569 results on '"Juey- Jen Hwang"'
Search Results
152. Cost-effectiveness of amlodipine compared with valsartan in preventing stroke and myocardial infarction among hypertensive patients in Taiwan
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Ruey Tay Lin, Jim Z. Li, Yi-Heng Li, Lung Chan, Kou Gi Shyu, Juey-Jen Hwang, San Jou Yeh, Wen Yi Shau, Larry Z. Liu, Te Chang Weng, and Chen Huan Chen
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medicine.medical_specialty ,Cost effectiveness ,International Journal of General Medicine ,030204 cardiovascular system & hematology ,Lower risk ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,030212 general & internal medicine ,Amlodipine ,Myocardial infarction ,Risk factor ,Stroke ,cost-effectiveness ,CCB ,health care economics and organizations ,Original Research ,business.industry ,General Medicine ,medicine.disease ,ARB ,Markov model ,pharmacoeconomic ,Valsartan ,Cohort ,Medical emergency ,business ,medicine.drug - Abstract
Lung Chan,1 Chen-Huan Chen,2 Juey-Jen Hwang,3 San-Jou Yeh,4 Kou-Gi Shyu,5 Ruey-Tay Lin,6 Yi-Heng Li,7 Larry Z Liu,8 Jim Z Li,9 Wen-Yi Shau,10 Te-Chang Weng,10 1Department of Neurology, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei, 2Department of Internal Medicine, Faculty of Medicine, National Yang-Ming University, 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, 5Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 6Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, 7Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 8Pfizer Inc, New York, NY, USA; 9Pfizer Inc, San Diego, CA ,USA; 10Pfizer Ltd., New Taipei City, Taiwan Abstract: Hypertension is a major risk factor for strokes and myocardial infarction (MI). Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs) associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov) model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective adopted. One-way sensitivity and scenario analyses were conducted. Compared with valsartan, amlodipine was associated with cost savings of New Taiwan Dollars (NTD) 2,251 per patient per year: costs were NTD 4,296 and NTD 6,547 per patient per year for amlodipine and valsartan users, respectively. Fewer cardiovascular events were reported in patients receiving amlodipine versus valsartan (342 vs 413 per 10,000 patients over 5 years, respectively). Amlodipine had a net gain of 58 QALYs versus valsartan per 10,000 patients over 5 years. Sensitivity analyses showed that the discount rate and cohort age had a larger effect on total cost and cost difference than on QALYs. However, amlodipine results were more favorable than valsartan irrespective of discount rate or cohort age. When administered to Taiwanese patients for hypertension control, amlodipine was associated with lower cost and more QALYs compared with valsartan due to a lower risk of stroke and MI events. Keywords: cost-effectiveness, pharmacoeconomic, Markov model, CCB, ARB
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- 2016
153. Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults
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Ta-Chen Su, Guang-Wen Lien, Pao-Chung Chen, Juey-Jen Hwang, Ming-Fong Chen, and Chin-Chi Kuo
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Adult ,Male ,0301 basic medicine ,Taiwan ,Physiology ,010501 environmental sciences ,Bioinformatics ,01 natural sciences ,Perfluorononanoic acid ,03 medical and health sciences ,chemistry.chemical_compound ,Risk Factors ,Diabetes mellitus ,Diabetes Mellitus ,Odds Ratio ,Prevalence ,medicine ,Homeostasis ,Humans ,Glucose homeostasis ,Prospective Studies ,lcsh:Environmental sciences ,0105 earth and related environmental sciences ,General Environmental Science ,lcsh:GE1-350 ,Fluorocarbons ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Abnormal glucose homeostasis ,Glucose ,Logistic Models ,030104 developmental biology ,Quartile ,chemistry ,Multivariate Analysis ,Perfluorooctanoic acid ,Environmental Pollutants ,Female ,Glycated hemoglobin ,business - Abstract
Background: The link among perfluoroalkyl and polyfluoroalkyl substances (PFASs), abnormal glucose homeostasis and the risk of diabetes has been intensively debated with conflicting evidence. Objectives: We evaluated the associations among PFASs, oral glucose tolerance testing (OGTT) curves and diabetes prevalence in 571 working-aged Taiwanese participants. Methods: Exposure measures included serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA). Outcomes were OGTT curves and prevalent diabetes defined by fasting blood glucose (FBG) ≥126 mg/dL, 2-h glucose ≥200 mg/dL, or glycated hemoglobin ≥6.5%. Analyses were performed with multiple logistic regression and functional data analysis. Results: A total of 39 participants (6.8%) had diabetes in this study. After full adjustment, the increase in the geometric means of FBG, 2-h glucose concentrations, and area under the OGTT curve (AUC120) with a doubling increase in PFOS was 3% (95% CI 1–4), 8% (5–12), and 6% (4–9), respectively. Compared to the lowest-quartile of PFOS concentrations (4.8 ng/ml) and the vertical shifting of the mean curve for each PFOS quartile showed a dose–response pattern. The adjusted odds ratio for diabetes comparing the highest to lowest quartile was 3.37 (95% CI 1.18–9.65). For PFOA, PFNA, and PFUA, the opposite pattern of OGTT trajectory and the opposite risk profile for diabetes were observed. Conclusions: Chronic PFOS exposure was associated with impaired glucose homeostasis and the increased prevalence of diabetes. However, PFOA, PFNA, and PFUA showed a potential protective effect against glucose intolerance and the risk of diabetes. Future research focusing on clarifying possible differential effects of different species of PFASs on glucose homeostasis and establishing the prospective associations between PFASs and diabetes is needed. Keywords: Perfluorinated chemicals, Oral glucose tolerance testing, Diabetes, Glucose homeostasis
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- 2016
154. Genome-wide screening identifies a KCNIP1 copy number variant as a genetic predictor for atrial fibrillation
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Lian-Yu Lin, Juey-Jen Hwang, Chia Shan Hsieh, Chin Feng Tsai, Cho-Kai Wu, Eric Y. Chuang, Fu-Tien Chiang, Jen Kuang Lee, Yi-Chih Wang, Chuen Den Tseng, Ling Ping Lai, Sheng-Nan Chang, Chia Ti Tsai, Chih Chieh Yu, Tsung-Hsien Lin, Kwo Chang Ueng, and Jiunn Lee Lin
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0301 basic medicine ,Science ,General Physics and Astronomy ,Genome-wide association study ,030204 cardiovascular system & hematology ,Biology ,Bioinformatics ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Atrial Fibrillation ,Animals ,Humans ,Myocytes, Cardiac ,Copy-number variation ,Allele ,Gene ,In Situ Hybridization ,Zebrafish ,Genetic association ,Genetics ,Cardiac transient outward potassium current ,Muscle Cells ,Multidisciplinary ,Kv Channel-Interacting Proteins ,General Chemistry ,030104 developmental biology ,Human genome ,Genome-Wide Association Study - Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Previous genome-wide association studies had identified single-nucleotide polymorphisms in several genomic regions to be associated with AF. In human genome, copy number variations (CNVs) are known to contribute to disease susceptibility. Using a genome-wide multistage approach to identify AF susceptibility CNVs, we here show a common 4,470-bp diallelic CNV in the first intron of potassium interacting channel 1 gene (KCNIP1) is strongly associated with AF in Taiwanese populations (odds ratio=2.27 for insertion allele; P=6.23 × 10−24). KCNIP1 insertion is associated with higher KCNIP1 mRNA expression. KCNIP1-encoded protein potassium interacting channel 1 (KCHIP1) is physically associated with potassium Kv channels and modulates atrial transient outward current in cardiac myocytes. Overexpression of KCNIP1 results in inducible AF in zebrafish. In conclusions, a common CNV in KCNIP1 gene is a genetic predictor of AF risk possibly pointing to a functional pathway., Tsai et al. here utilize a multi-stage genome-wide association study in Taiwanese population to show a copy number variation in the intron of potassium interacting channel 1 gene (KCNIP1) to be strongly associated with atrial fibrillation. The study also examines the functionality of KCNIP1 in heart electrophysiological function using cultured myocytes and zebrafish.
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- 2016
155. Spironolactone is associated with reduced risk of new-onset atrial fibrillation in patients receiving renal replacement therapy
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Juey-Jen Hwang, Chia Ti Tsai, Chih Chieh Yu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ling Ping Lai, Cho-Kai Wu, Lian-Yu Lin, Yao-Hsu Yang, Yi-Chih Wang, Jiunn Lee Lin, Pau-Chung Chen, and Yi Wei Chung
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Databases, Factual ,medicine.medical_treatment ,Spironolactone ,030204 cardiovascular system & hematology ,Lower risk ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Registries ,030212 general & internal medicine ,Renal replacement therapy ,Diuretics ,Dialysis ,Outpatient pharmacy ,Aged ,Retrospective Studies ,business.industry ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Surgery ,Renal Replacement Therapy ,chemistry ,Cohort ,Kidney Failure, Chronic ,Female ,Hemodialysis ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Objectives Whether the spironolactone treatment remains effective for the prevention of atrial fibrillation (AF) in dialysis patients is unclear. Methods We used a database from the Registry for Catastrophic Illness from the National Health Research Institute. All dialysis patients aged 18 or older without history of AF before ESRD were incorporated. A total of 113,191 dialysis patients were enrolled in the study. The median follow-up time was 4.17years. We collected information on prescribed drug dosage, number of days of treatment and the total number of pills dispensed from the outpatient pharmacy prescription database. All individuals in the study cohort with the first occurrence of AF were included as cases. Results In spironolactone group, the incidence of developing new AF was significantly lower than that in the control group both before (0.8% vs. 3.3%, P=0.019) and after PS matching (1.2% vs. 3.0%, P=0.019). Before PS matching, Cox's proportional hazard regression analyses showed that spironolactone was associated with 60% reduction of new AF (HR=0.372 [0.200–0.692], P=0.002) and the protective effect is dose-responsive in accumulated dose, treatment duration and mean daily dose. After PS matching, the overall AF prevention effect remained significant (HR=0.400 [0.179–0.895], P=0.026) while the dose–response relationship became borderline significant. Subgroup analyses showed that the protective effect was more evident in some specific subgroup patients. Conclusion Our study showed that spironolactone therapy was associated with lower risk of developing AF in a dose-responsive manner in patients with dialysis. Further randomized study is needed to confirm this observation.
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- 2016
156. Statin therapy lowers the risk of new-onset atrial fibrillation in patients with end-stage renal disease
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Ling Ping Lai, Juey-Jen Hwang, Yao-Hsu Yang, Li Ting Ho, Pau-Chung Chen, Jiunn Lee Lin, Yi-Chih Wang, Chia Ti Tsai, Jyh-Ming Jimmy Juang, Cho-Kai Wu, Lian-Yu Lin, and Fu-Tien Chiang
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Adult ,Male ,medicine.medical_specialty ,Catastrophic illness ,Statin ,Adolescent ,medicine.drug_class ,medicine.medical_treatment ,Taiwan ,Angiotensin-Converting Enzyme Inhibitors ,Lower risk ,End stage renal disease ,Renal Dialysis ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Dialysis ,Aged ,Aged, 80 and over ,Dose-Response Relationship, Drug ,business.industry ,Incidence ,Hazard ratio ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Treatment Outcome ,Propensity score matching ,Cardiology ,Kidney Failure, Chronic ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business - Abstract
The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in dialysis patients.We used a database from the Registry for Catastrophic Illness from the National Health Research Institute (NHRI), which encompasses almost 100% of the patients receiving dialysis started from 1997 to 2008 in Taiwan. All dialysis patients aged 18 or older without history of cardiovascular events in 1997 and 1998 were incorporated. Finally, 113,191 dialysis patients were enrolled. We used propensity score (PS) matching method and Cox's proportional hazard regression models to estimate hazard ratios for AF events for statin users vs. nonusers.In statin group, the incidence of developing new AF was significantly lower than that in control group (1.1% vs. 3.8%, P0.001). The PS-based selection process identified 2146 patients receiving statins and 2146 who did not receive statins. The incidence of developing AF remained lower in statin group than that in control group (2.4% vs. 4.9%, P0.001). After PS matching, Cox's proportional hazard regression analyses showed that there was a protective effect of developing AF in a dose-responsive manner. The protective effect was more obvious in subjects with younger age, female gender, hyperlipidemia, coronary artery disease and peripheral artery disease and in subjects without taking angiotensin converting enzyme inhibitor and angiotensin receptor blocker.Our analyses showed that statin therapy was associated with lower risk of newly diagnosed AF in patients with dialysis.
