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Background Little information is available in Asia about the real-world practice of dual antiplatelet therapy (DAPT) duration for acute coronary syndrome (ACS) and its influence on clinical outcomes.Methods and Results:The Taiwan ACS STENT Registry was a prospective, multicenter study to observe ACS patients using clopidogrel-based DAPT after percutaneous coronary intervention (PCI). The primary outcome was a composite of cardiovascular death, myocardial infarction, and stroke. Overall, 2,221 ACS patients (62 years, 83% men) were included. DAPT duration was ≤9 months in 935 (42.1%). The incidence of primary outcome was higher in patients receiving DAPT ≤9 months compared with those receiving DAPT >9 months at 1 year (3.5% vs. 1.6%, P=0.0026). The incidence of stent thrombosis (overall 0.5%) was similar between groups. Multivariable analysis showed that DAPT >9 months was associated with a significantly lower risk of primary outcome (odds ratio 0.725, 95% confidence interval 0.545-0.965). Conclusions Our data showed that short duration of DAPT (≤9 months) was common (42.1%) in Taiwan for ACS patients undergoing PCI. DAPT ≤9 months increased the risk of the primary outcome.

Background Prostaglandin E 2 has long been known to be an immune modulator. It is released after tissue injury and plays a role in modulating macrophage activities, which are essential for tissue regeneration. However, the involvement of prostaglandin E 2 receptor 2 ( EP 2)–dependent regulation of macrophages in postischemic heart is unclear. This study aims to evaluate the role of EP 2 in damaged heart. Methods and Results The effect of EP 2 in postischemic heart was evaluated using EP 2‐deficient transgenic mice. We demonstrated that cardiac function was worse after myocardial injury on loss of EP 2. Furthermore, EP 2 deficiency also altered proinflammatory response and resulted in a defect in macrophage recruitment to the injured myocardium. Transcriptome analysis revealed that the expression of erythroid differentiation regulator 1 ( Erdr1 ) was significantly induced in EP 2‐deficient macrophages. Knocking down Erdr1 expression restored migration ability of EP 2‐deficient cells both in vitro and in vivo. By using a genetic fate‐mapping approach, we showed that abolishment of EP 2 expression effectively attenuated cell replenishment. Conclusions The EP 2‐dependent signaling pathway plays a critical role in regulating macrophage recruitment to the injured myocardium, thereby exerting a function in modulating the inflammatory microenvironment for cardiac repair.

Despite the recent enormous advances in medicine, high mortality and morbidity rates among the chronic kidney disease (CKD) patients remain an important but unresolved issue. Cardiovascular disease is a major cause of mortality and morbidity in patients with CKD. Abnormal left ventricular geometry and functions are common in this patient group and have been proven to be correlated with a high cardiovascular mortality/morbidity and all-cause mortality. For this reason, echocardiographic study plays an important role in evaluating cardiac structure and functions as well as in stratifying prognostic risk. We here summarize the reported findings on the usefulness of echocardiographic methodologies and identify their roles in diagnostic and prognostic clinical approaches.

Accumulating evidence suggests that the benefits of cell therapy for cardiac repair are modest and transient due to progressive harmful cardiac remodeling as well as loss of transplanted cells. We previously demonstrated that injection of peptide nanofibers (NFs) reduces ventricular remodeling and facilitates cell retention at 1 month after acute myocardial infarction (MI) in pigs. However, it remains unclear whether these benefits still persist as the material is being degraded. In this study, 2 mL of placebo or NFs, with or without 1×10(8) mononuclear cells (MNCs), was injected into the pig myocardium after MI (n≥5 in each group), and cardiac function was assessed by echocardiography, including myocardial deformation analyses and catheterization at 3 months post-MI. Our results reveal that MNC-only injection slightly improved cardiac systolic function at 1 month post-MI, but this benefit was lost at later time points (ejection fraction: 42.0±2.3 in MI+normal saline [NS] and 43.5±1.1 in MI+MNCs). In contrast, NF-only injection resulted in improved cardiac diastolic function and reduced pathological remodeling at 3 months post-MI. Furthermore, combined injection of MNCs/NFs provided a greater and longer term cardiac performance (52.1±1.2 in MI+MNCs/NFs, p0.001 versus MI+NS and MI+MNCs) and 11.3-fold transplanted cell retention. We also found that about 30% NFs remained at 3 months after injection; however, endogenous myofibroblasts were recruited to the NF-injected microenvironment to replace the degraded NFs and preserved cardiac dimensions and mechanics. In conclusion, we demonstrated that injection of NFs contributes to preservation of ventricular mechanical integrity and sustains MNC efficacy at 3 months postinjection.

