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.

Machine learning-based prediction of coronary care unit readmission: A multihospital validation study.

Objective: Readmission to the coronary care unit (CCU) has significant implications for patient outcomes and healthcare expenditure, emphasizing the urgency to accurately identify patients at high readmission risk. This study aims to construct and externally validate a predictive model for CCU readmission using machine learning (ML) algorithms across multiple hospitals. Methods: Patient information, including demographics, medical history, and laboratory test results were collected from electronic health record system and contributed to a total of 40 features. Five ML models: logistic regression, random forest, support vector machine, gradient boosting, and multilayer perceptron were employed to estimate the readmission risk. Results: The gradient boosting model was selected demonstrated superior performance with an area under the receiver operating characteristic curve (AUC) of 0.887 in the internal validation set. Further external validation in hold-out test set and three other medical centers upheld the model's robustness with consistent high AUCs, ranging from 0.852 to 0.879. Conclusion: The results endorse the integration of ML algorithms in healthcare to enhance patient risk stratification, potentially optimizing clinical interventions, and diminishing the burden of CCU readmissions.

Prognostic Significance of Phenylalanine in Heart Failure: Clinical Insights and Inter-Organ Crosstalk Snapshot.

Background: Heart failure (HF) remains a leading cause of morbidity and mortality globally, necessitating the identification of reliable prognostic biomarkers to guide therapeutic interventions. Recent clinical observations have underscored phenylalanine (PHE) as a prognostic marker in HF, although the mechanisms involving inter-organ crosstalk remain understood. Methods: This study adopted a dull approach, with a retrospective analysis of 550 HF patients to establish the prognostic value of pre-discharge PHE levels and a study on the inter-organ crosstalk of PHE among 24 patients. We analyzed the correlations between PHE concentrations and clinical outcomes, alongside a comprehensive examination of PHE metabolism across the skeletal muscle, liver, heart, kidney, and lung. Results: In the clinical prognostic analysis of 550 patients hospitalized for acute decompensated HF, elevated PHE levels (≥65.6 µM) were significantly and independently associated with increased all-cause mortality during a median follow-up of 4.5 years (log rank = 36.7, p < 0.001), underscoring its value as a prognostic marker in HF. The inter-organic crosstalk study elucidated the mechanism associated with PHE elevation in patients with HF, characterized by an increase in PHE output in skeletal muscle and a decrease in hepatic and cardiac PHE uptakes. Notably, PHE concentration gradients across these organs were correlated with HF severity, such as the NYHA functional class, B-type natriuretic peptide levels, and the presence of acute HF. Conclusions: Our findings confirm the prognostic significance of PHE in patients with HF and unveil the complex metabolic interplay among key organs that contribute to PHE dysregulation. These insights not only reinforce the importance of metabolic monitoring in HF management but also open avenues for therapeutic targets.

2023 Expert Consensus of the Taiwan Society of Cardiology on the Diagnosis and Treatment of Cardiac Amyloidosis.

Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

Association between neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and long-term mortality in community-dwelling adults with heart failure: evidence from US NHANES 2005-2016.

BACKGROUND: Heart failure (HF) continues to be the major cause of hospitalizations. Despite numerous significant therapeutic progress, the mortality rate of HF is still high. This longitudianl cohort study aimed to investigate the associations between hematologic inflammatory indices neutrophil percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and all-cause mortality in community-dwelling adults with HF. METHODS: Adults aged 20 and older with HF in the US National Health and Nutrition Examination Survey (NHANES) database 2005-2016 were included and were followed through the end of 2019. Univariate and multivariable Cox regression analyses were performed to determine the associations between the three biomarkers and all-cause mortality. The receiver operating characteristics (ROC) curve analysis was conducted to evaluate their predictive performance on mortality. RESULTS: A total of 1,207 subjects with HF were included, representing a population of 4,606,246 adults in the US. The median follow-up duration was 66.0 months. After adjustment, the highest quartile of NPAR (aHR = 1.81, 95%CI: 1.35, 2.43) and NLR (aHR = 1.59, 95%CI: 1.18, 2.15) were significantly associated with increased mortality risk compared to the lowest quartile during a median follow-up duration of 66.0 months. Elevated PLR was not associated with mortality risk. The area under the ROC curve (AUC) of NPAR, NLR, and PLR in predicting deaths were 0.61 (95%CI: 0.58, 0.65), 0.64 (95%CI: 0.6, 0.67), and 0.58 (95%CI:0.55, 0.61), respectively. CONCLUSIONS: In conclusion, elevated NPAR and NLR but not PLR are independently associated with increased all-cause mortality among community-dwelling individuals with HF. However, the predictive performance of NPAR and NLR alone on mortality was low.

