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BACKGROUND: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF. METHODS: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month. RESULTS: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable. CONCLUSIONS: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

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.

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.

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.

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.

Green tea intake has been shown to improve endurance capacity in animal studies, but whether it has a similar effect on humans remains unclear. A randomized, double-blinded, parallel-controlled study was conducted to evaluate the short-term effect of STA-2, a pharmaceutical preparation of green tea polyphenols, in patients with effort-induced angina and documented positive exercise tolerance test.A total of 79 patients recruited from three medical centers were randomly assigned to receive 2 STA-2 250 mg capsules, each containing 100 mg green tea polyphenols, three times daily, or placebo for six weeks after two consecutive symptom-limited treadmill exercise tests to ascertain the reproducibility of exercise tolerance.There was no difference in total exercise tolerance time from baseline to Week 6 between two groups (p = 0.639). There were also no observed improvements in subgroup analyses stratified by age, gender, and BMI categories. However, a significant reduction in low-density lipoprotein levels was shown in patients in the STA-2 group (-8.99 ± 19.18 mg/dL) versus the placebo group (0.57 ± 19.77 mg/dL), p = 0.037, with greater benefits in patients not taking antihyperlipidemic drugs (STA-2: -9.10 ± 19.96 mg/dL vs. placebo: 4.42 ± 15.08 mg/dL, p = 0.037).STA-2 treatment for 6 weeks did not increase exercise time as measured on a treadmill. However, this study also indicated that STA-2 treatment could have potential beneficial effects on LDL-cholesterol concentrations.

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.

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.

The aim of this study was to evaluate the independent roles of proteinuria and reduced estimated glomerular filtration rate (GFR) in the development of acute myocardial infarction in a northern Taiwanese population.We conducted a community-based prospective cohort study in Keelung, the northernmost county of Taiwan. A total of 63,129 subjects (63% women) ≥ 20 years of age who had no history of coronary heart disease were recruited and followed-up. Univariate and multivariate proportional hazards regression analysis was performed to assess the association between proteinuria and estimated GFR and the risk of acute myocardial infarction.There were 305 new cases of acute myocardial infarction (114 women and 191 men) documented during a four-year follow-up period. After adjustment of potential confounding covariates, heavier proteinuria (dipstick urinalysis reading 3+) and estimated GFR of less than 60 ml/min/1.73 m(2) independently predicted increased risk of developing acute myocardial infarction. The adjusted hazard ratio (aHR) of heavier proteinuria for occurrence of acute myocardial infarction was 1.85 [95% confidence intervals (CI), 1.17-2.91, p0.01] (vs. the reference group: negative dipstick proteinuria). The aHR of estimated GFR of 30-59 ml/min/1.73 m(2) for occurrence of acute myocardial infarction was 2.4 (95% CI, 1.31-4.38, p0.01) (vs. the reference group: estimated GFR ≥ 90 ml/ min/1.73 m(2)), and that of estimated GFR of 15-29 ml/min/1.73 m(2) was 5.26 (95% CI, 2.26-12.26, p0.01).We demonstrated that both heavier proteinuria and lower estimated GFR are significant independent predictors of developing future acute myocardial infarction in a northern Taiwanese population.Acute myocardial infarction; Estimated glomerular filtration rate; Proteinuria.

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.

Chang S-N, Tsai C-T, Wu C-K, Lee J-K, Lai L-P, Huang S-W, Huang L-Y, Tseng C-D, Lin J-L, Chiang F-T, Hwang J-J (National Taiwan University Hospital Yun-Lin Branch, Yun-Lin; National Taiwan University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315. Objectives. In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. Results. Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Recently zebrafish has become a powerful vertebrate model system for cardiac arrhythmia and another advantage is that the heart could be rapidly excised for in-vitro electrophysiological recording.We made direct in-vitro recordings of adult zebrafish heart ECG using the microelectrode and tested the effects of various drugs on zebrafish heart ECG.The QT interval change in the ECG was verified by optically mapped action potential duration (APD). The mean in-vitro heart rate (HR) of the adult zebrafish was 118 ± 22 beats/min. The mean QT interval was 312 ± 36 ms and mean HR corrected QT interval (QTc) 439 ± 39 ms. The mean optically mapped APD was 308 ± 30 ms, which was close to the QT interval in ECG (p=0.815). We found that sympathomimetic drug isoproterenol increased HR, whereas L-type calcium channel blocker verapamil decreased HR. Sodium channel blocker quinidine and L-type calcium channel activator BayK8644 prolonged QTc interval in a dose-dependent manner (515 ± 24 ms and 519 ± 27 ms, respectively, both p0.01). The APD was also prolonged accordingly. Both rapidly and slowly activating delayed rectifier potassium channel (IKr and IKs) blockers E4031 and chromanol 293B, respectively, also prolonged QTc interval in a dose-dependent manner (523 ± 25 ms and 529 ± 27 ms, respectively, both p0.01). Quinidine, E4031 and chromanol 293B also decreased HR.Direct in-vitro recording of adult zebrafish heart is an efficient platform for test of drugs which exert electrophysiological effects on cardiomyocytes, and perturbation of ionic channels that are responsible for human long QT syndrome also modulates QT interval in adult zebrafish heart.