It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan.We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to

Objectives Atrial septal defects may result in pulmonary hypertension and right heart remodeling. We analyzed improvements in patients with flow-induced pulmonary hypertension and the activation of endothelial progenitor cells after flow reduction. Design This prospective cohort study included 37 patients who were admitted for an occluder implantation. Blood samples were collected before and after the procedure. We determined the number of endothelial progenitor cells in outgrowth colonies and serum Hsp27 concentrations. Daily performance and cardiothoracic ratio were reevaluated later. Results Closure of the defect significantly reduced the pulmonary pressure and B-type natriuretic peptide levels. The cardiothoracic ratio and daily performance status also improved. The number of endothelial progenitor cell outgrowth colony-forming units significantly increased and was positively correlated with daily performance. In patients with enhanced colony formation, Hsp27 levels were significantly increased. Conclusions The implantation of an occluder successfully improved hemodynamic, right ventricular, and daily performance. Qualitative enhancement of colony formation for endothelial progenitor cells was also noted and positively correlated with daily performance. Closure of defects may serve as a valid, reliable model to obtain a deeper understanding of the modulation of endothelial progenitor cell activity and its relationship with pulmonary hypertension prognosis.

Objective Plasma resistin level is a potential molecular link between obesity and diabetes. Causal role of resistin, type 2 diabetes mellitus (T2DM) and genetic variants have not been thoroughly investigated. Therefore, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci associated with resistin levels and investigated whether these variants were prospectively associated with the development of metabolic syndrome (MetS) and T2DM in an independent community-based cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS). Research Design and Methods We genotyped 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 chips and searched for quantitative trait loci (QTLs) of resistin in the 1st stage GWAS and confirmed the finding in another 559 YOH subjects. Logistic regression was used to examine the Mendelian randomization effects between genotypes of confirmed QTLs and metabolic outcomes in 3400 subjects of CVDFACTS. Results Two single nucleotide polymorphisms (SNP) (rs3745367 and rs1423096) were significantly associated with resistin levels (p = 5.52 × 10−15 and p = 2.54 × 10−20) and replicated in another 559 YOH subjects (p = 1.29 × 10−3 and p = 1.13 × 10−7), respectively. The SNP rs1423096 was further associated with the levels of HDL-C (p = 0.006), the risk of MetS (OR = 2.21, p = 0.0034) and T2DM (OR = 1.62, p = 0.0063) in the CVDFACTS. People with the haplotypes A-G and G-G determined by rs3745367 and rs1423096 showed a significantly increased T2DM risk (p = 0.0068 and p = 0.0035, respectively) compared with those with A-A haplotype. Conclusion We have found that rs3745367 and rs1423096 on the RETN gene were significantly associated with resistin levels. However, rs1423096, downstream of RETN, seems to be associated with MetS and T2DM risk more so than rs3745367. The established genotype–disease association points to a causal association of resistin and T2DM. Copyright © 2013 John Wiley & Sons, Ltd.

a Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan b Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan c Department of Internal Medicine, Tainan Municipal Hospital, Tainan, Taiwan d Department of Radiology, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan e Department of Emergency Medicine, National Cheng Kung University Hospital, Tainan, Taiwan f Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

BACKGROUND Although many large-scale genome-wide association studies (GWASs) have been performed, only a few studies have successfully identified replicable, large-impact hypertension loci; even fewer studies have been done on Chinese subjects. Young-onset hypertension (YOH) is considered to be a more promising target disorder to investigate than late-onset hypertension because of its stronger genetic component. METHODS To map YOH genetic variants, we performed a 3-stage study combining 1st-stage multilocus GWASs, 2nd-stage gene expression analysis, and 3rd-stage multilocus confirmatory study. RESULTS In the 1st stage, Illumina550K data from 400 case-control pairs were used, and 22 genes flanked by 14 single nucleotide polymorphism (SNP) septets (P values adjusted for false discovery rate (pFDR) < 3.16×10(-7)) were identified. In the 2nd stage, differential gene expression analysis was carried out for these genes, and 5 genes were selected (pFDR < 0.05). In the 3rd stage, we re-examined the finding with an independent set of 592 case-control pairs and with the joint samples (n = 992 case-control pairs). A total of 6 SNP septets flanking C1orf135, GSN, LARS, and ACTN4 remained significant in all 3 stages. Among them, the same septet flanking ACTN4 was also associated with blood pressure traits in the Hong Kong Hypertension Study (HKHS) and in the Wellcome Trust Case-Control Consortium Hypertension Study (WTCCCHS). LARS was detected in the HKHS, but not in the WTCCCHS. GSN may be specific to Taiwanese individuals because it was not found by either the HKHS or the WTCCCHS. CONCLUSIONS Our study identified 4 previously unknown YOH loci in Han Chinese. Identification of these genes enriches the hypertension susceptibility gene list, thereby shedding light on the etiology of hypertension in Han Chinese.

The presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary morphometric functions were assessed, and phenotypic switching of pulmonary vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval fistula significantly attenuated pulmonary blood flow and right ventricular mass, and potentiated the isometric contraction of pulmonary artery. Inflammatory cytokines IL-1β and IL-6 were reduced in the lung after ligation. Reduction of pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain and α-smooth muscle actin in pulmonary artery, indicating the switching of VSMCs to the contractile phenotype. Our study demonstrated that normalization of pulmonary blood flow in flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is functionally and morphometrically reversible by inducing transdifferentiation of pulmonary VSMC to contractile phenotypes and modulation of tissue inflammatory cytokines.

