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Osteopontin (OPN) is a noncollagenous matricellular protein which is mainly present in bone matrix. A high OPN level has been associated with heart failure and acute coronary syndrome, however data on patients with chronic coronary syndrome (CCS) are lacking. The present study aimed to evaluate the association between OPN and the prognosis of Taiwanese patients with CCS.We enrolled participants from the Biosignature Registry, a nationwide prospective cohort study conducted at nine different medical centers throughout Taiwan. The inclusion criteria were participants who had received successful percutaneous coronary intervention at least once previously, and stable under medical therapy for at least 1 month before enrollment. They were followed for at least 72 months. Logistic regression and Cox proportional hazard model were used to investigate the association between OPN and clinical outcomes. The outcomes of this study were the first occurrence of hard cardiovascular events and composite cardiovascular outcomes including cardiovascular mortality, revascularization, hospitalization for acute myocardial infarction (AMI) or heart failure.A total of 666 patients with both hs-CRP and osteopontin measurements were enrolled and followed for 72 months. OPN was correlated positively with AMI-related hospitalization, where the highest tertile (Tertile 3) of baseline OPN had the highest risk of AMI-related hospitalization, which remained significant after multivariate adjustments (HR 3.20, p = 0.017). In contrast, combining OPN and hs-CRP did not improve the prediction of CV outcomes.OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

This phase 4 study evaluated the efficacy and safety of azilsartan medoxomil (AZL-M) in patients with essential hypertension and type 2 diabetes mellitus (T2DM) in Hong Kong, Taiwan, and Thailand. This was a prospective, multicenter, single-arm, open-label study with patients aged 18–75 years with T2DM and essential hypertension and on stable treatment for T2DM. Patients with uncontrolled hypertension were treated with AZL-M 40 mg daily, with the option to uptitrate to 80 mg at 6 weeks. In all, 380 of the 478 patients screened in Hong Kong, Taiwan, and Thailand were enrolled. At week 6, 97 patients (25.5%) were titrated up to AZL-M 80 mg based on BP readings. At 12 weeks, 54.8% of patients reached the blood pressure (BP) goal of

Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.

BackgroundAcute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization.ObjectivesThis phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention.MethodsConsenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period.ResultsEight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline.ConclusionThis pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

ObjectiveTo implement an all-day online artificial intelligence (AI)-assisted detection of ST-elevation myocardial infarction (STEMI) by prehospital 12-lead electrocardiograms (ECGs) to facilitate patient triage for timely reperfusion therapy.MethodsThe proposed AI model combines a convolutional neural network and long short-term memory (CNN-LSTM) to predict STEMI on prehospital 12-lead ECGs obtained from mini-12-lead ECG devices equipped in ambulance vehicles in Central Taiwan. Emergency medical technicians (EMTs) from the 14 AI-implemented fire stations performed the on-site 12-lead ECG examinations using the mini portable device. The 12-lead ECG signals were transmitted to the AI center of China Medical University Hospital to classify the recordings as “STEMI” or “Not STEMI”. In 11 non-AI fire stations, the ECG data were transmitted to a secure network and read by available on-line emergency physicians. The response time was defined as the time interval between the ECG transmission and ECG interpretation feedback.ResultsBetween July 17, 2021, and March 26, 2022, the AI model classified 362 prehospital 12-lead ECGs obtained from 275 consecutive patients who had called the 119 dispatch centers of fire stations in Central Taiwan for symptoms of chest pain or shortness of breath. The AI's response time to the EMTs in ambulance vehicles was 37.2 ± 11.3 s, which was shorter than the online physicians' response time from 11 other fire stations with no AI implementation (113.2 ± 369.4 s, P < 0.001) after analyzing another set of 335 prehospital 12-lead ECGs. The evaluation metrics including accuracy, precision, specificity, recall, area under the receiver operating characteristic curve, and F1 score to assess the overall AI performance in the remote detection of STEMI were 0.992, 0.889, 0.994, 0.941, 0.997, and 0.914, respectively. During the study period, the AI model promptly identified 10 STEMI patients who underwent primary percutaneous coronary intervention (PPCI) with a median contact-to-door time of 18.5 (IQR: 16–20.8) minutes.ConclusionImplementation of an all-day real-time AI-assisted remote detection of STEMI on prehospital 12-lead ECGs in the field is feasible with a high diagnostic accuracy rate. This approach may help minimize preventable delays in contact-to-treatment times for STEMI patients who require PPCI.

Despite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19.Hospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaOFour out of eight patients with severe or critical COVID-19 received either one (Transplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.

Whether pharmaco-mechanical thrombolysis (PMT) results in superior outcomes to catheter-directed thrombolysis (CDT) in treating thrombotic or embolic arterial occlusion of the lower limbs is unclear.We enrolled 94 patients with Rutherford class I-IIb due to thrombotic or embolic arterial occlusion in the lower limbs and who received emergency endovascular treatment. Baseline demographics, laboratory data, angiography and clinical outcomes were collected through chart reviews and fluoroscopic imaging. The procedural characteristics (thrombolytic drug dosage, treatment duration, and additional procedures), immediate angiographic outcomes (patency of calf vessels, and complete lysis), complications (major bleeding, and fasciotomy), and primary composite end-points (30-day mortality, amputation, and reocclusion) were compared between patients who received CDT versus PMT.Compared with CDT, PMT was independently associated with lower total UK dosage (standardized coefficient β=- 0.44; P0.01) and higher prevalence of complete lysis (odds ratio =1.78, 95% confidence interval: 1.03-3.06; P=0.04) after adjustments of covariates. The PMT group had significantly shorter treatment duration (23.00 [7.25-39.13] vs. 41.00 [27.00-52.50]; P0.01). No significant intergroup differences were observed for the primary composite end point (10.7% vs. 9.1%; P=0.81), or prevalence of the major bleeding (9.1% vs. 0.0%; P=0.10) despite the PMT group comprising patients with more advanced chronic kidney disease and more diffuse thrombosis.PMT with a Rotarex is a safe and effective strategy for treating thrombotic or embolic lower limb ischemia. It significantly reduced the thrombolytic drug dosage, and resulted in the complete lysis being more likely.

