Thirty-five year-old Amadeus Mozart died in Vienna after an acute illness that lasted only 15 days but no consensus has been reached on the cause of his death. From many letters written by his farther it is almost certain that he experienced at least three episodes of acute rheumatic fever attack in his childhood, and a relapse of rheumatic fever was suggested to have killed Mozart, although death from acute rheumatic fever is very rare in adults. His last illness was characterized by high fever, massive edema, vomiting and skin rash. His last illness can be explained by infectious endocarditis and heart failure. During his last hours, he was given phlebotomy, possibly for the third time in two weeks, and soon after he became unconscious and died. As such, phlebotomy performed on a man dehydrated by high fever and vomiting may have caused systemic shock. In summary, Mozart probably died from chronic rheumatic heart disease complicated by infective endocarditis and heart failure, and repeated phlebotomy-induced hypovolemic shock.

Background and Objectives: Although circadian variation in the onset of acute myocardial infarction (AMI) has been reported in a number of studies, not much is known about the impact of circadian variation on 12-month mortality. The aim of this study was to investigate the impact of circadian variation on 12-month mortality in patients with AMI. Subjects and Methods: Eight hundred ninety two patients (mean age 67${\pm}$12; 66.1% men) with AMI who visited Kyungpook National University Hospital from November 2005 to December 2007 were included in this study. Patients were divided into groups based on four 6-hours intervals: overnight (00:00-05:59); morning (06:00-11:59); afternoon (12:00-17:59) and evening (18:00-23:59). Results: Kaplan-Meier survival curves showed 12-month mortality rates of 9.6%, 9.1%, 12.1%, and 16.7% in the overnight, morning, afternoon, evening-onset groups, respectively (p=0.012). Compared with the morning-onset AMI group, the serum creatinine levels (p=0.002), frequency of Killip class ${\geq}$3 (p=0.004), and prescription rate of diuretics (p=0.011) were significantly higher in the evening-onset AMI group, while the left ventricular ejection fraction (p=0.012) was significantly lower. The proportion of patients who arrived in the emergency room during routine duty hours was significantly lower in evening-onset groups irrespective of the presence or absence of ST-segment elevation (p<0.001). According to univariate analysis, the 12-month mortality rate in the evening group was significantly higher compared to the morning group (hazard ratio 1.998, 95% confidence interval 1.196 to 3.338, p=0.008). Conclusion: Patients with evening-onset AMI had poorer baseline clinical characteristics, and this might affect the circadian impact on 12-month mortality. Further studies are needed to clarify the role of circadian variation on the long-term outcome of AMI.

Background and Objectives: Pioglitazone has been known for its anti-atherogenic effects. We compared the effects of pioglitazone in reducing atherosclerosis progression and neointima volume in type 2 diabetic patients. Subjects and Methods: This was a prospective, randomized single-blinded, 8-month follow-up study. Patients with significant coronary artery stenosis were randomly assigned to either pioglitazone (n=19) or placebo (n=18) following zotarolimus-eluting stent (ZES) implantation. Intravascular ultrasonography of the culprit vessel was performed from 20 mm distal and proximal to the stent at baseline. and at 8-month, and volumetric analysis was performed. Changes in inflammation markers, insulin resistance and lipid profile were compared. Results: Changes in atherosclerosis progression from baseline in the pioglitazone group was significantly lower than that of the placebo group (0.06${\pm}$0.73 vs. 1.16${\pm}$1.41 $mm^3$/mm, p=0.024, respectively), and neointima volume was significantly lower in the pioglitazone group compared to the placebo group (1.74${\pm}$0.93 vs. 2.42${\pm}$1.98 mm$^3$/mm, p=0.007, respectively). Homeostatic model assessment-index, interleukin-6, and tumor necrosis factor-${\alpha}$ levels were significantly lower in the pioglitazone group at 8 months. Adiponectin levels increased significantly only in the pioglitazone group. No significant differences in retinol binding protein-4 levels between the 2 groups were seen during the 8-month follow-up period. Conclusion: Compared to placebo, pioglitazone was associated with significant reduction in atherosclerosis progression and neointima formation in type 2 diabetic patients with ZES implantation.