Background— During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results— Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE–eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69–1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04–1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80–1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions— During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00808067.

Background and Purpose— Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries. Methods— There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used. Results— Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3–4.7; P =0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03–0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06–0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19–0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13–0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year). Conclusions— Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00262600.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management.

OBJECTIVE Postsystolic shortening is associated with hypertensive heart disease, and the degree of postsystolic shortening can be measured by postsystolic strain index (PSI) of the left ventricle (LV) derived from speckle tracking echocardiography. We studied the association between PSI with delayed diastolic lengthening and diastolic dysfunction in hypertension. METHODS This study recruited 46 patients (mean age 56 ± 13 years, 24 men) with untreated hypertension, and 26 normal individuals (mean age 55 ± 11 years, 9 men) as controls. Hypertension patients were further divided into two groups based on the presence of diastolic dysfunction. PSI was calculated as [(postsystolic peak longitudinal strain - end-systolic strain)/end-systolic strain] × 100%. Timing of left-ventricular diastolic lengthening was determined by measurements of time to onset of early diastolic mitral annulus lengthening by tissue Doppler imaging. RESULTS Total PSI was significantly higher in patients with diastolic dysfunction (252 ± 257 vs. 98 ± 72%, P = 0.002). After multivariate analysis, PSI was independently associated with diastolic dysfunction in hypertension [every 10% increment of PSI, odds ratio (OR) 1.13, 95% confidence interval (CI) 1.01-1.27, P = 0.036]. PSI was independently correlated with serum procollagen type I carboxyterminal propeptide (beta = 0.382, P = 0.028) after multivariable analysis, and time delay from onset of early mitral inflow to onset of early diastolic medial (beta = 0.405, P = 0.004) or lateral (beta = 0.582, P

OBJECTIVE The plasma adiponectin level, a potential upstream and internal facet of metabolic and cardiovascular diseases, has a reasonably high heritability. Whether other novel genes influence the variation in adiponectin level and the roles of these genetic variants on subsequent clinical outcomes has not been thoroughly investigated. Therefore, we aimed not only to identify genetic variants modulating plasma adiponectin levels but also to investigate whether these variants are associated with adiponectin-related metabolic traits and cardiovascular diseases. RESEARCH DESIGN AND METHODS We conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) associated with high molecular weight forms of adiponectin levels by genotyping 382 young-onset hypertensive (YOH) subjects with Illumina HumanHap550 SNP chips. The culpable single nucleotide polymorphism (SNP) variants responsible for lowered adiponectin were then confirmed in another 559 YOH subjects, and the association of these SNP variants with the risk of metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and ischemic stroke was examined in an independent community–based prospective cohort, the CardioVascular Disease risk FACtors Two-township Study (CVDFACTS, n = 3,350). RESULTS The SNP (rs4783244) most significantly associated with adiponectin levels was located in intron 1 of the T-cadherin (CDH13) gene in the first stage (P = 7.57 × 10−9). We replicated and confirmed the association between rs4783244 and plasma adiponectin levels in an additional 559 YOH subjects (P = 5.70 × 10−17). This SNP was further associated with the risk of MS (odds ratio [OR] = 1.42, P = 0.027), T2DM in men (OR = 3.25, P = 0.026), and ischemic stroke (OR = 2.13, P = 0.002) in the CVDFACTS. CONCLUSIONS These findings indicated the role of T-cadherin in modulating adiponectin levels and the involvement of CDH13 or adiponectin in the development of cardiometabolic diseases.

Background: The impact of chronic kidney disease (CKD) and hemodialysis on heart function is not fully understood. We aimed to investigate the influence of different stages of CKD and maintenance hemodialysis on heart function. Methods: One hundred fifty-three patients were categorized into 3 subgroups [56 without CKD as controls; 37 with moderate-advanced CKD, stages 3, 4 or 5, and 60 with end-stage renal disease (ESRD) undergoing maintenance hemodialysis]. Left ventricular (LV) function was assessed by conventional echocardiography and 2-dimensional speckle-tracking echocardiography with strain analysis (2D strain analysis). Results: There was no significant difference of gender, age and LV ejection fraction among groups. Compared with controls, global peak systolic longitudinal strain (GSl), circumferential strain and strain rate were decreased in the CKD group. Along with the decline of renal function, GSl deteriorated. Moreover, compared with moderate-advanced CKD patients, GSl, circumferential strain and strain rate were better in ESRD group receiving maintenance hemodialysis. Conclusions: Worsening renal function was associated with a reduction of systolic function, and could be quantified by 2D strain analysis. The hemodialysis patients have better LV systolic function than the moderate-advanced CKD patients.