Background Polygenetic effect has rarely been addressed in the genetic studies of coronary artery disease (CAD). We used the largest and ethnically homogeneous angiographic cohort to analyze multilocus data in renin-angiotensin system genes, and provide an explicit demonstration of gene–gene interactions. Methods A total of 1254 consecutive patients who underwent cardiac catheterization (735 with coronary artery disease and 519 without) were recruited. Angiotensin converting enzyme(ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects, adjust non-genetic confounding effects and detect gene–gene interaction between ACE and AT1R genes. Results We found significant differences in global AGT gene haplotype profile and individual haplotypes between cases and controls. Significant two-way and three-way gene–gene interactions between ACE I/D, AT1R A1166C polymorphisms and AGT gene haplotypes were detected. However, subjects carrying both D allele and GGCATC haplotype had an increased risk of CAD (odds ratio = 1.63 [1.16–2.29]; P = 0.004). We also used haplotype counting to directly estimate the odds ratio of each specific AGT gene haplotype, and found that the effects of haplotypes were markedly different in subgroups with different ACE or AT1R gene genotype. Conclusions The regression-based haplotype analyses permits simultaneous dectection of multi-locus and multi-gene effects in determining the risk of CAD. We provide the paradigm for genetic studies of complex-trait diseases using candidate genes based on biological pathways.

Background We compared the haemodynamic and metabolic effects of acetyl-L-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) in streptozotocin-induced diabetes in male Wistar rats. Materials and methods Diabetes was induced by a single tail vein injection of 55 mg kg )1 streptozotocin. The diabetic animals daily treated with either acetyl-L-carnitine (150 mg kg )1 in drinking water) or oxfenicine (150 mg kg )1 by oral gavage) for 8 weeks,were compared with the untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. Thiobarbituric acid reactive substances (TBARS) measurement was used to estimate malondialdehyde (MDA) content. Results Oxfenicine, but not acetyl-L-carnitine, increased total peripheral resistance in diabetes, which paralleled its elevation in plasma levels of free fatty acids. By contrast, acetyl-L-carnitine, but not oxfenicine, resulted in a significant increase in wave transit time and a decrease in wave reflection factor, suggesting that acetyl-L-carnitine may attenuate the diabetes-induced deterioration in systolic loading condition for the left ventricle. This was in parallel with its lowering of MDA ⁄TBARS content in plasma and aortic walls in diabetes. Acetyl-L-carnitine therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Conclusion Acetyl-L-carnitine, but not oxfenicine, attenuates aortic stiffening and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived MDA ⁄TBARS in the rats with insulin deficiency.

Calcified aorta with acute iatrogenic aortic dissection is a potential but rarely reported complication of subclavian or innominate artery intervention. We report a patient who developed aortic dissection during stenting for left subclavian artery. A newly developed "calcium sign," signifying displacement of the intimal calcification from the outer soft-tissue margin and which is traditionally recognized on chest radiograph, was detected by real-time fluoroscopy and served as the diagnostic clue. Type B aortic dissection was further confirmed by chest computed tomography.