The nuance of autonomic cardiac control has been studied for more than 400 years, yet little is understood. This review aimed to provide a comprehensive overview of the current understanding, clinical implications, and ongoing studies of cardiac sympathetic modulation and its anti-ventricular arrhythmias’ therapeutic potential. Molecular-level studies and clinical studies were reviewed to elucidate the gaps in knowledge and the possible future directions for these strategies to be translated into the clinical setting. Imbalanced sympathoexcitation and parasympathetic withdrawal destabilize cardiac electrophysiology and confer the development of ventricular arrhythmias. Therefore, the current strategy for rebalancing the autonomic system includes attenuating sympathoexcitation and increasing vagal tone. Multilevel targets of the cardiac neuraxis exist, and some have emerged as promising antiarrhythmic strategies. These interventions include pharmacological blockade, permanent cardiac sympathetic denervation, temporal cardiac sympathetic denervation, etc. The gold standard approach, however, has not been known. Although neuromodulatory strategies have been shown to be highly effective in several acute animal studies with very promising results, the individual and interspecies variation between human autonomic systems limits the progress in this young field. There is, however, still much room to refine the current neuromodulation therapy to meet the unmet need for life-threatening ventricular arrhythmias.

Aims To develop an artificial intelligence-based approach with multi-labelling capability to identify both ST-elevation myocardial infarction (STEMI) and 12 heart rhythms based on 12-lead electrocardiograms (ECGs). Methods and results We trained, validated, and tested a long short-term memory (LSTM) model for the multi-label diagnosis of 13 ECG patterns (STEMI + 12 rhythm classes) using 60 537 clinical ECGs from 35 981 patients recorded between 15 January 2009 and 31 December 2018. In addition to the internal test above, we conducted a real-world external test, comparing the LSTM model with board-certified physicians of different specialties using a separate dataset of 308 ECGs covering all 13 ECG diagnoses. In the internal test, the area under the curves (AUCs) of the LSTM model in classifying the 13 ECG patterns ranged between 0.939 and 0.999. For the external test, the LSTM model for multi-labelling of the 13 ECG patterns evaluated by AUC was 0.987 ± 0.021, which was superior to those of cardiologists (0.898 ± 0.113, P Conclusions We demonstrated the usefulness of an LSTM model in the multi-labelling detection of both rhythm classes and STEMI in competitive testing against board-certified physicians. This AI tool exceeding the cardiologist-level performance in detecting STEMI and rhythm classes on 12-lead ECG may be useful in prioritizing chest pain triage and expediting clinical decision-making in healthcare.

Background Deep-learning algorithms to annotate electrocardiograms (ECGs) and classify different types of cardiac arrhythmias with the use of a single-lead ECG input data set have been developed. It remains to be determined whether these algorithms can be generalized to 12-lead ECG-based rhythm classification. Methods We used a long short-term memory (LSTM) model to detect 12 heart rhythm classes with the use of 65,932 digital 12-lead ECG signals from 38,899 patients, using annotations obtained by consensus of 3 board-certified electrophysiologists as the criterion standard. Results The accuracy of the LSTM model for the classification of each of the 12 heart rhythms was ≥ 0.982 (range 0.982-1.0), with an area under the receiver operating characteristic curve of ≥ 0.987 (range 0.987-1.0). The precision and recall ranged from 0.692 to 1 and from 0.625 to 1, respectively, with an F1 score of ≥ 0.777 (range 0.777-1.0). The accuracy of the model (0.90) was superior to the mean accuracies of internists (0.55), emergency physicians (0.73), and cardiologists (0.83). Conclusions We demonstrated the feasibility and effectiveness of the deep-learning LSTM model for interpreting 12 common heart rhythms according to 12-lead ECG signals. The findings may have clinical relevance for the early diagnosis of cardiac rhythm disorders.

Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.

We investigated the prognostic value of tenascin-C in patients with stable coronary heart disease.A total of 666 patients were enrolled and followed for 72 months. The primary outcome was a composite of cardiac events. The secondary outcomes were all-cause death, cardiovascular death, acute myocardial infarction (AMI), and heart failure hospitalization.The area under the curve of tenascin-C to discriminate the occurrence of composite cardiac events was 70 % (95 % CI: 64.2 % to 75.8 %), and the corresponding optimal cutoff value was 19.91 ng/ml. A higher concentration of tenascin-C was associated with a greater risk of composite cardiac events (P trend 0.001). Similar results were observed in all-cause death, AMI, and heart failure hospitalization.Tenascin-C was found to be an independent predictor of total cardiovascular events in patients with stable coronary heart disease at 72 months, and also for all-cause death, AMI, and heart failure hospitalization.

A routine change in the automatic capture management algorithm from “adaptive” to “off or monitor” is required to conserve device longevity in a permanent pacemaker with His‐bundle pacing.

