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Heart failure impairs the heart's pumping ability and triggers catecholamine production as an adaptive mechanism. Uterine leiomyomas are common tumors of the female reproductive tract. Their growth is promoted by dysregulated angiogenesis and gonadal steroid hormones. Although uterine leiomyomas share risk factors with most cardiovascular diseases, their relationship with heart failure has not been well described. Herein, we present the case of a 45-year-old woman with heart failure who visited the emergency department, where we incidentally discovered a giant uterine leiomyoma. The patient was admitted with progressive dyspnea and abdominal distension. Echocardiography revealed an enlarged right ventricle and a decreased systolic function. Computed tomography revealed cardiomegaly with bilateral pleural effusions and a tumor measuring 18.0 × 12.0 cm in the abdominal cavity with massive ascites. A diagnosis of heart failure in conjunction with a uterine leiomyoma was established, which prompted the prescription and adjustment of heart failure medications according to the patient's clinical presentation. Three weeks later, given the persistent symptoms of bilateral lower extremities pitting edema and abdominal distension, a total hysterectomy was performed. Postoperatively, echocardiography revealed marked improvement in her heart failure. The patient was discharged in a stable clinical and hemodynamic conditions, and reported good physical condition at the 4-month follow-up. Growth factors and the compression effect of uterine leiomyomas may predispose patients to heart failure and exacerbate its deterioration. Although reports of fibroid-related heart failure are rare, uterine leiomyomas should be considered a potential cause of refractory heart failure. Nevertheless, a direct association requires a longer follow-up period.

Background: Acute limb ischemia (ALI) is a medical emergency necessitating immediate action to avert irreversible tissue harm and limb loss. Rotarex mechanical thrombectomy (RMT) has become an efficient treatment alternative for ALI. However, there is a lack of data on RMT in Taiwan., Methods: We retrospectively analyzed 61 ALI patients treated with RMT at our hospital between January 2016 and January 2022. We collected baseline characteristics, laboratory and angiographic data. We also examined the outcomes at 30 days, 6 months, and 1 year, including major amputations, minor amputations, all-cause mortality, and major adverse limb events (MALEs)., Results: Among the 61 RMT-treated patients, the average age was 70 ± 14 years. ALI affected the upper extremities in 9 cases and lower extremities in 52 cases. One-year outcomes revealed 2 major amputations (3.3%), 2 minor amputations (3.3%), 6 all-cause deaths (9.8%), and 10 MALEs (16.4%). After multiple logistic regression analysis, hemoglobin drop was significantly associated with 1-year all-cause mortality, and a history of peripheral artery disease (PAD) was significantly associated with MALEs., Conclusions: Our research is the first investigation into the application of RMT for ALI in Taiwan. The short- and mid-term outcomes after RMT for ALI revealed reductions in amputation, mortality, and MALE rates. In addition, a decline in hemoglobin level was a significant predictor of increased mortality, and a history of PAD was a significant predictor of increased MALEs following RMT., Competing Interests: All the authors declare no conflict of interest.

Objective: Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies., Methods: Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years., Results: A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy., Conclusion: In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy., (Copyright © 2024 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have a variety of cardiovascular and renoprotective effects and have been developed as novel agents for the treatment of heart failure. However, the beneficial mechanisms of SGLT2i on cardiac tissue need to be investigated further. In this study, we established a mouse model of acute myocardial infarction (AMI) using coronary artery constriction surgery and investigated the role of dapagliflozin (DAPA) in protecting cardiomyocytes from hypoxic injury induced by AMI. In vitro experiments were done using hypoxic cultured H9c2 ventricular cells to verify this potential mechanism. Expression of the SIRT family and related genes and proteins was verified by qPCR, Western blotting and immunofluorescence staining, and the intrinsic potential mechanism of cardiomyocyte death due to AMI and hypoxia was comprehensively investigated by RNA sequencing. The RNA sequencing results of cardiomyocytes from AMI mice showed that the SIRT family may be mainly involved in the mechanisms of hypoxia-induced cardiomyocyte death. In vitro hypoxia-induced ventricular cells showed the role of dapagliflozin in conferring resistance to hypoxic injury in cardiomyocytes. It showed that SIRT1/3/6 were downregulated in H9c2 cells in a hypoxic environment, and the addition of dapagliflozin significantly increased the gene and protein expression of SIRT1, 3 and 6. We then verified the underlying mechanisms induced by dapagliflozin in hypoxic cardiomyocytes using RNA-seq, and found that dapagliflozin upregulated the hypoxia-induced gene downregulation, which includes ESRRA , EPAS1 , AGTRAP , etc., that associated with SIRTs-related and apoptosis-related signaling to prevent H9c2 cell death. This study provides laboratory data for SGLT2i dapagliflozin treatment of AMI and confirms that dapagliflozin can be used to treat hypoxia-induced cellular necrosis in cardiomyocytes, in which SIRT1 and SIRT3 may play an important role. This opens up further opportunities for SGLT2i in the treatment of heart disease.

Aims: Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel., Methods: Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes., Results: A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs., Conclusions: The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

The Taiwan Society of Cardiology (TSOC) and Taiwan Society of Plastic Surgery (TSPS) have collaborated to develop a joint consensus for the management of patients with advanced vascular wounds. The taskforce comprises experts including preventive cardiologists, interventionists, and cardiovascular and plastic surgeons. The consensus focuses on addressing the challenges in diagnosing, treating, and managing complex wounds; incorporates the perfusion evaluation and the advanced vascular wound care team; and highlights the importance of cross-disciplinary teamwork. The aim of this joint consensus is to manage patients with advanced vascular wounds and encourage the adoption of these guidelines by healthcare professionals to improve patient care and outcomes. The guidelines encompass a range of topics, including the definition of advanced vascular wounds, increased awareness, team structure, epidemiology, clinical presentation, medical treatment, endovascular intervention, vascular surgery, infection control, advanced wound management, and evaluation of treatment results. It also outlines a detailed protocol for assessing patients with lower leg wounds, provides guidance on consultation and referral processes, and offers recommendations for various wound care devices, dressings, and products. The 2024 TSOC/TSPS consensus for the management of patients with advanced vascular wounds serves as a catalyst for international collaboration, promoting knowledge exchange and facilitating advancements in the field of advanced vascular wound management. By providing a comprehensive and evidence-based approach, this consensus aims to contribute to improved patient care and outcomes globally., Competing Interests: All the authors declare no conflict of interest.