Hypertension is one of the most important risk factors for atherosclerosis-related mortality and morbidity. In this document, the Hypertension Committee of the Taiwan Society of Cardiology provides new guidelines for hypertension management. The key messages are as follows. (1) The life-time risk for hypertension is 90%. (2) Both the increase in the prevalence rate and the relative risk of hypertension for causing cardiovascular events are higher in Asians than in Caucasians. (3) The control rate has been improved significantly in Taiwan from 2.4% to 21% in men, and from 5% to 29% in women in recent years (1995-2002). (4) Systolic and diastolic blood pressure (BP) = 130/80 mmHg are thresholds of treatment for high-risk patients, such as those with diabetes, chronic kidney disease, stroke, established coronary heart disease, and coronary heart disease equivalents (carotid artery disease, peripheral arterial disease, and abdominal aortic aneurysm). (5) Ambulatory and home BP monitoring correlate more closely with end-organ damage and have a stronger relationship with cardiovascular events than office BP monitoring, but the feasibility of home monitoring makes it a more attractive alternative. (6) Patients with masked hypertension have higher cardiovascular risk than those with white-coat hypertension. (7) Lifestyle changes should be encouraged in all patients, and include the following six items: S-ABCDE (Salt restriction; Alcohol limitation; Body weight reduction; Cessation of smoking; Diet adaptation; Exercise adoption). (8) When pharmacological therapy is needed, physicians should consider “PROCEED” (Previous experience of patient; Risk factors; Organ damage; Contraindication or unfavorable conditions; Expert or doctor judgment; Expense or cost; Delivery and compliance) to decide the optimal treatment. (9) The main benefits of antihypertensive agents are derived from lowering of BP per se, and are generally independent of the drugs being used, except that certain associated cardiovascular conditions might favor certain classes of drugs. (10) There are five major classes of drugs: thiazide diuretics; β-blockers; calcium channel blockers; angiotensin-converting enzyme inhibitors (ACEIs); and angiotensin receptor blockers (ARBs). Any one of these can be used as the initial treatment, except for β-blockers, which are only indicated in patients with heart failure, a history of coronary heart disease, and hyperadrenergic state. (11) A standard dose of any one of the five major classes of antihypertensive drugs can produce an ∼10-mmHg decrease in systolic BP (rule of 10) and a 5-mmHg decrease in diastolic BP (rule of 5), after placebo subtraction. (11) Combination therapy is frequently needed for optimal control of BP, and the amount of the decrease in BP by a two-drug combination is approximately the same as the sum of the decrease by each individual drug (∼20 mmHg in systolic BP and 10 mmHg in diastolic BP) if their mechanisms of action are independent, with the exception of the combination of ACEIs and ARBs. (13) An ACEI or ARB plus a calcium channel blocker or a diuretic (A + C or A + D) are reasonable two-drug combinations, and A+C + D is a reasonable three-drug combination, unless patients have special indications for β-blockers. (14) Single-pill (fixed-dose) combinations that contain more than one drug in a single tablet are highly recommended because they reduce pill burden and cost, and improve compliance. (15) Very elderly patients (> 80 years) should be treated without delay, but BP should be reduced gradually and more cautiously. Finally, these guidelines are not mandatory; the responsible physician's decision remains most important in hypertension management.

Analysis of short-term (5-minute) heart rate variability (HRV) may provide useful information about autonomic nervous control of the cardiovascular system. The aim of the present study was to evaluate the association between the results of treadmill exercise testing (TET) and short-term (5-minute) HRV. Patients undertaking TET were anteriorly evaluated with short-term (5-minute) HRV over time (SDNN, RMSSD, NN50 count, pNN50) and frequency (LF, HF, total power) domains. Among 414 patients, 32 individuals (7.7%; 14 men) had nondiagnostic results. The nondiagnostic group had older age, higher body mass index, more hypertension, lower SDNN, lower LF, and higher HF than the negative group. After adjustment for potential confounders, SDNN (OR 0.94, 95% CI 0.91-0.97; P = 0.01), RMSSD (OR 0.96, 95% CI 0.93-0.99; P = 0.02), NN50 count (OR 0.98, 95% CI 0.97-1.00; P = 0.04) and LF (OR 0.96, 95% CI 0.96-0.99; P = 0.03) were negatively related to nondiagnostic results, and HF showed a positive effect (OR 1.04, 95% CI 1.01-1.05; P = 0.02). No HRV indices were significantly associated with positive results. Our study suggested that cardiac autonomic indices derived from short-term HRV recordings might predict nondiagnostic results of TET.

Inefficient cardiomyocyte differentiation limits the therapeutic use of embryonic stem (ES) cell-derived cardiomyocytes. While large collections of proprietary chemicals had been screened to improve ES cell differentiation into cardiomyocytes, the natural product library remained unexplored. Using a mouse ES cell line transfected with a cardiomyocyte-specific alpha-myosin heavy chain promoter-driven enhanced green fluorescent protein (EGFP) reporter, we screened 24 natural products with known cardioprotective actions. Salvianolic acid B (saB), while produced minimal effect on its own, concentration-dependently synergized with vitamin C in inducing cardiomyocyte differentiation, as demonstrated by an increase in EGFP(+) cells, beating area in embryoid bodies, and expression of cardiomyocyte maturity markers. This synergy is specific to cardiomyocyte differentiation, and is involved with collagen synthesis. The present study demonstrates the saB-vitamin C synergy in inducing ES cell differentiation into matured and functional cardiomyocytes, and this may lead to a practicable cocktail approach to generate ES cell-derived cardiomyocytes for cardiac stem cell therapy.