Combining Phenylalanine and Leucine Levels Predicts 30-Day Mortality in Critically Ill Patients Better than Traditional Risk Factors with Multicenter Validation.

In critically ill patients, risk scores are used; however, they do not provide information for nutritional intervention. This study combined the levels of phenylalanine and leucine amino acids (PLA) to improve 30-day mortality prediction in intensive care unit (ICU) patients and to see whether PLA could help interpret the nutritional phases of critical illness. We recruited 676 patients with APACHE II scores ≥ 15 or intubated due to respiratory failure in ICUs, including 537 and 139 patients in the initiation and validation (multicenter) cohorts, respectively. In the initiation cohort, phenylalanine ≥ 88.5 µM (indicating metabolic disturbance) and leucine < 68.9 µM (indicating malnutrition) were associated with higher mortality rate. Based on different levels of phenylalanine and leucine, we developed PLA scores. In different models of multivariable analyses, PLA scores predicted 30-day mortality independent of traditional risk scores (p < 0.001). PLA scores were then classified into low, intermediate, high, and very-high risk categories with observed mortality rates of 9.0%, 23.8%, 45.6%, and 81.8%, respectively. These findings were validated in the multicenter cohort. PLA scores predicted 30-day mortality better than APACHE II and NUTRIC scores and provide a basis for future studies to determine whether PLA-guided nutritional intervention improves the outcomes of patients in ICUs.

The Impact of FEV1/FVC Ratio on the Clinical Outcomes in Acute Coronary Syndrome Patients Treated with Dual Anti-Platelet Agents.

Background: Few studies have investigated the clinical efficacy and pulmonary side effects of different P2Y12 inhibitors in acute coronary syndrome (ACS) patients. The aim of this study was to explore the impact of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) ratio on the clinical outcomes in ACS patients treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Methods: ACS patients who underwent PCI, had documented pre-existing spirometry tests, and received aspirin with either ticagrelor or clopidogrel were enrolled for retrospective analysis. Results: Of the enrolled ACS patients, 275 and 247 received ticagrelor and clopidogrel, respectively. The incidence of wheeze was significantly higher in the ticagrelor group compared to the clopidogrel group within 360 days (14.91% vs. 8.09%, p = 0.016). Multivariable analysis revealed that ticagrelor treatment, as compared to clopidogrel treatment, independently predicted 1-year hospitalization for acute exacerbation (AE) of obstructive airway disease (hazard ratio: 3.44; 95% confidence interval: 1.92 to 6.15; p < 0.01). The receiver operating characteristic curve indicated that an FEV1/FVC ratio of 63.85% had the highest sensitivity and specificity for predicting the incidence of AE of obstructive airway disease within 1 year (p < 0.001). The 1-year hospitalization rate for AE of obstructive airway disease was significantly higher in the ticagrelor group when the FEV1/FVC ratio was < 63%. Conclusions: This study demonstrated higher incidence of wheeze and hospitalization for AE of obstructive airway disease in ACS patients treated with ticagrelor compared to clopidogrel. Furthermore, the FEV1/FVC ratio ≤ 63% in the ACS patients predicted hospitalization for AE of obstructive airway disease in 1 year.

Optimizing exercise testing-based risk stratification to predict poor prognosis after acute heart failure.