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- 2015
157. Global Expression Profiling Identifies a Novel Hyaluronan Synthases 2 Gene in the Pathogenesis of Lower Extremity Varicose Veins
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I-Hui Wu, Chia-Shan Hsieh, Eric Y. Chuang, Chia Ti Tsai, Yau-Hung Chen, Juey-Jen Hwang, and Sheng-Nan Chang
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0301 basic medicine ,Angiogenesis ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,RNA seq ,Medicine ,varicose veins ,Gene ,Zebrafish ,Messenger RNA ,Gene knockdown ,HAS2 ,biology ,business.industry ,lcsh:R ,RNA ,General Medicine ,biology.organism_classification ,Cell biology ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,030104 developmental biology ,business - Abstract
Lower extremities varicose veins (VV) are among the most easily recognized venous abnormalities. The genetic mechanism of VV is largely unknown. In this study, we sought to explore the global expressional change of VV and identify novel genes that might play a role in VV. We used next-generation ribonucleic acid (RNA) sequence (RNA seq) technology to study the global messenger RNA expressional change in the venous samples of five diseased and five control patients. We identified several differentially expressed genes, which were further confirmed by conventional reverse transcription polymerase chain reaction (RT-PCR). Using these significant genes we performed in silico pathway analyses and found distinct transcriptional networks, such as angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms that might be involved in the mechanism of VV. Among these significant genes, we also found hyaluronan synthases 2 gene (HAS2) played a pivotal role and governed all these pathways. We further confirmed that HAS2 expression was decreased in the venous samples of patients with VV. Finally, we used a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system and blood flow. We found that HAS2 knockdown in zebrafish resulted in dilated venous structural with static venous flow. HAS2 may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of HAS2 may underlie the mechanism of VV.
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- 2018
158. 2018 TSOC guideline focused update on diagnosis and treatment of pulmonary arterial hypertension
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Juey-Jen Hwang, Shu-Hao Wu, Wei-Chun Huang, Morgan Fu, Yu-Wei Chiu, Chun-Yuan Chu, Chin-Chang Cheng, Wan-Jing Ho, Tsu-Yi Hsieh, Chih-Ping Chang, Chun-Hsien Wu, Zen-Kong Dai, Chih Hsin Hsu, Ping-Hung Kuo, Yih-Jer Wu, Shoa-Lin Lin, Wei-Ting Chang, Shu-Meng Cheng, Lin Lin, Shih-Hsien Sung, and Hsao-Hsun Hsu
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medicine.medical_specialty ,Combination therapy ,Heart disease ,medicine.medical_treatment ,Cardiology ,Taiwan ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,polycyclic compounds ,Medicine ,Humans ,Intensive care medicine ,Societies, Medical ,lcsh:R5-920 ,Pulmonary Arterial Hypertension ,business.industry ,General Medicine ,Guideline ,medicine.disease ,Pulmonary hypertension ,Connective tissue disease ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Vascular resistance ,030211 gastroenterology & hepatology ,business ,Risk assessment ,lcsh:Medicine (General) - Abstract
Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension. Keywords: Guideline, Pulmonary arterial hypertension, Pulmonary hypertension
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- 2018
159. P5699Functional studies of a novel copy number deletion in GSTM3 gene associated with increase of ventricular arrhythmia in patients with Brugada syndrome and ICD implantation
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Juey-Jen Hwang, C.-Y. Chen, Fu-Tien Chiang, Ling Ping Lai, J Lin, J.-M Juang, Ilaria Rivolta, Lian-Yu Lin, and L Tp
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medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,In patient ,Implantable defibrillator ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Gene ,Brugada syndrome ,Icd implantation - Published
- 2018
160. P6217Global expression profiling identifies a novel hyaluronan synthases 2 gene in the pathogenesis of lower extremity varicose vein
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Chia Ti Tsai, Juey-Jen Hwang, Yau-Hung Chen, I-Hui Wu, Chia-Shan Hsieh, and Eric Y. Chuang
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Pathogenesis ,Gene expression profiling ,Pathology ,medicine.medical_specialty ,business.industry ,Varicose veins ,medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Gene - Published
- 2018
161. The dose-response effects of uric acid on the prevalence of metabolic syndrome and electrocardiographic left ventricular hypertrophy in healthy individuals
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K.-H. Chen, Wei Chou Chang, Yen-Wen Wu, Juey-Jen Hwang, C.-K. Tseng, and Cheng-Wei Liu
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Adult ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Population ,Prevalence ,Taiwan ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Hyperuricemia ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,Risk Assessment ,03 medical and health sciences ,Electrocardiography ,Young Adult ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Medicine ,Humans ,education ,Retrospective Studies ,Metabolic Syndrome ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,medicine.disease ,Uric Acid ,Cohort ,Population study ,Female ,Hypertrophy, Left Ventricular ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Biomarkers - Abstract
Background and aim Hyperuricemia (HUA) is associated with the prevalence of metabolic syndrome (MetS) and cardiovascular risks in various populations. HUA is also able to induce cardiomyocyte hypertrophy in mouse models. However, the dose-response effects of serum uric acid (SUA) on the prevalence of MetS and electrocardiographic left ventricular hypertrophy (LVH) are unclear. Methods and results We retrospectively collected data from 18,932 individuals who underwent an annual health examination between 1/1/2016 and 12/31/2016. We excluded those with systemic diseases or missing questionnaires. The primary study endpoints were the prevalence of MetS and LVH, which were defined by the criteria for the Taiwanese population and the “SPRINT” trial. The cohort consisted of 17,913 individuals with a mean age of 31.2 years (SD 7.4) and a mean body mass index of 24.6 kg/m2 (SD 3.6); 87.1% of the individuals were men. The prevalence rates of HUA, MetS, and LVH were 29.5%, 9.4%, and 0.32%, respectively, in the overall study population. The HUA group was predominantly male and had significantly poorer lifestyle choices and greater laboratory cardiometabolic biomarker values than did the normouricemic group. However, the frequencies of physical activity were comparable between the two groups. After adjusting for confounders, SUA was associated with MetS (OR:1.473, 95% CI:1.408–1.540, P Conclusion We demonstrated that the dose-response effects of SUA are associated with the prevalence of MetS and electrocardiographic LVH in healthy individuals from Taiwan. Based on this evidence, future studies should investigate urate-lowering therapy and cardiovascular benefits in individuals with HUA ( ClinicalTrials.gov number NCT03473951 ).
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- 2018
162. 2018 Expert Consensus on the Management of Adverse Effects of Antiplatelet Therapy for Acute Coronary Syndrome in Taiwan
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Yi-Heng, Li, Chih-Yuan, Fang, I-Chang, Hsieh, Wei-Chun, Huang, Tsung-Hsien, Lin, Shih-Hsien, Sung, Chiung-Zuan, Chiu, Chiung-Jen, Wu, Kou-Gi, Shyu, Po-Yuan, Chang, Ching-Chang, Fang, Tse-Min, Lu, Ching-Pei, Chen, Wei-Chen, Tai, Chau-Chyun, Sheu, Kai-Che, Wei, Yi-Hsiu, Huang, Hsing-Mei, Wu, and Juey-Jen Hwang, Hwang
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Review Article - Abstract
Antiplatelet therapy is a key component in the treatment of acute coronary syndrome (ACS). The management of ACS has evolved considerably over recent years with the development of new and more potent antiplatelet agents. Clinical trials on ACS have demonstrated that potent antiplatelet agents can more effectively reduce cardiovascular events. However, there is a tipping point between safety and efficacy, beyond which the risk of bleeding and other adverse effects can outweigh the benefits of antiplatelet therapy. Striking a balance between safety and efficacy remains a major challenge. A consensus meeting of an expert panel composed of Taiwanese experts was held to provide recommendations for the management of adverse effects in patients with ACS receiving antiplatelet therapy. The common adverse effects of antiplatelet therapy include upper gastrointestinal bleeding, ecchymosis, hematuria, epistaxis and ticagrelor-related dyspnea. In this study, a literature review of these adverse events was performed and recommendations for the management were made.
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- 2018
163. 2018 Guidelines of the Taiwan Society of Cardiology, Taiwan Society of Emergency Medicine and Taiwan Society of Cardiovascular Interventions for the management of non ST-segment elevation acute coronary syndrome
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Chiung-Zuan Chiu, Jiunn Lee Lin, Feng-You Kuo, Chun-Chi Chen, Wei-Chun Huang, Juey-Jen Hwang, Shu-Long Jen, I-Chang Hsieh, Yu-Chen Wang, Cheng Han Lee, Yi-Chih Wang, Shih-Hsien Sung, Ju-Chi Liu, Yi-Heng Li, and Jung-Cheng Hsu
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medicine.medical_specialty ,Acute coronary syndrome ,medicine.medical_treatment ,Psychological intervention ,Cardiology ,Taiwan ,Physical examination ,030204 cardiovascular system & hematology ,Coronary Angiography ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Percutaneous Coronary Intervention ,Risk Factors ,Health care ,medicine ,ST segment ,Humans ,Thrombolytic Therapy ,030212 general & internal medicine ,Acute Coronary Syndrome ,Societies, Medical ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Percutaneous coronary intervention ,Anticoagulants ,General Medicine ,Guideline ,medicine.disease ,Emergency medicine ,Emergency Medicine ,lcsh:Medicine (General) ,business ,Platelet Aggregation Inhibitors - Abstract
In Taiwan, the incidence of non-ST segment elevation acute coronary syndrome (NSTE-ACS) continues to increase in recent years. The purpose of this guideline is to help health care professionals in Taiwan to use adequate tests and treatments for management of NSTE-ACS. For rapid diagnosis, in addition to history and physical examination, 0/3 h rapid diagnosis protocol with high sensitivity cardiac troponin assay is recommended in this guideline. Dual antiplatelet and anticoagulation therapies are important parts in the initial treatment. Risk stratification should be performed to identify high risk patients for early coronary angiography. Through evaluation of the coronary anatomy and other clinical factors, the decision for coronary revascularization, either by percutaneous coronary intervention or coronary artery bypass grafting, should be decided by the heart team. The duration of dual antiplatelet therapy should be given for at least 12 months after discharge. Other secondary preventive medications are also recommended for long term use. Keywords: Acute coronary syndrome, Guideline, Taiwan
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- 2018
164. CYP2C19 Polymorphism is Associated With Amputation Rates in Patients Taking Clopidogrel After Endovascular Intervention for Critical Limb Ischaemia
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Hao-Chih Tai, Chia Ti Tsai, Jyh-Ming Jimmy Juang, Cho-Kai Wu, Lian-Yu Lin, Juey-Jen Hwang, Jen-Kuang Lee, Fu-Tien Chiang, Nai-Chen Cheng, and Jiunn Lee Lin
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Male ,Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,CYP2C19 ,030204 cardiovascular system & hematology ,030230 surgery ,Amputation, Surgical ,03 medical and health sciences ,0302 clinical medicine ,Ischemia ,Internal medicine ,medicine ,Humans ,In patient ,Postoperative Period ,Aged ,Retrospective Studies ,Aged, 80 and over ,Polymorphism, Genetic ,business.industry ,Proportional hazards model ,Critical limb ischaemia ,Endovascular Procedures ,Retrospective cohort study ,DNA ,Clopidogrel ,Prognosis ,Cytochrome P-450 CYP2C19 ,Amputation ,Lower Extremity ,Pharmacodynamics ,Purinergic P2Y Receptor Antagonists ,Surgery ,Female ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Clopidogrel is a pro-drug requiring cytochrome P450 (CYP) 2C19 enzyme to be oxidised to its active form. This study evaluated the association between the CYP 2C19 genetic polymorphism and clinical outcomes in patients with critical limb ischaemia (CLI) taking clopidogrel after endovascular therapy (EVT).This was a retrospective study. Patients with CLI who had undergone EVT between August 2014 and January 2017 were included. The study subjects were divided into three groups according to the loss of function (LOF) CYP2C19 alleles: (1) extensive metaboliser (EM); (2) intermediate metaboliser (IM); and (3) poor metaboliser (PM). All patients underwent a platelet function test (VerifyNow). Amputation free survival and all cause mortality were estimated using the Kaplan-Meier method. The association between baseline characteristics and clinical outcomes was assessed with the Cox proportional hazard model.A total of 278 CLI patients (EM: 153, IM: 79, PM: 46) who underwent EVT were included. There were 180/278 (64.7%, EM: 107, IM: 45, PM: 28) patients who completed the 12 month follow up examination. Carriers of at least one CYP2C19 LOF allele (44.9%, 125/278) had diminished pharmacodynamic responses to clopidogrel as measured using VerifyNow (174 ± 27 platelet reactivity units (PRU), 216 ± 21 PRU, and 245 ± 35 PRU for patients with EM, IM, and PM CYP2C19 profiles, respectively; EM vs. IM, p .0001 and EM vs. PM, p .0001). The estimated amputation free 12 month survival rates were EM 82.1%, IM 66.1.0%, and PM 56.6% with significant differences between groups (log-rank test p = .0006, p for trend.0001). The estimated all cause 12 month mortality rates were EM 83.7%, IM 72.2%, and PM 71.3% (log rank test p = .01, p for trend p = .007). The combined group consisting of IM and PM was associated with amputation free survival and all cause mortality based on a univariable analysis (hazard ratio [HR] = 2.23 [1.97-2.46], p = .011; HR = 1.43 [1.05-1.85], p = .043) and remained significant in a multivariable Cox analysis (HR = 2.65 [2.1-2.9], p = .009; HR = 1.39 [1.07-1.74], p = .037).CYP2C19 genetic profiles can significantly influence clinical outcomes (in both amputation free survival and all cause mortality) in CLI patients who are taking only clopidogrel after EVT.