Background: Left atrial strain can usefully reflect left atrial function. The follow-up periods in previous studies assessing left atrial strain as a survival predictor have been relatively short, and few studies have examined the ability of left atrial strain to predict mortality in patients with borderline diastolic function. This study sought to investigate the survival predictive value of left atrial strain with a longer follow-up duration. In addition, we also evaluated the survival predictive value of left atrial strain in patients with borderline diastolic function., Methods: In total, 652 participants who received routine echocardiography underwent 2-D speckle tracking echocardiography to evaluate left atrial reservoir function by peak atrial longitudinal strain. The study endpoints were all-cause and cardiovascular mortality., Results: The mean left atrial strain was 27.6%, and the median follow-up duration was 92 months. During follow-up, 72 patients died of cardiovascular causes and 181 died of all causes. Univariable Cox regression analysis revealed that lower left atrial strain significantly predicted an increase in all-cause and cardiovascular mortality. After adjusting for common clinical and echocardiographic parameters, lower left atrial strain was still associated with a higher risk of all-cause mortality [hazard ratio (HR) = 0.942, p = 0.011] and cardiovascular mortality (HR = 0.915, p = 0.018) in multivariable Cox-regression analysis. In addition, 293 patients had borderline left ventricular diastolic function. Multivariable analysis still revealed that left atrial strain could predict cardiovascular mortality in this population., Conclusions: Our data showed that left atrial strain could predict all-cause and cardiovascular mortality, even after adjusting for general clinical and echocardiographic parameters., Competing Interests: All the authors declare no conflict of interest.

Background: Hemostatic abnormality has contributed to vascular access thrombosis in patients with chronic kidney disease (CKD). Previous studies have demonstrated that far-infrared radiation (FIR) therapy can maintain the patency and maturity of arteriovenous fistulas of patients undergoing hemodialysis (HD). However, prolonged access bleeding is observed once FIR is conducted at the end of dialysis. FIR can block the binding of platelet and von Willebrand factor (vWF), a predictor of hemostatic abnormality and vascular access thrombosis. However, clinical studies exploring FIR and vWF are sparse., Methods: We recruited 20 HD patients, 21 CKD patients, and 20 controls to examine the alteration of vWF and a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) following a single 40-min session of FIR therapy. In addition, the alteration of these factors in the HD group was examined following a 40-min FIR session thrice a week for 3 months., Results: A decreasing trend in the vWF activity-antigen ratio of participants in all groups following a single FIR session was observed. In addition, the ratio in the HD group was significantly lower following 3 months of FIR therapy. The subgroup analysis revealed a consistent trend and multiple regression analysis showed that participants not taking hydroxymethylglutaryl-coenzyme A reductase inhibitor, diabetes mellitus, and higher hemoglobin levels were the significant factors. The alteration of the vWF activity-antigen ratio correlated moderately to that of ADAMTS13 antigen and activity., Conclusion: FIR may alter the ratio of ultra-large vWF multimers through ADAMTS13, contributing to inhibiting platelet-endothelium interactions of CKD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yen, Hsu, Lin, Chen, Hsiao and Hwang.)

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.

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

The aim of this study was to determine the predictors of new-onset hypertension when the definition of hypertension is changed from the traditional definition (140/90 mmHg) to a new definition (130/80 mmHg). Using data from the Taiwan Biobank, a total of 17,072 and 21,293 participants in the new and traditional definition groups were analyzed, respectively. During a mean follow-up period of 3.9 years, 3641 and 3002 participants developed hypertension in the new and traditional definition groups, respectively. After multivariable analysis, older age (OR, 1.035; 95% CI, 1.030 to 1.039; p < 0.001), male sex (OR, 1.332; 95% CI, 1.194 to 1.486; p < 0.001), high systolic blood pressure (SBP) (OR, 1.067; 95% CI, 1.062 to 1.073; p < 0.001), high diastolic blood pressure (DBP) (OR, 1.048; 95% CI, 1.040 to 1.056; p < 0.001), high heart rate (OR, 1.007; 95% CI, 1.002 to 1.012; p = 0.004), high body mass index (BMI) (OR, 1.091; 95% CI, 1.077 to 1.106; p < 0.001), high fasting glucose (OR, 1.004; 95% CI, 1.001 to 1.006; p = 0.002), and high triglycerides (OR, 1.001; 95% CI, 1.000 to 1.001; p = 0.004) were significantly associated with new-onset hypertension in the new definition group. In the traditional definition group, the predictors of new-onset hypertension were older age (OR, 1.038; 95% CI, 1.032 to 1.043; p < 0.001), high SBP (OR, 1.078; 95% CI, 1.072 to 1.084; p < 0.001), high DBP (OR, 1.039; 95% CI, 1.031 to 1.046; p < 0.001), high heart rate (OR, 1.005; 95% CI, 1.000 to 1.010; p = 0.032), high BMI (OR, 1.072; 95% CI, 1.058 to 1.087; p < 0.001), high fasting glucose (OR, 1.003; 95% CI, 1.000 to 1.005; p = 0.020), low cholesterol (OR, 0.998; 95% CI, 0.997 to 0.999; p = 0.004), high triglycerides (OR, 1.001; 95% CI, 1.000 to 1.001; p = 0.001), and low estimated glomerular filtration rate (eGFR) (OR, 0.995; 95% CI, 0.993 to 0.997; p < 0.001). In conclusion, older age, high SBP and DBP, high heart rate, high BMI, high fasting glucose, and high triglycerides were useful predictors of new-onset hypertension in both the new and traditional definition groups. However, male sex was a significant predictor of new-onset hypertension only in the new definition group, and low cholesterol and low eGFR were significant predictors of new-onset hypertension only in the traditional definition group. Hence, changing the diagnostic cut-off value for hypertension may have a significant impact on the association of some clinical and laboratory parameters with new-onset hypertension.

