Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Background/Aims: This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. Methods: We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. Results: During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. Conclusions QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

BACKGROUND AND OBJECTIVES: The burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF). SUBJECTS AND METHODS: We prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries. RESULTS: The mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high. CONCLUSION: While the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.
Demography ; Extracorporeal Membrane Oxygenation ; Follow-Up Studies ; Guideline Adherence ; Heart Failure* ; Heart Transplantation ; Heart* ; Hospital Mortality ; Hospitals, University ; Humans ; Ischemia ; Korea* ; Male ; Mineralocorticoid Receptor Antagonists ; Mortality ; Peptidyl-Dipeptidase A ; Prognosis ; Prospective Studies ; Quality of Health Care ; Registries ; Stroke Volume ; Treatment Outcome

The prevalence of heart failure (HF) is skyrocketing worldwide, and is closely associated with serious morbidity and mortality. In particular, HF is one of the main causes for the hospitalization and mortality in elderly individuals. Korea also has these epidemiological problems, and HF is responsible for huge socioeconomic burden. However, there has been no clinical guideline for HF management in Korea. 
The present guideline provides the first set of practical guidelines for the management of HF in Korea and was developed using the guideline adaptation process while including as many data from Korean studies as possible. The scope of the present guideline includes the definition, diagnosis, and treatment of chronic HF with reduced/preserved ejection fraction of various etiologies.
Aged ; Diagnosis* ; Heart Failure* ; Heart* ; Hospitalization ; Humans ; Korea ; Mortality ; Prevalence

BACKGROUNDCentral blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.

METHODSThis 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients (n = 200) were randomly assigned to receive benidipine (n = 101) or losartan (n = 99). Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity (PWV) and augmentation index (AIx). We also measured the metabolic and inflammatory markers.

RESULTSAfter 24 weeks, the central BP decreased significantly from baseline by (16.8 ± 14.0/10.5 ± 9.2) mmHg (1 mmHg = 0.133 kPa) (systolic/diastolic BP; P < 0.001) in benidipine group and (18.9 ± 14.7/12.1 ± 10.2) mmHg (P < 0.001) in losartan group respectively. Both benidipine and losartan groups significantly lowered peripheral BP (P < 0.001) and AIx (P < 0.05), but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.

CONCLUSIONBenidipine is as effective as losartan in lowering the central and peripheral BP, and improving arterial stiffness.

Adolescent ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Blood Pressure ; drug effects ; Calcium Channel Blockers ; therapeutic use ; Dihydropyridines ; adverse effects ; therapeutic use ; Essential Hypertension ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Vascular Stiffness ; drug effects

PURPOSE: The scaffold is essential for cartilage tissue engineering. Collagen, chitosan, or glycosaminoglycan( GAG) has separately been proposed as in vitro scaffolds. However, the influence of collagen:chitosanchondroitin sulfate(Col:Chi-CS) composites on cell behavior has not yet been thoroughly examined. Therefore, the aim of this study is to develop a novel Col:Chi-CS blended scaffold that binds covalently with CS for cartilage tissue engineering. MATERIALS AND METHODS: The behavior of rabbit chondrocytes seeded in vitro into collagen/chitosan/GAG scaffolds with different chitosan contents (collagen:chitosan ratios of 20:1, 5:1, and 1.25:1) was investigated. The porous scaffolds containing collagen and chitosan were fabricated by using a freeze drying technique and crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide(EDC) in the presence of CS. The physicochemical/ mechanical properties of scaffolds were determined by analyzing scanning electron microscopy, compression modulus, immobilized GAG content, and water-binding capacity. Rabbit chondrocytes seeded onto these scaffolds were cultured for 1, 3, 7, and 14 days. The cell proliferation rate was evaluated with 3H-thymidine uptake and total GAG content assay was done via DMB assay using ELISA method. For the histological assessment of extracellular matrix, staining with safranin-O/fast green and immunohistochemistry were used. RESULTS: Scanning electron microscope(SEM) views of the scaffolds showed that all three had interconnected pores of mean diameter 164, 353, and 567 micrometer at collagen:chitosan ratios of 20:1, 5:1, and 1.25:1. GAG was covalently bound onto these scaffolds at 6.4%(w/w) in all three cases, i.e., regardless of chitosan content. However, increased chitosan content resulted in enhanced mechanical properties and increased pore size. Biochemical analysis of these scaffolds showed that proliferation rate and GAG synthesis increased with time, and this became most significant in the collagen:chitosan(20:1)-CS scaffold on day 14. The histology of the cell-seeded constructs showed a significantly higher percentage of cells with spherical morphology, which is specific to mature chondrocyte, especially in the collagen:chitosan(20:1)-CS scaffold at each time point. This finding was consistent with the observation that the pericellular matrix was stained positive for proteoglycans and type II collagen on day 14. CONCLUSION: The novel collagen:chitosan(20:1)-CS scaffold seems to be a useful carrier material for cartilage tissue engineering.
Cartilage* ; Cell Proliferation ; Chitosan ; Chondrocytes ; Chondrogenesis* ; Collagen ; Collagen Type II ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix ; Freeze Drying ; Immunohistochemistry ; Microscopy, Electron, Scanning ; Proteoglycans ; Tissue Engineering*

