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Abstract Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly performed as an adjunct to conventional cardiopulmonary resuscitation (CCPR) for refractory out-of-hospital cardiac arrest (OHCA). However, the specific benefits of ECPR concerning survival with favorable neurological outcomes remain uncertain. This study aimed to investigate the potential advantages of ECPR in the management of refractory OHCA. We conducted a retrospective cohort study involved OHCA patients between January 2016 and May 2021. Patients were categorized into ECPR or CCPR groups. The primary endpoint assessed was survival with favorable neurological outcomes, and the secondary outcome was survival rate. Multivariate logistic regression analyses, with and without 1:2 propensity score matching, were employed to assess ECPR’s effect. In total, 1193 patients were included: 85underwent ECPR, and 1108 received CCPR. Compared to the CCPR group, the ECPR group exhibited notably higher survival rate (29.4% vs. 2.4%; p

Aims: To assess whether mechanical circulatory support (MCS), including intra-aortic balloon pump (IABP) or veno-arterial extracorporeal membrane oxygenation (ECMO), can help improve neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA). Methods: This is a retrospective observational cohort study performed in China Medical University Hospital, Taichung, Taiwan. Adult patients with OHCA admitted between January 2015 and June 2023. Quantitative score of vasoactive-inotropic agents and qualitative interventions of MCS, including IABP and ECMO after OHCA. Multivariate regression evaluated the efficacy of each MCS approach in patients stratified by the vasoactive-inotropic score (VIS). Results: A total of 334 patients were included and analyzed, 122 (36.5%) had favorable neurological outcomes and 215 (64.4%) survived ≥90 days. These patients were stratified by VIS: 0–25, 26–100, 101–250, and >250. In patients with a VIS > 100, ECMO with or without IABP ensured favorable neurological outcomes and survival after OHCA compared to non-MCS interventions (p 0.05). Conclusions: ECMO with or without IABP therapy may improve post-OHCA neurological outcomes and survival in patients with an expected VIS-24 h > 100 (e.g., epinephrine dose reaches 3 mg during CPR).

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan. Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68–0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53–2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60–2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63–6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group. Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

Abstract The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.

Abstract Background Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. Methods A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. Results Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P

BackgroundEarly ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI.MethodsWe analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE−/− mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF.ResultsIn 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P

Background: 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. Methods: 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. Results: 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. Conclusion: OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level >4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

Abstract 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.

Abstract Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32–4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64–4.70, P

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.

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.

BackgroundDespite 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.MethodsHospitalized 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 (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables.ResultsFour out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34–126.75) to 227.50 (185.25–237.50) and then 349.56 (293.03–367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50–237.61]; day 3: 100.00 [72.00–232.68]; day 7: 250.00 [71.00–251.43], P = 0.923).ConclusionTransplantation 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.

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.

Background: Fatty-acid binding protein-4 (FABP4) has been associated with the metabolic syndrome, diabetes mellitus, atherosclerosis, incident heart failure, and the prognosis of coronary heart disease (CHD). However, recent studies have not reported a significant correlation between FABP4 and cardiovascular (CV) mortality in high-risk patients or those with documented CHD. The present study aimed to evaluate the association between FABP4 and the prognosis in a cohort of patients with CHD who received coronary interventions. Methods: Serum FABP4 levels were measured in 973 patients after a successful intervention for CHD, who were then prospectively followed for 30 months. Result: During this period, 223 patients experienced composite CV outcomes (22.92%), defined as cardiovascular/cerebrovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for refractory or unstable angina, hospitalization for heart failure, and peripheral artery occlusive disease. Kaplan–Meier curves showed a significant association between FABP4 levels at baseline (categorized in tertiles) and composite CV outcomes during follow-up (log-rank test, p

Abstract 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.