AIMS: The timely selection of severe heart failure (HF) patients for cardiac transplantation and advanced HF therapy is challenging. Peak oxygen consumption (VO2 ) values obtained by the cardiopulmonary exercise testing are used to determine the transplant recipient list. This study reassessed the prognostic predictability of peak VO2 and compared it with the Heart Failure Survival Score (HFSS) in the modern optimized guideline-directed medical therapy (GDMT) era. METHODS AND RESULTS: We retrospectively selected 377 acute HF patients discharged from the hospital. The primary outcome was a composite of all-cause mortality, or urgent cardiac transplantation. We divided these patients into the more GDMT (two or more types of GDMT) and less GDMT groups (fewer than two types of GDMT) and compared the performance of their peak VO2 and HFSS in predicting primary outcomes. The median follow-up period was 3.3 years. The primary outcome occurred in 57 participants. Peak VO2 outperformed HFSS when predicting 1 year (0.81 vs. 0.61; P = 0.017) and 2 year (0.78 vs. 0.58; P < 0.001) major outcomes. The cutoff peak VO2 for predicting a 20% risk of a major outcome within 2 years was 10.2 (11.8-7.0) for the total cohort. Multivariate Cox regression analyses showed that peak VO2 , sodium, previous implantable cardioverter defibrillator (ICD) implantation, and estimated glomerular filtration rate were significant predictors of major outcomes. CONCLUSIONS: Optimizing the cutoff value of peak VO2 is required in the current GDMT era for advanced HF therapy. Other clinical factors such as ICD use, hyponatraemia, and chronic kidney disease could also be used to predict poor prognosis. The improvement of resource allocation and patient outcomes could be achieved by careful selection of appropriate patients for advanced HF therapies, such as cardiac transplantation.

Improve the Prevention of Sudden Cardiac Arrest in Patients With Post-Acute Myocardial Infarction.

Background: Implantable cardioverter-defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in post-myocardial infarction (MI) patients varies by geography but remains low in many regions despite guideline recommendations. Objectives: This study aimed to characterize the care pathway of post-MI patients and understand barriers to referral for further SCD risk stratification and management in patients meeting referral criteria. Methods: This prospective, nonrandomized, multi-nation study included patients ≥18 years of age, with an acute MI ≤30 days and left ventricular ejection fraction <50% ≤14 days post-MI. The primary endpoint was defined as the physician's decision to refer a patient for SCD stratification and management. Results: In total, 1,491 post-MI patients were enrolled (60.2 ± 12.0 years of age, 82.4% male). During the study, 26.7% (n = 398) of patients met criteria for further SCD risk stratification; however, only 59.3% of those meeting criteria (n = 236; 95% CI: 54.4%-64.0%) were referred for a visit. Of patients referred for SCD risk stratification and management, 94.9% (n = 224) attended the visit of which 56.7% (n =127; 95% CI: 50.1%-63.0%) met ICD indication criteria. Of patients who met ICD indication criteria, 14.2% (n = 18) were implanted. Conclusions: We found that ∼40% of patients meeting criteria were not referred for further SCD risk stratification and management and ∼85% of patients who met ICD indications did not receive a guideline-directed ICD. Physician and patient reasons for refusing referral to SCD risk stratification and management or ICD implant varied by geography suggesting that improvement will require both physician- and patient-focused approaches. (Improve Sudden Cardiac Arrest [SCA] Bridge Study; NCT03715790).

The Performance of Risk Scores for Bleeding and Ischemia as Outcome Predictors in Acute Myocardial Infarction Patients with End-Stage Renal Disease.