Background: Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram., Objective: The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS., Methods: We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning., Results: In the control group, women have higher aSKNA than do men at baseline (0.82 ± 0.25 μV vs 0.73 ± 0.20 μV; P = .009) but not during mental stress (1.21 ± 0.36 μV vs 1.16 ± 0.36 μV; P = .394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 ± 0.33 μV vs 1.04 ± 0.35 μV; P = .531), during mental stress (1.46 ± 0.32 μV vs 1.33 ± 0.37 μV; P = .113), and during recovery (1.30 ± 0.33 μV vs 1.11 ± 0.30 μV; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 μV aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level., Conclusion: ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Despite the progress made during the last two decades in the surgery and chemotherapy of ovarian cancer, more than 70 % of advanced patients are with recurrent cancer and decease. Surgical debulking of tumors following chemotherapy is the conventional treatment for advanced carcinoma, but patients with such treatment remain at great risk for recurrence and developing drug resistance, and only about 30 % of the women affected will be cured. Bevacizumab is a humanized monoclonal antibody, which blocks VEGF signaling in cancer, inhibits angiogenesis and causes tumor shrinkage, and has been recently approved by FDA as a monotherapy for advanced ovarian cancer in combination with chemotherapy. Considering the cost, potential toxicity, and finding that only a portion of patients will benefit from these drugs, the identification of new predictive method for the treatment of ovarian cancer remains an urgent unmet medical need. In this study, we develop weakly supervised deep learning approaches to accurately predict therapeutic effect for bevacizumab of ovarian cancer patients from histopathological hematoxylin and eosin stained whole slide images, without any pathologist-provided locally annotated regions. To the authors' best knowledge, this is the first model demonstrated to be effective for prediction of the therapeutic effect of patients with epithelial ovarian cancer to bevacizumab. Quantitative evaluation of a whole section dataset shows that the proposed method achieves high accuracy, 0.882 ± 0.06; precision, 0.921 ± 0.04, recall, 0.912 ± 0.03; F-measure, 0.917 ± 0.07 using 5-fold cross validation and outperforms two state-of-the art deep learning approaches Coudray et al. (2018), Campanella et al. (2019). For an independent TMA testing set, the three proposed methods obtain promising results with high recall (sensitivity) 0.946, 0.893 and 0.964, respectively. The results suggest that the proposed method could be useful for guiding treatment by assisting in filtering out patients without positive therapeutic response to suffer from further treatments while keeping patients with positive response in the treatment process. Furthermore, according to the statistical analysis of the Cox Proportional Hazards Model, patients who were predicted to be invalid by the proposed model had a very high risk of cancer recurrence (hazard ratio = 13.727) than patients predicted to be effective with statistical signifcance (p < 0.05)., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Diabetes mellitus (DM) is an increasing threat to human health and regarded as an important public issue. Coronary artery disease is one of the main causes of death in type 2 DM patients. However, the effect of hyperglycemia on coronary artery endothelial cells (CAECs) and the pathophysiologic mechanisms are still not well-explored. This study aims to explore the signal pathway and novel biomarkers of injury of CAECs in DM in understanding the microenvironment changes and mechanisms of diabetic heart disease. Next-generation sequence (NGS) and bioinformatics analysis to analyze the CAECs of one type 2 DM patient and one normal individual was performed, and it was found that tumor necrosis factor receptor superfamily member 21 (TNFRSF21) was a soluble factor in circulating system. Further experiments confirmed that advanced glycation end products (AGEs), the metabolite derived by hyperglycemia, increased the expression of TNFRSF21 in CAECs. TNFRSF21 induced endothelial-mesenchymal transition (EndoMT) in CAECs, resulting in increased permeability of CAECs. In addition, levels of serum TNFRSF21 were higher in type 2 DM patients with left ventricular hypertrophy (LVH) than those without LVH. Serum TNFRSF21 levels were also positively correlated with the LV mass index and negatively with LV systolic function. Serum TNFRSF21 levels were associated with changes in cardiac structure and function in patients with type 2 DM. In conclusion, TNFRSF21 plays a pathogenic role in heart disease of type 2 DM, and can be used as a biomarker of the impairment of cardiac structure and function in type 2 DM patients.

Ovarian cancer is a common malignant gynecological disease. Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer (EOC). Although careful patient selection is essential, there are currently no biomarkers available for routine therapeutic usage. To the authors’ best knowledge, this is the first automated precision oncology framework to effectively identify and select EOC and peritoneal serous papillary carcinoma (PSPC) patients with positive therapeutic effect. From March 2013 to January 2021, we have a database, containing four kinds of immunohistochemical tissue samples, including AIM2, c3, C5 and NLRP3, from patients diagnosed with EOC and PSPC and treated with bevacizumab in a hospital-based retrospective study. We developed a hybrid deep learning framework and weakly supervised deep learning models for each potential biomarker, and the experimental results show that the proposed model in combination with AIM2 achieves high accuracy 0.92, recall 0.97, F-measure 0.93 and AUC 0.97 for the first experiment (66% training and 34%testing) and high accuracy 0.86 ± 0.07, precision 0.9 ± 0.07, recall 0.85 ± 0.06, F-measure 0.87 ± 0.06 and AUC 0.91 ± 0.05 for the second experiment using five-fold cross validation, respectively. Both Kaplan-Meier PFS analysis and Cox proportional hazards model analysis further confirmed that the proposed AIM2-DL model is able to distinguish patients gaining positive therapeutic effects with low cancer recurrence from patients with disease progression after treatment (p < 0.005).

Aim: Abnormal ankle-brachial index (ABI) is regarded as peripheral artery disease and can be used to predict cardiovascular (CV) outcomes. However, the usefulness of ABI for the prediction of CV outcome in patients with normal ABI is limited. Upstroke time per cardiac cycle (UTCC) is recently reported to be associated with mortality in patients with acute myocardial infarction and the elderly. Therefore, we aimed to evaluate UTCC, left ventricular ejection fraction (LVEF), brachial-ankle pulse wave velocity (baPWV), and ABI for the prediction of mortality in patients with normal ABI., Methods: Patients arranged for echocardiographic examinations were enrolled, and 1076 patients with normal ABI were included. ABI, baPWV, and UTCC were measured by an ABI-form device., Results: The median follow-up to mortality was 95 months. There were 88 CV and 244 all-cause deaths. After multivariate analysis, UTCC was associated with increased CV and all-cause mortality (P ≤ 0.004). Age, diabetes, heart failure, left ventricular hypertrophy, baPWV, and LVEF were also independent predictors of CV and all-cause mortality, but ABI was not. Furthermore, UTCC had a better additive predictive value than ABI, baPWV, and LVEF for CV mortality ( P ≤ 0.012). It also had a better additive predictive value than ABI and LVEF for all-cause mortality (P ≤ 0.013)., Conclusions: UTCC is an independent predictor for CV and all-cause mortality in patients with normal ABI. It also has a better additive predictive value of CV and all-cause mortality than ABI and LVEF. Therefore, UTCC is a simple, novel, and useful parameter for identifying high-risk patients with normal ABI.

Ovarian cancer is the leading cause of gynecologic cancer death among women. Regardless of the development made in the past two decades in the surgery and chemotherapy of ovarian cancer, most of the advanced-stage patients are with recurrent cancer and die. The conventional treatment for ovarian cancer is to remove cancerous tissues using surgery followed by chemotherapy, however, patients with such treatment remain at great risk for tumor recurrence and progressive resistance. Nowadays, new treatment with molecular-targeted agents have become accessible. Bevacizumab as a monotherapy in combination with chemotherapy has been recently approved by FDA for the treatment of epithelial ovarian cancer (EOC). Prediction of therapeutic effects and individualization of therapeutic strategies are critical, but to the authors' best knowledge, there are no effective biomarkers that can be used to predict patient response to bevacizumab treatment for EOC and peritoneal serous papillary carcinoma (PSPC). This dataset helps researchers to explore and develop methods to predict the therapeutic effect of patients with EOC and PSPC to bevacizumab., (© 2022. The Author(s).)