Background and Aims. The identification of possible pathogens for an infectious etiology of atherosclerotic coronary artery disease (CAD) is an expanding field. The present study was undertaken to explore the role of parvovirus B19, a potent infectious agent. Methods. A total of 565 patients were analyzed (90 patients with CAD, and 475 controls). Serologic analysis for human paravovirus B19 (B19) specific IgM and IgG was carried out in all patients. In addition, tissue specimens were obtained from five patients who received heart transplants. Direct in situ polymerase chain reaction (PCR) and immunocytochemistry were performed in the samples to localize B19 DNA. Results. Enzyme immunoassay showed that the seropositive rate of anti-B19 IgG in patients with CAD was 1.5- to 2.7-fold more frequent than in healthy controls. Clinical characteristics did not affect the prevalence of seropositivity for B19. However, anti-B19 IgM and B19-specific DNA were not detected in healthy or individuals with CAD. Furthermore, nonradioactive in situ PCR found that the majority of B19-specific DNA was located in the endothelial cells of the thickened intima. Conclusions. Our results first demonstrate a seroepidemiological and histopathological association between chronic B19 infection and CAD, suggesting that B19 infection may have a potential role in the pathogenesis of coronary atherosclerosis. 2009 IMSS. Published by Elsevier Inc.

Introduction. The sarcoplasmic reticulum Ca2+ ATPase (SERCA) is essential for the regulation of the intracellular calcium level in cardiomyocytes. Previous studies have found that angiotensin II (Ang II) decreased SERCA2 gene expression in ventricular myocytes. Alteration of SERCA activity is important in the mechanism of atrial fibrillation. The present study was undertaken to examine Ang II effects on atrial myocytes. Materials and methods. An ~1.75-kb promoter region of SERCA2 gene was cloned with the pGL3 luciferase vector. The direct effects of Ang II on SERCA2 gene expression in HL-1 atrial myocytes were examined by promoter activity assay, followed by Western blot analysis for protein levels and quantitative real-time reverse transcription polymerase chain reaction for mRNA amounts. Results. Ang II did not increase the promoter activity of the 1,754-bp promoter-receptor construct of the SERCA2 gene. The levels of SERCA2 protein and mRNA were also unchanged at different time points after Ang II treatment. Conclusions. Although Ang II had prominent effects on SERCA2 in ventricular myocytes, it did not alter SERCA2 gene expression and protein levels in atrial myocytes. We provide a model for further investigation of the regulation of SERCA2 gene expression in atrial myocytes.

Objective Bilirubin is a potent antioxidant and a cyroprotectant. Low serum bilirubin is associated with atherosclerosis. Little is known about its role in metabolic syndrome (MS) among children and adolescents. Methods We examined 4723 children and adolescents aged 12–17 years with reliable measures of various serum hepatic profiles and metabolic risks from Health and Nutrition Examination Survey 1999–2004. Results The results showed that the prevalence of the MS was from 6.6 ± 1.2% in the lowest quartile to 2.1 ± 1.9% in the highest quartile of the concentration of total bilirubin. The graded association remained significant after the adjustment of other co-variates. The odds ratios for the MS were around 0.29 (0.08–0.99) and 0.23 (0.08–0.65) for the upper two quartiles when using the lowest quartile as reference for the concentration of total bilirubin. The quartiles of the serum total bilirubin levels were inversely correlated with the homeostasis model assessment (HOMA-IR) and insulin while not associated with the serum C-reactive protein (CRP) levels. Conclusions The serum total bilirubin levels are inversely correlated with the prevalence of the MS. The mechanism of the association between MS and total bilirubin may be related to the insulin resistance status.

The aim of the study was to investigate the association between angiotensin II type 1 receptor (AGTR1) gene polymorphisms and diastolic heart failure (DHF) in a case controlled study.Of 1752 consecutive patients analyzed, 176 diagnosed with DHF and confirmed by echocardiography were recruited. Controls were matched one-to-one by age, sex, hypertension, diabetes, renal function, and medication use. We genotyped 11 single nucleotide polymorphisms (SNPs) according to the HapMap Han Chinese Beijing databank across the AGTR1 gene to capture 96% of the haplotype variance in all SNPs with minor allele frequencies at least 5%. We also genotyped A1166C (rs5186) SNP with known associations with cardiovascular disease and analyzed associations of SNPs and haplotypes with DHF and linkage disequilibrium structure of the AGTR1 gene.In a single locus analysis, SNP rs16860760, rs389566, and rs5186 were associated with DHF (allele specific P = 0.004, 0.002, 0.002, respectively; permuted P = 0.045, 0.022, 0.027, respectively). SNP rs389566, with a minor allele frequency of 20.17%, had an odds ratio (OR) 2.03 for the autosomal dominant model [AA + AT: TT, 95% confidence interval (CI) 1.29-3.19; P = 0.0012] and 1.73 for the additive model (95% CI 1.21-2.48; P = 0.0018) corresponding to a population attributable risk fraction of 27.21%. The haplotypes in a linkage disequilibrium block of rs389566 (T-A-G and A-A-G) were also significantly associated with DHF (permuted P = 0.0125 and 0.0105, respectively).We identified risk-conferring genetic variants of the AGTR1 gene for DHF in a Chinese population.

Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated.494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included.Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively.There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.

Background Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. Materials and methods A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT1R) gene were genotyped. Results In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT1R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT1R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. Conclusions Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.

To study the association of renin gene polymorphism with essential hypertension in the Chinese population, 86 hypertensive and 107 normotensive subjects were enrolled from an epidemiologic survey. Leukocyte DNA was extracted and digested with Hind III and Bgl I restriction enzymes. Southern hybridization was done with digoxigenin-incorporated renin gene probes generated by polymerase chain reaction. The restriction fragments were detected by anti-digoxigenin antibody and enzyme methods. Two Hind III polymorphysms of the renin gene (8.7 kb and 6.2 kb) were identified. The allele frequences were 129(75%) and 43(25%), respectively, in hypertensives; they were 139(65%) and 75(35%), respectively, in normotensives (chi2 = 4.074, p = 0.044). The genotypes of 8.7/8.7,8.7/6.2 and 6.2/6.2 were significantly different between hypertensives and normotensives, being 45(52%), 39(45%), 2(3%) and 48(45%), 43(40%), and 16(15%), respectively (chi2 = 9.002, p = 0.11). The Bgl I polymorphism did not show a difference between hypertensives and normotensives. Thus, we conclude that the renin gene Hind III polymorphysm is associated with hypertension in this Chinese population.

OBJECTIVE—Heart rate recovery (HRR) is a marker for survival. Little is known about the association between HRR and metabolic risks in healthy children or adolescents. RESEARCH DESIGN AND METHODS—We examined 993 healthy children and adolescents aged 12–19 years with reliable measures of cardiovascular fitness from the National Health and Nutrition Examination Survey 1999–2002. HRR parameters 1–3 min after exercise were calculated from exercise test results. Anthropometric and metabolic risk factors as well as metabolic Z score were obtained. RESULTS—The HRR parameters were inversely correlated with most of the metabolic risks, including waist circumference, systolic blood pressure (SBP), serum triglycerides, and serum C-reactive protein (CRP) levels, and were positively correlated with serum HDL levels. In multiple linear regression analysis, among the metabolic risks, waist circumference was the only parameter associated with HRR parameters (P = 0.038, 0.001, and 0.001 for 1-, 2-, and 3-min HRR, respectively) in boys. In girls, waist circumference (P = 0.001 and CONCLUSIONS—Metabolic risks are inversely associated with HRR in healthy children and adolescents. Our finding suggests that there is a link between metabolic risks and autonomic nervous system functions in healthy young ages.

Diabetes mellitus may result in impaired cardiac contractility, but the underlying mechanisms remain unclear. We aimed to investigate the temporal alterations in cardiac force- and flow-generation capacity and loading conditions as well as mechanical efficiency in the evolution of systolic dysfunction in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were randomized into control and STZ-induced diabetic groups. Invasive hemodynamic studies were done at 8, 16, and 22 wk post-STZ injection. Maximal systolic elastance (Emax) and maximum theoretical flow (Qmax) were assessed by curve-fitting techniques, and ventriculoarterial coupling and mechanical efficiency were assessed by a single-beat estimation technique. In contrast to early occurring and persistently depressed Emax, Qmax progressively increased with time but was decreased at 22 wk post-STZ injection, which temporally correlated with the changes in cardiac output. The favorable loading conditions enhanced stroke volume and Qmax, whereas ventriculoarterial uncoupling attenuated the cardiac mechanical efficiency in diabetic animals. The changes in Emax and Qmax are discordant during the progression of contractile dysfunction in the diabetic heart. In conclusion, our study showed that depressed Qmax and cardiac mechanical efficiency, occurring preceding overt systolic heart failure, are two major determinants of deteriorating cardiac performance in diabetic rats.