Background/Purpose: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. Methods: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. Results: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. Conclusion: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type. Keywords: Atrial fibrillation, Dronedarone, Observational, Safety, Quality of life

Background: Pneumoconiosis (PCN) has several comorbidities, most notably pulmonary and cardiovascular diseases. However, much is still unknown about the relationship between PCN and acute myocardial infarction (AMI). The present study aimed to clarify the association between PCN and subsequent AMI risk using a retrospective cohort study design. Methods: This was a population-based, retrospective cohort study that used data from Taiwan’s National Health Insurance Database. A total of 7556 newly diagnosed patients with PCN and 7556 individuals without PCN were included in the PCN and comparison cohort (PC and CC), respectively, between 2008 and 2018, with propensity score matching for age, gender, comorbidity, medication, and date of PCN diagnosis. The occurrence of AMI was monitored until the end of 2019, and AMI risk was assessed using Cox proportional hazard regression models. Results: The overall incidence of AMI was 1.34-fold higher in the PC than in the CC (4.33 vs. 3.23 per 1000 person-years, respectively, p < 0.05), with an adjusted hazard ratio (aHR) of 1.36 (95% confidence interval (CI): 1.08–1.72) after controlling for age, gender, comorbidity, and medication. Further analyses showed a higher risk of AMI with increased annual number of emergency department visits among patients with PCN (aHR: 1.30, 95% CI: 1.01–1.66 (

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

To implement an all-day artificial intelligence (AI)-based system to facilitate chest pain triage in the emergency department.The AI-based triage system encompasses an AI model combining a convolutional neural network and long short-term memory to detect ST-elevation myocardial infarction (STEMI) on electrocardiography (ECG) and a clinical risk score (ASAP) to prioritize patients for ECG examination. The AI model was developed on 2907 twelve-lead ECGs: 882 STEMI and 2025 non-STEMI ECGs.Between November 1, 2019, and October 31, 2020, we enrolled 154 consecutive patients with STEMI: 68 during the AI-based triage period and 86 during the conventional triage period. The mean ± SD door-to-balloon (D2B) time was significantly shortened from 64.5±35.3 minutes to 53.2±12.7 minutes (P=.007), with 98.5% vs 87.2% (P=.009) of D2B times being less than 90 minutes in the AI group vs the conventional group. Among patients with an ASAP score of 3 or higher, the median door-to-ECG time decreased from 30 minutes (interquartile range [IQR], 7-59 minutes) to 6 minutes (IQR, 4-30 minutes) (P.001). The overall performances of the AI model in identifying STEMI from 21,035 ECGs assessed by accuracy, precision, recall, area under the receiver operating characteristic curve, F1 score, and specificity were 0.997, 0.802, 0.977, 0.999, 0.881, and 0.998, respectively.Implementation of an all-day AI-based triage system significantly reduced the D2B time, with a corresponding increase in the percentage of D2B times less than 90 minutes in the emergency department. This system may help minimize preventable delays in D2B times for patients with STEMI undergoing primary percutaneous coronary intervention.

Objective— Basic research indicates that TNFSF14 (tumor necrosis factor superfamily 14) may be involved in the pathogenesis of atherosclerosis. Given the requirements of new biomarkers for risk classification in coronary artery disease (CAD), we conducted a longitudinal analysis to investigate if TNFSF14 levels are associated with the risk of cardiovascular events among patients with stable CAD. Approach and Results— In total, 894 patients with CAD were enrolled in a multicenter prospective study. The primary outcome was the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. The secondary outcome was the occurrence of all-cause death, nonfatal myocardial infarction, stroke, revascularization, and hospitalization because of angina or heart failure. During the mean follow-up period of 22±9 months, 32 patients reached the primary outcome and 166 patients reached the secondary outcome. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first and fourth quartile groups in subjects categorized by TNFSF14 levels. In multivariate Cox proportional hazard regression analysis, TNFSF14 was independently associated with the risk of cardiovascular events after adjustment for various relevant factors (adjusted hazard ratio, 1.14; 95% CI, 1.04–1.25). In the validation cohort of 126 multivessel patients with CAD, TNFSF14 was confirmed to provide good prognostic predictive value for composite cardiovascular events (adjusted hazard ratio, 1.11; 95% CI, 1.04–1.19). Conclusions— This is the first study to demonstrate that increased TNFSF14 levels were independently associated with the occurrence of cardiovascular events in patients with stable CAD. Future studies are worthy to validate if TNFSF14 could be a novel prognostic biomarker for CAD outcomes over different populations.

Background: Some personality types are associated with cardiovascular (CV) diseases and may be related to clinical outcomes in coronary artery disease (CAD). This study investigates the association between type D personality and clinical outcomes in stable CAD patients in an Asian cohort. Methods: Stable CAD patients were enrolled and prospectively followed up for at least 1 year in Taiwan. The inclusion criteria were at least one successful percutaneous coronary intervention (PCI) and stable medical treatment for at least 1 month before enrollment. Vulnerability to psychological distress was measured by the Type D Personality Scale (DS14) after enrollment. The end point was the occurrence of total CV events. Cox regression models of CV events were used to investigate the role of type D personality in clinical outcomes. Results: The study included 777 patients, among which 122 (15.77%) had type D personality. Forty-two CV events were identified: 3 cardiac deaths, 5 nonfatal myocardial infarctions, 1 stroke, 4 congestive heart failures (CHF), 6 peripheral arterial occlusive disorder cases, and 23 readmissions for angina/revascularization treatment. Patients with type D personality had significantly higher incidence of future CV events (9.84% vs. 4.58%, p = 0.018%) and admission for angina/revascularization (5.74% vs. 2.44%, p = 0.049). Patients with subsequent CV events were more likely to have type D personality (28.57% vs. 14.97%, p=0.018). After proportional Cox regression analysis, type D personality remained an independent predictor of future CV events (HR: 3.21, 95% CI: 1.06–9.69). In subgroup analyses, type D personality was especially associated with higher risk of total CV events among females, the elderly, hypertension patients, diabetes patients, and non-smokers. Conclusion: Type D personality was an independent predictor of CV outcomes in an Asian cohort of stable CAD patients. This personality type may be identified in risk stratification for secondary prevention after PCI. Keywords: Type D personality, Coronary artery disease