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- 2018
165. Phthalate Exposure is associated with Carotid Intima-Media Thickness in Adolescents and Young Adults
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Juey-Jen Hwang, Fung-Chang Sung, Ta-Chen Su, and Pau-Chung Chen
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business.industry ,Cardiovascular risk factors ,Phthalate ,Physiology ,chemistry.chemical_compound ,Intima-media thickness ,chemistry ,Subclinical atherosclerosis ,General Earth and Planetary Sciences ,Medicine ,Endocrine system ,Young adult ,business ,General Environmental Science - Abstract
Background/Aim: Exposure to phthalates has been linked to cardiovascular risk factors. However, it is unclear regarding phthalates exposure and the risk of subclinical atherosclerosis. This study i...
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- 2018
166. Prevalence and prognosis of Brugada electrocardiogram patterns in an elderly Han Chinese population: a nation-wide community-based study (HALST cohort)
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Fu-Tien Chiang, Ying-Hsiang Chen, Jiunn Lee Lin, Chung-Chou Juan, Juey-Jen Hwang, Lei-Na Chen, Chih-Cheng Hsu, Chao A. Hsiung, I-Chien Wu, Feng-Cheng Tang, Hou-Chang Chiu, Jyh-Ming Jimmy Juang, I-Shou Chang, Chi-Chung Wang, Ching-Yu Julius Chen, Ling Ping Lai, and Huey-Ming Lo
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Male ,China ,Longitudinal study ,Pediatrics ,medicine.medical_specialty ,Han chinese ,Taiwan ,030204 cardiovascular system & hematology ,Cardiac mortality ,Community based study ,Sensitivity and Specificity ,Electrocardiography ,03 medical and health sciences ,Age Distribution ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Prevalence ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Sex Distribution ,Healthy aging ,Aged ,Brugada Syndrome ,Cause of death ,Aged, 80 and over ,business.industry ,Reproducibility of Results ,Middle Aged ,Prognosis ,Survival Rate ,Brugada ECG Pattern ,Cohort ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older. Methods and results The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 ± 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 ± 8 vs. 35 ± 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow-up (log-rank test, P = 0.21, 0.32, respectively). Conclusion The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality.
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- 2015
167. Carotid Intima-Media Thickness and Long-Term Exposure to Traffic-Related Air Pollution in Middle-Aged Residents of Taiwan: A Cross-Sectional Study
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Ta-Chen Su, Chang-Chuan Chan, Juey-Jen Hwang, and Yu-Cheng Shen
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Adult ,Male ,Cross-sectional study ,Health, Toxicology and Mutagenesis ,Taiwan ,Air pollution ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,010501 environmental sciences ,medicine.disease_cause ,complex mixtures ,Carotid Intima-Media Thickness ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Air pollutants ,Air Pollution ,Environmental health ,11. Sustainability ,medicine ,Humans ,cardiovascular diseases ,Particle Size ,Nitrogen oxides ,Aged ,Vehicle Emissions ,0105 earth and related environmental sciences ,Air Pollutants ,business.industry ,Research ,Public Health, Environmental and Occupational Health ,Environmental Exposure ,Environmental exposure ,Middle Aged ,Models, Theoretical ,3. Good health ,Cross-Sectional Studies ,Intima-media thickness ,13. Climate action ,cardiovascular system ,Female ,Nitrogen Oxides ,Particulate Matter ,Seasons ,business - Abstract
Background Associations between long-term exposure to air pollution and carotid intima-media thickness (CIMT) have inconsistent findings. Objectives In this study we aimed to evaluate association between 1-year average exposure to traffic-related air pollution and CIMT in middle-aged adults in Asia. Methods CIMT was measured in Taipei, Taiwan, between 2009 and 2011 in 689 volunteers 35–65 years of age who were recruited as the control subjects of an acute coronary heart disease cohort study. We applied land-use regression models developed by the European Study of Cohorts for Air Pollution Effects (ESCAPE) to estimate each subject’s 1-year average exposure to traffic-related air pollutants with particulate matter diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and the absorbance levels of PM2.5 (PM2.5abs), nitrogen dioxide (NO2), and nitrogen oxides (NOx) in the urban environment. Results One-year average air pollution exposures were 44.21 ± 4.19 μg/m3 for PM10, 27.34 ± 5.12 μg/m3 for PM2.5, and (1.97 ± 0.36) × 10–5/m for PM2.5abs. Multivariate regression analyses showed average percentage increases in maximum left CIMT of 4.23% (95% CI: 0.32, 8.13) per 1.0 × 10–5/m increase in PM2.5abs; 3.72% (95% CI: 0.32, 7.11) per 10-μg/m3 increase in PM10; 2.81% (95% CI: 0.32, 5.31) per 20-μg/m3 increase in NO2; and 0.74% (95% CI: 0.08, 1.41) per 10-μg/m3 increase in NOx. The associations were not evident for right CIMT, and PM2.5 mass concentration was not associated with the outcomes. Conclusions Long-term exposures to traffic-related air pollution of PM2.5abs, PM10, NO2, and NOx were positively associated with subclinical atherosclerosis in middle-aged adults. Citation Su TC, Hwang JJ, Shen YC, Chan CC. 2015. Carotid intima–media thickness and long-term exposure to traffic-related air pollution in middle-aged residents of Taiwan: a cross-sectional study. Environ Health Perspect 123:773–778; http://dx.doi.org/10.1289/ehp.1408553
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- 2015
168. Unique clinical characteristics and SCN5A mutations in patients with Brugada syndrome in Taiwan
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Yen-Bin Liu, Juey-Jen Hwang, Shih Fan Sherri Yeh, Chia Ti Tsai, Ling Ping Lai, Lian-Yu Lin, Fu-Tien Chiang, Chih Chieh Yu, Jiunn Lee Lin, Fu Chun Chiu, Huei-Ming Yeh, Jien Jiun Chen, Chuen Den Tseng, Jyh-Ming Jimmy Juang, and Wen-Jone Chen
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Adult ,Male ,SCN5A mutations ,Pediatrics ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Genotype ,Prevalence ,Mutation, Missense ,Taiwan ,Disease ,Sudden cardiac death ,NAV1.5 Voltage-Gated Sodium Channel ,Young Adult ,Asian People ,Seizures ,medicine ,Missense mutation ,Humans ,In patient ,Brugada syndrome ,cardiovascular diseases ,Family history ,Aged ,Medicine(all) ,lcsh:R5-920 ,business.industry ,fungi ,General Medicine ,Exons ,Middle Aged ,medicine.disease ,Death, Sudden, Cardiac ,Logistic Models ,Case-Control Studies ,Cohort ,cardiovascular system ,Female ,business ,lcsh:Medicine (General) ,sodium channel - Abstract
Background/Purpose Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20–25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. Methods We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon–intron boundaries of the SCN5A -encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. Results SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20–25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 ± 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. Conclusion The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD.
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- 2015
169. TNF- down-regulates sarcoplasmic reticulum Ca2+ ATPase expression and leads to left ventricular diastolic dysfunction through binding of NF- B to promoter response element
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Jiunn Lee Lin, Chia Ti Tsai, Juey-Jen Hwang, Yi-Chih Wang, Cho-Kai Wu, Yu Min Kuo, Fu-Tien Chiang, Jen Kuang Lee, Sheng-Nan Chang, and Ling Ping Lai
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medicine.medical_specialty ,Physiology ,Response element ,Promoter ,IκB kinase ,Biology ,Calcium ATPase ,Endocrinology ,Simvastatin ,Physiology (medical) ,Internal medicine ,Gene expression ,cardiovascular system ,medicine ,Phosphorylation ,Tumor necrosis factor alpha ,Cardiology and Cardiovascular Medicine ,circulatory and respiratory physiology ,medicine.drug - Abstract
Aims TNF-alpha (TNF-α) causes left ventricular diastolic dysfunction. Down-regulation of sarcoplasmic reticulum Ca2+-ATPase 2a protein (SERCA2a) expression is one of the major mechanisms underlying diastolic dysfunction. We investigated whether TNF-α modulates SERCA2a expression and alters cardiac diastolic function, and its detailed signalling pathway. Methods and results We used both in vitro cellular cardiomyocyte model and in vivo rat model to address this issue. We found that TNF-α decreased the levels of both SERCA2a mRNA and protein in the cardiomyocytes, with corresponding impairment of diastolic calcium reuptake, a cellular phenotype of cardiac diastolic function. An ∼2 kb promoter of the SERCA2a gene ( atp2a2 ) along with its serial deletions was cloned into the luciferase reporter system. TNF-α significantly decreased the promoter activity, and truncation of the SERCA2a gene promoter with the putative nuclear factor kappa-B (NF-κB) response element abolished TNF-α-induced SERCA2a gene suppression. Chromatin immunoprecipitation and gel retardation also confirmed the binding of NF-κB to this putative-binding site. TNF-α increased the phosphorylation of IKK and the degradation of IκB, resulted in NF-κB nuclear translocation, and decreased SERCA2a gene promoter activity. This process was attenuated by NF-κB blockers and simvastatin. In the in vivo rat model, lipopolysaccharide treatment significantly elevated the serum TNF-α level, as well as phosphorylation of IKK, resulting in a decrease in myocardial SERCA2a expression, diastolic calcium reuptake, and diastolic dysfunction. Oral treatment with simvastatin led to an increase in SERCA2a expression, alleviation, and prevention of the diastolic dysfunction. Conclusions TNF-α suppresses SERCA2a gene expression via the IKK/IκB/NF-κB pathway and binding of NF-κB to the SERCA2a gene promoter, and its effect is blocked by simvastatin, demonstrating the potential therapeutic effect of statins in treating inflammation-related diastolic dysfunction.