Increased arterial stiffness is an important marker for target organ damage in essential hypertension. Both serum uric acid (UA) and C-reactive protein (CRP) were reported to be associated with target organ damage. However, the influences of UA and CRP on large arterial stiffness were not well elucidated. This study included 200 essential hypertension patients (64 women) whose age was between 20 and 50 years old (mean age 41 ± 8 years). None of the patients had diabetes mellitus or overt end-organ damage. Arterial stiffness was assessed by pulse-wave velocity (PWV) measured by tonometry from carotid to radial artery. Serum UA, high-sensitivity CRP (hsCRP), glucose, insulin, and lipid profiles were measured at the same time in each patient. PWV levels were significantly correlated with mean blood pressure (r = 0.245, P < 0.001), diastolic blood pressure (r = 0.323, P < 0.001), high-density lipoprotein (r = −0.169, P = 0.016), and UA (r = 0.234, P = 0.001), but not age, body mass index, blood sugar, insulin, low-density lipoprotein, triglyceride, and hsCRP. Pulsewave velocity levels were significantly higher in males (8.9 ± 1.2 vs 8.2 ± 1.2 m/s, P < 0.001) and smokers (9.3 ± 1.1 vs 8.5 ± 1.2 m/s, P < 0.001). Uric acid was significantly correlated with hsCRP (r = 0.294, P < 0.001). After multivariate analysis controlling for all possible confounding factors, UA (odds ratio 1.28, 95% confidence interval 1.02–1.61, P = 0.032) was still independently associated with increased PWV. In conclusion, UA but not hsCRP was independently associated with increased PWV in essential hypertension. Although UA was correlated with hsCRP, the association between UA and PWV was not through the effect of enhanced inflammation.

To compare transthoracic 2-dimentional echocardiography (2DE) and real-time three-dimensional echocardiography (RT-3DE) evaluation of clinically suspected infective endocarditis (IE) and to determine the feasibility of RT-3DE in vegetation detection.There were 46 patients (mean age 61+/-17 years, 54% male) enrolled. We acquired 2DE and RT-3DE with full volume images. RT-3DE images were analyzed by 3D QLAB software. Parameters suggestive of vegetation for RT-3DE assessment included mobile nodules, focal thickness, and uneven surface. The diagnosis of IE was made according to the Duke criteria.The sensitivity and specificity were 91.6% and 88.2% for 2DE, and 91.6% and 100% for RT-3DE. Among three parameters of RT-3DE, presence of mobile nodule (83.3% vs. 0%, p0.001) were significantly higher in IE patients but not focal thickness (75% vs. 65%, p = 0.723), or uneven surface (33% vs. 10%, p = 0.064).The sensitivity of RT-3DE and 2DE was similar for endocarditis diagnosis, but the specificity of RT-3DE was higher. Mobile nodules viewed by RT-3DE might be a useful finding for vegetation detection.

Cytochrome P450 (CYP) 2J2 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which are potent endogenous vasodilators and inhibitors of vascular inflammation. We aimed to elucidate the relationship between the functional CYP2J2*7 polymorphism and smoking for the onset of premature myocardial infarction (MI).We studied 200 patients with acute MI onset under 45 years (84% men) and 200 sex- and age-matched controls. The polymorphism was determined using PCR and direct DNA sequencing analysis.The CYP2J2*7 GT+TT genotype was significantly more prevalent in premature MI patients (32.0% versus 22.0%; p=0.02). Multiple logistic regression analysis showed four independent risk factors: the CYP2J2*7 T allele (OR 1.78, 95% confidence interval [CI] 1.1-6.4; p=0.02), smoking (OR 3.05, 95% CI 1.6-7.3; p0.01), diabetes mellitus (OR 3.24, 95% CI 1.2-6.6; p0.01), and hypertension (OR 1.95, 95% CI 1.1-5.7; p0.01). Among non-smoking patients, the CYP2J2*7 T allele was associated with a 1.3-fold risk. However, smoking T-allele carriers had a significantly 6.7-fold higher risk (p=0.01 for interaction). This variant, but not wild type, significantly reduced promoter activity with nicotine in vitro. EET metabolites were significantly lower among CYP2J2*7 T allele carriers than the GG subjects (p0.05). Smoking could further lower EET concentrations in T allele carriers than the non-smokers, especially in MI patients (3.3+/-1.0 ng/mL versus 6.8+/-1.3 ng/mL; p=0.001).The CYP2J2*7 polymorphism and premature MI were synergistically and significantly associated in Taiwanese patients.

