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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.

Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet.CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients.Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel.Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

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.

Computed tomography (CT)-determined skeletal muscle measures have been used for predicting postoperative outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). We investigated the impact of CT-determined muscle quantity (measured as psoas muscle area [PMA] and psoas muscle index [PMI]) and quality (measured as psoas muscle density [PMD]) on hospital length of stay (LOS) after TAVI.We retrospectively identified 182 consecutive patients who underwent TAVI between March 2013 and August 2017 with adequate preprocedural CT imaging. Baseline demographic and clinical data, the Society of Thoracic Surgeons score, the essential frailty toolset (EFT) frailty rating, and precontrast PMD, PMA, and PMI were obtained in all study patients. The primary outcome was prolonged postoperative LOS defined as greater than 14 days.Patients with prolonged LOS had a significantly higher Society of Thoracic Surgeons score (p0.001) and significantly lower PMD (p0.001) than those with LOS ≤14 days. More patients with prolonged LOS had concomitant peripheral vascular disease (p = 0.001), had undergone percutaneous coronary interventions (p = 0.022), and had an EFT score ≥4 (p0.001) compared to those without prolonged LOS. Neither PMA (p = 0.123) nor PMI (p = 0.271) were associated with prolonged LOS. Multivariate analysis identified EFT score ≥4, the presence of peripheral vascular disease, and PMD as independent predictors of prolonged LOS.The precontrast CT-determined muscle quality measurement PMD is a simple and objective predictor of prolonged LOS after TAVI.

Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse.We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement.During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035).Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Background Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. Methods Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. Results Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51–0.85; p = 0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100 mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. Conclusions Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

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

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced and secreted mainly by endothelial cells. Recent studies indicate that ET-1 can regulate lipid metabolism, which may increase the risk of insulin resistance. Our previous studies revealed that ET-1 induced lipolysis in adipocytes, but the underlying mechanisms were unclear. 3T3-L1 adipocytes were used to investigate the effect of ET-1 on lipolysis and the underlying mechanisms. Glycerol levels in the incubation medium and hormone-sensitive lipase (HSL) phosphorylation were used as indices for lipolysis. ET-1 significantly increased HSL phosphorylation and lipolysis, which were completely inhibited by ERK inhibitor (PD98059) and guanylyl cyclase (GC) inhibitor (LY83583). LY83583 reduced ET-1-induced ERK phosphorylation. A Ca2+-free medium and PLC inhibitor caused significant decreases in ET-1-induced lipolysis as well as ERK and HSL phosphorylation, and IP3 receptor activator (D-IP3) increased lipolysis. ET-1 increased cGMP production, which was not affected by depletion of extracellular Ca2+. On the other hand, LY83583 diminished the ET-1-induced Ca2+ influx. Transient receptor potential vanilloid-1 (TRPV-1) antagonist and shRNA partially inhibited ET-1-induced lipolysis. ET-1-induced lipolysis was completely suppressed by CaMKIII inhibitor (NH-125). These results indicate that ET-1 stimulates extracellular Ca2+ entry and activates the intracellular PLC/IP3/Ca2+ pathway through a cGMP-dependent pathway. The increased cytosolic Ca2+ that results from ET-1 treatment stimulates ERK and HSL phosphorylation, which subsequently induces lipolysis. ET-1 induces HSL phosphorylation and lipolysis via the GC/cGMP/Ca2+/ERK/CaMKIII signaling pathway in 3T3-L1 adipocytes.

