rat IVD model. Methods The first coccygeal disc segments of a Sprague-Dawley rat was left undamaged as a control (NC) group, and other two segments were damaged by needle injection. Two weeks later, ADSCs (TS) group or saline (IN) group was transplanted into each of the two damaged segments. Results At 6 weeks after transplantation, the TS group showed a significantly smaller reduction in disc height than the IN group and exhibited a restoration of MRI signal intensity. Hematoxylin and eosin staining revealed a greater restoration of the inner annulus structure in the TS group. Anti-Human Nucleic Antibody, collagen type II, and aggrecan, staining showed positive findings at 2 weeks after transplantation in TS group. Conclusions ADSCs show potential for restoring degenerative discs and may prove effective in the treatment of IVD.

In this study, the authors explored the effect of human mesenchymal stem cell (MSC) implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat. A unique rat coccygeal model was used to investigate the effects of transplanting human MSCs and to examine MSC survival in degenerative discs. MSC implantations into rat coccygeal IVDs were performed at 2 weeks post-injury. Radiologic and histologic evaluations were performed at 2, 4, 6, and 8 weeks post-injury. MSC-injected segments (TS) retained disc height and signal intensity, but injured non-injected segment (IS) progressively lost disc height. Pathological results revealed that the TS group showed relative restoration of the inner annulus structure; however, the IS group showed destruction of the inner annulus structure. Immunohistochemical staining using Anti-Human Nucleic Antibody (#MAB1281 Chemicon) revealed positive staining in the TS group at 2 weeks post-transplantation (4 weeks post-injury). This study shows that human MSCs survive for 2 weeks after transplantation into the IVDs of rats, and that MSCs increased the heights and signal intensities of intervertebral disc.

Background: Long-term outcomes of isolated significant tricuspid regurgitation (TR) without significant left-side heart disease remain to be clearly demonstrated. Methods: We enrolled 547 consecutive patients (age: 64 ± 14 years) with isolated significant TR. The patients with atrial septal defect, significant pulmonary or pulmonary vascular disease, right ventricular dysplasia and constrictive pericarditis were excluded. Initial clinical and echocardiographic characteristics and clinical outcomes were analyzed for 5.6 ± 2.1 years. Results: Survival rate was not different between 39 patients who underwent tricuspid valve (TV) surgery and 508 patients who did not (p=0.48). Of 508 patients without TV surgery, 32 patients (6.3%) died with cardiac cause during the follow-up period. Those patients were older (71 ± 16 vs. 64 ± 13 years, p2 , p2 and PASP ≥36 mmHg were best cut-off values for predicting cardiac mortality (Figure ). Conclusions: Severity of TR and pulmonary hypertension are prognostic factors independent of age in medically-managed patients with isolated significant TR. The results may suggest an optimal surgical timing in these patients.