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the "Italian protocol"), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The "SKNA-SDNN index" was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) ( p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope ( p < 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Antiangiogenic therapy, such as bevacizumab (BEV), has improved progression-free survival (PFS) and overall survival (OS) in high-risk patients with epithelial ovarian cancer (EOC) according to several clinical trials. Clinically, no reliable molecular biomarker is available to predict the treatment response to antiangiogenic therapy. Immune-related proteins can indirectly contribute to angiogenesis by regulating stromal cells in the tumor microenvironment. This study was performed to search biomarkers for prediction of the BEV treatment response in EOC patients. We conducted a hospital-based retrospective study from March 2013 to May 2020. Tissues from 78 Taiwanese patients who were newly diagnosed with EOC and peritoneal serous papillary carcinoma (PSPC) and received BEV therapy were collected. We used immunohistochemistry (IHC) staining and analyzed the expression of these putative biomarkers (complement component 3 (C3), complement component 5 (C5), and absent in melanoma 2 (AIM2)) based on the staining area and intensity of the color reaction to predict BEV efficacy in EOC patients. The immunostaining scores of AIM2 were significantly higher in the BEV-resistant group (RG) than in the BEV-sensitive group (SG) (355.5 vs. 297.1, p < 0.001). A high level of AIM2 (mean value > 310) conferred worse PFS after treatment with BEV than a low level of AIM2 (13.58 vs. 19.36 months, adjusted hazard ratio (HR) = 4.44, 95% confidence interval (CI) = 2.01-9.80, p < 0.001). There were no significant differences in C3 ( p = 0.077) or C5 ( p = 0.326) regarding BEV efficacy. AIM2 inflammasome expression can be a histopathological biomarker to predict the antiangiogenic therapy benefit in EOC patients. The molecular mechanism requires further investigation.

Low ankle-brachial index (ABI) and high ABI difference (ABID) are each associated with poor prognosis. No study has assessed the ability of the combination of low ABI and high ABID to predict survival. We created an ABI score by assigning 1 point for ABI < 0.9 and 1 point for ABID ≥ 0.17 and examine the ability of this ABI score to predict mortality. We included 941 patients scheduled for echocardiographic examination. The ABI was measured using an ABI-form device. ABID was calculated as |right ABI-left ABI|. Among the 941 subjects, the prevalence of ABI < 0.9 and ABID ≥ 0.17 was 6.1% and 6.8%, respectively. Median follow-up to mortality was 93 months. There were 87 cardiovascular and 228 overall deaths. All ABI-related parameters, including ABI, ABID, ABI < 0.9, ABID ≥ 0.17, and ABI score, were significantly associated with overall and cardiovascular mortality in the multivariable analysis (P ≤ 0.009). Further, in the direct comparison of multivariable models, the basic model + ABI score was the best at predicting overall and cardiovascular mortality among the five ABI-related multivariable models (P ≤ 0.049). Hence, the ABI score, a combination of ABI < 0.9 and ABID ≥ 0.17, should be calculated for better mortality prediction.

Abstract: East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the "per-label adequate-dose" treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the "off-label reduced-dose" treatment group. The mean follow-up period was 17.5 ± 13 months. The "off-label reduced-dose" group did not have a lower major bleeding rate than the "per-label adequate-dose" group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69-2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71-2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: CHA 2 DS 2 -VASc score is a useful score to evaluate the risk of stroke in patients with atrial fibrillation (AF), and it has been shown to outperform CHADS 2 score. Our recent cross-sectional study showed that CHA 2 DS 2 -VASc score was associated with an ankle-brachial index < 0.9. The aim of the current study was to evaluate whether CHA 2 DS 2 -VASc score is a useful predictor of new-onset peripheral artery occlusive disease (PAOD) and whether it can outperform CHADS 2 and R 2 CHADS 2 scores., Methods: We used the National Health Insurance Research Database to survey 723750 patients from January 1, 2000 to December 31, 2001. CHADS 2 , R 2 CHADS 2 , and CHA 2 DS 2 -VASc scores were calculated for every patient. Finally, 280176 (score 0), 307209 (score 1), 61093 (score 2), 35594 (score 3), 18956 (score 4), 11032 (score 5), 6006 (score 6), 2696 (score 7), 843 (score 8), and 145 (score 9) patients were studied and followed to evaluate new-onset PAOD. We further divided the study patients into six groups: group 1 (score 0), group 2 (score 1-2), group 3 (score 3-4), group 4 (score 5-6), group 5 (score 7-8), and group 6 (score 9)., Results: Overall, 24775 (3.4%) patients experienced new-onset PAOD during 9.8 years of follow-up. The occurrence rate of PAOD increased from 1.3% (group 1) to 23.4% (group 6). Subgroup analysis by gender also showed an association between CHA 2 DS 2 -VASc score and the occurrence rate of PAOD. After multivariate analysis, groups 2-6 were significantly associated with new-onset PAOD. CHA 2 DS 2 -VASc score also outperformed CHADS 2 and R 2 CHADS 2 scores for predicting new-onset PAOD., Conclusions: CHA 2 DS 2 -VASc score was a more powerful predictor of new-onset PAOD than CHADS 2 and R 2 CHADS 2 scores in patients without AF.

Background: Pulse wave velocity (PWV) is an excellent index of arterial stiffness and can be used to predict long-term cardiovascular (CV) outcome. In recent years, estimated PWV (ePWV), calculated by equations using age and mean blood pressure, was also reported to be a significant predictor of CV outcomes. However, there was no literature discussing about usefulness of ePWV in patients of acute myocardial infarction (AMI) for prediction of long-term CV and overall mortality. Therefore, we conducted this study for further evaluation., Methods: A total of 187 patients with AMI admitted to cardiac care unit were enrolled. ePWV were calculated by the equations for each patient., Results: The median follow-up to mortality was 73 months (25th-75th percentile: 8-174 months). There were 35 and 125 patients documented as CV and overall mortality, respectively. Under univariable analysis, ePWV could independently predict long-term CV and overall mortality. However, after multivariable analysis, ePWV could only predict long-term CV mortality in AMI patients., Conclusions: To the best of our knowledge, our study was the first to evaluate the usefulness of ePWV in AMI patients for prediction of long-term CV and overall mortality. Our study showed ePWV was not only easy to calculate by formula, but also an independent predictor for long-term CV mortality in univariable and multivariable analyses. Therefore, ePWV was a simple and useful tool to measure arterial stiffness and to predict CV mortality outcome in AMI patients without the necessity for equipment to measure PWV., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Left ventricular systolic function is a good indicator of cardiac function and a powerful predictor of adverse cardiovascular (CV) outcomes. High ratio of pre-ejection period (PEP) to ejection time (ET) is associated with reduced left ventricular systolic function. Brachial PEP (bPEP) and brachial ET (bET) can be automatically calculated from an ankle-brachial index (ABI)-form device and bPEP/bET was recently reported to be a new and useful parameter of cardiac performance. However, there were no studies evaluating the utility of bPEP/bET for prediction of CV and overall mortality in patients with acute myocardial infarction (AMI). We included 139 cases of AMI admitted to our cardiac care unit consecutively. ABI, bPEP, and bET were obtained from the ABI-form device within the 24 hours of admission. There were 87 overall and 22 CV mortality and the median follow-up to mortality event was 98 months. After multivariable analysis, high bPEP/bET was not only associated with increased long-term CV mortality (hazard ratio (HR) = 1.046; 95% confidence interval (CI): 1.005-1.088; P = 0.029), but also associated with long-term overall mortality (HR = 1.023; 95% CI: 1.001-1.045; P = 0.042). In addition, age was also a significant predictor for CV and overall mortality after the multivariable analysis. In conclusion, bPEP/bET was shown to be a significant predictor for CV and overall mortality in AMI patients after multivariable analysis. Therefore, by means of this novel parameter, we could easily find out the high-risk AMI patients with increased CV and overall mortality., Competing Interests: The authors have declared that no competing interests exist.