Background: The aim of this study is to determine the relationship between the on-treatment lipid profiles and the CV events in CKD and non-CKD population. Method: This study was a multi-center observational registry, the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. This study follows up patients with CV diseases in Taiwan who have secondary prevention therapies. The primary outcome is the time of first occurrence of a major adverse cardiac events (MACEs). Result: 5388 patients with ASCVD were included and 1478 (27.4%) had CKD without dialysis. CKD patients had higher TG and lower LDL-C levels. The incidence of recurrent MACEs per 1000 person-years in CKD patients was 19.5 (95% CI 15.5–24.9), compared with 9.1 (95% CI 7.4–11.1) in non-CKD patients. In patients with statin therapy, there were no differences in MACE risk between each level of on-treatment LDL-C, TG and HDL-C level. Higher on-treatment non-HDL-C level was a significant predictor for higher MACE risk in patients without CKD, and borderline significant in CKD patients under statin therapy. Heart failure history was also associated with higher MACE risk in both group. Lower body mass index (BMI

A gap in the knowledge on the status of heart failure (HF) in Asia versus other regions led to the creation of a working group of Asian experts from 9 countries or regions (Hong Kong, Indonesia, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam). Each expert sought the best available data from local publications, registries, or clinical practice. The prevalence of HF in Asia was generally similar to global values (1% to 3%), but with some outliers. There were substantial variations in healthcare spending, and the average cost of HF hospitalization varied from 813 US$ in Indonesia to nearly 9000 US$ in South Korea. Comorbidities were frequent, particularly hypertension, diabetes mellitus, and dyslipidemia. Modifiable risk factors such as smoking were alarmingly common in some countries. Asian HF patients spent between 5 and 12.5days in hospital, and 3% to 15% were readmitted for HF by 30days. The pharmacological treatment of Asian patients generally followed international guidelines, including renin–angiotensin–aldosterone system inhibitors (61% to 90%), diuretics (76% to 99%), beta-blockers (32% to 78%), and digoxin (19% to 53%), with some room for improvement in terms of life-saving therapies. Our review supports implementation of a more comprehensive and organized approach to HF care in Asia.

Background The study was conducted to examine the nationwide temporal trends of incidence, treatment, and short-term outcomes for acute myocardial infarction (AMI) over a 15-year period in Taiwan. Methods We identified patients who were hospitalized for incident AMI between 1997 and 2011 from the inpatient medical claim dataset of the National Health Insurance Research Database. Age- and sex-adjusted incidence and in-hospital mortality rates were calculated for AMI, and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI). Results A total of 144,634 patients were identified. The incidence rates (per 100,000 population) of AMI increased from 30 in 1997 to 42 in 2011, which was mainly driven by the increase of NSTEMI. The in-hospital mortality rate after AMI decreased from 9.1% in 1997 to 6.5% in 2011, which was also driven by the case mortality rate for NSTEMI. Although the in-hospital mortality rates significantly decreased from 7.3% to 5.1% between 1997 and 2003 for STEMI, it did not change significantly from 2004 to 2011. Moreover, AMI patients undergoing revascularization treatment, particularly PCI, was the most important independent predictor for improved in-hospital survival. Conclusion The results of this study demonstrated a recent dramatic increase in the incidence rates and a decrease in short-term mortality in patients with NSTEMI; while the incidence and in-hospital morality of STEMI only modestly changed over time in Taiwan. Further quality improvement approaches for AMI prevention and treatment to favorably affect the incidence and outcomes from both major types of AMI are highly recommended.

Patient initials or identifier number Lin ### Relevant clinical history and physical exam The 63-year-old male patient presented to the ER with chest pain and progressively worsening dyspnea. On physical examination, oxygen saturation was 88% under NRM, BP was 104/63 mmHg, HR was 107 bpm

The frequency of radial artery occlusion was compared between patients receiving 4Fr versus 6Fr transradial coronary interventions (TRIs) in an open-label randomized trial (ClinicalTrials.gov identifier: NCT00815997). The primary outcome measure was radial artery occlusion on the day after TRI. The secondary outcome measures were the procedural success, major advanced cardiac events, access site-related complications, procedural times, fluoroscopy times, and contrast dye usage. A total of 160 patients were included. The procedure was successful in 79 of 80 patients (99%) in both groups. Whereas the 4Fr group showed no access site-related complications, the 6Fr developed 5 (6%), including 3 radial artery occlusions and 2 bleedings (1 radial artery perforation and 1 massive hematoma; p = 0.02). Although the radial artery occlusion rate was lower in the 4Fr versus the 6Fr groups, the difference was not significant (0% vs 4%, p = 0.08). The mean hemostasis time was significantly shorter in the 4Fr than in the 6Fr groups (237 ± 105 vs 320 ± 238 minutes, p = 0.007). In conclusion, these findings suggest that 4Fr TRI may become a less invasive alternative to 6Fr TRI in treating coronary artery diseases.