OBJECTIVE: The authors analyzed clinical features, long-term treatment outcome, and prognostic factors of the olfactory neuroblastoma. METHODS: Twenty-one cases of olfactory neuroblastomas, treated from 1979 to 2000, were retrospectively reviewed with medical records and radiological findings. Mean follow-up periods are 28.7 months(range 4-178). Extent of tumor was classified by UCLA staging system. Statistical analysis for survival was done using Kaplan Meier method and log-lank test. RESULTS: Mean age was 27 years(13-62), and most common group are second decades(8/21, 38%). Male to female ratio was 13: 8. Common symptoms are nasal obstruction, epistaxis, exopthalmos and headache. There were three cases of T1, five T2, six T3, and seven T4 according to UCLA staging system. The 5-year survival rate was 21.3% and average time was 28.9 months in surgical resection group(n=14) as primary modality have higher survival rate than radiation and chemotherapy group(n=7)[2-year survival rate: 39.2% vs 14.3%, 5-year survival rate: 19.6% vs 14.3%(p=0.0274)]. Early stage(T1, T2) groups showed better survival rate than advanced(T3, T4) groups(38.1% vs 9.1% p=0.0336). The local and regional recurrences were observed in 6(27%) and 2(9%) cases. Mean recurrence free time was 7.8 months(range 1-25). CONCLUSION: Early detection and extent of resection are the important prognostic factors. Regular follow up is mandatary for the detection of recurrence or metastasis.
Drug Therapy ; Epistaxis ; Esthesioneuroblastoma, Olfactory* ; Female ; Follow-Up Studies ; Headache ; Humans ; Male ; Medical Records ; Nasal Obstruction ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome*

Carcinomas derived from ameloblastomas have been designated by a variety of terms, including malignant ameloblastoma, ameloblastic carcinoma, metastatic ameloblastoma, and primary intra-alveolar epidermoid carcinoma. The term of ameloblastic carcinoma is differentiated from the term of malignant amelblastoma and is defined as an ameloblastoma in which there is histologic evidence of malignancy in the primary tumor or the recurrent tumor(or metastasis), regardless of whether it has metastasized. The well-documented and adequately followed cases are currently lacking and this report described an instance of ameloblastic carcinoma with good result after treatment and review of literature.
Ameloblastoma ; Ameloblasts* ; Carcinoma, Squamous Cell ; Mandible*