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

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

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

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 (

Abstract Background Spironolactone can improve endothelial dysfunction in the setting of heart failure and diabetes models. However, its beneficial effect in the cardiovascular system is not clear in the setting of non-diabetic renal failure. We conducted this study to investigate whether spironolactone can ameliorate endothelial dysfunction in a 5/6 nephrectomy model, and to determine the underlying mechanism. Methods Twenty-four Sprague-Dawley rats were divided into four groups. A renal failure model was created using the 5/6 nephrectomy method. The four groups included: Sham-operation group (Group1), chronic kidney disease (CKD; Group2), CKD + ALT-711 (advanced glycation end products [AGEs] breaker; Group 3), and CKD + spironolactone group (Group4). Acetylcholine (Ach)-mediated vasodilatation responses were compared between the four groups. To investigate the underlying mechanism, we cultured human aortic endothelial cells (HAECs) for in-vitro assays. Differences between two groups were determined with the paired student’s t test. Differences between three or more groups were determined through one-way analysis of variance (ANOVA) with post-hoc analysis with LSD method. Results Compared with Group 1, Group 2 has a significantly impaired Ach-mediated vasodilatation response. Group 3 and 4 exhibited improved vasoreactivity responses. To determine the underlying mechanism, we performed an in-vitro study using cultured HAECs. We noted significant sirtuin-3 (SIRT3) protein downregulation, reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 (p-eNOS), and increased intracellular oxidative stress in cultured HAECs treated with AGEs (200 μg/mL). These effects were counter-regulated when cultured HAECs were pretreated with spironolactone (10 μM). Furthermore, the increased p-eNOS production by spironolactone was abrogated when the HAECs were pretreated with tenolvin (1 μM), a SIRT3 inhibitor. Conclusions Spironolactone could ameliorate endothelial dysfunction in a 5/6 nephrectomy renal failure model through AGEs/Receptor for AGEs (RAGEs) axis inhibition, SIRT3 upregulation, and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX-2) and its associated intracellular oxidative stress attenuation.

Background The circulating level of soluble lectin‐like oxidized low‐density lipoprotein receptor‐1 (sLOX‐1) is a valuable biomarker of acute myocardial infarction (AMI). The most electronegative low‐density lipoprotein, L5, signals through LOX‐1 to trigger atherogenesis. We examined the characteristics of LOX‐1 and the role of L5 in aspirated coronary thrombi of AMI patients. Methods and Results Intracoronary thrombi were aspirated by performing interventional thrombosuction in patients with ST‐segment–elevation myocardial infarction (STEMI; n=32) or non–ST‐segment–elevation myocardial infarction (n=12). LOX‐1 level and the ratio of sLOX‐1 to membrane‐bound LOX‐1 were higher in thrombi of STEMI patients than in those of non–ST‐segment–elevation myocardial infarction patients. In all aspirated thrombi, LOX‐1 colocalized with apoB100. When we explored the role of L5 in AMI, deconvolution microscopy showed that particles of L5 but not L1 (the least electronegative low‐density lipoprotein) quickly formed aggregates prone to retention in thrombi. Treating human monocytic THP‐1 cells with L5 or L1 showed that L5 induced cellular adhesion and promoted the differentiation of monocytes into macrophages in a dose‐dependent manner. In a second cohort of AMI patients, the L5 percentage and plasma concentration of sLOX‐1 were higher in STEMI patients (n=33) than in non–ST‐segment–elevation myocardial infarction patients (n=25), and sLOX‐1 level positively correlated with L5 level in AMI patients. Conclusions The level of LOX‐1 and the ratio of sLOX‐1 to membrane‐bound LOX‐1 in aspirated thrombi, as well as the circulating level of sLOX‐1 were higher in STEMI patients than in non–ST‐segment–elevation myocardial infarction patients. L5 may play a role in releasing a high level of sLOX‐1 into the circulation of STEMI patients.

Abstract Electronegative low-density lipoprotein (LDL) has been shown to increase coronary artery disease risk in hemodialysis patients, but its effect on the risk of peripheral artery disease (PAD) remains unclear. We separated plasma LDL from 90 uremia patients undergoing hemodialysis into 5 subfractions (L1–L5) according to charge by using fast-protein liquid chromatography with an anion-exchange column and examined the distribution of L5—the most electronegative LDL subfraction—in total LDL (i.e. L5%). During a 5-year period, we followed up with these patients until the occurrence of ischemic lower-extremity PAD. During the follow-up period, ischemic lower-extremity PAD developed in 24.4% of hemodialysis patients. L5% was higher in hemodialysis patients in whom ischemic lower-extremity PAD occurred (3.03% [IQR, 2.36–4.54], n = 22) than in hemodialysis patients in whom PAD did not occur (1.13% [IQR, 0.90–1.83], n = 68) (p