Background Sudden cardiac death (SCD) occurs commonly after heart transplantation (HTX). The utilization of surface electrocardiography (ECG) to assess post-HTX SCD has not been investigated thoroughly. This study aimed to investigate the specific changes in surface ECG in HTX patients with SCD. Methods A total of 227 HTX patients (age 48±14y/o, mean donor age 34±14y/o, 173males) were followed up regularly at the outpatient clinic. Twelve-lead ECG's were recorded during 1–2 monthly visits. Serial ECG parameters and relevant clinical data were collected and analyzed. Results During the follow-up period of 96±51months, SCD occurred in 28 (12.3%) patients. The baseline ECG parameters were comparable between patients with and without SCD. Important ECG trends of rising rest heart rates and prolongation of corrected QT (QTc) and JT (JTc) intervals were observed prior to development of SCD. After adjustment for other clinical variables, the independent predictors for SCD were older donor age (p=0.014, OR 1.05, 95% CI 1.01–1.09), faster heart rate (p=0.006, OR 1.06, 95% CI 1.02–1.1) and longer JTc interval (p=0.015, OR 1.03, 95% CI 1.01–1.06). SCD occurred in 71.4% patients presenting with all three risk predictors. Conclusions Besides older donor age, important ECG signs, including prolongation of the JTc interval and increased heart rate during post HTX follow up, could predict SCD.

Introduction Chinese herbs are widely used as important remedies in Oriental integrative medicine. Magnolol is a small polyphenolic molecule with low toxicity that is isolated from the herb genus Magnolia . In preclinical experiments, magnolol was found to have anti-oxidative, anti-inflammatory, anti-tumorigenic, anti-diabetic, anti-microbial, anti-neurodegenerative and anti-depressant properties. Magnolol can also effectively regulate pain control, hormonal signalling, gastrointestinal and uterus modulation as well as provide cardiovascular and liver protective effects. Materials and methods We briefly conducted PubMed and MEDLINE database reviews for articles that related to magnolol. Results The major biological mechanisms of action and potential health benefits of magnolol are described. Conclusions These health benefits of magnolol have provided an increased interest in bringing this herbal compound to the clinic as a novel therapeutic agent. Knowledge of the multiple activities of magnolol can assist with the development of magnolol derivatives and the design of clinical trials that will maximize the potential benefit of magnolol in the patient setting.

Current guidelines recommend that >75% of patients with ST-elevation myocardial infarction (STEMI) receive primary percutaneous coronary intervention (PPCI) within 90 minutes. The goal has been hardly achievable, so we conducted a 2-year before-and-after study to determine the impact of emergency department (ED) tele-electrocardiographic (tele-ECG) triage and interventional cardiologist activation of the infarct team at door-to-balloon time (D2BT) and the proportion of patients undergoing PPCI within 90 minutes since arrival. In total 105 consecutive patients with acute STEMI (mean age 62 ± 13 years, 82% men) were studied, 54 before and 51 after the change in protocol. The 51patients in the tele-ECG group underwent tele-electrocardiography at the ED and electrocardiograms were transmitted to a third-generation mobile telephone of an on-call interventional cardiologist within 10 minutes of ED arrival. The infarct team was activated and PPCI was performed by the interventional cardiologist. Fifty-four patients with acute STEMI who underwent PPCI in the year before implementation of tele-electrocardiography served as control subjects. Median D2BT of the tele-ECG group was 86 minutes, significantly shorter than the median time of 125 minutes of the control group (p