BACKGROUND Lifestyle modification is suggested for patients with coronary artery disease (CAD), but the impact of adherence to a healthy lifestyle remains undetermined. The aim of this study is to investigate the association of adherence to a healthy lifestyle with future outcomes and biochemical markers in CAD patients. METHODS The Biosignature CAD study examined 716 CAD patients who underwent a percutaneous coronary intervention (PCI). Information was collected on whether these patients adhered to a healthier lifestyle after PCI, including healthy diet, not smoking, and exercise. The clinical outcomes included major cardiovascular events and unplanned revascularization procedures, hospitalization for refractory or unstable angina, and other causes. RESULTS The average follow-up period was 26.8 ± 8.1 months, during which 175 (24.4%) patients experienced at least one event. The combination of healthy lifestyle factors was associated with lower risk, and the maximum risk reduction reached 50% (hazard ratio: 0.50, 95% confidence interval: 0.25-0.99). As the number of healthy lifestyle factors increased, there were decreases in inflammatory markers, C-reactive protein, waist circumference, low-density lipoprotein cholesterol, and the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (p < 0.05). The benefits of modifiable healthy lifestyle factors were especially observed in the younger population, males, patients with HDL

Background Whether a sex difference exists in long-term cardiovascular (CV) outcomes after acute myocardial infarction (AMI) is worth exploration. This study is sought to investigate the relationships among sex, age and the long-term prognosis after AMI. Methods This population-based retrospective cohort study used Taiwan's National Health Insurance Research Database (NHIRD) to investigate the sex differences in in-hospital and long-term CV outcomes in patients with AMI. We enrolled patients who were first diagnosed with AMI from January 1, 2000 to December 31, 2013. The outcomes of interest included all-cause mortality, CV death, nonfatal stroke, nonfatal heart failure, and AMI recurrence during hospitalization and 5-year follow up. The CV outcomes were also analyzed by age stratification. Results Overall, 201,921 patients with AMI were analyzed; 68.72% were men and 31.28% were women, with mean ages of 65.34 ± 14.12 and 73.05 ± 12.22 years, respectively. Major adverse cardiac events (MACE) during hospitalization and up to 5 years were consistently greater in women than in men. Multivariable regression analysis revealed no sex difference existed in long-term all-cause and CV mortality. Men of all age groups consistently showed higher risk of both short- and long-term recurrence of AMI. Nonetheless, the female sex still independently predicted increased risk of nonfatal stroke and heart failure from hospitalization until 3-year follow up. Conclusion Women with AMI had poorer short-term and long-term outcomes. The sex differences in long-term all-cause and CV death disappear after multivariate analysis. Nonetheless, female AMI patients independently predicted higher risk of stroke and heart failure from hospitalization until a 3-year follow-up. To better understand the pathophysiology of female patients with AMI and develop more effective management, more studies in this field are necessary in the future.

BACKGROUND: Premature ventricular complexes (PVC) may cause ventricular dyssynchrony and lead to left atrium and ventricle mechanical abnormalities. Although ventricular cardiomyopathy due to PVCs has been well studied, little is known about atrial adaptation to PVCs. OBJECTIVES: To assess atrial and ventricular responses to PVC therapy. METHODS: All patients with PVC burden > 5000 beats/day on Holter monitoring were enrolled. Baseline demographics, comorbidities, social habits, Holter parameters, and echocardiography profiles were recorded. Follow-up Holter electrocardiography (ECG) and echocardiography data were compared between PVC-treated and non-treated patients. RESULTS: Two hundred and eighty-six patients were enrolled, of whom 139 received PVC treatment. Among the treated patients, 125 who underwent follow up Holter ECG or echocardiography were included in the final analysis. The mean follow-up times of Holter ECG and echocardiography were 9.40 ± 6.70 and 9.40 ± 5.52 months, respectively. Ventricular arrhythmic burden was significantly reduced in the treatment group (16.46% vs. 13.41%, p = 0.041) but was significantly increased in the observation group (7.58% vs. 14.95%, p = 0.032). A significant increase in left atrial (LA) diameter (36.94 mm vs. 39.46 mm, p = 0.025) and reduction in left ventricular ejection fraction (LVEF) (57.26% vs. 53.8%, p = 0.040) were noted in the observation group. There were no significant differences in supraventricular arrhythmic burden in the observation group and LA diameter and LVEF in the treatment group. CONCLUSIONS: PVC therapy effectively reduced ventricular arrhythmic burden in the treatment group on follow-up. Our data suggest that PVC treatment may prevent LA dilation and LVEF decline.