Pulse wave velocity (PWV) was a good marker of arterial stiffness and could predict cardiovascular (CV) outcomes. Recently, estimated PWV (ePWV) calculated by equations using age and mean blood pressure was reported to be an independent predictor of major CV events. However, there was no study comparing ePWV with brachial-ankle PWV (baPWV) for CV and overall mortality prediction. We included 881 patients arranged for echocardiographic examination. BaPWV and blood pressures were measured by ankle-brachial index-form device. The median follow-up period to mortality was 94 months. Mortality events were documented during the follow-up period, including CV mortality (n = 66) and overall mortality (n = 184). Both of ePWV and baPWV were associated with increased CV and overall mortality after the multivariable analysis. ePWV had better predictive value than Framingham risk score (FRS) for CV and overall mortality prediction, but baPWV did not. In direct comparison of multivariable analysis using FRS as basic model, ePWV had a superior additive predictive value for CV mortality than baPWV (p = .030), but similar predictive valve for overall mortality as baPWV (p = .540). In conclusion, both ePWV and baPWV were independent predictors for long-term CV and overall mortality in univariable and multivariable analysis. Besides, ePWV had a better additive predictive value for CV mortality than baPWV and similar predictive value for overall mortality as baPWV. Therefore, ePWV obtained without equipment deserved to be calculated for overall mortality prediction and better CV survival prediction., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Abnormal low and high ankle brachial index (ABI) is regarded as peripheral artery disease (PAD) which has extremely high morbidity and mortality. How to identify high-risk PAD patients with increased mortality is very important to improve the outcome. CHADS 2 , R 2 CHADS 2 , and CHA 2 DS 2 -VASc score are clinically useful scores to evaluate the annual risk of stroke in patients with atrial fibrillation. However, there was no literature discussing the usefulness of these scores for cardiovascular (CV) and all-cause mortality prediction in the patients with abnormal ABI. This longitudinal study enrolled 195 patients with abnormal low (< 0.9) and high ABI (> 1.3). CHADS 2 , R 2 CHADS 2 , and CHA 2 DS 2 -VASc score were calculated for each patient. CV and all-cause mortality data were collected for outcome prediction. The median follow-up to mortality was 90 months. After multivariate analysis, CHADS 2 , R 2 CHADS 2 , and CHA 2 DS 2 -VASc score were significant predictors of CV and all-cause mortality (all P < 0.001). CHA 2 DS 2 -VASc score had a better additive predictive value than CHADS 2 and R 2 CHADS 2 score for CV mortality prediction. R 2 CHADS 2 and CHA 2 DS 2 -VASc score had better additive predictive values than CHADS 2 score for all-cause mortality prediction. In conclusion, our study is the first study to investigate the usefulness of CHADS 2 , R 2 CHADS 2 , and CHA 2 DS 2 -VASc score for mortality prediction in patients with abnormal ABI. Our study showed all three scores are significant predictors for CV and all-cause mortality although there are some differences between the scores. Therefore, using the three scoring systems may help physicians to identify the high-risk PAD patients with increased mortality., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

No study has investigated the predictive ability of ankle-brachial index (ABI) calculated using diastolic blood pressure (DBP) (ABIdbp) and mean arterial pressure (MAP) (ABImap) for overall and cardiovascular (CV) mortality in hemodialysis (HD) patients. Our study was aimed to investigate the issue. Two hundred and seven routine HD patients were enrolled. ABI values were measured by ABI-form device. During the follow-up period (122 months), 124 of the 207 patients (59.0%) died, and 59 deaths due to CV cause. Multivariate analysis showed that low ABIsbp, ABIdbp, and ABImap were all significantly associated with increased overall ( p ≤ 0.015) and CV mortality ( p ≤ 0.015) in whole study patients. A subgroup analysis after excluding 37 patients with ABIsbp < 0.9 or > 1.3 found ABIsbp and ABIsbp < 0.9 were not associated with overall and CV mortality. However, ABImap and ABIdbp < 0.87 were significantly associated with overall mortality ( p ≤ 0.042). Furthermore, ABIdbp and ABIdbp < 0.87 were significantly associated with CV mortality ( p ≤ 0.030). In conclusion, ABIsbp, ABIdbp, and ABImap were all useful in predicting overall and CV mortality in our HD patients. In the subgroup patients with normal ABIsbp, ABIsbp and ABIsbp < 0.9 were not useful to predict overall and CV mortality. Nevertheless, ABImap and ABIdbp < 0.87 could still predict overall mortality, and ABIdbp and ABIdbp < 0.87 could predict CV mortality. Hence, calculating ABI using DBP and MAP may provide benefit in survival prediction in HD patients, especially in the patients with normal ABIsbp., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Chronic kidney disease (CKD) is a public health issue and is associated with high morbidity and mortality. How to identify the high-risk CKD patients is very important to improve the long-term outcome. CHADS 2 and CHA2DS2-VASc scores are clinically useful scores to evaluate the risk of stroke in patients with atrial fibrillation. However, there was no literature discussing about the usefulness of CHADS 2 and CHA2DS2-VASc scores for cardiovascular (CV) and all-cause mortality prediction in CKD patients. This longitudinal study enrolled 437 patients with CKD. CHADS 2 and CHA2DS2-VASc scores were calculated for each patient. CV and all-cause mortality data were collected for long-term outcome prediction. The median follow-up to mortality was 91 (25th-75th percentile: 59-101) months. There were 66 CV mortality and 165 all-cause mortality. In addition to age and heart rate, CHADS 2 and CHA 2 DS 2 -VASc scores (both P value < 0.001) were significant predictors of CV and all-cause mortality in the multivariate analysis. Besides, in direct comparison of multivariate model, basic model + CHA 2 DS 2 -VASc score had a better additive predictive value for all-cause mortality than basic model + CHADS 2 score (P = 0.031). In conclusion, our study showed both of CHADS 2 and CHA 2 DS 2 -VASc scores were significant predictors for long-term CV and all-cause mortality in CKD patients and CHA 2 DS 2 -VASc score had a better predictive value than CHADS 2 score for all-cause mortality in direct comparison of multivariate model. Therefore, using CHADS 2 and CHA 2 DS 2 -VASc scores to screen CKD patients may be helpful in identifying the high-risk group with increased mortality.