Background/Purpose Drug eluting stents (DES) have been shown to reduce in-stent restenosis rate and target vessel revascularization in large clinical trials. However, the safety and efficacy of DES use in the Taiwanese population has not been reported. We designed this trial to analyze the clinical results in patients using DES in a single tertiary center. Methods We retrospectively analyzed the clinical data of all patients treated at National Taiwan University Hospital, Taipei, Taiwan, with sirolimus- or paclitaxel-eluting stents between September 2003 and January 2005. Results A total of 585 patients (466 men, 119 women; mean age, 64.5 ± 11.2 years) were enrolled. Meanwhile, 205 sirolimus- and 717 paclitaxel-eluting stents were implanted, with a mean of 1.6 stents per patient. Half (50.2%) of the stents were placed in the left anterior descending artery. Among the enrolled patients, 41.8% had diabetes mellitus, 25% had a diagnosis of acute coronary syndrome, and 10.7% was treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Overall 8-month target vessel revascularization, major adverse cardiac event rate, and cardiac death rate were 8.8%, 9.7% and 2.5%, respectively. There was no difference in clinical events between sirolimus- and paclitaxel-eluting stents. The overall subacute stent thrombosis rate was 1.36%, significantly lower than that in patients who presented with acute coronary syndrome (4%). Conclusion The use of DES in the Taiwanese population yielded comparable results as those in large clinical trials. Subacute stent thrombosis rate was higher in acute coronary syndrome. The safety of DES in these situations should be further clarified.

Background: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs). Design, Setting, and Patients: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0–5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0–7) was defined as the number of seropositivities to several agents. Results: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively). Conclusion: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.

Angiotensin II (Ang II) is involved in the pathogenesis of atrial fibrillation (AF). L-type calcium channel (LCC) expression is altered in AF remodeling. We investigated whether Ang II modulates LCC current through transcriptional regulation, by using murine atrial HL-1 cells, which have a spontaneous calcium transient, and an in vivo rat model. Ang II increased LCC α1C subunit mRNA and protein levels and LCC current density, which resulted in an augmented calcium transient in atrial myocytes. An ≈2-kb promoter region of LCC α1C subunit gene was cloned to the pGL3 luciferase vector. Ang II significantly increased promoter activity in a concentration- and time-dependent manner. Truncation and mutational analysis of the LCC α1C subunit gene promoter showed that cAMP response element (CRE) (−1853 to −1845) was an important cis element in Ang II-induced LCC α1C subunit gene expression. Transfection of dominant-negative CRE binding protein (CREB) (pCMV-CREBS133A) abolished the Ang II effect. Ang II (1 μmol/L, 2 hours) induced serine 133 phosphorylation of CREB and binding of CREB to CRE and increased LCC α1C subunit gene promoter activity through a protein kinase C/NADPH oxidase/reactive oxygen species pathway, which was blocked by the Ang II type 1 receptor blocker losartan and the antioxidant simvastatin. In the rat model, Ang II infusion increased LCC α1C subunit expression and serine 133 phosphorylation of CREB, which were attenuated by oral losartan and simvastatin. In summary, Ang II induced LCC α1C subunit expression via a protein kinase C–, reactive oxygen species–, and CREB-dependent pathway and was blocked by losartan and simvastatin.

Background/purposeElevation of C-reactive protein (CRP) level is associated with increased risk of cardiovascular events. The 1059 G > C polymorphism in exon 2 of the CRP gene has been shown to affect plasma concentration of CRP. We want to elucidate the effect of this polymorphism on the development of coronary artery disease (CAD) among the Chinese population in Taiwan.MethodsWe scrutinized 536 patients undergoing coronary angiography (365 patients with CAD and 171 controls with patent coronaries) and evaluated the association of CRP gene 1059 G > C polymorphism with CAD. Genotyping of the polymorphism was performed by polymerase chain reaction and MaeIII restriction enzyme digestion.ResultsThe CC genotype was associated with lower plasma CRP concentration (GG, 6.5 ± 5.8; GC, 3.3 ± 4.4; CC, 2.3 ± 3.1 mg/L; p = 0.02). Subjects with CAD or myocardial infarction (MI) had significantly higher plasma CRP concentration than that in controls (CAD vs. controls, 8.9 ± 18.9 vs. 3.3 ± 7.2 mg/L; p < 0.001), while patients with MI showed higher CRP when compared to those with chronic stable angina (13.5 ± 22.9 vs. 5.2 ± 14.1 mg/L; p < 0.001). However, this polymorphism was not associated with CAD in our population.ConclusionOur data suggest that human CRP gene 1059 G > C polymorphism is associated with plasma CRP concentration among Chinese in Taiwan receiving coronary angiography.