Background The aim of this study was to determine the influence of various antidiabetic therapies on the relationship between body mass index and all‐cause mortality in patients with diabetes mellitus and acute coronary syndrome. Methods and Results This was a prospective, observational study comprising 1193 patients diagnosed with type 2 diabetes mellitus and acute coronary syndrome. The patients were stratified into 4 body mass index categories, and their mortality rates were compared using time‐dependent Cox regression analysis using normal weight (body mass index, 18.5–23.9) as the reference. Subsequently, the influence of antidiabetic therapies on the association between BMI and mortality were analyzed. Seventy‐four patients (6.2%) died over 2 years of follow‐up. The mortality rate was lowest in the class I obese group (3.35%) and highest in the normal‐weight group (9.67%). After adjusting for covariates, class I obesity paradoxically remained significantly protective against mortality compared with normal weight (hazard ratio, 0.141; P=0.049); interaction term analysis showed that insulin therapy influenced this “obesity paradox” (P=0.045). When the patients were stratified by insulin use, the protective effect of obesity disappeared in the insulin‐treated patients but persisted in the non–insulin‐treated patients. Conclusions In patients with type 2 diabetes mellitus and acute coronary syndrome, the relationship between body mass index and mortality rate is U‐shaped, with class I obesity representing the nadir and normal weight the peak. The protective effect of obesity disappeared in patients treated with insulin.

Skin autofluorescence (AF) has been validated as a tool for estimating tissue advanced glycation end products (AGEs) accumulation and predicting long-term cardiovascular outcomes. However, whether measurements of skin AF could predict renal function decline remains controversial. From April, 2014 to April, 2015, we enrolled 245 subjects with at least two conventional risk factors for coronary artery disease (CAD). All were measured for body height and weight, blood pressure, plasma creatinine level, and skin AF at the start of the study. Baseline demographics and laboratory tests data were obtained by chart reviews and patient interviews. Serial plasma creatinine levels were followed regularly every 6-12 months for 2 years. In a stepwise multivariate linear regression analysis, skin AF, was an independent factor for predicting the relative renal function decline rate after adjustment of multiple covariates (ß = -0.036±0.016; p = 0.03). Subgroups analysis revealed that skin AF was a significant factor for relative renal function decline rate in subgroups of age < 65 years (ß = -0.068±0.024; p = 0.02), male sex (ß = -0.053±0.016; p< 0.01), body mass index≧25 Kg/m2(ß = -0.042±0.021; p = 0.04), and estimated glomerular filtration rate ≥ 60 ml/min/1.73m2(ß = -0.043±0.020; p = 0.04). However, only an interaction between skin AF and age attained significance (p for interaction = 0.04). Skin AF is a useful predictor for renal function decline in patients at increased risk of CAD.

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

Familial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.Overall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.Two transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16-3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.Transforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

Despite great advances in therapy over the past decades, ischemic heart disease (IHD) remains the leading cause of death worldwide because the decrease in mortality after acute myocardial infarction (AMI) leads to a longer life span in patients with chronic postinfarct heart failure (HF). There are no existing medical treatments that can cure chronic HF and the only currently available therapeutic option for end-stage HF is heart transplantation. However, transplantation is limited by the shortage of donor organs and patients require lifelong immunosuppression. In the past 10 years, stem cell-based cardiac therapy has been proposed as a promising approach for the treatment of IHD. There is a variety of potential stem cell types for cardiac repair and regeneration, including bone marrow cells (BMCs), resident cardiac stem cells (CSCs) and induced pluripotent stem cells (iPSCs). Stem cell-based therapy may comprise cell transplantation or cardiac tissue engineering (CTE), which might be an attractive alternative to solve the problems of low retention and poor survival of transplanted cells. This review focuses on the characteristics of stem cells from various sources and discusses the strategies of stem cell-based therapy for the treatment of IHD.

BACKGROUND: It is well known that familial sick sinus syndrome (SSS) is caused by functional alterations of ion channels and gap junction. Limited information is available on the mechanism of age-related non-familial SSS. Although evidence shows a close link between arrhythmia and the renin-angiotensin system (RAS), it remains to be determined whether the RAS is involved in the pathogenesis of non-familial SSS. METHODS: In this study, 113 patients with documented non-familial SSS and 125 controls were screened for angiotensinogen (AGT) and gap junction protein-connexin 40 (Cx40) promoter polymorphisms by gene sequencing, followed by an association study. A luciferase assay was used to determine the transcriptional activity of the promoter polymorphism. The interaction between nuclear factors and the promoter polymorphism was characterized by an electrophoretic mobility shift assay (EMSA). RESULTS: Association study showed the Cx40 -44/+71 polymorphisms are not associated with non-familial SSS; however, it indicated that four polymorphic sites at positions -6, -20, -152, and -217 in the AGT promoter are linked to non-familial SSS. Compared to controls, SSS patients had a lower frequency of the G-6A AA genotype (OR 2.88, 95% CI 1.58-5.22, P = 0.001) and a higher frequency of the G allele at -6 position (OR 2.65, 95% CI 1.54-4.57, P = 0.0003). EMSA and luciferase assays confirmed that nucleotide G at position -6 modulates the binding affinity with nuclear factors and yields a lower transcriptional activity than nucleotide A (P