Pulmonary embolism (PE) is a potential life-threatening condition and risk-adapted diagnostic and therapeutic management conveys a favorable outcome. For patients at high risk for early complications and mortality, prompt exclusion or confirmation of PE by imaging is the key step to initiate and facilitate reperfusion treatment. Among patients with hemodynamic instability, systemic thrombolysis improves survival, whereas surgical embolectomy or percutaneous intervention are alternatives in experienced hands in scenarios where systemic thrombolysis is not the best preferred thromboreduction measure. For patients with suspected PE who are not at high risk for early complications and mortality, the organized approach using a structured evaluation system to assess the pretest probability, the age-adjusted D-dimer cut-offs, the appropriate selection of imaging tools, and proper interpretation of imaging results is important when deciding the allocation of treatment strategies. Patients with PE requires anticoagulation treatment. In patients with cancer and thrombosis, low-molecular-weight heparin (LMWH) used to be the standard regimen. Recently, three factor Xa inhibitors collectively show that non-vitamin K oral anticoagulants (NOACs) are as effective as LMWH in four randomized clinical trials. Therefore, NOACs are suitable and preferred in most conditions. Finally, chronic thromboembolic pulmonary hypertension is the most disabling long-term complication of PE. Because of its low incidence, the extra caution should be given when managing patients with PE.

A low ankle-brachial index (ABI) calculated using systolic blood pressure (SBP) (ABIsbp) is associated with poor cardiovascular outcome in patients with acute myocardial infarction (AMI). ABI is always calculated using SBP clinically. However, there was no study investigating ABI calculated using mean artery pressure (MAP)(ABImap) and diastolic blood pressure (DBP)(ABIdbp) for mortality prediction in AMI patients. Therefore, our study was aimed to investigate the issue. 199 AMI patients were enrolled. Different ABIs were measured by an ABI-form device. The median follow-up to mortality was 64 months. There were 40 cardiovascular and 137 all-cause mortality. The best cutoff values of ABImbp and ABIdbp for mortality prediction were 0.91 and 0.78, respectively. After multivariate analysis, only ABIdbp and ABIdbp < 0.78 could predict cardiovascular mortality (P ≤ .047). However, all of six ABI parameters, including ABIsbp, ABImap, ABIdbp, ABIsbp < 0.90, ABImap < 0.91, and ABIdbp < 0.78, could predict all-cause mortality (P ≤ .048). In a direct comparison of six ABI models for prediction of all-cause mortality, basic model + ABIdbp <0.78 had the highest predictive value (P ≤ .025). In conclusion, only ABIdbp and ABIdbp < 0.78 could predict cardiovascular and all-cause mortality after multivariate analysis in our study. Furthermore, when adding into a basic model, ABIdbp < 0.78 had the highest additively predictive value for all-cause mortality in the six ABI parameters. Hence, calculation of ABI using DBP except SBP might provide an extra benefit in prediction of cardiovascular and all-cause mortality in AMI patients., (© 2020 Wiley Periodicals LLC.)

Background and Aims: Low ankle-brachial index (ABI) calculated using systolic blood pressure (SBP) is associated with poor prognosis. However, there is no study assessing ABI calculated using mean artery pressure (MAP) and diastolic blood pressure (DBP) in predicting mortality., Methods: Two cohort populations were enrolled. The first population comprised 379 patients (106 patients with angiography-proved peripheral artery disease (PAD) and 273 relative normal patients) to evaluate the best cutoff values of ABImbp and ABIdbp for prediction of PAD. The second population included 941 patients undergoing echocardiographic examinations to assess the ability of different ABIs in predicting mortality. ABIs were measured using an ABI-form device., Results: The best cutoff values of ABImbp and ABIdbp for prediction of PAD were 0.92 and 0.88. In our second population, median follow-up to mortality was 93 months. There were 87 cardiovascular and 228 overall deaths. Multivariable analysis showed ABIsbp, ABImap, ABIdbp, ABIsbp <0.9, and ABImap <0.92 could predict overall and cardiovascular mortality (all p < 0.001). ABIdbp <0.88 could only predict CV mortality (p = 0.033). In a direct comparison of 6 multivariable models, the basic model consisting of significant variables in the univariable analysis plus ABImap <0.92 had the highest predictive value for overall and cardiovascular mortality (all p < 0.001)., Conclusions: In a direct comparison of 6 multivariable models, the basic model + ABImap < 0.92 was the best model in predicting overall and cardiovascular mortality. Hence, calculation of ABI using MAP except SBP might provide extra benefit in survival prediction., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Upstroke time (UT), measured from the foot-to-peak peripheral pulse wave, is a merged parameter used to assess arterial stiffness and target vascular injuries. In this study, we aimed to investigate UT for the prediction of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). This longitudinal study enrolled 472 patients with CKD. Blood pressure, brachial pulse wave velocity (baPWV), and UT were automatically measured by a Colin VP-1000 instrument. During a median follow-up of 91 months, 73 cardiovascular and 183 all-cause mortality instances were recorded. Multivariable Cox analyses indicated that UT was significantly associated with cardiovascular mortality (hazard ratio (HR) = 1.010, p = 0.007) and all-cause mortality (HR = 1.009, p < 0.001). The addition of UT into the clinical models including traditional risk factors and baPWV further increased the value in predicting cardiovascular and all-cause mortality (both p < 0.001). In the Kaplan-Meier analyses, UT ≥ 180 ms could predict cardiovascular and all-cause mortality (both log-rank p < 0.001). Our study found that UT was a useful parameter in predicting cardiovascular and all-cause mortality in CKD patients. Additional consideration of the UT might provide an extra benefit in predicting cardiovascular and all-cause mortality beyond the traditional risk factors and baPWV.