Coronary artery perforation is a rare, but well recognized, compli-cation of percutaneous coronary intervention (PCI), with a reportedincidence of 0.14–0.35%, but with a mortality as high as 10% [1].Optical coherence tomography (OCT) has emerged as a powerfultool for use in stent assessment, and, within a short time, it hasbecome the modality of choice for study of stent and vascularinteractions in vivo. However, in a first generation pullback Time-Domain OCT imaging wire system (TD-OCT; M2 OCT systems andImageWire, LightLab Imaging, Inc, Westford, MA), blood clearancewas achievedby proximal balloonocclusion andflushingof the vesselusing the distal end holes of the occlusion balloon (Helios OcclusionBalloon Catheter, Goodman-Avantec Vascular Corp, Sunnyvale, CA).We report on a case of coronary perforation during first generationTD-OCT imaging as routine follow-up angiography.A 64-year-old woman with a history of previous percutaneouscoronary intervention (PCI) was admitted for follow-up coronaryangiography and OCT imaging. She had undergone PCI at the leftanterior descending artery (LAD) 1 year ago and had no anginalsymptoms after PCI. Cardiac examination was unremarkable, with aheart rate of 72 bpm and blood pressure (BP) 130/80 mm Hg.Diagnostic coronary angiogram, which was performed via the righttransradial approach using 6 Fr equipment, revealed no in-stentrestenosis of previously implanted stents with moderate distal leftanterior descending(LAD)artery stenosis (Fig. 1). TD-OCT imaging wasperformedusingaroutineprocedure,suchasproximalballoonocclusionatproximalLADand flushingwithRinger'slactateat1 ml/s.DuringOCT,abrupt BP depression and loss of consciousness developed. Followingimmediate removal of the OCT device and occluding balloon, coronaryangiography showed a huge coronary perforation with extravasation atthe distal LAD-D2 bifurcated lesion. We reinserted a guidewire and aconventionalballoonwasinflated just proximal to thelesion in order tosealtheperforation.Resuscitationwithinotropesandpericardiocentesiswere performed.The contrast leakcontinued inspiteofalongperiodofballoon inflation; therefore, a 3.0×15 mm Coronary Stent Graft™ wasinserted,butfailedtosealtheperforationduetoasmallcoronaryarteryand bulky graft stent (Fig. 2). The patient was transferred to theoperating room for surgical repair. Following sternotomy, a hugeperforated artery measuring approximately 6 –7mm was observed.Leftinternalmammaryartery(LIMA)graftstoLADandasaphenousveingrafttodiagonalwereplaced.Followingsuturingofthepericardiumandsternum, the patient returned to the CCU. She expired due to suddencardiac arrest at 7 days after surgery.OCT is high resolution, and, combined with the blood-free environ-ment, provides a substantial advantage for the study of coronary stent,when compared with previous intravascular ultrasound (IVUS) [2].Thistool enables detailed evaluation of tissue coverage and stent malapposi-tion in follow-up analysis. This specific parameter has been used as a

Background The purpose of this study was to evaluate whether performing an assessment of myocardial deformation using speckle tracking imaging during the recovery period after dobutamine stress echocardiography (DSE) allows detection of significant coronary artery disease (CAD) in patients with chest discomfort. Methods DSE and coronary angiography were performed in 44 patients with chest discomfort. The mean global longitudinal peak systolic strain (GLS) was measured at rest, at low stress (dobutamine infusion rate of 10 µg/kg/min) and at recovery (5 min after cessation of dobutamine infusion) of DSE using automated function imaging with apical views. Fractional flow reserve (FFR) was also performed in patients with intermediate coronary stenosis. CAD was defined as having a ≥ 70% diameter stenosis on coronary angiography or as having a FFR < 0.8. Patients were divided two groups based on the absence or presence of CAD [CAD (-) group vs. CAD (+) group]. Results There were no significant differences in the clinical characteristics and results of conventional echocardiography between the two groups. GLS at recovery was lower in the CAD (+) group than in the CAD (-) group (-18.0 ± 3.4% vs. -21.0 ± 1.9%, p = 0.003). The optimal cutoff of GLS at recovery for detection of CAD was -19% (sensitivity of 70.6%, specificity of 83.3%). Conclusion Assessment of GLS at recovery of DSE is a reliable and objective method for detection of CAD. This finding may suggest that systolic myocardial stunning remains even after recovery of wall motion abnormalities in patients with CAD.

A 36-year-old man who had been previously healthy presented with a 4-day history of fever and headache and was admitted to our neurological department with suspected meningitis. He denied drug abuse and had no recent travel history. On admission, his pulse rate was 72 beats/min, respiratory rate was 20 breaths/min, blood pressure was 110/60 mmHg, and body temperature was 40.3 C. Spinal tap and brain magnetic resonance imaging showed no abnormal findings. Laboratory testing disclosed a white blood cell count of 10.5 9 10/L, an erythrocyte sedimentation rate of 31 mm/h, and C-reactive protein of 9.32 mg/dL. Blood culture from two separate specimens revealed methicillin-sensitive staphylococcus aureus. Despite 3 days of antibiotic therapy, fever was not reduced and the cause of fever was not found. As recommended by our infection department, echocardiography was scheduled. The initial transthoracic echocardiogram (Fig. 1) showed a highly mobile mass moving like a ping-pong ball with a stalk attached on the posteromedial papillary muscle in the left ventricle. Clinical diagnosis of infective endocarditis was made according to the modified Duke criteria because of two major positive findings (positive blood culture and evidence of endocardial involvement as an oscillating intracardiac mass on the echocardiogram [1]). The patient underwent open heart surgery for excision of the mass at high risk for embolization to prevent embolic events. Surgical biopsy specimen showed inflammatory granulation tissue and thrombus suggesting vegetation (Fig. 2). The patient was discharged uneventfully and has been doing well.