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- 2015
170. Acute Effects of Biventricular Pacing in Heart Failure Patients with a Normal Ejection Fraction and Mechanical Dyssynchrony
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Ruth N. Klepfer, Kathryn Hilpisch, Fu Chun Chiu, Chia Ti Tsai, Vincent E. Splett, Jiunn Lee Lin, Chih Chieh Yu, Yi-Chih Wang, Ling Ping Lai, and Juey-Jen Hwang
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Male ,Acute effects ,medicine.medical_specialty ,Systole ,Heart Ventricles ,Hemodynamics ,Cardiac Resynchronization Therapy ,Diastole ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Cardiac Resynchronization Therapy Devices ,Heart Atria ,Aged ,Ultrasonography ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,medicine.disease ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives: We tested the acute effects of resynchronization in heart failure patients with a normal (>50%) left ventricular (LV) ejection fraction (HFNEF) and mechanical dyssynchrony. Methods: Twenty-four HFNEF patients (72 ± 6 years, 5 male) with mechanical dyssynchrony (standard deviation of electromechanical time delay among 12 LV segments >35 ms) were studied with temporary pacing catheters in the right atrium, LV, and right ventricle (RV), and high-fidelity catheters for pressure recording. Using selected atrioventricular (AV) intervals of 60, 90, 120, 150, and 180 ms to optimize transmitral flow during simultaneous biventricular pacing, the RV-LV (VV) interval was then evaluated at RV30, RV15, 0, LV15, LV30, and LV45 (RV or LV indicates which ventricle was paced first, the number indicates by how many ms). Results: During simultaneous pacing, longer AV intervals were associated with improved LV pressure-derivative minimums and increased aortic pressures (p < 0.05 vs. normal sinus rhythm). In the VV interval from RV30 to LV45, there was a graded increase in the aortic velocity time integral and a decrease in dyssynchrony during simultaneous or LV-first pacing (p < 0.05 vs. normal sinus rhythm). Conclusions: For HFNEF patients with mechanical dyssynchrony, acute simultaneous biventricular or LV-first pacing with longer AV intervals reduced mechanical dyssynchrony and improved diastolic and systolic hemodynamics.
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- 2015
171. Renin-angiotensin-aldosterone blockade reduces atrial fibrillation in hypertrophic cardiomyopathy
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Lian-Yu Lin, Jiunn Lee Lin, Yao-Hsu Yang, Juey-Jen Hwang, Pau-Chung Chen, Chen-Yu Huang, and Chia Ti Tsai
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Taiwan ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Lower risk ,Disease-Free Survival ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,Young Adult ,0302 clinical medicine ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Propensity Score ,Aged ,Retrospective Studies ,business.industry ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,Retrospective cohort study ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Blockade ,Survival Rate ,Relative risk ,Heart failure ,Propensity score matching ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
ObjectivesAtrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is associated with increased mortality, mainly mediated by increased thromboembolic events and progressive heart failure. Many studies suggested inhibition of renin–angiotensin–aldosterone system (RAAS) could reduce new AF in various clinical conditions. However, evidence concerning the effects of RAAS inhibitors on AF prevention remains unclear in HCM. Our study is to investigate whether treatment with ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) could lower the risk of new AF in HCM.MethodsWe conducted a retrospective study including subjects diagnosed HCM between January 1997 and December 2013 by using a nationwide database covering almost all Taiwanese from National Health Research Institute. All participants, aged 18 or older, had no ACEIs or ARBs exposure or AF diagnosis before enrolment. Propensity score matching and multivariate Cox hazard regression were employed to estimate the risk of new AF occurrence.ResultsTotal 18 266 subjects were included in the analysis with median follow-up duration 8.13 years. Patients taking ACEIs or ARBs are associated with lower risk of developing new AF than those without taking neither of medications (3.16% vs 5.65%, relative risk 0.56 (95% CI 0.49 to 0.64), HR 0.572 (95% CI 0.480 to 0.683)). The correlation is more prominent with longer ACEIs or ARBs treatment (HRs from T1 to T3: 0.741, 0.579, 0.337, PConclusionIn patients with HCM, lower risk of new AF is observed in patients treated with either ACEIs or ARBs compared with those receiving neither of these medications.
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- 2017
172. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial
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Paul M Ridker, Jean G MacFadyen, Brendan M Everett, Peter Libby, Tom Thuren, Robert J Glynn, John Kastelein, Wolfgang Koenig, Jacques Genest, Alberto Lorenzatti, John Varigos, Peter Siostrzonek, Peter Sinnaeve, Francisco Fonseca, Jose Nicolau, Nina Gotcheva, Huo Yong, Miguel Urina-Triana, Davor Milicic, Renata Cifkova, Riina Vettus, Stephan D Anker, Athanasios J Manolis, Fernando Wyss, Tamas Forster, Axel Sigurdsson, Prem Pais, Alessandro Fucili, Hisao Ogawa, Hiroaki Shimokawa, Irina Veze, Birute Petrauskiene, Leon Salvador, Jan Hein Cornel, Tor Ole Klemsdal, Felix Medina, Andrzej Budaj, Luminita Vida-Simiti, Zhanna Kobalava, Petar Otasevic, Daniel Pella, Mitja Lainscak, Ki-Bae Seung, Patrick Commerford, Mikael Dellborg, Marc Donath, Juey-Jen Hwang, Hakan Kultursay, Marcus Flather, Christie Ballantyne, Seth Bilazarian, William Chang, Cara East, Les Forgosh, Barry Harris, Monica Ligueros, ACS - Atherosclerosis & ischemic syndromes, Vascular Medicine, and ACS - Pulmonary hypertension & thrombosis
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0301 basic medicine ,Male ,medicine.medical_specialty ,Interleukin-1beta ,Myocardial Infarction ,030204 cardiovascular system & hematology ,Placebo ,Antibodies, Monoclonal, Humanized ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,cardiovascular diseases ,Mortality ,Randomized Controlled Trials as Topic ,biology ,business.industry ,C-reactive protein ,Hazard ratio ,Confounding ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,medicine.disease ,Thrombosis ,Lipids ,Surgery ,Canakinumab ,030104 developmental biology ,C-Reactive Protein ,biology.protein ,Female ,business ,medicine.drug - Abstract
Background: Canakinumab, a monoclonal antibody targeting interleukin-1β reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients. Methods: The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10 061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. In a prespecified secondary analysis designed to address the relationship of hsCRP reduction to event reduction in CANTOS, we evaluated the effects of canakinumab on rates of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality according to on-treatment concentrations of hsCRP. We used multivariable modelling to adjust for baseline factors associated with achieved hsCRP and multiple sensitivity analyses to address the magnitude of residual confounding. The median follow-up was 3·7 years. The trial is registered with ClinicalTrials.gov, number NCT01327846. Findings: Baseline clinical characteristics did not define patient groups with greater or lesser cardiovascular benefits when treated with canakinumab. However, trial participants allocated to canakinumab who achieved hsCRP concentrations less than 2 mg/L had a 25% reduction in major adverse cardiovascular events (multivariable adjusted hazard ratio [HRadj]=0·75, 95% CI 0·66–0·85, p
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- 2017
173. P1339Trans-ethnic fine mapping of previously identified QT interval loci in han Chinese discover ethnic-specific signals associated with inflammation pathway
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Juey-Jen Hwang, Y.H. Chen, C.C. Hsu, L.H. Chien, C.C. Juan, C.C. Wang, I.S. Chang, C. Hsiung, J.M. Juang, I.C. Wu, Huey-Ming Lo, Jiunn Lee Lin, F.C. Tang, H.C. Chiu, and L.N. Chen
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Genetics ,Han chinese ,business.industry ,Ethnic group ,Medicine ,Inflammation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,QT interval - Published
- 2017
174. P1780Statin therapy reduces the risk of new-onset acute coronary syndrome in patients with rheumatoid arthritis
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Juey-Jen Hwang, T.-T. Lin, J. L. Lin, Lian-Yu Lin, Chang-Jen Huang, Yao-Hsu Yang, Chia Ti Tsai, and Pau-Chung Chen
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medicine.medical_specialty ,Acute coronary syndrome ,business.industry ,Rheumatoid arthritis ,Internal medicine ,medicine ,In patient ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,New onset - Published
- 2017
175. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial
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Paul M Ridker, Jean G MacFadyen, Tom Thuren, Brendan M Everett, Peter Libby, Robert J Glynn, Paul Ridker, Alberto Lorenzatti, Henry Krum, John Varigos, Peter Siostrzonek, Peter Sinnaeve, Francisco Fonseca, Jose Nicolau, Nina Gotcheva, Jacques Genest, Huo Yong, Miguel Urina-Triana, Davor Milicic, Renata Cifkova, Riina Vettus, Wolfgang Koenig, Stephan D Anker, Athanasios J Manolis, Fernando Wyss, Tamas Forster, Axel Sigurdsson, Prem Pais, Alessandro Fucili, Hisao Ogawa, Hiroaki Shimokawa, Irina Veze, Birute Petrauskiene, Leon Salvador, John Kastelein, Jan Hein Cornel, Tor Ole Klemsdal, Felix Medina, Andrzej Budaj, Luminita Vida-Simiti, Zhanna Kobalava, Petar Otasevic, Daniel Pella, Mitja Lainscak, Ki-Bae Seung, Patrick Commerford, Mikael Dellborg, Marc Donath, Juey-Jen Hwang, Hakan Kultursay, Marcus Flather, Christie Ballantyne, Seth Bilazarian, William Chang, Cara East, Brendan Everett, Les Forgosh, Robert Glynn, Barry Harris, Monica Ligueros, Erin Bohula, Bindu Charmarthi, Susan Cheng, Sherry Chou, Jacqueline Danik, Graham McMahon, Bradley Maron, MingMing Ning, Benjamin Olenchock, Reena Pande, Todd Perlstein, Aruna Pradhan, Natalia Rost, Aneesh Singhal, Viviany Taqueti, Nancy Wei, Howard Burris, Angela Cioffi, Anne Marie Dalseg, Nilanjan Ghosh, Julie Gralow, Tina Mayer, Hope Rugo, Vance Fowler, Ajit P Limaye, Sara Cosgrove, Donald Levine, Renato Lopes, John Scott, Robert Hilkert, Georgia Tamesby, Carolyn Mickel, Brian Manning, Julian Woelcke, Monique Tan, Sheryl Manfreda, Tom Ponce, Jane Kam, Ravinder Saini, Kehur Banker, Thomas Salko, Panjat Nandy, Ronda Tawfik, Greg O'Neil, Shobha Manne, Pravin Jirvankar, Shankar Lal, Deepak Nema, Jaison Jose, Rory Collins, Kent Bailey, Roger Blumenthal, Helen Colhoun, and Bernard Gersh
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Neutropenia ,Interleukin-1beta ,Placebo-controlled study ,Anti-Inflammatory Agents ,Myocardial Infarction ,Placebo ,Antibodies, Monoclonal, Humanized ,law.invention ,03 medical and health sciences ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Sepsis ,Cancer screening ,medicine ,Humans ,Lung cancer ,Aged ,biology ,Dose-Response Relationship, Drug ,business.industry ,Interleukin-6 ,Incidence ,C-reactive protein ,Smoking ,Cancer ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,medicine.disease ,Atherosclerosis ,Thrombocytopenia ,Surgery ,Canakinumab ,030104 developmental biology ,C-Reactive Protein ,Cell Transformation, Neoplastic ,Editorial ,biology.protein ,Female ,business ,medicine.drug - Abstract
Inflammation in the tumour microenvironment mediated by interleukin 1β is hypothesised to have a major role in cancer invasiveness, progression, and metastases. We did an additional analysis in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised trial of the role of interleukin-1β inhibition in atherosclerosis, with the aim of establishing whether inhibition of a major product of the Nod-like receptor protein 3 (NLRP3) inflammasome with canakinumab might alter cancer incidence.We did a randomised, double-blind, placebo-controlled trial of canakinumab in 10 061 patients with atherosclerosis who had had a myocardial infarction, were free of previously diagnosed cancer, and had concentrations of high-sensitivity C-reactive protein (hsCRP) of 2 mg/L or greater. To assess dose-response effects, patients were randomly assigned by computer-generated codes to three canakinumab doses (50 mg, 150 mg, and 300 mg, subcutaneously every 3 months) or placebo. Participants were followed up for incident cancer diagnoses, which were adjudicated by an oncology endpoint committee masked to drug or dose allocation. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, NCT01327846. The trial is closed (the last patient visit was in June, 2017).Baseline concentrations of hsCRP (median 6·0 mg/L vs 4·2 mg/L; p0·0001) and interleukin 6 (3·2 vs 2·6 ng/L; p0·0001) were significantly higher among participants subsequently diagnosed with lung cancer than among those not diagnosed with cancer. During median follow-up of 3·7 years, compared with placebo, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26-41% and of interleukin 6 of 25-43% (p0·0001 for all comparisons). Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group (p=0·0007 for trend across groups), but was significantly lower than placebo only in the 300 mg group individually (hazard ratio [HR] 0·49 [95% CI 0·31-0·75]; p=0·0009). Incident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0·61 [95% CI 0·39-0·97]; p=0·034) and 300 mg groups (HR 0·33 [95% CI 0·18-0·59]; p0·0001; p0·0001 for trend across groups). Lung cancer mortality was significantly less common in the canakinumab 300 mg group than in the placebo group (HR 0·23 [95% CI 0·10-0·54]; p=0·0002) and in the pooled canakinumab population than in the placebo group (p=0·0002 for trend across groups). Fatal infections or sepsis were significantly more common in the canakinumab groups than in the placebo group. All-cause mortality did not differ significantly between the canakinumab and placebo groups (HR 0·94 [95% CI 0·83-1·06]; p=0·31).Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality. Replication of these data in formal settings of cancer screening and treatment is required.Novartis Pharmaceuticals.