Based on clinical presentation, pathophysiology, high infectivity, high cardiovascular involvement, and therapeutic agents with cardiovascular toxicity of coronavirus disease 2019 (COVID-19), regular cardiovascular treatment is being changing greatly. Despite angiotensin-converting enzyme 2 serving as the portal for infection, the continuation of clinically indicated renin-angiotensin-aldosterone blockers is recommended according to the present evidence. Fibrinolytic therapy can be considered a reasonable option for the relatively stable ST segment elevation myocardial infarction (STEMI) patient with suspected or known COVID-19. However, primary percutaneous coronary intervention is still the standard of care in patients with definite STEMI if personal protective equipment is available and cardiac catheterization laboratory has a good infection control. In patients with elevated cardiac enzymes, it is very important to differentiate patients with Type 2 myocardial infarction or myocarditis from those with true acute coronary syndromes because invasive percutaneous intervention management in the former may be unnecessary, especially if they are hemodynamically stable. Finally, patients with baseline QT prolongation or those taking QT prolonging drugs must be cautious when treating with lopinavir/ritonavir and hydroxychloroquine for COVID-19., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Four-limb blood pressure measurement could improve mortality prediction in the elderly. However, there was no study to evaluate whether such measurement was still useful in predicting overall and cardiovascular (CV) mortality in acute myocardial infarction (AMI). Two hundred AMI patients admitted to cardiac care unit were enrolled. The 4-limb blood pressures, inter-limb blood pressure differences, and ankle brachial index (ABI) were measured using an ABI-form device. The median follow-up to mortality was 64 months (25th-75th percentile: 5-174 months). There were 40 and 138 patients documented as CV and overall mortality, respectively. After multivariable adjustment, the ankle diastolic blood pressure (DBP) on the lower side, ABI value, ABI < 0.9, interarm DBP difference, interankle systolic blood pressure (SBP) and DBP differences, interankle SBP difference ≥ 15 mmHg, and interankle DBP difference ≥ 10 mmHg could predict overall mortality (P ≤ 0.025). The ankle DBP on the lower side, interankle DBP difference, and interankle DBP difference ≥ 10 mmHg could predict CV mortality (P ≤ 0.031). In addition, in the Nested Cox model, the model including the ankle DBP on the lower side and the model including interankle DBP difference had the best value for overall and CV mortality prediction, respectively (P ≤ 0.031). In AMI patients, 4-limb blood pressure measurement could generate several useful parameters in predicting overall and CV mortality. Furthermore, ankle DBP on the lower side and interankle DBP difference were the most powerful parameters in prediction of overall and CV mortality, respectively., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Atherosclerotic cardiovascular disease (ASCVD) including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contributes to the major causes of death in the world. Although several studies have evaluated the association between gender and major adverse cardiovascular outcomes in old ASCVD patients, the result is not consistent. Hence, we need a large-scale study to address this issue.This retrospective cohort study included aged over 60 year-old patients with a diagnosis of ASCVD, including CVD, CAD, or PAD, from the database contained in the Taiwan National Health Insurance Bureau during 2001 to 2004. The matched cohort was matched by age, comorbidities, and medical therapies at a 1:1 ratio. A total of 9696 patients were enrolled in this study, that is, there were 4848 and 4848 patients in the matched male and female groups, respectively. The study endpoints included acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, in-hospital mortality, and so on. In multivariate Cox regression analysis in matched cohort, the adjusted hazard ratios (HRs) for female group in predicting acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, and in-hospital mortality were 0.67 (P < .001), 0.73 (P = .0015), 0.78 (P < .001), 0.59 (P < .001), and 0.77 (P = .0007), respectively.In this population-based propensity matched cohort study, age over 60 year-old female patients with ASCVD were associated with lower rates of acute myocardial infarction, hemorrhagic stroke, ischemic stroke, vascular procedures, and in-hospital mortality than male patients. Further prospective studies may be investigated in Taiwan.

In non-haemodialysis (HD) patients, increased epicardial adipose tissue (EAT) thickness was significantly associated with adverse cardiovascular (CV) events. This study was designed to investigate whether EAT thickness was a useful parameter in the prediction of adverse CV events in HD patients. In addition, we also evaluated the major correlates of EAT thickness in these patients. In 189 routine HD patients, we performed a comprehensive transthoracic echocardiographic examination with assessment of EAT thickness. The definition of CV events included CV death, non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease, and hospitalization for heart failure. The follow-up period for CV events was 2.5 ± 0.7 years. Thirty-one CV events were documented. The multivariable analysis demonstrated that older age, smoking status, the presence of diabetes mellitus and coronary artery disease, and low albumin levels were independently correlated with adverse CV events. However, increased EAT thickness was not associated with adverse CV events (P = 0.631). Additionally, older age, female sex, low haemoglobin, and low early diastolic mitral annular velocity were correlated with high EAT thickness in the univariable analysis. In the multivariable analysis, older age and female sex were still correlated with high EAT thickness. In conclusion, high EAT thickness was associated with older age and female sex in the multivariable analysis in our HD patients. However, EAT thickness was not helpful in predicting adverse CV events in such patients. Further large-scale studies are necessary to verify this finding.

Background: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. How to simply predict mortality for AMI patients is important because the appropriate treatment should be done for the patients with higher risk. Recently, a novel parameter of upstroke time per cardiac cycle (UTCC) in lower extremities was reported to be a good predictor of peripheral artery disease and mortality in elderly. However, there was no literature discussing the usefulness of UTCC for prediction of cardiovascular (CV) and overall mortality in AMI patients. Methods: 184 AMI patients admitted to the cardiac care unit were enrolled. Ankle-brachial index (ABI) and UTCC were measured by an ABI-form device in the same day of admission. Results: The median follow-up to mortality was 71 months. There were 36 CV and 124 overall mortality. Higher UTCC was associated with increased CV and overall mortality after multivariable analysis ( P = 0.033 and P < 0.001, respectively). However, ABI was only associated with CV mortality and overall mortality in the univariable analysis but became insignificant after the multivariable analysis. In addition, after adding UTCC into a basic model including important clinical parameters, left ventricular ejection fraction, Charlson comorbidity index, and ABI, we found the basic model + UTCC had a better predictive value for overall mortality than the basic model itself ( P < 0.001). Conclusion s : Our study is the first one to evaluate the usefulness of UTCC in AMI patients for prediction of long-term mortality. Our study showed UTCC was an independent predictor of long-term CV and overall mortality and had an additive predictive value for overall mortality beyond conventional parameters. Therefore, screening AMI patients by UTCC might help physicians to identify the high-risk group with increased mortality., Competing Interests: The authors have declared no competing interest exists.

A large interarm and interleg systolic blood pressure (SBP) difference and ankle-brachial index (ABI) <0.9 were associated with peripheral artery disease and left ventricular hypertrophy. These 3 parameters were derived from 4-limb SBP data. However, there is no study to assess clinical significance of SBP heterogeneity in 4 limbs. The aim of this study was to evaluate the association of 4-limb SBP standard deviation (SD) with peripheral vascular parameters and echocardiographic data in patients with or without clinical findings of peripheral artery disease.A total of 1240 patients were included, of whom 1020 had no clinical evidence of overt peripheral artery disease. The 4-limb blood pressures, brachial-ankle pulse wave velocity, and ABI were measured simultaneously by an ABI-form device.In the multivariable linear regression analysis, increased left ventricular mass index (LVMI), ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg (P ≤ .030) were associated with increased 4-limb SBP SD. Additionally, a subgroup multivariable linear regression analysis in 1020 patients without ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg found 4-limb SBP SD still had a positive correlation with LVMI (P < .001).In addition to significant association with ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg, 4-limb SBP SD was positively correlated with LVMI in the multivariable linear regression analysis in all study patients. Furthermore, in the subgroup of patients without clinical evidence of peripheral artery disease, 4-limb SBP SD still had a positive correlation with LVMI. Hence, assessment of 4-limb SBP heterogeneity is useful in identification of high-risk group of peripheral artery disease and/or increased LVMI, irrespective of the presence of overt peripheral artery disease.