Background Vascular inflammation and endothelial dysfunction are evident in patients with chronic heart failure (CHF). We hypothesized that circulating peripheral blood mononuclear cells (PBMCs) may be activated and the resultant increased endothelial monocyte adhesion may be functionally and pathophysiologically relevant in CHF. In the present study, we investigated the clinical significance of the activity of PBMCs in patients with CHF. Methods PBMCs were isolated from 34 CHF patients, from 10 healthy volunteers (normal control group) and from 17 patients admitted for investigation of suspected coronary artery disease (disease control group). In each patient, the adhesiveness of PBMCs to cultured human aortic endothelial cells (HAECs) with or without tumor necrosis factor-alpha (TNF-α) stimulation was determined. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening heart failure) were determined in the 34 CHF patients during a median follow-up period of 182 days. Results Compared with those from both control groups and from mild CHF patients, PBMCs isolated from severe CHF patients adhered more to the HAECs. The endothelial adhesiveness of PBMCs correlated positively with the circulating levels of CAMs and can supply prognostic information in CHF patients. The difference between event-free curves based on the median levels of endothelial-PBMC adhesion was significant (log rank test, p =0.0139). Conclusions Endothelial adhesiveness of PBMCs is increased and correlated to clinical outcomes, and may be pathophysiologically relevant to the progression of CHF.

Summary Background We investigated the effects of oral l-arginine on endothelial function, intravascular oxidative stress, and circulating inflammatory markers in patients with stable coronary artery disease (CAD). Methods Thirty-one stable CAD patients were randomly assigned to oral l-arginine (10g) or vitamin C (500mg, an antioxidant, as active control) daily for 4 weeks, with crossover to the alternate therapy after 2 weeks off therapy, in this study. Brachial artery endothelial function studies were performed and serum concentrations of lipids and inflammatory markers were measured at baseline, at the end of each 4-week treatment period and at the 2-week wash-out period. Susceptibility of low-density lipoprotein (LDL) particles to oxidation, a marker of oxidative stress, was determined in 11 patients at random before and after 4-week treatment of oral l-arginine. Results We demonstrates that consumption of either l-arginine or vitamin C significantly increased brachial artery flow-mediated dilatation (mean diameter change from baseline of 4.87%, P 0.0001 and of 3.17%, P = 0.0003 , respectively). Neither oral l-arginine nor vitamin C affected lipid profiles and circulating levels of inflammatory markers. However, in the 11 patients whose LDL susceptibility to oxidation was determined, lag time significantly increased by 27.1% ( P = 0.045 ) after consumption of l-arginine for 4 weeks. Conclusions Oral l-arginine supplement improved endothelial function and reduced LDL oxidation in stable CAD patients.

It is known that an electrocardiogram (ECG) after transvenous right ventricular (RV) pacing should yield left bundle branch block (LBBB) QRS patterns. When right bundle branch block (RBBB) pacing morphology appears in a patient with a permanent or temporary transvenous RV pacemaker, myocardial perforation or malposition of the pacing lead must be ruled out, even though the patient may be asymptomatic. We report a case of a 77-year-old man who underwent permanent transvenous VDD pacemaker implantation for symptomatic heart block. The postoperative ECG revealed a RBBB pacing configuration, but his chest X-ray and echocardiographic studies confirmed uncomplicated RV pacing. We review and discuss the literature concerning the differential diagnosis of such a safe RBBB ECG pattern.

Transcatheter aortic valve replacement (TAVR) has been established as alternative treatment for inoperable or high-risk patients with symptomatic severe aortic stenosis. We sought to evaluate the clinical outcomes of TAVR in Asian Pacific countries. The Asian TAVR registry was conducted in 12

Patient initials or identifier number 18224033 ### Relevant clinical history and physical exam 68-year-old gentleman Chief complaint: progressive worsening of dyspnea on exertion for 5 months (NYHA functional class II-III)Past history: mitral valve prolapse with infective endocarditis and