Impact of the Integrated Activation System on Door-to-Balloon Times and Clinical Outcomes in STEMI Patients Receiving Primary PCI.

Background: The door-to-balloon (D2B) time is a critical quality measure in managing ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI). We developed an integrated STEMI activation system, named Acute Myocardial Infarction Software Aids (AMISTAD), to optimize care for STEMI patients. This study aimed to evaluate the impact of the AMISTAD system on D2B times and clinical outcomes. Methods: We retrospectively collected data of consecutive STEMI patients receiving primary PCI between July 2017 and December 2018 at a single center. The patients were categorized into AMISTAD and non-AMISTAD groups. Outcomes included D2B time, length of hospital stay, and 12-month cardiovascular outcomes. Data were analyzed using multiple regression models; subgroup and sensitivity analyses were applied to examine the robustness of the results. Results: A total of 114 STEMI patients were enrolled (38 AMISTAD, 76 non-AMISTAD). The AMISTAD group had a significantly shorter mean D2B time (66.7 ± 13.2 vs. 76.6 ± 24.9 minutes, p = 0.02) and non-significantly shorter length of hospital stay (4.7 vs. 7.2 days, p = 0.09). The 12-month cardiovascular outcomes between the two groups were not significantly different (adjusted hazard ratio 0.79, 95% confidence interval 0.30-2.09, p = 0.64). Subgroup and sensitivity analyses had consistent outcomes. Conclusions: Integrating the AMISTAD system into the STEMI workflow was associated with a reduced D2B time and shorter hospital stay. Further research involving larger cohorts and extended follow-up periods is needed to assess the generalizability and impact on cardiovascular outcomes. The AMISTAD system has the potential to improve the quality of care for STEMI patients.

2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.

Comparison of Surgical or Medical Castration-Related Cardiotoxicity in Patients with Prostate Cancer.

PURPOSE: Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies. MATERIALS AND METHODS: Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years. RESULTS: The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies. CONCLUSIONS: Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

Dapagliflozin protects against doxorubicin-induced cardiotoxicity by restoring STAT3.

Doxorubicin (Dox), an effective therapy in different types of cancer, is known to exhibit cardiotoxic effects. Despite previous studies indicating the benefits of dapagliflozin (DAPA) in patients experiencing heart failure, it remains uncertain whether DAPA exerts a protective effect on Dox-induced cardiac dysfunction. Signal transducer and activator of transcription 3 (STAT3) participates in various mechanisms of cardioprotection. Herein, we aimed to investigate the effects of DAPA on Dox-induced cardiotoxicity and the role of STAT3. Sprague-Dawley rats were pretreated with oral DAPA for 6 weeks followed by Dox for 4 weeks. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes were treated with 10 µM DAPA and subsequently exposed to 1 µM Dox. The expression of reactive oxygen species- and apoptosis-related proteins was measured. Using STAT3 siRNA, we further examined the effects of STAT3 effect on DAPA-associated protection against Dox-induced apoptosis. In rats treated with Dox, DAPA significantly reduced cardiac fibrosis and improved cardiac function and hemodynamics. Additionally, DAPA effectively inhibited Dox-induced apoptosis and reactive oxygen species (ROS) in cardiomyocytes. Mechanistically, we showed that DAPA decreased cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2 expression. DAPA also significantly rescued Dox-suppressed STAT3 expression. Conversely, knocking down STAT3 in cardiomyocytes reversed the DAPA-related protective effects on Dox-induced cell apoptosis and ROS. Collectively, our findings indicate that DAPA could be useful for preventing Dox-induced cardiotoxicity by restoring STAT3.

An artificial intelligence approach for predicting cardiotoxicity in breast cancer patients receiving anthracycline.