Background and Objectives: The aim of this study was to evaluate the efficacy of lacidipine in reducing blood pressure (BP) and to determine its effect on endothelial function in mild-to-moderate hypertensive patients with type 2 diabetes mellitus (DM). Subjects and Methods: This was a prospective, multicenter, open-label, single-arm study, enrolling 290 patients with mild-to-moderate hypertension and type 2 DM. Patients were initially treated with 2 mg lacidipine orally once daily for 4 weeks, which was then increased as necessary every 4 weeks to a maximal dose of 6 mg daily. The primary endpoint was the mean change in systolic blood pressure (SBP) from baseline after 12 weeks of treatment. Secondary endpoints included mean changes in diastolic blood pressure (DBP), flow-mediated vasodilatation (FMD), and serum concentrations of biochemical markers such as high-sensitivity C-reactive protein (hs-CRP), monocyte chemo-attractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), and plasminogen activator inhibitor-1 (PAI-1). Results: Lacidipine treatment significantly reduced SBP by -13.4${\pm}$13.0 mmHg (p<0.001) and DBP by -6.2${\pm}$9.3 mmHg (p<0.001). Lacidipine treatment did not improve endothelial-dependent vasodilatation, despite significantly improved nitroglycerin-induced, endothelial-independent vasodilatation. MCP-1 levels significantly decreased from 283.66${\pm}$110.08 pg/mL to 257.83${\pm}$100.23 pg/mL (p<0.001); whereas there were no significant changes in the levels of hs-CRP, MMP-9, or PAI-1. Conclusion: Twelve weeks of treatment with lacidipine was effective and well tolerated in mild-to-moderate hypertensive patients with type 2 DM. In spite of inducing a significant reduction in MCP-1 levels, lacidipine did not improve endothelial function.

Background and Objectives: The purpose of this study was to evaluate the relationship between myocardial strain and coronary flow reserve (CFR) in the prediction of myocardial functional recovery after acute myocardial infarction (AMI). Subjects and Methods: Consecutive patients with anterior ST elevation AMI were analyzed. Left ventricular (LV) strain, determined by 2-dimensional speckle tracking imaging and CFR, determined by intracoronary flow measurement, were obtained on the same day, 3-5 days after primary percutaneous coronary intervention. A-strain was defined as the mean systolic longitudinal strain of 11 LV segments (out of 18) assumed to be supplied by the left anterior descending coronary artery (LAD). Functional recovery was defined as improved wall motion >1 grade seen in at least 2 contiguous dysfunctional segments by echocardiography at the 6-month follow-up. Results: Of 20 patients, 8 patients had preserved CFR (>2.0) and 12 patients had impaired CFR (${\leq}$2.0). There were no differences between the 2 CFR groups in LV ejection fractions and wall motion score indices in the LAD territory. However, A-strain was greater in patients with preserved CFR than in patients with impaired CFR (-6.4${\pm}$2.0% vs. -4.6${\pm}$1.4%, p=0.03). A-strain and CFR correlated well with each other (r=-0.49, p=0.03). Ten of 20 patients showed functional recovery at 6 months. Of clinical and echocardiographic parameters, A-strain was the only predictor of recovery (odds ratio 2.02, 95% confidence interval=1.03-3.97, p=0.04). For predicting recovery, the sensitivity and specificity were 80.0% and 80.0%, respectively, for CFR (cutoff=1.60), and 60.0% and 90.0%, respectively, for A-strain (cutoff=-6.13%). Conclusion: Myocardial strain correlates well with the extent of microvascular integrity and can be used as a noninvasive method for predicting recovery after AMI.