Metabolic syndrome (MetS) is a cluster of atherosclerotic cardiovascular disease risk factors and is closely associated with insulin resistance and obesity (1,2). The precise diagnosis of MetS, however, is still somewhat controversial, and no serological markers are available for its detection. Nevertheless, according to the criteria of National Cholesterol Educational Program Adult Treatment Panel (ATP)-III (3), the prevalence of MetS in U.S. adults who are older than 20 years of age is approximately 24% (4). Metabolic syndrome is a growing problem worldwide, particularly in the Asian population (5). The World Health Organization Expert Consultation recommended a lower cut-off point for observed risk in Asian populations than that for non-Asian populations, varying from 22 to 25 kg/m2 (6). Some studies on migrants from Asian countries to Western countries also indicated that Asian populations might be more susceptible to the Western diet and lifestyle than white ones in developing the MetS (7,8). Patients with MetS have twice the incidence of developing new-onset diabetes compared with those without MetS (9). Metabolic syndrome, therefore, is associated with increasing risk of developing diabetes and cardiovascular disease. Several inflammatory mediators and adipocytokines, including tumor necrosis factor (TNF)-alpha (10), interleukin (IL)-6 (11), high-sensitivity C-reactive protein (hs-CRP) (12,13), and adiponectin (14) are associated with the development of insulin resistance and MetS (15,16). Despite these associations, the pathogenesis of MetS remains unknown. We recently reported that Rho kinase (ROCK) mediates the expression of plasminogen activator inhibitor-1 under hyperglycemic conditions (17). Furthermore, ROCK is upregulated under inflammatory conditions (18) and may be involved in adipocyte differentiation (19). Thus, growing evidence suggest that ROCK may contribute to the pathogenesis of MetS. However, clinical studies are lacking, which definitively link ROCK activity with MetS. Rho kinase is a serine/threonine kinase that mediates the downstream signaling of the small guanosine triphosphate-binding protein, Rho, on the actin cytoskeleton (20). ROCK consists of 2 isoforms, ROCK1 and ROCK2. In mostly animal models, the inhibition of ROCK ameliorates many cardiovascular conditions, including hypertension (21), atherosclerosis (22), myocardial fibrosis (23), and stroke (24). Furthermore, ROCK also could regulate insulin signaling and glucose metabolism through direct phosphorylation of the insulin receptor substrate (IRS)-1 (25). Thus, it is likely that ROCK plays an important role in the pathogenesis of MetS and diabetes. However, evidence is lacking showing that ROCK activity is increased in human subjects with MetS. In the current study, we measured ROCK activity in Taiwanese population with MetS and determined whether ROCK activity is an independent marker of MetS and whether it correlates with other components and risk markers of MetS.

Sarcopenia is an aging condition involving low muscle mass and function. Fetuin-A (FetA) appears to be a factor for body composition remodeling. We hypothesized that age increases FetA levels and deteriorates the myocardial function by affecting diastolic function, especially in people with sarcopenia. We enrolled 541 asymptomatic elderly (≥65 years) patients. Compared with non-sarcopenic population, FetA levels were significantly elevated in the ninety-two (17%) patients (79 ± 6 years; male: 34.7%) diagnosed with sarcopenia (621.1 ± 140.7 vs. 697.3 ± 179.6 μg/ml

We have found that cilostazol may have beneficial effects on endothelial progenitor cells (EPCs) in vitro and can provide vasculo-angiogenic effect in vivo. This study, for the first time, investigated the vasculo-angiogenic effects of cilostazol on EPCs and flow-mediated dilatation (FMD) in

We seek to evaluate the association of serial plasma soluble thrombomodulin (TM) change and outcome in survivals of acute coronary syndrome (ACS).Plasma TM is a marker of endothelial damage. Elevated cross-sectional TM level has been found to be associated with worse outcome in survivals of acute myocardial infarction (MI). However, the association of serial TM change with ACS is not clear.In 47 survivals of ACS [39 males; age, 64.7+/-9.3 years; 15 unstable angina (UA), 32 acute MI], plasma soluble TM and serum high sensitivity C-reactive protein (hs-CRP) levels are measured at index ACS and at 3-month follow-up. Using hierarchical cluster analysis, patients are classified into ascending (n=29) and descending group (n=18) according to the change in TM level. Composite study end-point is recurrent UA, MI and sudden cardiac death (SCD).The magnitude of change of plasma soluble TM is not related to demographic characteristics, diagnosis and pattern of revascularization. The change of TM level in ascending and descending group is 1.80+/-1.13 and -1.73+/-0.48 ng/ml (p0.001), respectively. There is no significantly difference in demographic characteristics, diagnosis and pattern of revascularization between both groups. The mean hs-CRP levels at index ACS and at 3-months follow-up are also not statistically different between two groups. At 6-month follow-up, 6 patients in ascending group reach end-point (1 SCD, 1 UA, and 4 MIs), however, no patient in descending group suffers from subsequent event (p=0.044). After a mean follow-up of 317 days (range, 60 to 541 days), 9 (19%) patients reach end-point. Kaplan-Meier survival analysis reveals that increasing plasma TM predicts worse clinical outcome (hazard ratio=0.13, log-transformed 95% confidence interval 0.03 to 0.48, p=0.0224 by the log-rank test).Increasing plasma TM level associates with worse outcome in patients surviving ACS.