Although anti-cancer therapy-induced cardiotoxicity is known, until now it lacks a reliable risk predictive model of the subsequent cardiotoxicity in breast cancer patients receiving anthracycline therapy. An artificial intelligence (AI) with a machine learning approach has yet to be applied in cardio-oncology. Herein, we aimed to establish a predictive model for differentiating patients at a high risk of developing cardiotoxicity, including cancer therapy-related cardiac dysfunction (CTRCD) and symptomatic heart failure with reduced ejection fraction. This prospective single-center study enrolled patients with newly diagnosed breast cancer who were preparing for anthracycline therapy from 2014 to 2018. We randomized the patients into a 70%/30% split group for ML model training and testing. We used 15 variables, including clinical, chemotherapy, and echocardiographic parameters, to construct a random forest model to predict CTRCD and heart failure with a reduced ejection fraction (HFrEF) during the 3-year follow-up period (median, 30 months). Comparisons of the predictive accuracies among the random forest, logistic regression, support-vector clustering (SVC), LightGBM, K-nearest neighbor (KNN), and multilayer perceptron (MLP) models were also performed. Notably, predicting CTRCD using the MLP model showed the best accuracy compared with the logistic regression, random forest, SVC, LightGBM, and KNN models. The areas under the curves (AUC) of MLP achieved 0.66 with the sensitivity and specificity as 0.86 and 0.53, respectively. Notably, among the features, the use of trastuzumab, hypertension, and anthracycline dose were the major determinants for the development of CTRCD in the logistic regression. Similarly, MLP, logistic regression, and SVM also showed higher AUCs for predicting the development of HFrEF. We also validated the AI prediction model with an additional set of patients developing HFrEF, and MLP presented an AUC of 0.81. Collectively, an AI prediction model is promising for facilitating physicians to predict CTRCD and HFrEF in breast cancer patients receiving anthracycline therapy. Further studies are warranted to evaluate its impact in clinical practice.

The impact of COVID-19 on cardio-oncology care in Taiwan.

COVID-19 has not only affected the respiratory but the cardiovascular system. Taiwan has encountered a less severe COVID-19 pandemic. We reported the current situation in Taiwan. In this study, we retrospectively analyzed the data from our cardio-oncology program since October of 2019 to April of 2020 (the initial months of COVID-19 pandemic). In our cardio-oncology program, newly diagnosed breast cancer patients preparing for epirubicin therapy were included. Echocardiography, 6-min walking distance and major adverse cardiovascular events (MACEs) were recorded. To evaluate whether the social atmosphere affects cardio-oncology care, we analyzed the objective (physical) and subjective (emotional) parameters before and after January 21, 2020, when the first case of COVID-19 was confirmed in Taiwan. There was no significant decrease in patients' return ratio and LVEFs. However, there was a trend of subjective shortness of breath reported by the patients but no decline in 6 MWT. Notably, none of the enrolled patients reported MACEs during the COVID pandemic. We observed an impact of anxiety on patients receiving epirubicin but it did not influence their return ratio.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities.

BACKGROUND: Despite the increasing prevalence of therapies utilizing immune checkpoint inhibitors (ICIs), the associated cardiovascular complications have been poorly reported. Given the fatality of ICI-related complications, especially myocarditis, optimal risk stratification to predict major adverse cardio- and cerebrovascular events (MACCEs) in patients receiving ICIs is mandatory. METHODS: We collected clinical data from patients receiving ICIs, and the primary outcomes were MACCEs, including myocarditis, heart failure, and ischemic stroke. Other systemic immune responses relating to ICIs were also recorded. The median follow-up duration was 3 years. RESULTS: Among 580 patients, the incidence of MACCEs was 3.9%. Older patients, male patients, and patients with lung cancer, liver cirrhosis, or diabetes had higher risks of MACCEs. There was no significant difference between the use of PD-1/PD-L1 inhibitors or CTLA inhibitors in terms of developing cardiovascular toxicities. The development of ICI-related MACCEs was associated with worse survival. Notably, after re-review by specialists, three patients eventually diagnosed with ICI-related myocarditis had not previously been identified. Only one was treated with pulse steroids, and none survived. The most common concomitant extracardiac immune-related adverse events were myositis/dermatitis, endocrine toxicity and hepatitis. CONCLUSIONS: Collectively, ICIs may lead to severe cardiovascular toxicities and require more attention. Early identification, proper diagnosis, and prompt treatment are pivotal for improving survival.

The Efficacy and Safety of Short-Term Tolvaptan Usage in Patients with Acute Decompensated Heart Failure.

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.

Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

Effects of renal impairment on cardiac remodeling and clinical outcomes after myocardial infarction.