Background and Objectives: B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) levels may serve as a useful marker of cardiovascular risk for screening of the general population. We evaluated reference levels and distribution of NT-proBNP in the Korean general population based on a large cohort study. Subjects and Methods: We included 1,518 adult subjects (ages 40-69) of a community-based cohort from the Korea Rural Genomic Cohort (KRGC) Study. Thorough biochemical and clinical data were recorded for all subjects. Levels of NT-proBNP from all participants were determined. In order to determine normal reference levels, subjects with factors known to influence NT-proBNP levels were excluded. Results: The characteristics of the cohort are described below; subjects were 41.2% male, and the mean age was 54.8${\pm}$8.4 years. The distribution of risk factors for cardiovascular disease in the cohort included hypertension (25%), left ventricular hypertrophy by electrocardiography (ECG-LVH) (15%), hypercholestolemia (4.5%), smoking (32%), diabetes (10.9%), history of coronary heart disease (4.9%), history of heart failure (0.9%), symptoms of heart failure (6.1%), elevated serum creatinine (${\geq}$1.5, 3.7%), and severe obesity (body mass index >30 kg/m$^2$, 4.6%). The levels of NT-proBNP of all subjects are shown below; the mean was 60.1${\pm}$42.1, and the median was 36.5 pg/mL. In addition, the levels of NT-proBNP of normal subjects (which did not have any risk factors, n=224) are shown below; the mean was 40.8, and the median was 32.1 pg/mL. In normal subjects, the NTproBNP level was slightly higher in females (25.7${\pm}$24.8 vs. 46.9${\pm}$35.4, p<0.001). NT-proBNP level increased with age in both the normal population and the total population. There were no significant differences in NT-proBNP levels in subjects who smoked, or had diabetes mellitus, hypertension or ECG-LVH. However, in subjects with a history of congestive heart failure (CHF) (58.5${\pm}$103.29 vs. 213.8${\pm}$258.8, p<0.005), elevated serum creatinine levels (${\geq}$1.5 mg/dL, 146.2${\pm}$98.2 vs. 54.3${\pm}$38.1, p<0.001), or who were older (${\geq}$60, 48.4 vs. 84.2${\pm}$139.5 pg/mL, p<0.05), the BNP level was higher. In addition, patients with more than 3 risk factors for CHF had higher BNP levels (risk 0: 40.8${\pm}$34.0, 1-2: 57.4${\pm}$93.2, ${\geq}$3: 85.0${\pm}$152.9 pg/mL). NT-proBNP levels were also related with age, sex, urine albumin, serum Cr, and high sensitivity C-reactive protein (p<0.05). Conclusion: We determined the reference value and distribution of NT-proBNP in the Korean adult general population. We also found that adjustments for the independent effects of age, sex and renal function appear necessary when determining cardiac risk based on proBNP levels.

Background and Objectives: The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. Subjects and Methods: Hypoxia was induced with 1% O$_2$, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. Results: Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. Conclusion: Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.

Background and Objectives: Pulmonary arterial hypertension (PAH) is a life threatening disease characterized by progressive pulmonary arterial occlusion which may ultimately result in death. Currently, the available treatments are diverse, but no therapy alone can reverse the disease process although they may have some clinical benefits. This study was designed to investigate single and combination therapy of simvastatin and sildenafil, which have different mechanisms of action, in monocrotaline (MCT)-induced PAH. Meterials and Methods: Rats were randomized to receive saline (control, n=8) or MCT treatment (n=32). MCT treated rats were randomized to vehicle, simvastatin (2 mg/kg/day), sildenafil (25 mg/kg/day) and a combination simvastatin and sildenafil (n=8, respectively). Three weeks later, hemodynamic study and histologic changes of pulmonary arterioles were measured. Proliferating cell nuclear antigen (PCNA) as well as Western blot for endothelial nitric oxide synthase (eNOS) were performed. Results: Systolic right ventricular pressure was significantly decreased in monotherapy groups (simvastatin and sildenafil) and the combination group compared to MCT group (p<0.05). Right ventricular hypertrophy and medial wall thickness of pulmonary arterioles were significantly attenuated with sole and combination therapy (p< 0.05). However, combination therapy did not confer additive benefits over monotherapy. Altered PCNA or eNOS in lung tissue was normalized by either monotherapy or combination therapy. Conclusion: The results suggest that either simvastatin or sildenafil has the therapeutic potential in MCT-induced PAH, although combination therapy of these two drugs has failed to show greater benefits in the study.