OBJECTIVES: Endovascular therapy with ultrasound-assisted catheter-directed thrombolysis (UACDT) theoretically provides higher efficacy while reducing the bleeding risk compared with conventional systemic thrombolysis. The clinical outcomes of UACDT in treating intermediate-to-high-risk pulmonary embolism (PE) are lacking in an Asian population. METHODS: Forty-two patients who presented with intermediate-to-high-risk PE received UACDT. The patients were divided into two groups based on the incidence of procedure-related bleeding events, and baseline demographics were compared between the two groups. A paired-Student’s t test was conducted to evaluate the efficacy of UACDT. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for significant bleeding events. RESULTS: The average age was 58.93 ± 20.48 years, and 33.33% of the study participants were male. A total of 85.7% of the participants had intermediate-risk PE. Compared with pre-intervention pulmonary artery pressure, the mean pulmonary artery pressure decreased significantly (37.61 ± 9.57 mmHg vs. 25.7 ± 9.84 mmHg, p < 0.01) after UACDT. The cumulative total tissue plasminogen activator dosage and total infusion duration were 44.54 ± 20.55 mg and 39.14 ± 19.06 hours respectively. Overall, 21.43% of the participants had severe bleeding events during the endovascular fibrinolysis treatment period. Forward conditional multivariate logistic regression analysis revealed that the lowest fibrinogen level during thrombolysis was an independent factor associated with moderate-to-severe bleeding (odds ratio: 0.40, 95% confidence interval: 0.19-0.88, p = 0.02). CONCLUSIONS: UACDT exhibited high efficacy, but resulted in a higher-than-expected bleeding rate in this real-world study of an Asian population. The lowest fibrinogen level during thrombolysis was an independent risk factor associated with procedure-related bleeding events.

The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. The total diabetic population is expected to increase from 415 million in 2015 to 642 million by 2040. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of patients with type 2 diabetes died of ASCVD. The association between hyperglycemia and elevated cardiovascular (CV) risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction by conventional antidiabetic agents did not significantly reduce macrovascular outcomes.In December 2008, U.S. Food and Drug Administration issued a mandate that every new antidiabetic agent requires rigorous assessments of its CV safety. Thereafter, more than 200,000 patients have been enrolled in a number of randomized controlled trials (RCTs). These trials were initially designed to prove noninferiority. It turned out that some of these trials demonstrated superiority of some new antidiabetic agents versus placebo in reducing CV endpoints, including macrovascular events, renal events, and heart failure. These results are important in clinical practice and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases.In 2018, the Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC) published the first joint consensus on the "Pharmacological Management of Patients with Type 2 Diabetes and Cardiovascular Diseases." In 2020, TSOC appointed a new consensus group to revise the previous version. The updated 2020 consensus was comprised of 5 major parts: (1) treatment of diabetes in patients with multiple risk factors, (2) treatment of diabetes in patients with coronary heart disease, (3) treatment of diabetes in patients with stage 3 chronic kidney disease, (4) treatment of diabetes in patients with a history of stroke, and (5) treatment of diabetes in patients with heart failure. The members of the consensus group thoroughly reviewed all the evidence, mainly RCTs, and also included meta-analyses and real-world evidence. The treatment targets of HbA1c were finalized. The antidiabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.

Relationship between pulmonary vein (PV) anatomy and the pathophysiology of paroxysmal atrial fibrillation (PAF) remains incompletely studied. The aim of this study was to determine whether PV anatomy predicts arrhythmogenic PVs. Twenty-six consecutive PAF patients with spontaneous PAF or consistently frequent ectopic beats during electrophysiological study were enrolled. Computed tomography (CT) images for PVs were reconstructed into 3D images. The PV diameter and volume were measured based on the 3D images. The PV myocardial sleeve area was measured based on the 3D voltage mapping results. The PV myocardial sleeve area index was calculated by dividing the sleeve area of each PV by the average sleeve area of all PVs in each patient. The diameter and volume of the arrhythmogenic PVs were larger than those of the non-arrhythmogenic PVs (21.08 ± 4.57 mm vs. 16.47 ± 3.31 mm, P

Limited studies are available regarding the pathophysiological mechanism of acquired atrioventricular block (AVB). Matrix metalloproteinases (MMPs) and angiotensin-converting enzyme (ACE) have been implicated in the pathogenesis of arrhythmia. However, the relationship between these molecules and acquired AVB is still unclear. One hundred and two patients with documented acquired AVB and 100 controls were studied. Gene polymorphisms of the MMP1 and ACE encoding genes were screened by the gene sequencing method or polymerase chain reaction-fragment length polymorphism assay, followed by an association study. The frequencies of the MMP1 −1607 2G2G genotype and MMP1 −1607 2 G allele were significantly higher in the AVB group than that in the controls (OR = 1.933, P = 0.027 and OR = 1.684, P = 0.012, respectively). Consistently, the level of serum MMP1 was significantly greater in acquired AVB patients than that in controls (6568.9 ± 5748.6 pg/ml vs. 4730.5 ± 3377.1 pg/ml, P = 0.019). In addition, the MMP1 2G2G genotype showed a higher MMP-1 serum level than the other genotypes (1G1G/1G2G) (7048.1 ± 5683.0 pg/ml vs. 5072.4 ± 4267.6 pg/ml, P = 0.042). MMP1 1 G/2 G gene polymorphism may contribute to determining the disease susceptibility of acquired AVB by linking the MMP serum protein level.