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- 2017
176. Comparisons of clinical impacts on individuals with Brugada electrocardiographic patterns defined by ISHNE criteria or EHRA/HRS/APHRS criteria: a nationwide community-based study
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Ying-Hsiang Chen, Ling Ping Lai, Shih-Fan Sherri Yeh, Chao A. Hsiung, I-Shou Chang, Fu-Tien Chiang, Kwo-Ching Chen, I-Chien Wu, Dun-Hui Yang, Chih-Chien Yu, Jen-Kuang Lee, Ching-Yu Julius Chen, Chih-Cheng Hsu, Wen-Jin Liaw, Jyh-Ming Jimmy Juang, Lian-Yu Lin, Juey-Jen Hwang, Li-Ting Ho, Tsung-Lung Tsai, Ray-Chin Wu, Cho-Kai Wu, and Jiunn Lee Lin
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Male ,Han chinese ,Pediatrics ,medicine.medical_specialty ,Taiwan ,030204 cardiovascular system & hematology ,Community based study ,Sudden cardiac death ,03 medical and health sciences ,Electrocardiography ,0302 clinical medicine ,Prevalence ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Aged ,Brugada Syndrome ,medicine.diagnostic_test ,business.industry ,Mean age ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Stratified sampling ,Clinical Practice ,Death, Sudden, Cardiac ,Cohort ,Electrocardiography, Ambulatory ,Female ,business - Abstract
Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by International Society for Holter and Noninvasive Electrocardiography (ISHNE) and Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society (HRS/EHRA/APHRS) were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before.This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria.A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased by 71%. However, all-cause mortality and cardiovascular mortality were not different between individuals with or without BrP, irrespective of the criteria used.The two different criteria may impact the diagnostic yield of individuals with BrP, but do not affect the prognosis of the individuals with BrP. Key messages Comparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria. The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different.
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- 2017
177. Everolimus-Eluting Bioresorbable Vascular Scaffold in Real World Practice - A Single Center Experience
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Huai-Wen, Liang, Hsien-Li, Kao, Yen-Hung, Lin, Juey-Jen, Hwang, Mao-Shin, Lin, Fu-Tien, Chiang, Chii-Ming, Lee, Chih-Fan, Yeh, Tzung-Dau, Wang, Cho-Kai, Wu, Lian-Yu, Lin, Chia-Ti, Tsai, and Ying-Hsien, Chen
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Original Article - Abstract
Drug-eluting stents are widely used in coronary artery intervention. However, vessel caging and very late thrombotic events are of persistent and substantial concern. Bioresorbable vascular scaffolds (BVS) were developed to deliver vascular reparative therapy, by eliminating permanent mechanical restraint. However, data regarding its clinical performance is lacking.After the BVS implantation procedure received national approval in May 2014, patients receiving BVS implantation until November 2014 in National Taiwan University Hospital (NTUH) were enrolled. Clinical variables, angiographic data, procedural details, and follow-up information were collected and compared with those receiving BVS at NTUH as part of the global ABSORB EXTEND trial.A total of 35 patients (38 target vessels) with 48 BVS implanted after approval were enrolled, as the "real-world practice" group. Data of the 34 patients (34 target vessels) with 37 BVS implanted in the ABSORB EXTEND trial were also obtained. Differences in lesion complexity (0% type B2/C lesion in ABSORB EXTEND, versus 23.7% in real-world, p = 0.007) and lesion length (20.9 ± 6.1 mm in ABSORB EXTEND, versus 29.5 ± 15.9 mm in real-world, p = 0.008) were noted. The ischemia-driven target vessel revascularization after an average of 732 days follow-up was 11.8% in the ABSORB EXTEND trial. However, there was no ischemia-driven target lesion revascularization (TLR), no scaffold thrombosis, no myocardial infarction (MI), and no patients passed during the follow-up period. In real-world patients, there is 5.3% of MI, 2.6% ischemia-driven TLR, and 2.6% of non-fatal probable scaffold thrombosis.The use of BVS in real-world practice is feasible, with clinical outcomes comparable to those in the ABSORB EXTEND trial.
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- 2017
178. Three-Dimensional Echocardiography-Derived Right Ventricular Ejection Fraction Correlates with Success of Decannulation and Prognosis in Patients Stabilized by Venoarterial Extracorporeal Life Support
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Kuan-Chih Huang, Chien-Heng Lai, Juey-Jen Hwang, Lung-Chun Lin, Yih-Sharng Chen, and Lian-Yu Lin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Circulatory collapse ,medicine.medical_treatment ,Heart Ventricles ,Population ,Echocardiography, Three-Dimensional ,Shock, Cardiogenic ,030204 cardiovascular system & hematology ,Extracorporeal ,Ventricular Function, Left ,03 medical and health sciences ,0302 clinical medicine ,Extracorporeal Membrane Oxygenation ,Internal medicine ,Extracorporeal membrane oxygenation ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Ejection fraction ,business.industry ,Cardiogenic shock ,Central venous pressure ,030208 emergency & critical care medicine ,Stroke Volume ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,ROC Curve ,Ventricle ,Cardiology ,Ventricular Function, Right ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been proved to effectively rescue patients from refractory cardiogenic shock. The role of the right ventricle in VA-ECMO has been emphasized, but quantitative right ventricular (RV) analysis in this population has been lacking. Three-dimensional echocardiography (3DE) is currently suggested for RV volumetric analysis. The aims of this study were to assess 3DE-derived RV ejection fraction (RVEF) in patients with refractory cardiogenic shock stabilized by VA-ECMO and to explore the association between 3DE-derived RVEF and weaning success as well as the prognosis after the first intent of decannulation.Three-dimensional echocardiographic data sets before the first intent of decannulation were retrospectively selected and analyzed in 46 patients who underwent VA-ECMO for refractory acute circulatory collapse.Twenty-eight of the 46 patients had protocol-defined success in weaning from VA-ECMO. In the success group, both ventricles were smaller and had better pumping function. By stepwise multivariate linear regression, RV free wall strain, left ventricular ejection fraction, RV fractional area change, and central venous pressure were found to be independently associated with RVEF. Receiver operating characteristic curve analysis showed that RVEF had the highest area under the curve (0.90, P .001) for weaning success with a cutoff value of 24.6%. Worse RVEF (≤24.6%) was also associated with poor prognosis in terms of all-cause mortality within 30 days (hazard ratio, 15.86; 95% CI, 3.56-70.73; P .001).Three-dimensional echocardiography-derived RVEF might represent the composite results of RV contractility, left ventricular performance, and fluid status. Under mechanical circulatory support of VA-ECMO, RVEF 24.6% was associated with higher weaning success and lower 30-day mortality after the first intent of decannulation.
- Published
- 2017
179. Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients
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Cho-Kai Wu, Jiunn Lee Lin, Yi Fan Wu, Jien Jiun Chen, Mao-Yuan M. Su, Hao Yuan Tsai, Juey-Jen Hwang, and Lian-Yu Lin
- Subjects
Male ,medicine.medical_specialty ,Cardiac fibrosis ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,03 medical and health sciences ,0302 clinical medicine ,Fibrosis ,Cardiac magnetic resonance imaging ,Internal medicine ,Extracellular fluid ,Internal Medicine ,Medicine ,Body Fat Distribution ,Humans ,030212 general & internal medicine ,Aged ,Heart Failure ,Nutrition and Dietetics ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Endomyocardial Fibrosis ,Magnetic Resonance Imaging ,Adipose Tissue ,Heart failure ,Cardiology ,Myocardial fibrosis ,Female ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies ,Pericardium - Abstract
Objectives The aim of this study was to characterize the characteristics of epicardial fat (EAT) in different stage heart failure (HF) patients and its relationship between cardiac fibrosis. Background EAT is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiac fibrosis, but the relationship between cardiac fibrosis and EAT is unknown. Methods EAT volume was measured using cardiac magnetic resonance imaging (CMR) in 180 subjects: 58 patients with systolic HF, 63 patients with HF and preserved ejection fraction, and 59 patients without HF. CMR derived myocardial extracellular volume (ECV) was used for fibrosis quantification. Results Patients with systolic HF had significantly more EAT compared with patients with HF and preserved ejection fraction or the control group (patients without HF) (indexed EAT volume [mL/m 2 ], 27.0 [22.7–31.6] vs 25.6 [21.4–31.2] and 24.2 [21.0–27.6], P P Conclusions EAT volume is highly associated with CMR ECV independent of traditional risk factors and left ventricular mass or volume. Whether EAT plays a role in the long-term prognosis of HF requires future investigation.
- Published
- 2017
180. Anti-anxiety drugs use and cardiovascular outcomes in patients with myocardial infarction: A national wide assessment
- Author
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Chia Ti Tsai, Jyh-Ming Jimmy Juang, Cho-Kai Wu, Jiunn Lee Lin, Ling Pin Lai, Fu-Tien Chiang, Pau-Chung Chen, Yin Tseng Huang, Jen Kuang Lee, Juey-Jen Hwang, and Lian-Yu Lin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Myocardial Infarction ,Taiwan ,Sudden death ,Anti-Anxiety Agents ,Risk Factors ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Aged ,Heart Failure ,First episode ,Diazepam ,Proportional hazards model ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Hospitalization ,Heart failure ,Cardiology ,Anxiety ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Anti-anxiety medication in patients with anxiety may lessen the stress and thereby lower their risk for myocardial infarction (MI). The aim of current study is to examine an association between the use of anti-anxiety medication and long-term mortality risk in patients following MI.A universal national health insurance (NHI) program has been implemented in Taiwan since 1995. We used system sampling database from 1997 to 2008 with a total of 1,000,000 subjects. We included subjects with first episode of MI and were above 30 years old. Sudden death, cardiovascular mortality, and heart failure hospitalization were assessed in all included subjects. Anti-anxiety as well as other medications and risk factors were obtained. Cox regression analysis was used to evaluate the adjusted hazard ratio (HR) for all patients and subgroups.The adjusted HRs of sudden death were significantly associated with increased benzodiazepam (BZD) dosage (HRs = 0.639, 1.003, 1.957 from Q2 to Q4 vs. Q1, p = .019 for trend) during approximately 4.8 years. For cardiac mortality and heart failure hospitalization, there was a J-curve dose-response relationship. The HRs for cardiac mortality were 0.255 (p .001) and 0.385 (p .001) for Q2 and Q3 vs. Q1, respectively. For patients receiving higher doses of daily BZDs (5 mg), protective effects for cardiac mortality and heart failure hospitalization decreased and a J-curve dose-response relationship was seen.Anti-anxiety medications are independent associated with a decreased risk of cardiac mortality and heart failure hospitalization in patients after a new MI.