How renal function influences post-acute myocardial infarction (AMI) cardiac remodeling and outcomes remains unclear. This study evaluated the impact of levels of renal impairment on drug therapy, echocardiographic parameters, and outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI). A total of 611 patients diagnosed with AMI underwent successful PCI, and two echocardiographic examinations were performed within 1 year after AMI. Patients were categorized according to Group 1: severely impaired estimated glomerular filtration rate (eGFR)<30, Group 2: mildly impaired 30≤eGFR<60, Group 3: potentially at risk 60≤eGFR<90 and normal eGFR≥90 ml/min/1.73 m2. During the 5-year follow-up period, the primary endpoints were cardiovascular mortality and outcomes. Patients with worse renal function (eGFR<30) were older and had a higher prevalence of hypertension and diabetes, but relatively few were smokers or had hyperlipidemia. Despite more patients with lesions of the left anterior descending artery, those with worse renal function received suboptimal guideline-directed medical therapy (GDMT). Notably, patients with worse renal function presented with worse left ventricular function at baseline and subsequent follow-up. Kaplan-Meier analysis revealed increased cardiovascular death, development of heart failure, recurrent AMI and revascularization in patients with worse renal function. Notably, as focusing on patients with ST elevation MI, the similar findings were observed. In multivariable Cox regression, impaired renal function showed the most significant hazard ratio in cardiovascular death. Collectively, in AMI patients receiving PCI, outcome differences are renal function dependent. We found that patients with worse renal function received less GDMT and presented with worse cardiovascular outcomes. These patients require more attention.

Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients.

Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes. We aimed to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity. Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin for 6 weeks followed by Dox for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose were treated with dapagliflozin at 10 µM and subsequently exposed to Dox at 1 µM. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured. Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2α, ATF-4, and CHOP. Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

The S Protein of SARS-CoV-2 Injures Cardiomyocytes Indirectly through the Release of Cytokines Instead of Direct Action.

BACKGROUND: Emerging evidence has shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with cardiac injury, but it remains unclear whether cardiac injury is mainly caused by direct viral infection or is secondary to SARS-CoV-2-induced cytokine storm. METHODS: Through directly treating cardiomyocytes with S protein, a crucial surface protein of SARS-CoV-2, and indirectly treating cardiomyocytes with S protein-derived human T lymphocyte conditioned medium, we compared the intensities of cardiomyocyte injuries caused by either S protein of the virus or S protein of virus-triggered cytokines. RESULTS: The directly treated cardiomyocytes did not show increasing cell apoptosis. In contrast, cardiomyocytes treated with the supernatant medium of S protein pre-conditioned peripheral blood mononuclear cells showed significantly suppressed viability. In addition, using a cardiovascular disease-specific PCR array, genes associated with hypertrophy, apoptosis, inflammation and angiogenesis were observed to be affected by cytokine stress. CONCLUSIONS: Collectively, we found that SARS-CoV-2-induced heart injury may be mainly through the S protein of the virus enhancing host immune responses instead of the S protein of the virus per se. With regards to clinical application, the strategy for treating COVID-19 should not only focus on anti-viral therapy but also on suppressing over-activated immunity.

The Impact of COVID-19 on Elective Cardiovascular Procedures in Taiwan - A Single-Center Experience.

COVID-19 has reached a pandemic level and affected both individual's health and global healthcare systems. Although Taiwan has encountered a less severe COVID-19 pandemic than many other countries, it has impacted the workflow of all cardiovascular examinations and procedures. Compared to before January 21st, 2020 (the date of the first confirmed COVID-19 in Taiwan), the number of patients who have received echocardiography and cardiac catheterization has since fallen. However, the number of percutaneous coronary interventions being performed has remained at the usual level. Based on our experience, we suggest that healthcare providers in Taiwan should carefully evaluate the urgency of cardiovascular procedures and deferred non-emergent procedures. Given that the pandemic has not yet plateaued, we should remain prepared for future challenges to maintain our medical service.

A performance guide for major risk factors control in patients with atherosclerotic cardiovascular disease in Taiwan.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

The Effectiveness and Safety between Monoplane and Biplane Imaging During Coronary Angiographies.