The aim of this study was to investigate the efficacy of simvastatin to improved lipid profiles in hypercholesterolemic Korean patients. METHODS: From 25 hospitals in Korea, 478 hypercholesterolemic patients were enrolled from November 1996 to April 1998. The inclusion criteria was hypercholesterolemia over 240 mg/dl after diet therapy for 1 month or hypercholesterolemia over 220 mg/dl in patients with definite evidence of ischemic heart disease. Simvastatin 10mg was started and doubled up to 40mg if total cholesterol level remained higher than 200 mg/dl at monthly check. Of 478 subjects, 344 patients in whom study protocol was not violated were analyzed. RESULTS: Male to female ratio was 27:73 and 47% of the subjects were in 6th decade. Hypertension, coronary artery disease, and diabetes mellitus were present in 30, 10, and 4% of the subjects. Baseline lipid profile (mean of total cholesterol-LDL-HDL-triglyceride mg/dl) was 274-185-52-188. The dose of simvastatin for 3 months was 10/10/10mg in 61% of subjects, 10/20/20mg in 21%, 10/10/20mg in 7%, and 10/20/40mg in 12%. The change of total cholesterol level(before-4wk-8wk-12wk-withdrawal 4wk) was 274-209- 205-198-250, and the maximal reduction rate was 27%. The change of LDL-cholesterol was 185-123-116-110-159, with maximal reduction rate 39%. The change of HDL-cholesterol was 52-54-56-55-54, with maximal increase rate 9%. The change of tryglyceride was 188-161- 164-162-189, with maximal reduction rate 15%. The value before/after treatment of ApoA1, ApoB, and Lp(a) was 129/129, 138/83, and 9.3/10.7, respectively. The level of LDL-cholesterol at the end of treatment was below 100mg/dl in 36% of subjects, 100-130 in 45%, 130-160 in 16%, and over 160mg/dl in 4%. The reduction rate of LDL-cholesterol was different between subjects whose LDL decreased below 100 and those whose LDL did not decrease below 130mg/dl, which suggests the existence of the individual difference of responsiveness to simvastatin. There were only 3 subjects (0.9%) who showed increase of liver enzyme over 3 times as the upper normal limit. Conclusion: Simvastatin is effective in improving lipid profiles in hypercholesterolemic Korean patients without serious side effects.
Apolipoproteins B ; Cholesterol ; Coronary Artery Disease ; Diabetes Mellitus ; Diet Therapy ; Female ; Humans ; Hypercholesterolemia ; Hypertension ; Individuality ; Korea ; Liver ; Male ; Myocardial Ischemia ; Simvastatin*

The aim of this study was to investigate the efficacy of simvastatin to improved lipid profiles in hypercholesterolemic Korean patients. METHODS: From 25 hospitals in Korea, 478 hypercholesterolemic patients were enrolled from November 1996 to April 1998. The inclusion criteria was hypercholesterolemia over 240 mg/dl after diet therapy for 1 month or hypercholesterolemia over 220 mg/dl in patients with definite evidence of ischemic heart disease. Simvastatin 10mg was started and doubled up to 40mg if total cholesterol level remained higher than 200 mg/dl at monthly check. Of 478 subjects, 344 patients in whom study protocol was not violated were analyzed. RESULTS: Male to female ratio was 27:73 and 47% of the subjects were in 6th decade. Hypertension, coronary artery disease, and diabetes mellitus were present in 30, 10, and 4% of the subjects. Baseline lipid profile (mean of total cholesterol-LDL-HDL-triglyceride mg/dl) was 274-185-52-188. The dose of simvastatin for 3 months was 10/10/10mg in 61% of subjects, 10/20/20mg in 21%, 10/10/20mg in 7%, and 10/20/40mg in 12%. The change of total cholesterol level(before-4wk-8wk-12wk-withdrawal 4wk) was 274-209- 205-198-250, and the maximal reduction rate was 27%. The change of LDL-cholesterol was 185-123-116-110-159, with maximal reduction rate 39%. The change of HDL-cholesterol was 52-54-56-55-54, with maximal increase rate 9%. The change of tryglyceride was 188-161- 164-162-189, with maximal reduction rate 15%. The value before/after treatment of ApoA1, ApoB, and Lp(a) was 129/129, 138/83, and 9.3/10.7, respectively. The level of LDL-cholesterol at the end of treatment was below 100mg/dl in 36% of subjects, 100-130 in 45%, 130-160 in 16%, and over 160mg/dl in 4%. The reduction rate of LDL-cholesterol was different between subjects whose LDL decreased below 100 and those whose LDL did not decrease below 130mg/dl, which suggests the existence of the individual difference of responsiveness to simvastatin. There were only 3 subjects (0.9%) who showed increase of liver enzyme over 3 times as the upper normal limit. Conclusion: Simvastatin is effective in improving lipid profiles in hypercholesterolemic Korean patients without serious side effects.
Apolipoproteins B ; Cholesterol ; Coronary Artery Disease ; Diabetes Mellitus ; Diet Therapy ; Female ; Humans ; Hypercholesterolemia ; Hypertension ; Individuality ; Korea ; Liver ; Male ; Myocardial Ischemia ; Simvastatin*