Background: In patients with end-stage renal disease (ESRD), acute myocardial infarction (AMI) increases the risks of cardiovascular events, death, and bleeding. Several scores have been developed for predicting ischemic and bleeding outcomes in AMI patients, but none have been validated specifically for ESRD patients. Objectives: To compare and validate different risk scores as predictors of ischemic and bleeding outcomes in AMI patients with ESRD. Methods: This retrospective study enrolled 340 patients who had received percutaneous coronary intervention for AMI while undergoing maintenance hemodialysis for ESRD. Ischemic risk scores (TIMI-STEMI, TIMI-NSTEMI, GRACE, DAPT) and bleeding risk scores (PRECISE-DAPT, CRUSADE, ACUITY, ACTION, SWEDEHEART) were calculated. The ischemic outcome mainly focused on major adverse cardiovascular events (MACEs) within 14 days after hospitalization, and the bleeding outcome was 14-day major bleeding according to the CRUSADE criteria. Results: The GRACE score was superior in discriminating ischemic outcomes, especially in 14-day MACEs [area under curve (AUC) 0.791, p < 0.001]. None of the scores could ideally discriminate 14-day CRUSADE major bleeding, while the PRECISE- DAPT score had the best discriminative power (AUC 0.636, p < 0.001). Either GRACE score > 222 or PRECISE-DAPT score > 48 was associated with higher net adverse cardiovascular events (a composite of 14-day MACEs and 14-day CRUSADE major bleeding). Conclusions: In AMI patients with ESRD, the GRACE score can effectively discriminate the risk of short-term ischemic events. None of the scores could ideally discriminate the bleeding risk, but a high PRECISE-DAPT score still represented a higher rate of bleeding events.

Outcomes With Multidisciplinary Cardiac Rehabilitation in Post-acute Systolic Heart Failure Patients-A Retrospective Propensity Score-Matched Study.

Background: Cardiac rehabilitation (CR) is recommended for patients with acute heart failure (HF). However, the results of outcome studies and meta-analyses on CR in post-acute care are varied. We aimed to assess the medium- to long-term impact of CR and ascertain the predictors of successful CR. Methods: In this propensity score-matched retrospective cohort study, records of consecutive patients who survived acute HF (left ventricular ejection fraction <40) and participated in a multidisciplinary HF rehabilitation program post-discharge between May 2014 and July 2019 were reviewed. Patients in the CR group had at least one exercise session within 3 months of discharge; the others were in the non-CR group. After propensity score matching, the primary (all-cause mortality) and secondary (HF readmission and life quality assessment) outcomes were analyzed. Results: Among 792 patients, 142 attended at least one session of phase II CR. After propensity score matching for covariates related to HF prognosis, 518 patients were included in the study (CR group, 137 patients). The all-cause mortality rate was 24.9% and the HF rehospitalization rate was 34.6% in the median 3.04-year follow-up. Cox proportional hazard analysis revealed that the CR group had a significant reduction in all-cause mortality compared to the non-CR group (hazard ratio [HR]: 0.490, 95% confidence interval [CI]: 0.308-0.778). A lower risk of the primary outcome with CR was observed in patients on renin-angiotensin-aldosterone system (RAAS) inhibitors, but was not seen in patients who were not prescribed this class of medications (interaction p = 0.014). Conclusions: Cardiac rehabilitation participation was associated with reduced all-cause mortality after acute systolic heart failure hospital discharge. Our finding that the benefit of CR was decreased in patients not prescribed RAAS inhibitors warrants further evaluation.

Risk Stratification Model for Predicting Coronary Care Unit Readmission.

Background: Use of statistical models for assessing the clinical risk of readmission to medical and surgical intensive care units is well established. However, models for predicting risk of coronary care unit (CCU) readmission are rarely reported. Therefore, this study investigated the characteristics and outcomes of patients readmitted to CCU to identify risk factors for CCU readmission and to establish a scoring system for identifying patients at high risk for CCU readmission. Methods: Medical data were collected for 27,841 patients with a history of readmission to the CCU of a single multi-center healthcare provider in Taiwan during 2001-2019. Characteristics and outcomes were compared between a readmission group and a non-readmission group. Data were segmented at a 9:1 ratio for model building and validation. Results: The number of patients with a CCU readmission history after transfer to a standard care ward was 1,790 (6.4%). The eleven factors that had the strongest associations with CCU readmission were used to develop and validate a CCU readmission risk scoring and prediction model. When the model was used to predict CCU readmission, the receiver-operating curve characteristic was 0.7038 for risk score model group and 0.7181 for the validation group. A CCU readmission risk score was assigned to each patient. The patients were then stratified by risk score into low risk (0-12), moderate risk (13-31) and high risk (32-40) cohorts check scores, which showed that CCU readmission risk significantly differed among the three groups. Conclusions: This study developed a model for estimating CCU readmission risk. By using the proposed model, clinicians can improve CCU patient outcomes and medical care quality.