Summary. Background: Oxidation of low density lipoproteins is an initial step of atherogenesis that generates pro-inflammatory phospholipids, including platelet-activating factor (PAF). PAF is degraded by PAF-acetylhydrolase (PAF-AH), which has been postulated to be a risk factor for myocardial infarction (MI). The role of PAF-AH for the onset of premature MI is unclear. Methods: Polymorphisms located in putatively functional regions were investigated in a cohort of patients having premature MI onset prior to 46 years of age (n = 200) and a sex-age-matched control group (n = 200). The activity of PAF-AH and coronary angiograms were evaluated for the severity of coronary atherosclerosis. Results: The V allele of A379V (exon 11) polymorphism on PAF-AH gene was more frequent in patients with premature MI (P = 0.001). This V allele polymorphism was also associated with a lower activity of plasma PAF-AH and a more complex coronary atherosclerosis (p Trends

UNLABELLED The objective of the present study was to develop a simple clinical model for predicting pulmonary embolism (PE) in patients with acute dyspnea in the emergency room. PATIENTS AND MEASUREMENTS We enrolled 56 patients diagnosed with PE, and 92 consecutive patients without PE, all of whom presented with acute dyspnea in the emergency room. Primary emergency-room physicians assessed the initial evaluation and interpretation of various laboratory findings. Some significantly independent predictors of PE were identified and integrated into a clinical model of pretest probability: low ( or= 30%, 70%). After setting up the model, another 40 patients (16 with PE, 24 without PE) were tested using the pretest model. Clinical variables associated with an increased likelihood of PE were being female and having unilateral low-leg edema, a high alveolar-arterial oxygen gradient, a clear chest x-ray, and electrocardiographic findings of right ventricular strain. Variables associated with a decreased likelihood of PE were cough, chest tightness, and unclear breath sounds. Our clinical model predicted that 95% of patients with PE had a high or low probability of PE. The positive predictive value for high probability was 94.1% and the negative predictive value for low probability was 94.4%. In the tested group, the positive predictive value for high probability was 92.9%. The negative predictive value for low probability was 91.3%. This simple and easily available prediction model was useful for estimating the pretest probability of PE in patients with acute dyspnea.

Objectives: The aim of this study was to analyze clinical characteristics and the outcome of patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a Taiwan tertiary referral medical center. Background: ApHCM is regarded as a subgroup of nonobstructive HCM that occurs largely in Japanese patients. The clinical features, gender differences and prognosis of the disease in Taiwan are poorly understood. Methods: A retrospective cohort study with 40 patients was performed. Diagnosis was based on the demonstration of left ventricular hypertrophy by echocardiography. Clinical features, cardiovascular morbidity and mortality were analyzed. Multiple logistic regression was used to adjust for potential confounding factors. Results: Among 40 patients, males predominated with a percentage of 75%. The female patients obviously had later onset of presentation (mean age ± SD, 62.2 ± 5.7 vs. 54.1 ± 11.4 years; p = 0.038). During a mean follow-up of 72.2 ± 60.1 months, there was no mortality. However, 13 patients (32.5%) had one or more major cardiovascular morbidities, the most frequent being syncope or near syncope (15%) and ischemic stroke-associated atrial fibrillation (10%). In a multivariate analysis, left atrial enlargement (odds ratio 5.85, 95% CI 1.15–29.40; p = 0.034) was the only predictor of cardiovascular morbidity. Conclusions: Patients with ApHCM in Taiwan have a benign clinical course without association with sudden death and cardiovascular mortality. Left atrial enlargement was the only identified predictor of cardiovascular morbidity

Background: Early coronary revascularization and medical therapy advancement improve the survival of patients (pts) with acute myocardial infarction (AMI). However, survivors of AMI are at heightened risk of developing heart failure (HF) and there is a paucity of information regarding this issue in Asian countries. This study described the temporal trends in the incidence of HF after the first AMI and the predicting factors of HF development in Taiwan. Methods: We conducted a nationwide population-based cohort study by using 1999 to 2009 National Health Insurance Research Database. Pts aged≧18 years, with no history of HF, who hospitalized with a first AMI between January 2002 and December 2008 were identified and followed up for one year. The primary outcome was HF. We evaluated the incidence of HF during the index hospitalization, 30 days, 6 months, and one year after the discharge. The predicting factors of HF were identified by Cox proportional hazard model. Results: Overall, 42,011 first AMI pts (mean age 64.4 ± 13.8 years; male 75.0%) from 2002 to 2008 were identified. The HF incidence during the index hospitalization was 14.8%. After exclusion of HF during the hospitalization, the overall HF prevalence at 30 days, 6 months, and 1 year was 9.6%, 14.2%, and 16.8%, respectively. The HF prevalence at 1 year declined from 17.9% to 14.9% (p Conclusions: Survivors of AMI without prior HF remain at risk of developing HF in Taiwan and most episodes occur within 6 months after AMI. Five important clinical factors of HF were identified that may help us for risk stratification.