While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

❙ABSTRACT❙ Background: Valsartan is an angiotensin II receptor blocker and is used for patient with hypertension. Although response to valsartan varies each individual, there is no study about factors affecting the variability of valsartan response. Methods: To investigate the effects of valsartan on the baseline characteristics of blood pressure, single group, open label, pre- and postcomparison clinical study was conducted. Total 21 male Korean volunteers were enrolled. Each subject was administered no drugs in first period and valsartan 80 mg (Diovan HCT) in second period. For pharmacodynamic analysis, 24 hours blood pressure changes were monitored by ambulatory blood pressure monitoring. Twenty-four hour blood pressure changes were matched to valsartan concentration and analyzed by correlation analysis. Changes in blood pressure pattern were also analyzed. Subjects were divided into responder, non-responder, and reverse responder according to pre- and post- 24 hours blood monitoring results. For determination of pharmacokinetic parameters, plasma concentration of valsartan was measured by a validated ultra-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters including area under the plasma concentration versus time curve from 0 hour to the last measurable concentration (AUCt), area under the plasma concentration versus time curve extrapolated to infinity, maximum plasma concentration (Cmax), and time required to reach maximum plasma concentration (Tmax) were calculated by noncompartmental models in the BA-CALC 2008 program ver. 1.0.0. Results: There were no significant associations between blood pressure changes and pharmacokinetic parameters of valsartan. Blood pressure pattern change analysis showed significant results. For AUCt, total amount of absorbed valsartan was 25,808 ± 6,863.0 ng․hr/mL , 20,683 ± 8,782.7 ng․hr/mL, and 12,502 ± 5,566.6 ng․hr/mL in responder, non-responder, and reverse responder, respectively (p = 0.041). In Cmax, maximum concentration of valsartan was 4,314 ± 1,522.6 ng/mL, 2,588 ± 1,273.9 ng/mL, and 2,056 ± 1,075.5 ng/mL, respectively. Conclusions: These results showed that response to valsartan was not associated with blood concentration in healthy volunteers and changes in blood pressure patterns to valsartan might be associated with the amount of drugs which are absorbed to subjects. (J Korean Soc Hypertens 2012;18(3):88-96)

Background and objectives Treadmill exercise stress echocardiography (TSE) has superior diagnostic accuracy than exercise electrocardiography (ECG). The objectives of the study are 1) to define the diagnostic accuracy and safety of TSE in patients without a history of coronary artery disease (CAD), 2) to identify the clinical characteristics that predict positive TSE results and 3) to assess the differential predictive value between TSE and concomitant exercise ECG in a Korean population. Subjects and methods A total of 1,287 patients among 1,500 consecutive patients with no prior history of CAD and who were referred for TSE during a 4-year 3-month period were enrolled. Results Of the 1,287 patients, 95 (7.4%) showed positive TSE results (newly developed regional wall motion abnormality). Among the 154 patients with coronary angiography, 94 patients (61%) showed significant CAD (30 of 77 patients with negative TSE results and 64 of 77 patients with positive TSE results). The TSE positive population had more cardiovascular risk factors and showed a higher Duke treadmill score and wall motion score index than the TSE negative group. TSE showed relatively good sensitivity (68%), specificity (78%) and positive and negative predictive values (83% and 61%, respectively), and TSE also had higher diagnostic accuracy than concomitant exercise ECG (72% vs. 64%, respectively). Conclusion TSE is safe and offers greater diagnostic power for CAD than exercise ECG in Korean population without a history of CAD. Its prognostic value in this population needs to be confirmed in a larger prospective study.