6-methoxyflavone suppresses neuroinflammation in lipopolysaccharide- stimulated microglia through the inhibition of TLR4/MyD88/p38 MAPK/NF-κB dependent pathways and the activation of HO-1/NQO-1 signaling.

BACKGROUND: Microglia-related neuroinflammation is associated with a variety of neurodegenerative diseases. Flavonoids have demonstrated different pharmacological effects, such as antioxidation, neuroprotection and anti-inflammation However, the effect of flavonoid 6-methoxyflavone (6-MeOF) on microglia-mediated neuroinflammation remain unknown. PURPOSE: The current study aim to study the antineuroinflammatory effects of 6-MeOF in lipopolysaccharide- (LPS-) induced microglia in vitro and in vivo. METHODS: Pretreatment of BV2 microglia cells with 6-MeOF for 1 h then stimulated with LPS (100 ng/ml) for 24 h. The expression levels of pro-inflammatory factors, NO and reactive oxygen species (ROS) were performed by the enzyme-linked immunosorbent assay (ELISA), Griess assay and flow cytometry. Western blotting was used to assess MAPK, NF-κB signal transducer and antioxidant enzymes-related proteins. Analysis of ROS and microglial morphology was confirmed in the zebrafish and mice brain, respectively. RESULTS: Our results demonstrated that 6-MeOF dose-dependently prevent cell death and decreased the levels of pro-inflammatory mediators in LPS-stimulated BV2 microglia cells. Phosphorylated NF-κB/IκB and TLR4/MyD88/p38 MAPK/JNK proteins after exposure to 6-MeOF was suppressed in LPS-activated BV-2 microglial cells. 6-MeOF also presented antioxidant activity by reduction of NO, ROS, iNOS and COX-2 and the induction of the level of HO-1 and NQO1 expressions in LPS-activated BV2 microglial cells. Furthermore, we demonstrated that 6-MeOF inhibited LPS-induced NO generation in an experimental zebrafish model and prevent the LPS-induced microgliosis in the prefrontal cortex and substantia nigra of mice. CONCLUSION: These results explored that 6-MeOF possesses potential as anti-inflammatory and anti-oxidant agents against microglia-associated neuroinflammatory disorders.

Comparison of Different Risk Scores for Prediction of In-Hospital Mortality in STEMI Patients Treated with PPCI.

Background: Several risk scores have been developed to predict and analyze in-hospital mortality and short- and long-term outcomes of ST-elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PPCI); these can classify patients as having a high or low risk of death or complications. Objective: To compare the prognostic precision of four risk scores for predicting in-hospital mortality in patients with STEMI treated with PPCI. Methods: We performed a retrospective cohort analysis of patients with STEMI who underwent PPCI between 2012 and 2019 (N = 1346). GRACE (Global Registry of Acute Cardiac Events), CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications), Zwolle, and TIMI (Thrombolysis in Myocardial Infarction) risk scores were calculated for each patient according to different variables. We evaluated the predictive accuracy of these scores for in-hospital mortality using the C statistic, which was obtained using logistic regression and receiver operating characteristic curves. Results: The GRACE, CADILLAC, Zwolle, and TIMI risk scores all had good predictive precision for in-hospital mortality, with C statistics ranging from 0.842 to 0.923. The GRACE and CADILLAC risk scores were found to be superior. Conclusions: All GRACE, CADILLAC, Zwolle, and TIMI risk scores showed a high predictive value for in-hospital mortality due to all causes in patients with STEMI treated with PPCI. The GRACE and CADILLAC risk scores revealed a better accuracy for predicting in-hospital mortality than the Zwolle and TIMI risk scores.