BACKGROUND: Avoiding unnecessary radiation exposure is the main issue during coronary angiography. Herein, we aimed to investigate whether performing coronary angioplasties with monoplane or biplane imaging most effectively reduces radiation load and shortens the procedure time. METHODS: We retrospectively enrolled 294 patients who required either coronary angiography or coronary angioplasty. They were divided into groups of only diagnostic angiography, one-, two- or three-vessel diseases. The fluoroscopy dose-area product (DAP), skin dose, fluoroscopy and procedure time were recorded. RESULTS: Among the studied patients, 148 received the procedures with monoplane imaging. Compared with the radiation exposure in the monoplane group, there were significant increases in DAP and skin dose in those who received biplane imaging independently of the number of lesions. This phenomenon was also observed in the patients receiving either diagnostic angiography only or coronary interventions. In addition, there were no significant differences in contrast volume and procedure time between the monoplane and biplane groups. Notably, the average fluoroscopy time in those who received biplane imaging was significantly longer than in those who received monoplane imaging in the one- and two-vessel groups, while there were no significant differences in the diagnostic angiography only and three-vessel diseases groups. CONCLUSIONS: Our findings indicated that using monoplane imaging resulted in lesser radiation exposure and similar procedure times in coronary diagnostic and interventional settings compared to using biplane imaging. This observation should be verified in prospective randomized studies.

Cost-Effectiveness Analysis of Oral Anticoagulants in Stroke Prevention among Patients with Atrial Fibrillation in Taiwan.

BACKGROUND: Non-vitamin K oral antagonist anticoagulants (NOACs) have been widely used in stroke prevention in atrial fibrillation (SPAF). The aim of this study was to compare the pharmacoeconomic impact of oral anticoagulants (OACs) including warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in SPAF in Taiwan. METHODS: A decision tree, Markov model, and multiple sensitivity analyses were used to project the lifetime costs and quality-adjusted life years (QALYs) of OACs. Transitional probabilities were derived from a systematic review and network meta-analysis for Asian populations. Utilities and costs were obtained from published studies and the Taiwan National Health Insurance Research Database. Threshold of the willingness to pay (WTP) at USD 20,000 was applied to evaluate the results. RESULTS: In base-case analysis, warfarin had the lowest cost at $13,363 ± 4,036, and edoxaban 60 mg produced the most QALYs at 11.92 ± 1.98. The incremental cost-effectiveness ratios of dabigatran 150 and 110 mg, rivaroxaban 20 and 15 mg, apixaban 5 mg, and edoxaban 60 mg versus warfarin were $6,415, $4,225, $4,115 and $5,458 per QALY gained, respectively. Monte Carlo analysis revealed that dabigatran 150 and 110 mg, rivaroxaban 20 and 15 mg, apixaban 5 mg and edoxaban 60 mg were most cost-effective at 21.9%, 27.1%, 23.6%, and 27.4% of $20,000 compared to warfarin. CONCLUSIONS: From a Taiwan national payer perspective, all NOACs are cost-effective substitutes for warfarin in SPAF. However, the likelihood of cost-effective iterations for NOACs is highly driven by their market prices at the time and different WTP thresholds of policymakers.

Risk of ischaemic stroke in thyrotoxic atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is the most common cardiac complication of thyrotoxicosis and is strongly implicated in thromboembolic events. However, the incidence of stroke in thyrotoxic AF remains unclear. Herein, we aimed to investigate the risks of mortality and ischaemic stroke between patients with thyrotoxic AF and nonthyrotoxic AF. DESIGNS AND METHODS: From Taiwan's National Health Insurance Research Database, 1868 patients with the concomitant diagnoses of AF and thyrotoxicosis identified between 2001 and 2010 were compared to 7472 patients with nonthyrotoxic AF using propensity score matching for age, sex and comorbidities. RESULTS: There was no significant difference in either CHA2 DS2 -VASc score or anticoagulant usage between the groups. Alternatively, the thyrotoxic group contained more ß-blocker/digoxin users, whereas the nonthyrotoxic group contained more statin users. Patients with thyrotoxic AF exhibited lower risks of all-cause mortality (HR: 0.66, CI: 0.59-0.73, P < .0001) and ischaemic stroke (HR: 0.73, CI: 0.64-0.84, P < .0001) than those with nonthyrotoxic AF, especially thyrotoxic patients with CHA2 DS2 -VASc scores ≥1. Comorbidities, including diabetes, hyperlipidaemia, hypertension and coronary artery disease, contributed to all-cause mortality in patients with nonthyrotoxic AF; however, this effect was diminished in thyrotoxic AF. CONCLUSIONS: Patients with thyrotoxicosis and AF have a lower risk of stroke than patients with nonthyrotoxic AF. Treatment for thyrotoxicosis is also crucial as the prescription of anticoagulants based on CHA2DS2-VASc scores.