The aim of this study was to examine atrial fibrillation (AF) patients' preferences regarding oral anticoagulation (OAC) characteristics and to investigate differences across 5 different countries. A multicenter discrete choice experiment was conducted in Germany, Sweden, Switzerland, Spain, and Taiwan. Study sites enrolled patients with nonvalvular AF who received continuous OAC therapy. The discrete choice experiment design considered the following 4 attributes with 2 attribute levels each: need for bridging (yes/no), interactions with food/alcohol (yes/no), need for regular international normalized ratio (INR) assessments, and frequency of intake (once/twice daily). Generally, patients (n = 1391) preferred treatment alternatives that were characterized by "no need of bridging," "no need for regular INR controls," "no interactions with food/alcohol," and "once daily intake." For this desired treatment regimen, patients were willing to accept a substantially higher travel distance/time. German patients with AF were strongly impacted in their hypothetical treatment decision by the frequency of intake (37.5%). Swedish patients on the other hand gave little importance to intake frequency (12.6%). In Switzerland, patients were especially concerned with food/alcohol interactions of the medication (34.7%), whereas this was the least important attribute for Taiwanese patients (18.9%), who ascribed the most homogenous importance to the different treatment attributes overall. In Spain, the need for regular INR assessments especially impacted the patient's treatment decision (31.9%). Patients of all countries attributed a moderate importance to the need for bridging (25.9%-34.2%). These findings may facilitate country-specific consideration of patients' preferences regarding OAC therapy, potentially increasing treatment acceptance on the patient's side with the ultimate goal of improving treatment adherence and persistence.

Objective To identify the incidence and prehospital predictors of ventricular tachycardia/ventricular fibrillation (VT/VF) as the initial arrhythmia in patients with out-of-hospital cardiac arrest (OHCA) in central Taiwan. Patients and Methods The Taichung Sudden Unexpected Death Registry program encompasses the Taichung metropolitan area in central Taiwan, with a population of 2.7 million and 17 destination hospitals for patients with OHCA. We performed a detailed analysis of demographic characteristics, circumstances of cardiac arrest, and emergency medical service records using the Utstein Style. Results From May 1, 2013, through April 30, 2014, resuscitation was attempted in 2013 individuals with OHCA, of which 384 were excluded due to trauma and noncardiac etiologies. Of the 1629 patients with presumed cardiogenic OHCA, 7.9% (n=129) had initial shockable rhythm; this proportion increased to 18.8% (61 of 325) in the witnessed arrest subgroup. Male sex (odds ratio [OR], 2.45; 95% CI, 1.46-4.12; P P P P Conclusion The proportion of patients with OHCA presenting with VT/VF was generally low in this East Asian population. Of the prehospital factors associated with VT/VF, public location of OHCA was the strongest predictor of VT/VF in this population, which may affect planning and deployment of emergency medical services in central Taiwan.

QRS duration has been associated with the response to cardiac resynchronization therapy (CRT). However, the methods for defining QRS duration to predict the outcome of CRT have discrepancies in previous reports. The aim of this study was to determine an optimal measurement of QRS duration to predict the response to CRT.Sixty-one patients who received CRT were analyzed. All patients had class III-IV heart failure, left ventricular ejection fraction not more than 35%, and complete left bundle branch block. The shortest, longest, and average QRS durations from the 12 leads of each electrocardiogram (ECG) were measured. The responses to CRT were determined using the changes in echocardiography after 6 months. Thirty-five (57.4%) patients were responders and 26 (42.6%) patients were non-responders. The pre-procedure shortest, average, and longest QRS durations and the QRS shortening (ΔQRS) of the shortest QRS duration were significantly associated with the response to CRT in a univariate logistic regression analysis (P = 0.002, P = 0.03, P = 0.04 and P = 0.04, respectively). Based on the measurement of the area under curve of the receiver operating characteristic curve, only the pre-procedure shortest QRS duration and the ΔQRS of the shortest QRS duration showed significant discrimination for the response to CRT (P = 0.002 and P = 0.038, respectively). Multivariable logistic regression showed the pre-procedure shortest QRS duration is an independent predictor for the response to CRT.The shortest QRS duration from the 12 leads of the electrocardiogram might be an optimal measurement to predict the response to CRT.

BACKGROUND: Body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) are all simple anthropometric tools used to categorize obesity status. This study aimed to determine associations between different anthropometric indices and the attainment of therapeutic lipid goals in patients with atherosclerotic cardiovascular disease (CVD) undergoing secondary prevention. METHODS: Between 2010 and 2014, this multi-center study enrolled 5718 patients undergoing secondary prevention for CVD. At study enrollment, total cholesterol, high-density lipoprotein protein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were recorded. This cross-sectional study analyzed these three anthropometric obesity indices and correlations with achieving therapeutic lipid goals. RESULTS: Among the 5718 patients, multivariate analysis revealed that those with higher BMI or WC tended not to meet their HDL-C and TG therapeutic goals. However, neither BMI nor WC showed a relationship with achieving the LDL-C target. The patients with an elevated WHR (≥ 0.98 for males and ≥ 0.97 for females) were less likely to achieve all three lipid target values, including LDL-C (p = 0.05), HDL-C (p < 0.001) and TG (p < 0.001). CONCLUSIONS: Among Taiwanese patients undergoing secondary prevention for CVD, the higher the WHR the lower the likelihood of achieving the lipid therapeutic goals.