- Published
- 2014
181. Additive effect of the metabolic syndrome score to the conventional CHADS2 score for the thromboembolic risk stratification of patients with atrial fibrillation
- Author
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Ling Ping Lai, Shu Hsuan Chang, Chia Ti Tsai, Huei-Ming Yeh, Cho-Kai Wu, Jiunn Lee Lin, Chuen Den Tseng, Fu-Tien Chiang, Sheng-Nan Chang, Yi-Chih Wang, and Juey-Jen Hwang
- Subjects
medicine.medical_specialty ,education.field_of_study ,Receiver operating characteristic ,business.industry ,Proportional hazards model ,Population ,Atrial fibrillation ,medicine.disease ,Thrombosis ,Confidence interval ,Physiology (medical) ,Internal medicine ,parasitic diseases ,Cardiology ,Medicine ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,education ,Body mass index - Abstract
Background The CHA 2 DS 2 -VASC scoring scheme may not be better than the CHADS 2 scoring scheme in predicting thromboembolic risk for patients with atrial fibrillation (AF) in Asians. Metabolic syndrome is associated with an increased risk of thrombosis. Objective To evaluate whether metabolic syndrome offers incremental information over the CHADS 2 scheme in predicting thromboembolic risk for patients with AF in the Taiwanese population. Methods The study population consisted of 721 consecutive patients with AF who had been followed up for a median of 10.8 years. Thromboembolic end points were defined as ischemic stroke/transient ischemic accident and peripheral embolisms. Clinical factors associated with thromboembolic end points were identified by Cox regression analysis. Different scoring systems were compared by receiver operating characteristic (ROC) analysis. Results We found that components in the CHADS 2 scheme were associated with an increased risk of thromboembolism. The CHA 2 DS 2 -VASC scheme did not provide information additional to that provided by the CHADS 2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.665; P > .05). Metabolic syndrome components were also associated with increased risk of thromboembolism. The incident thromboembolic rate increased incrementally when metabolic syndrome score increased. Additional metabolic syndrome components provide additional information to the CHADS 2 scheme on thromboembolism risk (ROC area: 0.670 vs 0.729; P = .034). We therefore proposed a new scoring scheme called CHADS 2 -MS scoring scheme. In patients with low to intermediate CHADS 2 scores (0–1), the use of the CHADS 2 -MS score may additionally identify patients with high-risk AF for future thromboembolism. Conclusions We, for the first time, demonstrated that metabolic syndrome components were associated with thromboembolic risk in Taiwanese patients with AF. In addition to the conventional CHADS 2 scheme, the calculation of the CHADS 2 -MS score provides additional information on stroke risk assessment.
- Published
- 2014
182. Novel application of amino-acid buffered solution for neuroprotection against ischemia/reperfusion injury
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Jou-Wei Lin, Shengpin Yu, Yung-Wei Chen, Ming-Chieh Ma, Juey-Jen Hwang, Jiun Hsu, Shu-Chien Huang, Yih-Sharng Chen, and Chih-Hsien Wang
- Subjects
Male ,0301 basic medicine ,Resuscitation ,Critical Care and Emergency Medicine ,030204 cardiovascular system & hematology ,Pharmacology ,Pathology and Laboratory Medicine ,Biochemistry ,Vascular Medicine ,chemistry.chemical_compound ,0302 clinical medicine ,Animal Cells ,Ischemia ,Medicine and Health Sciences ,Brain Damage ,Amino Acids ,Hypoxia ,Neurons ,Cerebral Ischemia ,Multidisciplinary ,Organic Compounds ,Neuroprotection ,Chemistry ,Neuroprotective Agents ,Neurology ,NADPH Oxidase 4 ,Reperfusion Injury ,Physical Sciences ,cardiovascular system ,Medicine ,Cellular Types ,Basic Amino Acids ,medicine.symptom ,Nicotinamide adenine dinucleotide phosphate ,Research Article ,Science ,Brain damage ,Buffers ,Asphyxia ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,In vivo ,medicine ,Animals ,Histidine ,business.industry ,Organic Chemistry ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Hydrogen Peroxide ,Cell Biology ,Hypoxia (medical) ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Rats ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,chemistry ,Cellular Neuroscience ,business ,Reperfusion injury ,Biomarkers ,Neuroscience - Abstract
Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.
- Published
- 2019
183. Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan Diastolic Heart Failure Registry and molecular basis by cellular and animal models
- Author
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Fu-Tien Chiang, Sheng-Nan Chang, Ming-Jai Su, Jin Jer Chen, Jiunn Lee Lin, Mao-Yuan M. Su, Chia Ti Tsai, Jen Kuang Lee, Juey-Jen Hwang, Huei-Ming Yeh, Cho-Kai Wu, and Yi-Chih Wang
- Subjects
medicine.medical_specialty ,Pathology ,integumentary system ,Cardiac fibrosis ,business.industry ,Diastole ,Diastolic heart failure ,Connective tissue ,medicine.disease ,CTGF ,medicine.anatomical_structure ,Fibrosis ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Myocardial fibrosis ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data. Methods and results A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler imaging (E/e'). Cardiac magnetic resonance imaging (CMRI) was used to evaluate myocardial fibrosis in some of the patients (n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction (DD). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e' in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF. In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD (r = 0.40, P Conclusion Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF.
- Published
- 2013
184. Combination of Plasma Biomarkers and Clinical Data for the Detection of Myocardial Fibrosis or Aggravation of Heart Failure Symptoms in Heart Failure with Preserved Ejection Fraction Patients
- Author
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Juey-Jen Hwang, Mao-Yuan M. Su, Yi-Fan Wu, Cho-Kai Wu, and Lian-Yu Lin
- Subjects
heart failure with preserved ejection fraction ,medicine.medical_specialty ,medicine.drug_class ,Cardiac fibrosis ,cardiac diastolic dysfunction ,cardiac magnetic resonance imaging ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cardiac magnetic resonance imaging ,Fibrosis ,Internal medicine ,medicine ,Natriuretic peptide ,030212 general & internal medicine ,medicine.diagnostic_test ,business.industry ,lcsh:R ,fibrosis ,Area under the curve ,biomarkers ,General Medicine ,medicine.disease ,Heart failure ,Cardiology ,Myocardial fibrosis ,business ,Heart failure with preserved ejection fraction - Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms and structural change (including fibrosis). The relationship between novel biomarkers and the above components remains unclear. Methods: Seventy-seven HFpEF patients were recruited. All patients underwent echocardiography with tissue doppler imaging, cardiac magnetic resonance imaging (CMRI), and measurement of plasma inflammatory, remodelling, endothelial function, and heart failure biomarker levels. Myocardial fibrosis was defined by CMRI-extracellular volume. Forward conditional logistic regression was applied to demonstrate the determinants of myocardial fibrosis or heart failure symptoms. Results: The levels of growth differentiation factor, tissue inhibitor of metalloproteinase (TIMP)-1, galectin-3, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were significantly higher in patients with more myocardial fibrosis. Matrix metalloproteinase-2 (MMP-2) and galectin-3 were independent markers of ECV. After adjusting for confounding factors, plasma galectin-3 and MMP-2 levels were correlated with myocardial fibrosis levels (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.02 to 1.09, p = 0.005 and OR: 2.11, 95% CI: 1.35&ndash, 3.28, respectively), while NT-proBNP level only was associated with heart failure symptoms. We developed a score system consisted of biomarkers and clinical parameters. The area under the curve of the scoring system receiver operating characteristic curve is 0.838 to predict the degree of myocardial diffuse fibrosis. Conclusions: In conclusion, we found that galectin-3 and MMP-2 were significantly associated with global cardiac fibrosis in HFpEF patients. We also combined plasma biomarkers and clinical data to identify HFpEF patients with more severe cardiac fibrosis.
- Published
- 2018
185. Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human
- Author
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Pei-Chi Wei, Lee-Ming Chuang, Yen-Hui Chen, Wen-Hwa Lee, Jin-Yuh Shew, Juey-Jen Hwang, Wei-Jei Lee, Yi-Cheng Chang, Yu-Hsiang Yu, and Yet-Ran Chen
- Subjects
Adipose tissue ,N-Acetylcysteine ,Npgpx ,Social and Behavioral Sciences ,medicine.disease_cause ,Antioxidants ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine and Health Sciences ,Adipocytes ,Phospholipid-hydroperoxide glutathione peroxidase ,Research Articles ,Metabolic Syndrome ,chemistry.chemical_classification ,0303 health sciences ,Adipogenesis ,Glutathione peroxidase ,Life Sciences ,C/Ebp ,Diet-Induced Obesity ,C/EBPβ ,Molecular Medicine ,Protects ,Signal Transduction ,medicine.medical_specialty ,Oxidative Stress Alpha-Lipoic Acid ,Biology ,CCAAT-Enhancer-Binding Protein-beta ,Association ,03 medical and health sciences ,Glutathione-Peroxidase ,Internal medicine ,Adipocyte Differentiation ,medicine ,Animals ,Humans ,Body-Mass Index ,Cell-Death ,NPGPx ,Obesity ,Protein kinase A ,030304 developmental biology ,Reactive oxygen species ,Insulin-Resistance ,Body Weight ,N-acetylcysteine ,Oxidative Stress ,Endocrinology ,chemistry ,Reactive Oxygen Species ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBPβ). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management. Deficiency of the glutathione peroxidase NPGPx increases ROS levels in preadipocytes and promotes adipocyte differentiation via increasing oxidative stress and consequent increased fat mass and adipocyte hypertrophy.
- Published
- 2013
186. Impacts of Mitral E/e′ on Myocardial Contractile Motion and Synchronicity in Heart Failure Patients With Reduced Ejection Fraction: An Exercise-Echocardiography Study
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Fu Chun Chiu, Jiunn Lee Lin, Juey-Jen Hwang, Ling Ping Lai, Chih Chieh Yu, Chia Ti Tsai, and Yi-Chih Wang
- Subjects
medicine.medical_specialty ,Ejection fraction ,business.industry ,Diastole ,General Medicine ,Odds ratio ,medicine.disease ,Confidence interval ,Tissue Doppler echocardiography ,Internal medicine ,Heart failure ,cardiovascular system ,medicine ,Cardiology ,Decompensation ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,Ventricular dyssynchrony ,business - Abstract
Background The association between diastolic abnormality and postexercise contractile decompensation is uncertain in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF). Hypothesis The higher mitral E/annular early diastolic velocity (E/e′) is relevant to postexercise regional myocardial contractile maladaptation. Methods Seventy HF patients with LVEF 65 ms (OR: 64, 95% CI: = 6–651, P < 0.001) in HF patients with reduced LVEF in multivariate analysis. Conclusions The higher mitral E/e′-related postexercise maladaptation of myocardial contractile motion and synchronicity suggests the involvement of systolic abnormality in exercise pathophysiology in HF patients with reduced LVEF.