Comparison of Home and Ambulatory Blood Pressure Measurements in Association With Preclinical Hypertensive Cardiovascular Damage.

OBJECTIVE: To evaluate whether home or ambulatory blood pressure (BP) monitoring was associated with preclinical hypertensive cardiovascular target organ damage (TOD). METHODS: We enrolled participants with prehypertension and stage 1 hypertension from 11 medical centers within the Taiwan hypertension-associated cardiac disease consortium. Recordings of clinical BP measurement, ambulatory BP monitoring for 24 hours, and home BP monitoring during morning and evening were made. The measured parameters of target organ damage included left ventricular mass index (LVMI), left atrial volume index (LAVI), and carotid-femoral pulse wave velocity (PWV). RESULTS: Data were collected from 561 study participants (mean age, 65.0 ± 10.8 years; men, 61.3%). Morning and evening home BP values were slightly higher than the daytime and nighttime ABP values (difference for systolic morning-daytime/evening-nighttime, 7.3 ± 14.2/11.3 ± 18.5 mm Hg, P < .001; for diastolic, 5.4 ± 9.4/7.3 ± 12.1, P < .001). Daytime ambulatory (r = 0.114), nighttime ambulatory (r = 0.130), morning home (r = 0.310), and evening home (r = 0.220) systolic BPs (SBPs) were all associated with LVMI (all P < .05). The correlation coefficient was significantly greater for the relationship between daytime home SBP and LVMI than for the relationship between ambulatory SBP and LVMI (P < .01). The goodness of fit of the association between SBP and LVMI improved by adding home daytime SBP to the other SBPs (P < .001). Similar findings were observed for LAVI, but not for PWV. CONCLUSION: These findings indicate that morning SBP assessed by home monitoring appears to be a better predictor than other BP measures to determine preclinical hypertensive cardiovascular damage in patients with early-stage hypertension.

Evaluation of Radiation Exposure on Physicians During Angioplasty for Hemodialysis Access Dysfunction.

BACKGROUND: Percutaneous interventions help patients with various cardiovascular diseases, however radiation exposure is a safety concern for both patients and health care providers. We previously reported that dose area product (DAP) is apparently different in central body and upper-limb areas during percutaneous transluminal angioplasty for arteriovenous shunt dysfunction. In this study, we investigated the precise radiation dose at the patients' back and at the non-targeted organs of the operators. METHODS: The radiation dose was measured with optically stimulated luminescent dosimeters and DAP on several sites including the backs of the patients, gonads, hands and lens of the operators. The studied populations were categorized into central, upper arm and forearm groups based on the lesion sites. RESULTS: The results indicated that there was a significantly higher radiation dose in the central lesion group than in the upper arm and forearm groups. Conversely, there were no specific differences in total procedure time and fluoroscopy time among groups. The radiation exposure doses in the operators showed that regardless of the site, including lens, hands and gonads of the operators, the radiation dose was significantly higher in the central lesion group. CONCLUSIONS: The closer the lesion site to the body center, the higher the radiation exposure in both the patients and operators.

CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide-stimulated macrophages through ceramide-initiated protein phosphatase 2A activation.

CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME-1-treated RAW 264.7 cells, LPS-induced IκBα degradation and the phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38, were reduced. Treatment with a protein phosphatase 2A (PP2A)-specific inhibitor, significantly reversed the CME-1-suppressed iNOS expression; IκBα degradation; and p65, Akt and MAPK phosphorylation. PP2A activity up-regulation and PP2A demethylation reduction were also observed in the cells. Moreover, CME-1-induced PP2A activation and its subsequent suppression of LPS-activated RAW 264.7 cells were diminished by the inhibition of ceramide signals. LPS-induced reactive oxygen species (ROS) and hydroxyl radical formation were eliminated by treating RAW 264.7 cells with CME-1. Furthermore, the role of ceramide signalling pathway and anti-oxidative property were also demonstrated in CME-1-mediated inhibition of LPS-activated primary peritoneal macrophages. In conclusion, CME-1 suppressed iNOS expression by up-regulating ceramide-induced PP2A activation and reducing ROS production in LPS-stimulated macrophages. CME-1 is a potential therapeutic agent for treating inflammatory diseases.