The Beneficial Effect of the SGLT2 Inhibitor Dapagliflozin in Alleviating Acute Myocardial Infarction-Induced Cardiomyocyte Injury by Increasing the Sirtuin Family SIRT1/SIRT3 and Cascade Signaling.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have a variety of cardiovascular and renoprotective effects and have been developed as novel agents for the treatment of heart failure. However, the beneficial mechanisms of SGLT2i on cardiac tissue need to be investigated further. In this study, we established a mouse model of acute myocardial infarction (AMI) using coronary artery constriction surgery and investigated the role of dapagliflozin (DAPA) in protecting cardiomyocytes from hypoxic injury induced by AMI. In vitro experiments were done using hypoxic cultured H9c2 ventricular cells to verify this potential mechanism. Expression of the SIRT family and related genes and proteins was verified by qPCR, Western blotting and immunofluorescence staining, and the intrinsic potential mechanism of cardiomyocyte death due to AMI and hypoxia was comprehensively investigated by RNA sequencing. The RNA sequencing results of cardiomyocytes from AMI mice showed that the SIRT family may be mainly involved in the mechanisms of hypoxia-induced cardiomyocyte death. In vitro hypoxia-induced ventricular cells showed the role of dapagliflozin in conferring resistance to hypoxic injury in cardiomyocytes. It showed that SIRT1/3/6 were downregulated in H9c2 cells in a hypoxic environment, and the addition of dapagliflozin significantly increased the gene and protein expression of SIRT1, 3 and 6. We then verified the underlying mechanisms induced by dapagliflozin in hypoxic cardiomyocytes using RNA-seq, and found that dapagliflozin upregulated the hypoxia-induced gene downregulation, which includes ESRRA, EPAS1, AGTRAP, etc., that associated with SIRTs-related and apoptosis-related signaling to prevent H9c2 cell death. This study provides laboratory data for SGLT2i dapagliflozin treatment of AMI and confirms that dapagliflozin can be used to treat hypoxia-induced cellular necrosis in cardiomyocytes, in which SIRT1 and SIRT3 may play an important role. This opens up further opportunities for SGLT2i in the treatment of heart disease.

Directed crystalline symmetry transformation of blue-phase liquid crystals by reverse electrostriction.

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials.

Novel prognostic impact and cell specific role of endocan in patients with coronary artery disease.

BACKGROUND: Both the clinical and mechanistic impacts of endocan were not well elucidated especially in coronary artery disease (CAD). OBJECTIVE: This study aimed to investigate the prognostic and potential pathological role of endocan for cardiovascular (CV) events in stable CAD patients. METHODS: A total of 1,071 stable CAD patients with previous percutaneous coronary intervention (PCI) were enrolled prospectively in a nationwide Biosignature study. Another cohort of 76 CAD patients with or without PCI were enrolled for validation. Baseline biomarkers including endocan level was measured and total CV events especially hard CV events (including CV mortality, non-fatal myocardial infection and stroke) during follow-up were identified. Circulating endothelial progenitor cells (EPCs) as an in vivo biological contributor to vascular repairment from CAD patients were used for the in vitro functional study. RESULTS: After 24 months, there were 42 patients (3.92%) with hard CV events and 207 (19.3%) with total CV events in the study group. The incidence of both events was increased with the tertiles of baseline endocan level (hard events: 1.7%,3.4%, and 6.7% in 1st,2nd, and 3rd tertile respectively, p = 0.002; total events: 13.8%vs.16.2%vs.28.0%, p < 0.0001). Multivariate regression analysis revealed the independent association of endocan level with total and hard CV events. These findings were validated in another cohort with a 5-year follow-up. Furthermore, in vitro inhibition of endocan improved cell migration and tube formation capacities, and reduced cell adhesiveness of EPCs from CAD patients. CONCLUSIONS: Endocan might be a novel prognostic indicator, mechanistic mediator, and potential therapeutic target for clinical CAD.

Taiwan Society of Cardiology Heart Failure Registry 2020: Rationale and Design.

Background: Heart failure (HF) is a significant public health problem worldwide. Death and rehospitalization rates are similar across different HF phenotypes. However, the existing Taiwanese HF registries mainly enrolled inpatients with HF and reduced ejection fraction (HFrEF) before 2019, so their results may not apply to outpatients or patients with HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF) phenotypes. Methods: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a prospective, multicenter, observational registry that will enroll patients with HF from 27 hospitals in Taiwan between 2020 and 2022 and will be followed for two years. Patients eligible for enrollment include those admitted due to acute decompensated heart failure or outpatients with a history of hospitalization for heart failure within the past six months. The registry will collect patient demographics, medical history, HF diagnosis, medication use, examination results, and comorbidities. The registry plans to enroll 3,370 patients, with the distribution of HFrEF/HFmrEF/HFpEF as 59%/13%/28%. Follow-up intervals will occur every six months for up to two years to monitor clinical outcomes and major cardiac interventions. The registry will conclude in December 2024. Conclusions: The Taiwan Society of Cardiology Heart Failure Registry 2020 is a comprehensive and meticulous effort to demonstrate the epidemiology, adherence to guidelines, clinical outcomes, and disease progression of Taiwanese patients with HF in contemporary clinical practice.

Exercise capacity-hemodynamics mismatch in elderly patients with pulmonary hypertension: A nationwide multicenter study from Taiwan Society of Cardiology Pulmonary Hypertension Registry (TAIPANS).