- Published
- 2013
187. Soluble ST2 as a Biomarker for Detecting Stable Heart Failure With a Normal Ejection Fraction in Hypertensive Patients
- Author
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Jiunn Lee Lin, Yi-Chih Wang, Juey-Jen Hwang, Ling Ping Lai, Chih Chieh Yu, Chia Ti Tsai, and Fu Chun Chiu
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Diastole ,Receptors, Cell Surface ,Diagnostic aid ,Internal medicine ,medicine ,Natriuretic peptide ,Humans ,Aged ,Heart Failure ,Ejection fraction ,Receiver operating characteristic ,business.industry ,Stroke Volume ,Odds ratio ,Middle Aged ,medicine.disease ,Interleukin-1 Receptor-Like 1 Protein ,Heart failure ,Hypertension ,Cardiology ,Biomarker (medicine) ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
We investigated the measurement of soluble ST2 (sST2) in stable heart failure (HF) with a normal ejection fraction (HFNEF) in hypertensive patients.Echocardiography and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and sST2 concentrations were evaluated in 107 hypertensive patients (65 ± 12 years, 57 male) with ejection fraction (EF)50%. Among them, 68 patients with stable HF in functional class II and III were the HFNEF group. We found that the area under the receiver operating characteristic curve (AUC) for sST2 was 0.80 (95% CI 0.70-0.89; P.001), relatively better than that for NT-proBNP (AUC 0.70, 95% CI 0.58-0.79; P = .003) to detect HFNEF. However, the NT-proBNP concentration, rather than sST2, was higher in HFNEF patients with functional class III (562 ± 891 vs 185 ± 242 pg/mL in functional class II; P = .009), and correlated better with mitral E/e' (annular early diastolic velocity) (r = 0.327; P = .008) than sST2 concentrations in HFNEF patients. Multivariate analysis showed that sST213.5 ng/mL was independently associated with HFNEF in hypertensive patients (odds ratio 11.7, 95% CI = 2.9-47.4; P = .001).sST2 measurement provides diagnostic aid of stable HFNEF for hypertensive patients. Addition of NT-proBNP to sST2 could give further information regarding HF functional class and diastolic abnormality.
- Published
- 2013
188. Genome-wide methylation profiles in coronary artery ectasia
- Author
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Kuo-Liang Chien, Jyh-Ming Jimmy Juang, Cho-Kai Wu, Lian-Yu Lin, Chin-Yu Cheng, Tzu-Pin Lu, Shih-Fan Sherri Yeh, Cheng-An Hsu, Yi-Chih Wang, Jen-Kuang Lee, Juey-Jen Hwang, Nai-Chen Chuang, and Yen-Hong Lin
- Subjects
0301 basic medicine ,Adult ,Male ,Pathology ,medicine.medical_specialty ,Microarray ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Biology ,Bioinformatics ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Proto-Oncogene Proteins ,medicine ,Humans ,Genetic Predisposition to Disease ,Receptor, Notch4 ,Aged ,Inflammation ,Receptors, Notch ,Coronary artery ectasia ,General Medicine ,Methylation ,DNA Methylation ,Middle Aged ,medicine.disease ,Coronary Vessels ,Coronary arteries ,030104 developmental biology ,medicine.anatomical_structure ,Toll-Like Receptor 6 ,TLR6 ,Case-Control Studies ,DNA methylation ,Female ,Dilatation, Pathologic ,Genome-Wide Association Study - Abstract
Coronary artery ectasia (CAE) is a disease characterized by abnormally dilated coronary arteries. The mechanism of CAE remains unclear, and its treatment is limited. Previous studies have shown that risk factors for CAE were related to changes in DNA methylation. However, no systematic investigation of methylation profiles has been performed. Therefore, we compared methylation profiles between 12 CAE patients and 12 propensity-matched individuals with normal coronary arteries using microarrays. Wilcoxon's rank sum tests revealed 89 genes with significantly different methylation levels (P |0.1|). Functional characterization using the DAVID database and gene set enrichment analysis indicated that these genes were involved in immune and inflammatory responses. Of these genes 6 were validated in 29 CAE patients and 87 matched individuals with CAE, using pyro-sequencing. TLR6 and NOTCH4 showed significant differences in methylation between the two groups, and lower protein levels of toll-like receptor 6 (TLR6) were detected in CAE patients. In conclusion, this genome-wide analysis of methylation profiles in CAE patients showed that significant changes in both methylation and expression of TLR6 deserve further study to elucidate their roles in CAE.
- Published
- 2016
189. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy and Safety of Ethyl-Ester Omega-3 Fatty Acid in Taiwanese Hypertriglyceridemic Patients
- Author
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Kuo-Chin Huang, Kuo-Liong Chien, Kuo Yang Wang, Runar Vige, Fu-Tien Chiang, Ta-Chen Su, Min Ji Charng, Lian-Yu Lin, Chuen Den Tseng, José Emilio Ruiz Olivar, Wei-Chuan Tsai, and Juey-Jen Hwang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Eicosapentaenoic acid ,Docosahexaenoic Acids ,Taiwan ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Placebo ,Gastroenterology ,Severity of Illness Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Fatty Acids, Omega-3 ,Internal Medicine ,medicine ,Clinical endpoint ,Omega-3 fatty acids ,Humans ,Adverse effect ,Omega 3 fatty acid ,Life Style ,Triglycerides ,Hypolipidemic Agents ,Omacor ,Hypertriglyceridemia ,Triglyceride ,business.industry ,Ethnic chinese ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,Drug Combinations ,Docosahexaenoic acid ,Treatment Outcome ,chemistry ,Biochemistry ,Dietary Supplements ,Female ,Original Article ,Safety ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aim: Information regarding the effects of omega-3 fatty acid on hypertriglyceridemic patients in Chinese is still limited. This study aimed to investigate the efficacy and safety of Omacor®, a prescription ethyl-ester omega-3 fatty acid for the treatment of hypertriglyceridemia, administered at doses of 2 g/day and 4 g/day to Taiwanese hypertriglyceridemic patients. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel study in adults with hypertriglyceridemia was conducted. After a five-week diet lead in period patients with triglycerides = 200–1000 mg/dL were randomized to receive Omacor®, a concentrated preparation of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) in a dose of 1 g twice daily (2 g Omacor ®), 2 g twice daily (4 g Omacor®) or placebo, for eight weeks. The primary endpoint was the percentage change in triglyceride serum levels from baseline to the end of treatment. Results: A total of 253 Taiwanese patients were randomized, of which 65.6% (166) were men. At the end of the treatment, the percentage change in triglyceride serum levels in both the Omacor® 4 g/day (−32.1%) and 2 g/day (−29.7%) groups was larger than in the placebo group (−5.4%) (p < 0.001). The incidence of drug-related adverse events was as follows: 0.0%, 1.2%, and 0.0% in Omacor ® 4 g/day, Omacor® 2 g/day, and placebo groups, respectively. No drug-related serious adverse events were reported during the study. Conclusions: Omacor® may be a feasible option to treat hypertriglyceridemia in Taiwanese patients.
- Published
- 2016
190. Renal function, serum sodium level, and outcomes in hospitalized systolic heart failure patients: An analysis of the COAST study
- Author
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Junbo Ge, Ming Shien Wen, Juey-Jen Hwang, Seok Min Kang, Dong-Ju Choi, Shing Jong Lin, Jin Joo Park, Jian Zhang, Byung Su Yoo, and In Ho Chae
- Subjects
Male ,medicine.medical_specialty ,China ,Sodium ,Taiwan ,Renal function ,chemistry.chemical_element ,Observational Study ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Republic of Korea ,medicine ,Humans ,030212 general & internal medicine ,Renal Insufficiency ,Intensive care medicine ,Survival rate ,hospitalized heart failure, low sodium level, predictor of clinical outcomes, renal impairment ,Aged ,Inpatients ,Ejection fraction ,business.industry ,Mortality rate ,Incidence ,Stroke Volume ,General Medicine ,Stroke volume ,Middle Aged ,medicine.disease ,Prognosis ,Survival Rate ,chemistry ,Heart failure ,Female ,business ,Low sodium ,Heart Failure, Systolic ,Research Article - Abstract
Both renal function and serum sodium level are well-known prognostic markers in heart failure (HF) patients. We investigated the prognostic value of the renal impairment (RI) stratified by the serum sodium level in systolic HF patients. The Clinical Characteristics and Outcomes in Relation with Serum Sodium Level in Asian Patients Hospitalized for Heart Failure (the COAST) Study enrolled hospitalized systolic HF patients (ejection fraction
- Published
- 2016
191. Association of Small-Conductance Calcium-Activated Potassium Channels and Atrial Fibrillation - How Far Have We Gone?
- Author
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Shu-Hsuan, Chang, Sheng-Nan, Chang, Lian-Yu, Lin, Ling-Ping, Lai, Chuen-Den, Tseng, Yi-Chih, Wang, Chih-Chieh, Yu, Fu-Tien, Chiang, Juey-Jen, Hwang, Jiunn-Lee, Lin, and Chia-Ti, Tsai
- Subjects
Mini Forum for EPS - Abstract
Atrial fibrillation (AF) is the most common sustained and most important arrhythmia in clinical practice. The mechanisms underlying AF initiation and maintenance are known to be complex and heterogeneous. The general understanding of the detailed molecular basis of AF is still incomplete. Recently, these is increasing evidence that small conductance calcium-activated potassium (SK) channels are associated with atrial action potential repolarization and the pathogenesis of AF. Although the functional role of SK channels in the genesis of AF is not entirely clear, new insights into the basic pathophysiological mechanism of AF have been provided. Besides, genome-wide association studies also implicate that genes coding for SK channels are related to the risk of developing AF. This article reviews recent work on the association of SK channels and AF, genetic studies of SK channels, and discuss future investigation and developments regarding this field.Atrial fibrillation; Genetics; Small conductance calcium-activated potassium channels.
- Published
- 2016
192. The Impact of Metabolic Syndrome, Homocysteine, and B Vitamins on Carotid Artery Intima-Media Thickness in Hypertensive Patients
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Chung-Pin, Liu, Yu-Li, Lin, Yen-Hung, Lin, Kuan-Yin, Pao, Vin-Cent, Wu, Ta-Chen, Su, Chi-Sheng, Hung, Churn-Shiouh, Gau, and Juey-Jen, Hwang
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Mini Forum for Hypertension - Abstract
To examine the correlation between metabolic syndrome (MS), plasma total homocysteine (tHcy) level, and serum B vitamin levels on carotid intima-media thickness (CIMT) in hypertensive patients.A total of 73 medically treated hypertensive patients (42 men, mean age 70.7 years), fasted for 10 hours, and provided fasting blood samples for measurement of plasma tHcy, serum folic acid, and serum vitamin B12 levels. Additionally, B-mode ultrasound of the distal right common carotid arteries was performed on all participants.There were 50 patients with and 23 patients without MS. Patients with MS had larger CIMT than patient without (0.81 ± 0.13 vs. 0.74 ± 0.10 mm, p = 0.018). Patients with MS had larger waist circumference (p0.001), higher body mass index (p0.001), elevated serum triglyceride level (p0.001), lower serum high density lipoprotein level (p = 0.016), higher prevalence of diabetes mellitus (p = 0.012), higher prevalence of hyperlipidemia (p = 0.019), and a higher prevalence of fibrate usage (p = 0.025) than patients without MS. In univariate analysis, CIMT correlated significantly with the presence of MS (r = 0.256; p = 0.029), usage of angiotensin receptor blocker (ARB; r = -0.256; p = 0.029), and male gender (r = 0.247; p = 0.035). The relationships between CIMT and serum folic acid level (r = -0.212; p = 0.072) or statin usage (r = 0.207; p = 0.079) were borderline significant. In multivariate regression analysis, after adjusting for age and gender, only usage of ARB (β value -0.078, 95% CI: -0.140 to -0.015, p = 0.016) and the presence of MS (β value 0.075, 95% CI: 0.020 to 0.131, p = 0.009) were associated with CIMT. In anothermodel, after adjusting four additional parameters including age, gender, systolic blood pressure and usage of statin, usage of ARB (β value -0.074, 95% CI: -0.137 to -0.011, p = 0.022) and presence of MS (β value 0.069, 95% CI: 0.012 to 0.125, p = 0.017) remained significantly correlated with CIMT.MS and usage of ARB are associated with CIMT in hypertensive patients.Folic acid; Homocysteine, Intima-media thickness, Metabolic syndrome.