Impaired left atrial appendage ejection fraction (LAA-EF) and peak LAA flow velocity (LAA-FV) are associated with high thromboembolic risks in patients with atrial fibrillation (AF). Herein, we examined LAA function among patients with atrial flutter (AFL) stratified by the CHA2DS2-VASc score using transesophageal echocardiography (TEE). Of 231 consecutive patients with typical AFL, 84 who fulfilled the inclusion criteria were enrolled. Among them, 57 had ongoing AFL and were divided into the isolated AFL (n = 38) and AFL with paroxysmal AF (PAF) (n = 19) groups, depending on whether they had sporadic AF before TEE. The remaining 27 patients with spontaneous sinus rhythm during TEE were designated as controls. Both the LAA-FV (31.9 cm/s vs. 51.5 cm/s, P = 0.004) and LAA-EF (28.4% vs. 36.5%, P = 0.024) measured during AFL were significantly lower in the AFL + PAF group than in the isolated AFL group. Significant inverse correlations between the CHA2DS2-VASc score and LAA-EF were identified in the AFL (P = 0.008) and AFL + PAF (P = 0.032) groups. We observed progressive LAA dysfunction in patients with AFL + PAF compared with that in patients with isolated AFL, and the LAA-EF was inversely correlated with the CHA2DS2-VASc score in these patients. Our findings may have implications on the application of thromboprophylactic therapy in patients with AFL.

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. Keywords: Atherosclerosis, Risk factors, Performance guide

The objective of the study was to determine whether chronic osteomyelitis (COM) is associated with increased risk of new-onset atrial fibrillation (AF).A national insurance claim data set of 23 million enrollees was used to identify 19,002 patients with newly-diagnosed COM and 76,008 randomly selected age- and sex-matched control subjects between January 1, 2000 and December 31, 2009 for comparing the risk and incidence of AF. The study end point was defined as the first diagnosis of AF, death, withdrawal from the insurance program, or the end of 2010.During a follow-up period of 91,927 person-years, the incidence of new-onset AF in COM cohort was 1.42-fold higher than for the non-COM cohort (4.54 vs 3.19 per 1000 person-years). After adjusting for age, sex, and classical AF risk factors such as hypertension, diabetes, heart failure, coronary artery disease, and valvular heart disease, the risk of new-onset AF remained significantly higher in the COM cohort (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.18-1.49; P0.0001). In age-stratified analysis, the younger population carried a higher risk for incident AF than the elderly population (from HR 2.05; 95% CI, 1.12-3.74 in age younger than 50 years to HR 1.19; 95% CI, 0.95-1.49 in age 80 years and older). The adjusted Kaplan-Meier analysis showed a lower AF-free survival rate in the COM group compared with the control group (log-rank P0.0001) during the follow-up period.This study showed that patients with COM carry an increased risk for developing new-onset AF, particularly in the younger population. Further studies are required to explore the underlying mechanisms that link COM and AF.

To investigate the age-dependent impact of the superfast door-to-balloon (D2B) times of ≤60min as recommended by the new ESC Guideline for patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) on mid-term survival rates based on a single center registry dataset.This study enrolled consecutive STEMI patients who underwent PPCI from Jan 1, 2009 through Sep 30, 2013. We compared demographics, clinical characteristics and the D2B-survival relationships between patients aged ≥65 and65.The younger group comprised 242 patients (68%) aged65 and the elder group consisted of 115 patients (32%) aged ≥65. In patients aged65, the mortality rate decreased linearly with D2B time shortening (90min vs. 61-90min vs. ≤60min=14.9% vs. 13.3% vs. 1.2%, P=0.001). Contrarily, shortening of D2B time was not associated with reduced mortality rate in patients aged ≥65 (90min vs. 61-90min vs. ≤60min=23.5% vs. 19% vs. 18.9%, P=0.99). In younger patients but not the elderly, a D2B time of60min has sufficient power to predict mortality with a sensitivity of 0.83, specificity of 0.74, and Youden index of 0.57.Our results show that the new ESC Guideline recommendation of D2B time ≤60min is associated with better survival rates in younger STEMI patients undergoing PPCI. Our findings stress the importance of guideline adherence to minimize reperfusion delay to improve survival in these patients.

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aβ release via IκB kinase 2 (IKK2). Furthermore, L5+Aβ synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IκBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor-κB (NF-κB). Injecting L5+Aβ shortened tail-bleeding time by 50% (n = 12; P < .05 vs L1-injected mice), which was prevented by the IKK2 inhibitor. Our findings suggest that, through LOX-1, atherogenic L5 potentiates Aβ-mediated platelet activation, platelet aggregation, and hemostasis via IKK2/NF-κB signaling. L5 elevation may be a risk factor for cerebral atherothrombosis, and downregulating LOX-1 and inhibiting IKK2 may be novel antithrombotic strategies.

L5, a highly electronegative subtype of low-density lipoprotein (LDL), is likely associated with the development of atherosclerosis and cardiovascular diseases. Normal LDL is composed mainly of apolipoprotein (Apo) B, but L5 has additional proteins such as ApoE. We previously demonstrated that L5 induces endothelial cell senescence by increasing mitochondrial reactive oxygen species. In the present study, we examined the effect of L5 on mitochondrial function in cardiomyocytes.We used the Seahorse XF24 extracellular flux analyzer to examine the effect of L5 and its components on mitochondrial energy production. The effects of L5 on mitochondrial morphology were examined by immunofluorescence using MitoTracker Green FM and the corresponding probes in H9c2 cardiomyoblasts. Mitochondrial permeability was assessed by using a calcium-induced swelling assay with a voltage-dependent anion-selective channel (VDAC) inhibitor to determine VDAC-dependence both in vitro and in vivo. L5 without ApoE, referred to as △L5, was used to clarify the role of ApoE in L5-induced mitochondrial dysfunction.L5 not only significantly decreased basal (P 0.05) and maximal respiration (P 0.01) but also reduced spare respiratory capacity (P 0.01) in H9c2 cells. Additionally, L5 caused phosphorylation of Drp1 and mitochondrial fission. Recombinant ApoE mimicked the mitochondrial effects of L5, but △L5 did not cause similar effects. After entering cells, ApoE on L5 colocalized with mitochondrial VDAC and caused mitochondria swelling both in vitro and in vivo. This effect was also seen with recombinant ApoE but not △L5.ApoE may play an important role in electronegative LDL-induced mitochondrial dysfunction through the opening of the mitochondrial permeability transition pore via the interaction of ApoE and VDAC.