Weather Impact on Acute Myocardial Infarction Hospital Admissions With a New Model for Prediction: A Nationwide Study.

Introduction: Cardiovascular disease is one of the leading causes of mortality worldwide. Acute myocardial infarction (AMI) is associated with weather change. The study aimed to investigate if weather change was among the risk factors of coronary artery disease to influence AMI occurrence in Taiwan and to generate a model to predict the probabilities of AMI in specific weather and clinical conditions. Method: This observational study utilized the National Health Insurance Research Database and daily weather reports from Taiwan Central Weather Bureau to evaluate the discharge records of patients diagnosed with AMI from various hospitals in Taiwan between January 1, 2008 and December 31, 2011. Generalized additive models (GAMs) were used to estimate the effective parameters on the trend of the AMI incidence rate with respect to the weather and health factors in the time-series data and to build a model for predicting AMI probabilities. Results: A total of 40,328 discharges were listed. The minimum temperature, maximum wind speed, and antiplatelet therapy were negatively related to the daily AMI incidence; however, a drop of 1° when the air temperature was below 15°C was associated with an increase of 1.6% of AMI incidence. By using the meaningful parameters including medical and weather factors, an estimated GAM was built. The model showed an adequate correlation in both internal and external validation. Conclusion: An increase in AMI occurrence in colder weather has been evidenced in the study, but the influence of wind speed remains uncertain. Our analysis demonstrated that the novel GAM model can predict daily onset rates of AMI in specific weather conditions.

Oxidized low-density lipoprotein induced hepatoma-derived growth factor upregulation mediates foam cell formation of cultured rat aortic vascular smooth muscle cells.

Vascular smooth muscle cells (SMCs) are important vascular components that are essential for the regulation of vascular functions during vascular atherosclerogenesis and vascular injury. Oxidized low-density lipoprotein (oxLDL) is known to induce SMC activation and foam cell transformation. This study characterized the role of hepatoma-derived growth factor (HDGF) in oxLDL-induced foam cell formation in cultured primary rat aortic SMCs. OxLDL exposure significantly increased HDGF expression and extracellular release. It also upregulated atherogenic regulators in SMCs, including TLR4, MyD88, LOX-1, and CD36. Exogenous HDGF stimulation not only increased the expression of cognate receptor nucleolin, but also the innate immunity regulators TLR4/MyD88 and lipid metabolism regulators, including LOX-1 and CD36. Oil red O staining showed that HDGF did not initiate, but enhanced oxLDL-driven foam cell formation in SMCs. Further signaling characterization demonstrated that oxLDL evoked activation of PI3K/Akt and p38 MAPK signaling pathways, both of which were involved in the upregulation of HDGF, LOX-1, and CD36 induced by oxLDL. Gene knockdown experiments using LOX-1 targeted siRNA demonstrated that LOX-1 expression was critical for oxLDL-induced HDGF upregulation, while HDGF gene depletion completely abolished oxLDL-triggered TLR4, LOX-1, and CD36 overexpression and foam cell formation in SMCs. These findings strongly suggest that oxLDL-induced HDGF upregulation participates in subsequent LOX-1 and CD36 expression in aortic SMCs and mechanistically contributes to the formation of SMC-derived foam cells. The oxLDL/LOX-1/HDGF axis may serve as a target for anti-atherogenesis therapy.

Feature and impact of guideline-directed medication prescriptions for heart failure with reduced ejection fraction accompanied by chronic kidney disease.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Influence of the Coronavirus Disease 2019 Pandemic on Patients with ST-Segment Elevation Myocardial Infarction in Taiwan.