Amiodarone-related pneumonitis is a potentially limiting factor for amiodarone usage. However, it is believed that amiodarone-related pneumonitis is unlikely to occur during low-dose and short courses of therapy. We report three patients who received low-dose amiodarone, 200 mg/day, for an average of 6.6 months and who developed amiodarone-related pneumonitis. All patients were male with age of 75, 93 and 85, respectively, and had the habit of cigarette smoking. The initial presentation was dyspnea without symptoms and signs of heart failure. Their chest radiographs showed diffuse interstitial pneumonitis pattern and chest computed tomography scan also confirmed interstitial pneumonitis. Treatment included cessation of amiodarone and corticosteroid usage. All patients improved symptomatically by early detection and early treatment. This case report implies that old age and possible pre-existing pulmonary abnormalities caused by smoking could be associated with amiodarone-related pulmonary toxicity. Clinicians must remain alert to detect amiodarone-related pneumonitis even under low dosage and short duration of amiodarone usage. Immediate withdrawal of amiodarone and prompt steroid therapy will ensure full recovery.

An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50 mg plus hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80 mg.A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95-115 mmHg and a mean trough sitting systolic blood pressure (SiSBP)190 mmHg entered the baseline period of treatment with valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained90 mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily for a further 4 weeks.Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (por = 0.001 for both outcomes). The goal of SiDBPor = 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80 mg/day. Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5 mg combination was99%.These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBPor = 90 mmHg with valsartan monotherapy at 80 mg once-daily, switching to a single-tablet combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.

Background Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. Materials and methods The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg−1 nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg−1 streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg−1 AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. Results After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18·8% reduction of aortic characteristic impedance (P

The formation of advanced glycation endproducts (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study was to examine the role of aminoguanidine (AG), an inhibitor of AGEs formation, in the prevention of arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) induced diabetes in rats. Diabetes was induced in animals by a single tail vein injection with 65 mg kg−1 STZ. After confirmation of the development of hyperglycemia (2 days later), rats were treated for 8 weeks with AG (daily peritoneal injections of 50 mg kg−1) and compared with the age-matched untreated diabetic controls. After exposure to AG, the STZ-diabetic rats showed no alterations in cardiac output, aortic pressure profiles, total peripheral resistance, and aortic characteristic impedance. By contrast, treatment of this experimental diabetes with AG resulted in a significant increase in wave transit time (τ), from 20.4±0.6 to 24.7±0.5 ms (P

Background We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. Methods Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg−1 of NA, 30 min before an intravenous injection of 50 mg kg−1 STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. Results In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1·49 ± 0·33 (mean ± SD) to 1·95 ± 0·28 mmHg s mL−1 (P

Background Large-scale clinical trials have demonstrated that patients with atrial fibrillation (AF), when treated with a rhythm-control strategy, are still at risk for embolic events. We hypothesized that left atrial (LA) dysfunction persisted even after successful maintenance of sinus rhythm for > 3 months. Methods A total of 93 patients with AF and satisfactory rhythm control for > 3 months were included. Satisfactory rhythm control was defined as being free of AF based on patient-reported symptoms, monthly ECG follow-up, and ambulatory Holter ECG if needed. Among the 93 patients, 25 patients had sustained AF that was terminated by electrical or pharmacologic cardioversion, while 68 patients had paroxysmal AF under good medical control. Clinical data were obtained, and transthoracic and transesophageal echocardiography were performed after satisfactory rhythm control for > 3 months. Results Among the 93 patients, 34 patients (37%) had LA dysfunction, defined as LA appendage (LAA) peak emptying velocity 65 years, and prior cerebral vascular accident. LA dysfunction was found in 10 of 17 patients (59%) with three or more risk factors. The odds ratio for having LA dysfunction was 3.1 (p = 0.04; 95% confidence interval, 1.1 to 9.1) when compared with patients with less than three risk factors. Conclusions LA dysfunction was present in more than one third of AF patients after satisfactory rhythm control for > 3 months. Patients with higher burden (three or more) of clinical risk factors were more likely to have impaired LA function.