Background and Objectives: Coronary artery disease (CAD) is a major cause of heart failure associated with left ventricular systolic dysfunction (LVSD). The prognosis of LVSD is significantly influenced by the etiology of heart failure and therefore, differentiation of significant CAD from other etiologies is important. Carotid intima-media thickness (IMT) and plaque are useful predictors for cardiovascular events, including stroke and CAD. The purpose of this study was to evaluate the predictive value of carotid IMT and plaque for the diagnosis of CAD in LVSD patients. Subjects and Methods: Seventy-three (n= 73, 47 male, 67.6${\pm}$12.4 years) patients hospitalized for heart failure with severe LVSD were retrospectively enrolled. The severity of CAD was analyzed by the Duke Jeopardy Score system, and carotid IMT and plaque were measured according to the Mannheim Carotid IMT Consensus. Results: Significant CAD was found in 41 patients (56.1%, CAD group) on coronary an-giography. Mean common carotid artery (CCA) IMT (0.74${\pm}$0.05 mm vs. 1.04${\pm}$0.04 mm, p<0.01) was significantly higher in the CAD group. Plaque in CCA (6.25% vs. 19.5%, p<0.01) and plaque in bulb (25.0% vs. 60.9%, p<0.001) were significantly higher in the CAD group. Mean CCA IMT {odds ratio (OR) 2.61, 95% confidence interval (CI) 1.134-4.469, p<0.01} and plaque in bulb (OR 4.69, 95% CI 1.702-12.965, p<0.01) were significant predictors for the diagnosis of CAD according to multivariate logistic regression analysis. Conclusion: In patients with severe LVSD, mean CCA IMT and bulb plaque can be useful additional predictors for the diagnosis of CAD.

Cardiac amyloidosis describes a clinical disorder caused by infiltration of abnormal insoluble fibrils in the heart, characterized by progressive heart failure and a grave prognosis. Pleural effusion in cardiac amyloidosis may represent a sign of heart failure, but it can also result from pleural infiltration of amyloid, manifested by recurrent large fluid accumulations. Recently, the role of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of refractory pleural effusion. We report a case of a 53 year-old female patient with cardiac amyloidosis who presented with recurrent accumulation of large pleural effusions. She was initially treated with high dose loop diuretics, but the pleural effusion persisted, with the daily amount of drainage averaging 1 L/day. Accumulation of pleural fluid did not subside after 3 cycles of melphalan/prednisolone therapy. After the introduction of bevacizumab, an anti-VEGF antibody, the amount of pleural effusion decreased significantly. Efficacy of anti-VEGF therapy for refractory pleural effusions needs to be defined through further studies.

The percutaneous transfemoral approach has been routinely used for cardiac catheterization and coronary angioplasty. Local vascular complications following angioplasty are seen in 5% to 10% of patients, especially in those who need prolonged anticoagulation. Transradial access for coronary procedures dramatically reduces access site complications. We report a rare case of radial arteriovenous fistula, which developed after coronary angiography perfomed using the transradial approach.

Cogan's syndrome is a rare systemic inflammatory disease and can be diagnosed on the basis of typical inner ear and ocular involvement with the presence of large vessel vasculitis. We report a case of Cogan's syndrome with stable angina resulting from coronary ostial stenosis caused by aortitis.

A pulmonary arteriovenous malformation (PAVM) is a rare pulmonary vascular anomaly presenting as dyspnea or recurrent epistaxis. Ebstein's anomaly (EA), a congenital cardiac malformation, is also a rare condition. There have been no reports concerning the co-existence of PAVM with hereditary hemorrhagic telangiectasia (HHT) and EA. A 40-year-old woman was admitted with a 2-month history of increasing dyspnea and several years of recurrent epistaxis. On transthoracic echocardiography, she was diagnosed with EA and agreed to undergo surgical treatment. A chest CT angiography showed a 12-mm serpig-inous vascular structure suspicious for a PAVM and a liver CT suggested HTT. Although it is unclear whether or not a concur-rent PAVM and EA have an embryologic or genetic relationship, we report a case of a PAVM with EA. Further genetic and em-bryonic studies are needed to identify a possible relationship of the two medical conditions.