The outbreak of the new coronavirus disease 2019 (COVID-19) has notably affected the medical system worldwide and influenced the health-seeking behavior of people while depleting medical resources, causing a delay in ST-elevation myocardial infarction (STEMI) management. In this single-center, retrospective cohort study, we compared the clinical pictures of nontransfer patients who presented to the emergency department directly and received primary percutaneous cardiovascular intervention (PPCI) from February 1 to April 30, 2020 (group 2, N = 28), with patients who received PPCI from February 1 to April 30, 2016-2019 (group 1, N = 130). A total of 158 patients with STEMI who received PPCI were included in the study. A decrease in the percentage of patients with door-to-balloon time <90 minutes was found in group 2 (64.3% vs. 81.5%, p = 0.044). The adjusted odds ratio was calculated using logistic regression, according to potential confounding factors such as age, sex, off-hours, and Killip class. An adjusted odds ratio of 2.45 (95% confidence interval, 1.1-6.0, p = 0.048) was reported for group 2. A decrease in the percentage of patients meeting the criteria of door-to-balloon time <90 minutes was demonstrated, and differences were revealed in the clinical pictures of patients with STEMI after the pandemic. While systemic factors contributed the most, improvements and adjustments in the protocols for managing patients with STEMI for better outcomes in the COVID-19 era have yet to be studied.

Feasibility and Safety of Chronic Total Occlusion Percutaneous Coronary Intervention via Distal Transradial Access.

Aims: The current study aims to verify the feasibility and safety of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) via the distal transradial access (dTRA). Methods: Between April 2017 and December 2019, 298 patients who underwent CTO PCI via dTRA were enrolled in this study. The baseline demographic and procedural characteristics were listed and compared between groups. The incidences of access-site vascular complications and procedural complications and mortality were recorded. Results: The mean J-CTO (Japanese chronic total occlusion) score was 2.6 ± 0.9 points. The mean access time was 4.6 ± 2.9 min, and the mean procedure time was 115.9 ± 55.6 min. Left radial snuffbox access was performed successfully in 286 patients (96.5%), and right radial snuffbox access was performed successfully in 133 patients (97.7%). Bilateral radial snuffbox access was performed in 107 patients (35.9%). 400 dTRA (95.5%) received glidesheath for CTO intervention. Two patients (0.7%) developed severe access-site vascular complications. None of the patients experienced severe radial artery spasm and only 2 patients (0.5%) developed radial artery occlusion during the follow-up period. The overall procedural success rate was 93.5%. The procedural success rate was 96.5% in patients with antegrade approach and 87.7% in patients with retrograde approach. Conclusions: It is both safe and feasible to use dTRA plus Glidesheath for complex CTO intervention. The incidences of procedure-related complications and severe access-site vascular complications, and distal radial artery occlusion were low.

Residual Right Coronary Artery Stenosis after Left Main Coronary Artery Intervention Increased the 30-Day Cardiovascular Death and 3-Year Right Coronary Artery Revascularization Rate.

BACKGROUND: The outcomes of patients with concomitant left main coronary artery (LMCA) and right coronary artery (RCA) diseases are reportedly worse than those with only LMCA disease. To date, only few studies have investigated the clinical impact of percutaneous coronary intervention (PCI) on RCA stenosis during the same hospitalization, in which LMCA disease was treated. This study was aimed at comparing the outcomes between patients with and without right coronary artery intervention during the same hospital course for LMCA intervention. METHODS AND RESULTS: From a total of 776 patients who were undergoing PCI to treat LMCA disease, 235 patients with concomitant RCA significant stenosis (more than 70% stenosis) were enrolled. The patients were divided into two groups: 174 patients received concomitant PCI for RCA stenosis during the same hospitalization, in which LMCA disease was treated, and 61 patients did not receive PCI for RCA stenosis. Patients without intervention to the right coronary artery had higher 30-day cardiovascular mortality rates and 3-year RCA revascularization rates compared to those with right coronary artery intervention. Patients without RCA intervention at the same hospitalization did not increase the 30-day total death, 3-year myocardial infarction rate, 3-year cardiovascular death, and 3-year total death. CONCLUSIONS: In patients with LM disease and concomitant above or equal to 70% RCA stenosis, PCI for RCA lesion during the same hospitalization is recommended to reduce the 30-day cardiovascular death and 3-year RCA revascularization rate.