The ratio of transmitral E-wave velocity (E) to a left ventricular diastolic parameter is reported to be well correlated with left ventricular filling pressure and is useful in the prediction of mortality. Left atrial (LA) strain has been demonstrated to be associated with left ventricular diastolic function. The aim of the study is to examine the ability of E/LA strain in predicting total and cardiovascular mortality in hemodialysis (HD) patients. In 197 routine HD patients, global LA strain during the reservoir phase was estimated by taking the average of longitudinal strain data obtained from the apical four-chamber and two chamber views by two-dimensional speckle tracking echocardiography. Twenty-nine total mortality and 14 cardiovascular mortality were documented during the 2.7 ± 0.6-year follow-up. After adjusting age, comorbidities, albumin, E/early diastolic mitral annular velocity (Ea), and LA strain, increased E/LA strain (hazard ratio (HR) = 1.191, 95% confidence interval (CI) = 1.072-1.324, p = 0.001) was still associated with increased total mortality. After adjusting age, comorbidities, albumin, E/Ea, left ventricular ejection fraction, and LA strain, increased E/LA strain (HR = 1.195, 95% CI = 1.041-1.372, p = 0.011) was still associated with increased cardiovascular mortality. In conclusion, E/LA strain is a useful parameter in the prediction of total and cardiovascular mortality in HD patients. Hence, E/LA strain deserves to be calculated in HD patients for better survival prediction.

Stumpless chronic total occlusion is associated with a higher failure rate of recanalization. Intravascular ultrasound (IVUS) is useful for identifying the entry point; however, 8-F guide catheters are necessary for real-time IVUS-guided wiring. This case reports the novel use of the "ping-pong" guide catheter technique to facilitate real-time IVUS-guided wiring for a stumpless chronic total occlusion. ( Level of Difficulty: Advanced. )., (© 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: Left ventricular ejection fraction (LVEF) is a good indicator of cardiac function, and brachial-ankle pulse wave velocity (baPWV) is a good indicator of vascular function. Both of them can predict cardiovascular (CV) outcomes. Objectives: There is scarce literature discussing the impact of simultaneous consideration of cardiac and vascular function on overall and CV mortality. Methods: We included 958 patients and classified them into four groups. Groups 1 to 4 were patients with LVEF ≥ 50% and baPWV below the median, LVEF < 50% but baPWV below the median, LVEF ≥ 50% but baPWV above the median, and LVEF < 50% and baPWV above the median, respectively. Results: The median follow-up to mortality was 93 (25th-75th percentile: 69-101) months. There were 91 cases of CV mortality and 238 cases of all-cause mortality. After multivariable analysis, age, gender, diabetes, mean blood pressure, group 2 versus group 1, and group 4 versus group 1 were significant predictors of all-cause mortality ( P ≤ 0.038) and age, diabetes, mean blood pressure, group 2 versus group 1, and group 4 versus group 1 were significant predictors of CV mortality ( P ≤ 0.008). Conclusions: Patients with higher LVEF and lower baPWV had a similar overall and CV mortality as patients with higher LVEF and baPWV. Patients with lower LVEF and higher baPWV had the highest overall and CV mortality among the four study groups. In addition, patients with lower LVEF alone had a higher CV mortality than the patients with higher baPWV alone. Therefore, simultaneous consideration of cardiac and vascular function may be useful in predicting overall and CV mortality.

Pulse volume recording is an accurate modality for detecting arterial occlusion in the lower extremities. There are two indexes of pulse volume recording measured at ankle, percentage of mean arterial pressure (%MAP) and upstroke time (UT). The aim of the study was to examine the ability of %MAP and UT for the prediction of overall and cardiovascular mortality in hemodialysis (HD) patients. In 197 routine HD patients, ankle %MAP, ankle UT, and ankle-brachial index (ABI) were automatically measured by Colin VP-1000 instrument. Fourteen cardiovascular mortality and 29 overall mortalities were documented during 2.7 ± 0.6 years follow-up. In the univariate analysis, in addition to co-morbidities and traditional clinical parameters, increased total mortality was associated with decreased ABI, ABI < 0.9, increased %MAP and UT, %MAP > 50%, and UT > 169 ms (p < 0.041) and increased cardiovascular mortality was associated with increased UT and %MAP > 50% (p < 0.022). After multivariate analysis, increased %MAP and %MAP > 50% (p < 0.047) were still the predictors of total mortality and %MAP > 50% (p = 0.024) was still the predictor of cardiovascular mortality. In HD patients, we found that ankle %MAP and %MAP > 50% could predict total mortality and ankle %MAP > 50% could predict cardiovascular mortality in the multivariate analysis. Hence, assessment of %MAP from pulse volume recording at ankle might be helpful in identifying the high-risk group for poor prognosis in HD patients., Competing Interests: The authors declare no other conflict of interest.

Background: Secondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, β-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan., Methods: This national population-based cohort study was conducted by analyzing the Longitudinal Health Insurance Database 2000 from the National Health Insurance Research Database of Taiwan. Patients who underwent CABG or PCI from 2004 to 2009 were included in the analysis. The baseline characteristics of the patients and ACC/AHA class I medication use at 12 months were analyzed. The primary endpoints were a composite of major adverse cardiac and cerebrovascular events., Results: A total of 5544 patients comprising 895 CABG and 4649 PCI patients were evaluated. CABG patients had more comorbidities and a higher rate of major adverse event during the follow-up period. However, use of antiplatelet agents and RASB at 12 months was significantly lower in CABG patients than in PCI patients (44.2% vs. 50.9% and 38.6% vs. 48.9%, both p < 0.01). Age, diabetes, and chronic kidney disease were independent risk factors while statin use was a protective factor for the primary endpoints in both PCI and CABG groups., Conclusion: There is still much room to improve class I medication use in secondary prevention for patients after revascularization in Taiwan. Statin could be an effective treatment to improve the outcomes., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Although novel oral-anticoagulants are widely used in patients with atrial fibrillation (AF) for stroke prevention, there was only limited evidence for their use in left ventricular (LV) thrombus., Patient Concerns: A 41-year-old man who presented with acute onset of right-hand clumsiness and aphasia even under high international normalized ratio (INR: 7.64) from warfarin use. He was previously treated with warfarin for the LV thrombus and non-valvular AF. Brain magnetic resonance imaging (MRI) showed multiple acute infarction in the cortex of the bilateral frontal lobes, left parietal lobe, and bilateral central semiovale, which highly suggested embolic stroke., Diagnosis: The repeated transthoracic echocardiogram still revealed LV thrombus (1.27 × 0.90 cm), which failed to respond to warfarin therapy., Interventions: Due to acute infarctions occurred under supratherapeutic range of INR, we switched warfarin to edoxaban (dose: 60 mg/day) after INR decreased to less than 2., Outcomes: The thrombus disappeared after receiving edoxaban for 23 days, and no more recurrent stroke was noted for more than 6 months., Lessons: This is the first case demonstrates that while facing ineffective treatment of warfarin for LV thrombus, edoxaban could be safely and effectively used under this situation.