Summary Background: Left ventricular early diastolic fillings can be reduced by inspiration. However, the effects of left ventricular hypertrophy on such changes have not been studied before. This study was undertaken to investigate whether respiratory changes in transmitral Doppler flow were affected by left ventricular hypertrophy in hypertension patients. Methods: Eighty-three patients (mean age 46 ± 8 years, 49 males) with untreated essential hypertension were included in this study. Transmitral Doppler flow velocity was measured both at end-expiration and end-inspiration. Left ventricular mass was measured by M-mode echocardiography. We divided patients into two groups based on the presence of left ventricular hypertrophy or not. Results: Twenty-one patients were diagnosed to have left ventricular hypertrophy. In patients without left ventricular hypertrophy, the peak early filling velocity decreased significantly (from 74 ± 15 to 71 ± 18 cm s−1, P = 0·003), the peak atrial velocity increased significantly (from 65 ± 17 to 74 ± 15 cm s−1, P

We report a case with multiple thrombosis that underwent sudden circulatory collapse due to acute pulmonary embolism and ischemic stroke. Further confirmed by transesophageal echocardiography, the thrombus in both atria was detected by transthoracic echocardiography. In addition, patent foramen ovale and another thrombus in the descending aorta were readily identified by transesophageal echocardiography. Aspirin was prescribed and thrombi disappeared 1 month later. Our case report suggests that patients undergoing sudden collapse with unexplained hypoxemia and new neurological deficit secondary to coexistence of pulmonary and systemic embolism should be promptly evaluated by echocardiography, especially transesophageal one, with high suspicion for paradoxical embolism.

Summary. Objective: To evaluate the prognostic roles of multiple polymorphisms and smoking cessation for premature myocardial infarction (MI). Methods: We studied 170 patients with MI onset before the age of 45 years (range 27–45 years, 84% men) and analyzed the traditional risk factors and several candidate genes’ associations with their subsequent coronary events. Results: Follow-up data were available for a total of 162 individuals (95.3%) with the other 38 individuals (4.7%) being lost-to-follow-up premature MI patients. During a mean period of 4.43 years’ follow-up, diabetes mellitus (DM), hypertension, hypercholesterolemia and Killip's status ≥II were more frequent among patients with subsequent cardiac events (all P-values

Background While mortality from coronary heart disease (CHD) has declined substantially in most developed countries in recent decades, discordant rising trends have been observed in many developing and newly developed countries. In this study, we examined the trends of CHD mortality and its hospitalization rate, and correlated the trends with changes in major cardiovascular risk factors in Taiwan. Methods Mortality data during the period 1971–2001 were obtained from official vital statistics. Hospitalization rates were calculated using information extracted from the National Health Insurance Database, which was available from 1996 to 2001. Changes in major cardiovascular risk factors were obtained from official statistics and review of previous epidemiologic studies. Results In 2001, the age-standardized CHD mortality in Taiwan was 28.7 per 100,000 for men and 15.5 per 100,000 for women. For both men and women, age-adjusted CHD mortality increased slowly but steadily from 1971 to 1992, but after that, a downward trend was observed. Hospitalization rates for CHD, however, increased substantially from 1996 to 2001. Levels of per-capita cigarette consumption, dietary fat intake, body mass index, and prevalence of hypertension and diabetes had all increased over the past three decades. Conclusions The overall cardiovascular risk profile has worsened in the general population in Taiwan. The decline in CHD mortality observed in recent years was most likely attributable to the improvement in acute cardiac care and medical treatment among patients with CHD. We anticipated that CHD incidence and prevalence would continue to rise in Taiwan.

OBJECTIVE: To report a rare but severe reaction of refractory anaphylactic shock with ketoconazole treatment—associated hypotensive episodes in an elderly patient. CASE SUMMARY: A 72-year-old woman received antifungal therapy for her almost completely occluded cornea infected with Candida albicans. She was initially prescribed oral ketoconazole 200 mg twice daily. She developed hypotension over the first 2 days of therapy (BP 136/82 mm Hg at baseline; 90/50 mm Hg on day 2). Severe hypotension (BP 90/49 mm Hg) unresponsive to fluid therapy or high-dose dopamine developed on day 4 of therapy. An invasive Swan—Ganz catheterization study showed a very low level of peripheral vascular resistance with high cardiac output index without clinical signs of infection. When laboratory tests showed a high level of plasma tryptase, anaphylactic redistribution shock was diagnosed. Her vital signs became more stable after treatment with hydrocortisone and epinephrine infusion. She was discharged in good condition after 24 hours of observation. DISCUSSION: As of December 2004, refractory anaphylactic shock resulting from ketoconazole use had not been reported. The events of hypotension were strongly associated with the intake of ketoconazole. The hemodynamic results obtained with Swan—Ganz catheterization were compatible with anaphylactic shock. The Naranjo probability scale showed a probable association of the adverse event with ketoconazole. CONCLUSIONS: Ketoconazole may cause severe anaphylactic shock even when taken orally. Invasive catheterization and elevated tryptase levels can provide important information in the management of anaphylactic shock.

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] or = 10 mmHg and/or post-treatment DBP or = 10 mmHg and/or post-treatment SBP