Background: Identification of good responders to rhythm control in the management of atrial fibrillation (AF) is worthwhile in terms of increasing hemodynamic benefit and decreasing the likelihood of unstable anticoagulation even after the Atrial Fibrillation Follow-Up Investigation of Rhythm Management. Methods: We tested the hypothesis that atrial substrate determines the risk of recurrence on rhythm control both in patients with paroxysmal AF (PAF) and in those with persistent or sustained AF (≧1 week, SAF). There were 90 consecutive patients (mean age 63 ± 12 years, 67 males and 23 females) with previous PAF (n = 66) or SAF (n = 24). They were maintained in sinus rhythm successfully for at least 1 month after conversion and then studied by transthoracic and transesophageal echocardiography. All of the patients were followed regularly by determination of symptoms, 12-lead ECG and intermittent Holter recording to determine recurrence of AF after echocardiographic study. Results: After 9.1 ± 3.8 (range 3–12) months of follow-up, 23 of the 90 (26%) patients had documented recurrence of AF (67 without recurrence). Univariate analysis of demographic characteristics, medications, ECG and echocardiographic parameters revealed that, compared with the group of patients without recurrent AF, the group of those with it included more members of the SAF group (11/27 vs. 13/67, p = 0.039), included more male subjects (22/23 vs. 45/67, p = 0.045), had a larger left atrial volume index (LAVI; 27 ± 9 vs. 22 ± 9 ml/m2, p = 0.024) and had lower LA appendage peak emptying velocity (LAAPEV; 42 ± 15 vs. 55 ± 22 cm/s, p = 0.01). Multivariate Cox proportional hazards regression analysis adjusted for age, gender and AF group revealed that patients with LAVI 2 and LAAPEV >46 cm/s had the least recurrence of AF (relative risk 0.18, 95% confidence interval 0.06–0.55, vs. with LAVI >30 ml/m2 or LAAPEV 2 (log-rank p = 0.02), LAAPEV > 46 cm/s (p = 0.013) or both (p = 0.004). The superiority to predict the rate of sinus rhythm maintenance was the same in the PAF and SAF groups. Conclusions: Good responders to rhythm control in the PAF and SAF groups share the characteristics of smaller LA volume and better LAA contractile function, emphasizing the critical role of atrial substrate remodeling in recurrence of AF.

Although some single polymorphism analyses of the angiotensinogen (AGT) gene have been found to be associated with hypertension, the results are still inconsistent. The objectives of this study are to evaluate the association of the genotype and haplotype distributions of three single-nucleotide polymorphisms (SNPs) (G-217A, A-6G, and M235T) in the AGT gene with hypertension. In a sample of 461 hypertensive and 327 normotensive patients in Taiwan, we found that -217AA and -6GG homozygotes conferred independently an increased risk to hypertension (P = 0.008 and P = 0.037, respectively), as illustrated by their significant associations with hypertension in both single SNP and pair-wise SNPs analyses. Meanwhile, a very weak linkage disequilibrium was found between the G-217A and the A-6G polymorphisms in terms of r2 (0.05). On the basis of likelihood ratio test, only the set of haplotypes that constituted the A-6G and the M235T polymorphisms was associated with hypertension (chi2 = 20.91, P = 0.0008), which was mainly due to the increased frequency of the recombinant haplotypes (-6A identical with 235M and -6G identical with 235T), and a pathophysiological role in the predisposition to hypertension was hence indicated. In functional assays, the promoter activities of the haplotypes -217A identical with -6A and -217G identical with -6G were significantly higher than the most common haplotype -217G identical with -6A. These results highlight the necessity of a thorough analysis of all reported variants of a candidate gene in the elucidation of genetic susceptibility to a complex disease like hypertension, even when the variants are in the same haplotype block.

Background— The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. Methods and Results— A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (χ 2 =62.5, P =0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls ( P =0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. Conclusions— This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

Percutaneous transcatheter closure of persistent ductus arteriosus (PDA) has been well established in the pediatric field. For moderate- to large-sized PDA, the newly developed Amplatzer duct occluder had offered a good solution, but it depends on stiff wire and delivery sheath. We reported two elderly patients of PDA with vascular anatomy too difficult to be antegradely approached and were closed by a retrograde technique by an assisting wire from the descending aorta. The wire served as a guide and tracked the delivery system to cross the ductus from the venous side smoothly. This retrograde wire-assisted technique could be utilized to overcome the PDA of difficult vascular anatomy, which could not be easily fulfilled by conventional antegrade venous approach.

BACKGROUND Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38–1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease. Cancer 2004. © 2004 American Cancer Society.