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- 2016
193. Renin-Angiotensin System Genes Polymorphisms and Long-Term Prognosis in Taiwanese Patients with Hypertension and Coronary Artery Disease
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Cho-Kai, Wu, Jen-Kuang, Lee, Lian-Yu, Lin, Yin-Tsen, Huang, Juey-Jen, Hwang, Chunn-Lee, Lin, Chuen-Den, Tseng, and Fu-Tien, Chiang
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Mini Forum for Hypertension - Abstract
The objective of this study was to evaluate the renin-angiotensin system genetic effects and pharmacogenetic interactions for angiotensin-converting enzyme (ACE) inhibitors in hypertensive coronary artery disease (CAD) patients.Subjects with hypertension and angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphism, six polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphisms of the angiotensin II type I receptor gene (AGT1R)] were collected. Patients were assigned to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed-for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models.Of the 518 patients in our study, 290 were treated with ACE inhibitors and 228 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D was associated with a higher rate of MACE in a multivariate regression analysis [hazard ration (HR): 1.64, 95% confidence interval (CI): 1.27-1.98, p0.001]. This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE in hibitors*ACE D gene, HR: 0.68, 95% CI: 0.52-0.84, p = 0.014).The use of ACE inhibitors was associated with a significant decrease in MACE in hypertensive patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.Angiotensin-converting enzyme inhibitors; Coronary artery disease; Hypertension; Pharmacogenetic.
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- 2016
194. Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study
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Jen-Kuang, Lee, Cho-Kai, Wu, Jyh-Ming, Juang, Chia-Ti, Tsai, Juey-Jen, Hwang, Jiuun-Lee, Lin, and Fu-Tien, Chiang
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Original Article - Abstract
The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved.Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet Mapping(TM) (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays.Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI.Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome.Clopidogrel • CYP2C19 polymorphism • Platelet aggregation • Proton pump inhibitors • TEG • VASP.
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- 2016
195. Next-Generation Sequencing in the Genetics of Human Atrial Fibrillation
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Chia-Shan, Hsieh, Eric Y, Chuang, Jyh-Ming Jimmy, Juang, Juey-Jen, Hwang, Chuen-Den, Tseng, Fu-Tien, Chiang, Ling-Ping, Lai, Jiunn-Lee, Lin, and Chia-Ti, Tsai
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Mini Forum for Current Status of AF in Taiwan - Abstract
The International Human Genome Sequencing Consortium published the first draft of the human genome in the journal Nature in February 2001, providing the sequence of the entire genome's three billion base pairs. The Human Genome Project involves a concerted effort to better understand the human DNA sequence through identification of all the genes. The knowledge that can be derived from the genome could result in the development of novel diagnostic assays, targeted therapies and the improved ability to predict the onset, severity and progression of diseases. This has been made possible by many parallelized, high-throughput technologies such as next-generation sequencing. In this review, we discuss the possible application of next-generation sequencing in finding the susceptibility gene(s) or disease mechanism of an important human arrhythmia called atrial fibrillation.Arrhythmia; Atrial fibrillation; Genetics, Next-generation sequencing.
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- 2016
196. Effects of Additional Intra-aortic Balloon Counter-Pulsation Therapy to Cardiogenic Shock Patients Supported by Extra-corporeal Membranous Oxygenation
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Juey-Jen Hwang, Yih-Sharng Chen, Nai-Kuan Chou, Hsi-Yu Yu, Lian-Yu Lin, Nai-Hsin Chi, Jiunn Lee Lin, Fu-Tien Chiang, Che-Wei Liao, and Chih-Hsien Wang
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Adult ,Male ,medicine.medical_specialty ,Critical Care ,Systole ,medicine.medical_treatment ,Shock, Cardiogenic ,030204 cardiovascular system & hematology ,Intra-Aortic Balloon Pumping ,Balloon ,Article ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Extracorporeal Membrane Oxygenation ,Afterload ,Internal medicine ,Extracorporeal membrane oxygenation ,Medicine ,Humans ,030212 general & internal medicine ,Aged ,Multidisciplinary ,business.industry ,Cardiogenic shock ,Middle Aged ,medicine.disease ,Preload ,surgical procedures, operative ,Treatment Outcome ,Shock (circulatory) ,Cardiology ,Female ,medicine.symptom ,business - Abstract
Extra-corporeal membranous oxygenation (ECMO) has been applied in patients with cardiopulmonary failure. One critical drawback of peripheral ECMO is an increase in left ventricular (LV) afterload which could be counterbalanced by the combination of intra-aortic balloon counter-pulsation (IABP) therapy. We hypothesized that an add-on therapy with IABP could improve outcomes in patients receiving ECMO support. We included patients (>18 years old) from 2002 to 2013 requiring ECMO support due to cardiogenic shock in a medical center. A total of 529 patients (227 ECMO alone and 302 combined IABP plus ECMO) were included. The mortality rates at 2 weeks (48.5 vs. 47.7%) after ECMO implantation were not different between the two groups (ECMO vs. combined group). After adjustment for propensity score and potential confounders, the odds ratios of outcomes within 14 days (combined group vs. ECMO) for poor LV systolic function, high preload, multi-organ failure and mortality were not different. The results remained similar for subgroup analysis. Compared with ECMO alone, combined IABP and ECMO treatment did not improve outcomes in patients with circulatory failure.
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- 2016
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197. Myocardial Regional Interstitial Fibrosis is Associated With Left Intra-Ventricular Dyssynchrony in Patients With Heart Failure: A Cardiovascular Magnetic Resonance Study
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Fu-Tien Chiang, Mao-Yuan M. Su, Wen Yih Issac Tseng, Ling Ping Lai, Jiunn Lee Lin, Lian-Yu Lin, Juey-Jen Hwang, Jyh-Ming Jimmy Juang, Cho-Kai Wu, and Yi-Chih Wang
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Male ,medicine.medical_specialty ,Heart Ventricles ,Endomyocardial fibrosis ,030204 cardiovascular system & hematology ,Interstitial fibrosis ,Ventricular Function, Left ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,Ventricular dyssynchrony ,Aged ,Heart Failure ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Endomyocardial Fibrosis ,Magnetic Resonance Imaging ,Pathophysiology ,Heart failure ,Cardiology ,Female ,business ,Heart failure with preserved ejection fraction - Abstract
Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short-axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age (1.87, 95% CI: 0.61–3.13, p = 0.004) and ECV (3.77, 95% CI: 2.72–4.81, p
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- 2016
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198. Anti-Hyperglycemic Agents and New-Onset Acute Myocardial Infarction in Diabetic Patients with End-Stage Renal Disease Undergoing Dialysis
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Juey-Jen Hwang, Chih Chen Wu, Yao-Hsu Yang, Ting-Tse Lin, Lian-Yu Lin, Jiunn Lee Lin, and Pau-Chung Chen
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Male ,medicine.medical_treatment ,Myocardial Infarction ,lcsh:Medicine ,Disease ,Cardiovascular Medicine ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Biochemistry ,Vascular Medicine ,Geographical Locations ,Endocrinology ,0302 clinical medicine ,Risk Factors ,Chronic Kidney Disease ,Medicine and Health Sciences ,Insulin ,Coronary Heart Disease ,Medicine ,Registries ,030212 general & internal medicine ,Myocardial infarction ,lcsh:Science ,Multidisciplinary ,Incidence ,Middle Aged ,Prognosis ,Nephrology ,Cardiovascular Diseases ,Cardiology ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Asia ,Adolescent ,Endocrine Disorders ,Taiwan ,Hypoglycemia ,Risk Assessment ,End stage renal disease ,Young Adult ,03 medical and health sciences ,Renal Dialysis ,Internal medicine ,Diabetes mellitus ,Medical Dialysis ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Dialysis ,Aged ,Retrospective Studies ,Glycemic ,Diabetic Endocrinology ,business.industry ,lcsh:R ,Biology and Life Sciences ,medicine.disease ,Hormones ,Metabolic Disorders ,People and Places ,Kidney Failure, Chronic ,lcsh:Q ,business ,Follow-Up Studies ,Kidney disease - Abstract
Background Diabetes and chronic kidney disease (CKD) are a high-stakes combination for cardiovascular disease. Patients with decreased kidney function and end-stage renal disease (ESRD) have increased risk of hypoglycemia when attaining better glycemic control, leading to higher risk of myocardial infarction (MI). For these patients, which kinds of anti-hyperglycemic agents would be associated with higher risk of MI is not clear. Methods We identified patients from a nation-wide database called Registry for Catastrophic Illness, which encompassed almost 100% of the patients receiving dialysis therapy in Taiwan from 1995 to 2008. Patients with diabetes and ESRD were selected as the study cohort. Propensity score adjustment and Cox's proportional hazards regression model were used to estimate the hazard ratios (HRs) for new-onset MI. Results Among 15,161 patients, 39% received insulin, 40% received sulfonylureas, 18% received meglitinides and 3% received thiazolidinedione (TZD). After a median follow-up of 1,357 days, the incidence of MI was significant increase in patients taking sulfonylureas (HR = 1.523, 95% confidence interval [CI] = 1.331–1.744), meglitinides (HR = 1.251, 95% CI = 1.048–1.494) and TZD (HR = 1.515, 95% CI = 1.071–2.145) by using patients receiving insulin therapy as the reference group. The risk of MI remains higher in other three groups in subgroup analyses. Conclusions In conclusion, among diabetic patients with ESRD undergoing dialysis, the use of sulfonylureas, meglitinides and TZD are associated with higher risk of new-onset MI as compared with insulin.
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- 2016
199. CABG Versus PCI in Multilesional Vessel Disease
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Juey-Jen Hwang, Jiunn Lee Lin, and Yi-Chih Wang
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medicine.medical_specialty ,Medical treatment ,business.industry ,medicine.medical_treatment ,Percutaneous coronary intervention ,Disease ,medicine.disease ,Revascularization ,Coronary artery disease ,Coronary artery bypass surgery ,surgical procedures, operative ,Internal medicine ,Conventional PCI ,medicine ,Cardiology ,cardiovascular diseases ,business - Abstract
With numerous trials conducted during the 1970s and 1980s evaluating coronary artery bypass surgery (CABG) versus medical treatment for patients with coronary artery disease (CAD), the absolute benefit of surgery was shown to be prominent especially for those with more extensive coronary involvement. However, the pronounced effect of CABG for patients with multivessel CAD (MVD) has faced continuing challenges since the introduction of percutaneous coronary intervention (PCI) and evolving revascularization technology, such as coronary stents.
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- 2016
200. Additional file 1: of Impact of routine coronary catheterization in low extremity artery disease undergoing percutaneous transluminal angioplasty: study protocol for a multi-center randomized controlled trial
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I-Chih Chen, Cheng-Han Lee, Ting-Hsing Chao, Wei-Kung Tseng, Tsung-Hsien Lin, Wen-Jung Chung, Jen-Kwan Li, Hsuan-Li Huang, Ping-Yen Liu, Ting-Kuang Chao, Chuin-Yuan Chu, Chih-Chan Lin, Po-Chao Hsu, Wen-Huang Lee, Po-Tseng Lee, Li, Yi-Heng, Shih-Ya Tseng, Liang-Miin Tsai, and Juey-Jen Hwang
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humanities - Abstract
Checklist of items for reporting trials of non-pharmacologic treatment. The information addressed in our study protocol complying with CONSORT extension for trials assessing non-pharmacologic intervention is provided in this checklist table. CONSORT Consolidated Standards of Reporting Trials. (PDF 613 kb)
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- 2016
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