Idiopathic ventricular fibrillation (IVF) is a cause of sudden cardiac death (SCD). The frequency of mutations in disease-causing genes ranges, on average, between 16 and 48% in SCD cases. This study aimed to identify novel mutations in IVF patients withoutGenomic DNA extracted from peripheral blood samples obtained from five patients with IVF and WES was used to identify mutations associated with IVF. Candidate variants were validated by Sanger sequencing.Four patients harbored suspected mutations in 100 inherited cardiomyopathy-and channelopathy-associated genes (e.g.,This study revealed the effectiveness of WES for IVF patients without

To investigate the prognostic value of heart-type fatty acid binding protein (H-FABP) in patients with stable coronary heart disease (SCHD). A total of 1,071 patients with SCHD were prospectively enrolled in this Taiwan multicenter registry study, followed for 24 months. The cut-off value of H-FABP, 4.143 ng/mL, was determined using receiver operating characteristic curves. The primary cardiovascular (CV) outcome was composite CV events, defined as cardiovascular or cerebrovascular death, myocardial infarction (MI), stroke, angina related-hospitalization, PAOD-related hospitalization and heart failure. Secondary outcomes included CV or cerebrovascular death, nonfatal MI, nonfatal stroke, and acute heart failure-related hospitalization. We found that the high H-FABP group had more than a two-fold higher rate of primary CV outcomes than the low H-FABP group (32.36% vs. 15.78%, p p

The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type 2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15% from heart failure (HF), and 10% from stroke. The association between hyperglycemia and elevated CV risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction did not significantly reduce macrovascular outcomes. It remains unclear whether the absence of demonstrable benefits is attributed to the inclusion of patients with far advanced ASCVD in whom a short treatment period is barely enough for CV protective effects to be shown, or complications associated with the treatment such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose-lowering per se is ineffective. Since the US FDA issued a mandate in December 2008 that every new anti-diabetic agent requires rigorous assessments of its CV safety, there have been more than 200,000 patients enrolled in a number of randomized controlled trials (RCTs), and around half of them have been completed and published. The results of these CV outcome trials are important for clinicians in their clinical practice, and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases. The Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients with CVD, have appointed a jointed consensus group for the 2018 Consensus of TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2 Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1) Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic kidney disease, 4) Treatment of diabetes in patients with a history of stroke, and 5) Treatment of diabetes in patients with HF. The members of the consensus group comprehensively reviewed all the evidence, mainly RCTs, and also included meta-analyses, cohort studies, and studies using claim data. The treatment targets of HbA1c were provided. The anti-diabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.

Background ICIs with a programmed death protein 1 (PD-1) or programmed death protein ligand 1 (PD-L1) antibodies have shown survival benefits for various metastatic cancer patients. However, some patients treated with ICIs may suffer from AEs. We investigated the association between AEs and survival in metastatic cancer patients treated with PD-1/PD-L1 inhibitors. Methods We retrospectively reviewed medical records of metastatic cancer patients treated with pembrolizumab, nivolumab or atezolizumab from April 2016 to June 2019 for AEs, progression-free survival (PFS), and overall survival (OS). Kaplan-Meier curve was used to estimate survival probability and the Cox proportional hazard model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) between each interesting group. Results We enrolled 101 patients. Primary cancers were urothelial carcinoma (n = 52), lung cancer (n = 42), hepatocellular carcinoma (n = 5), and cholangiocarcinoma (n = 2). Atezolizumab was the most common prescribed agents (n = 69), followed by pembrolizumab (n = 29) and nivolumab (n = 3). The AEs happened more frequently were associated with lung (n = 25), skin (n = 24), endocrine (n = 17), and liver (n = 11). Median time for these AEs happened was 1.4 months. Median OS (mOS) for these patients was 16.9 months and median PFS (mPFS) was 9.1 months. Among various AEs, patients with skin AE had significantly longer PFS and OS compared to those without skin AE (mPFS: 11.9 months vs. 4.9 months, p = 0.0016 ; mOS: 16.4 months vs. 10.3 months, p = 0.0022). In comparison with those without endocrine AE, the occurrence of endocrine AE was associated with an improved PFS (mPFS: 19.2 months vs. 6.0 months, p = 0.0476 ) and a trend toward to OS (mOS: 19.4 months vs. 10.9 months, p = 0.1731 ). There were no survival difference between patients who experienced lung or liver AEs. Conclusions In metastatic cancer patients treated with anti-PD-1/PD-L1 ICIs, development of skin or endocrine AEs may indicate improved survival time. The patients with AEs involved visceral organ, like lung or liver, have no better survival time. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Although advances in pharmacotherapy and interventional cardiology have greatly reduced the mortality and morbidity following myocardial infarction (MI), there remains an ongoing need for innovative cell transplantation techniques that can reverse cardiac ventricular remodeling post-MI. Despite the barriers facing the application of cell-based interventions (1,2), a growing number of preclinical studies and clinical trials have demonstrated the safety of a variety of adult stem cell types. Mesenchymal stem cells (MSCs) are one of the most well-studied cell types used in regenerative medicine (3).