2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

Epicardial adipose tissue thickness is not associated with adverse cardiovascular events in patients undergoing haemodialysis.

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

2019 Focused Update of the Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure.

Heart failure is a growing epidemic, especially in Taiwan because of the aging population. The 2016 Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry showed that the guideline-recommended therapies were prescribed suboptimally both at the time of hospital discharge and during follow-up. We, therefore, conducted this 2019 focused update of the guidelines of the Taiwan Society of Cardiology for the diagnosis and treatment of heart failure to reinforce the importance of new diagnostic and therapeutic modalities of heart failure. The 2019 focused update discusses new diagnostic criteria, pharmacotherapy, non-pharmacological management, and certain co-morbidities of heart failure. Angiotensin receptor neprilysin inhibitor and If channel inhibitor is introduced as new and recommended medical therapies. Latest criteria of cardiac resynchronization therapy, implantable cardioverter-defibrillator, heart transplantation, and ventricular assist device therapy are reviewed in the non-pharmacological management chapter. Co-morbidities in heart failure are discussed including chronic kidney disease, diabetes, chronic obstructive pulmonary disease, and sleep-disordered breathing. We also explain the adequate use of oxygen therapy and non-invasive ventilation in heart failure management. A particular chapter for chemotherapy-induced cardiac toxicity is incorporated in the focused update to emphasize the importance of its recognition and management. Lastly, implications from the TSOC-HFrEF registry and post-acute care of heart failure are discussed to highlight the importance of guideline-directed medical therapy and the benefits of multidisciplinary disease management programs. With guideline recommendations, we hope that the management of heart failure can be improved in our society.

The effects of secondary prevention after coronary revascularization in Taiwan.

BACKGROUND: Secondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, ß-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan. METHODS: This national population-based cohort study was conducted by analyzing the Longitudinal Health Insurance Database 2000 from the National Health Insurance Research Database of Taiwan. Patients who underwent CABG or PCI from 2004 to 2009 were included in the analysis. The baseline characteristics of the patients and ACC/AHA class I medication use at 12 months were analyzed. The primary endpoints were a composite of major adverse cardiac and cerebrovascular events. RESULTS: A total of 5544 patients comprising 895 CABG and 4649 PCI patients were evaluated. CABG patients had more comorbidities and a higher rate of major adverse event during the follow-up period. However, use of antiplatelet agents and RASB at 12 months was significantly lower in CABG patients than in PCI patients (44.2% vs. 50.9% and 38.6% vs. 48.9%, both p < 0.01). Age, diabetes, and chronic kidney disease were independent risk factors while statin use was a protective factor for the primary endpoints in both PCI and CABG groups. CONCLUSION: There is still much room to improve class I medication use in secondary prevention for patients after revascularization in Taiwan. Statin could be an effective treatment to improve the outcomes.

Eugenosedin-A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide-induced diabetic rats.

This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes.

Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 µM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 µg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance.

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.

OBJECTIVE: To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. DESIGN: National prospective cohort study. SETTING: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. PARTICIPANTS: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). CONCLUSIONS: Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Chewing areca nut increases the risk of coronary artery disease in Taiwanese men: a case-control study.

BACKGROUND: Areca nut chewing has been reported to be associated with obesity, metabolic syndrome, hypertension, and cardiovascular mortality in previous studies. The aim of this study was to examine whether chewing areca nut increases the risk of coronary artery disease (CAD) in Taiwanese men. METHODS: This study is a hospital-based case-control study. The case patients were male patients diagnosed in Taiwan between 1996 and 2009 as having a positive Treadmill exercise test or a positive finding on the Thallium-201 single-photon emission computed tomography myocardial perfusion imaging. The case patients were further evaluated by coronary angiography to confirm their CAD. Obstructive CAD was defined as a ≥ 50% decrease in the luminal diameter of one major coronary artery. The patients who did not fulfill the above criteria of obstructive CAD were excluded.The potential controls were males who visited the same hospital for health check-ups and had a normal electrocardiogram but no history of ischemic heart disease or CAD during the time period that the case patients were diagnosed. The eligible controls were randomly selected and frequency-matched with the case patients based on age. Multiple logistic regression analyses were used to estimate the odds ratio of areca nut chewing and the risk of obstructive CAD. RESULTS: A total of 293 obstructive CAD patients and 720 healthy controls, all men, were analyzed. Subjects who chewed areca nut had a 3.5-fold increased risk (95% CI = 2.0-6.2) of having obstructive CAD than those without, after adjusting for other significant covariates. The dose-response relationship of chewing areca nut and the risk of obstructive CAD was also noted. After adjusting for other covariates, the 2-way additive interactions for obstructive CAD risk were also significant between areca nut use and cigarette smoking, hypertension and dyslipidemia. CONCLUSIONS: Long-term areca nut chewing was an independent risk factor of obstructive CAD in Taiwanese men. Interactive effects between chewing areca nut and cigarette smoking, hypertension, and dyslipidemia were also observed for CAD risk. Further exploration of their underlying mechanisms is necessary.

Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity.

BACKGROUND: The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity. METHODS: Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay. RESULTS: All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media. CONCLUSIONS: Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.

Ruptured acute type B aortic dissection presenting with bilateral hemathoraces.

Hemathorax is an uncommon but well-described complication of type B acute aortic dissection. Due to the location and anatomic relations of the descending aorta, aortic rupture of acute type B aortic dissection usually causes a left hemathorax. We now report the case of a 42-year-old male who presented with an acute type B aortic dissection and bilateral hemathoraces.

Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.

BACKGROUND: Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. METHODS: Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). RESULTS: We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. CONCLUSIONS: These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.

Association between hypertension and primary mitral chordae tendinae rupture.

BACKGROUND: Mitral regurgitation from chordae tendinae rupture (CTR) may cause severe clinical symptoms and is a progressive disease that eventually results in the need for mitral valve surgery. Early recognition of CTR and identification of risk factors are important because early intervention increases the chances of survival. Hypertension may increase mitral valve complex mechanical strain and cause the chordae tendinae to rupture. METHOD: Using a cross-sectional study of medical files in one medical center in Taiwan, we enrolled 98 patients with mitral CTR and classified them into two groups, comprising 68 subjects (69%) without obvious predisposing factors (primary group) and 30 subjects (31%) with known predisposing causes (secondary group). RESULT: Of the subjects, 63 (64%) were men with a mean age of 57.5 +/- 1.5 years. The posterior mitral leaflet was most commonly involved (64%). The known predisposing factors in secondary group include mitral valve prolapse, infective endocarditis, and rheumatic heart disease. The patients who had primary CTR were older (59.9 +/- 1.6 v 52.1 +/- 3.1 years, P = .029), had a higher prevalence of hypertension (56% v 30%, P = .018) and complained more often of dyspnea (82% v 53%, P = .003) than the patients in the secondary group. Using binary logistic regression analyses, the variation in primary group was found to be independently explained by age (P = .039, odds ratio = 1.039, 95% confidence interval = 1.002 to 1.077) and hypertension (P = .048, odds ratio = 2.717, 95% confidence interval = 1.008 to 7.326). CONCLUSION: We conclude that hypertension was an independent predictor for primary CTR in this study.

Effects of total coronary artery occlusion on vascular endothieial growth factor and transforming growth factor beta.

Vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta1) play an important role in angiogenesis. We wanted to determine if concentrations of growth factors in the coronary sinus (CS) and right atrium (RA) are higher in coronary artery disease patients with total occlusions than in those with partial occlusions. Fifty-one patients scheduled for coronary artery angiography were evaluated for possible recruitment. A 6F Goodale-Lubin catheter was used to collect blood from the CS and RA. Data for all but four patients were gathered successfully, leaving 47 study patients. The reviewer was blinded to growth factor data when interpreting coronary angiographic findings. Of the 47 enrolled patients, 32 had at least one diseased vessel, seven of whom had at least one major total epicardial coronary occlusion. In all 32 patients, the concentrations of VEGF in the CS were higher than those in the RA (31.5 +/- 2.7 vs 27.1 +/- 1.8 pg/mL; p = 0.005). Patients with total occlusions had higher VEGF concentrations in the CS than those with non-total occlusions (38.9 +/- 8.0 vs 29.5 +/- 2.6 pg/mL; p = 0.037). The differences in TGF-beta1 in the two groups were not statistically significant. The higher CS VEGF concentrations in patients with total occlusion indicate that VEGF may play a part in the development of angiogenesis.

Arrhythmogenic right ventricular cardiomyopathy: three cases.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare disease characterized by replacement of myocardium with fibrofatty tissue. It mainly involves the right ventricle (RV) and causes abnormal RV performance. ARVC is the most common cause of sudden cardiac death in young Italian athletes because it induces malignant ventricular tachyarrhythmias. Clinical manifestations of ARVC may be different between Chinese and Western patients. In this paper, we share our experience of the clinical manifestations of ARVC and review previous reports of ARVC.