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Female showed favorable left ventricle hypertrophy regression during post-TAVR follow-up.

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.

Fatty acid-binding protein-3 and renal function decline in patients with chronic coronary syndrome.

BACKGROUND: Renal dysfunction is common in patients with coronary artery disease. Due to the shared vascular pathogenesis between the two conditions, novel biomarkers such as the fatty acid-binding protein-3 (FABP-3) have been proposed for diagnosis and prognosis prediction. This multicentre prospective cohort study investigates the association between FABP-3 and renal dysfunction. HYPOTHESIS: We hypothesized that higher FABP-3 levels are correlated to worse renal outcome. METHODS: Patients with chronic coronary syndrome were classified into three groups based on the initial serum FABP-3 levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the patient's renal function. Renal events were defined as >25% and >50% decline in estimated glomerular filtration rate (eGFR). Cox multivariable regression was employed to delineate the correlation between FABP-3 and renal dysfunction. RESULTS: A total of 1606 subjects were included. During a mean follow-up of 35.9 months, there were 239 patients with eGFR >25% reduction and 60 patients with >50% reduction. In the Kaplan-Meier survival curve and log-rank test, increased levels of FABP-3 were significantly correlated with eGFR >25% reduction (p < .001) and >50% reduction (p < .001). Multivariate Cox regression model revealed that subjects with higher FABP-3 exhibited a greater risk of eGFR >25% reduction (Group 2: hazard ratio [HR] = 2.328, 95% confidence interval [CI] = 1.521-3.562, p < .001; Group 3: HR = 3.054, 95% CI = 1.952-4.776, p < .001) and >50% reduction (Group 3: HR = 4.838, 95% CI = 1.722-13.591, p = .003). CONCLUSIONS: Serum FABP-3 may serve as a novel biomarker to predict eGFR decline in patients with chronic coronary syndrome.

Left Atrial Strain Predicts Cardiovascular and All-Cause Mortality.

Background: Left atrial strain can usefully reflect left atrial function. The follow-up periods in previous studies assessing left atrial strain as a survival predictor have been relatively short, and few studies have examined the ability of left atrial strain to predict mortality in patients with borderline diastolic function. This study sought to investigate the survival predictive value of left atrial strain with a longer follow-up duration. In addition, we also evaluated the survival predictive value of left atrial strain in patients with borderline diastolic function. Methods: In total, 652 participants who received routine echocardiography underwent 2-D speckle tracking echocardiography to evaluate left atrial reservoir function by peak atrial longitudinal strain. The study endpoints were all-cause and cardiovascular mortality. Results: The mean left atrial strain was 27.6%, and the median follow-up duration was 92 months. During follow-up, 72 patients died of cardiovascular causes and 181 died of all causes. Univariable Cox regression analysis revealed that lower left atrial strain significantly predicted an increase in all-cause and cardiovascular mortality. After adjusting for common clinical and echocardiographic parameters, lower left atrial strain was still associated with a higher risk of all-cause mortality [hazard ratio (HR) = 0.942, p = 0.011] and cardiovascular mortality (HR = 0.915, p = 0.018) in multivariable Cox-regression analysis. In addition, 293 patients had borderline left ventricular diastolic function. Multivariable analysis still revealed that left atrial strain could predict cardiovascular mortality in this population. Conclusions: Our data showed that left atrial strain could predict all-cause and cardiovascular mortality, even after adjusting for general clinical and echocardiographic parameters.

Taiwan Association for the Study of the Liver-Taiwan Society of Cardiology Taiwan position statement for the management of metabolic dysfunction- associated fatty liver disease and cardiovascular diseases.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

2023 TAMIS/TSOC/TACVPR Consensus Statement for Patients with Acute Myocardial Infarction Rehabilitation.

Cardiac rehabilitation is a comprehensive intervention recommended in international and Taiwanese guidelines for patients with acute myocardial infarction. Evidence supports that cardiac rehabilitation improves the health-related quality of life, enhances exercise capacity, reduces readmission rates, and promotes survival in patients with cardiovascular disease. The cardiac rehabilitation team is comprehensive and multidisciplinary. The inpatient, outpatient, and maintenance phases are included in cardiac rehabilitation. All patients admitted with acute myocardial infarction should be referred to the rehabilitation department as soon as clinically feasible. Pre-exercise evaluation, including exercise testing, helps physicians identify the risks of cardiac rehabilitation and organize appropriate exercise prescriptions. Therefore, the Taiwan Myocardial Infarction Society (TAMIS), Taiwan Society of Cardiology (TSOC), and Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation (TACVPR) address this consensus statement to assist healthcare practitioners in performing cardiac rehabilitation in patients with acute myocardial infarction.

Machine Learning Models for ASCVD Risk Prediction in an Asian Population - How to Validate the Model is Important.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is prevalent worldwide including Taiwan, however widely accepted tools to assess the risk of ASCVD are lacking in Taiwan. Machine learning models are potentially useful for risk evaluation. In this study we used two cohorts to test the feasibility of machine learning with transfer learning for developing an ASCVD risk prediction model in Taiwan. Methods: Two multi-center observational registry cohorts, T-SPARCLE and T-PPARCLE were used in this study. The variables selected were based on European, U.S. and Asian guidelines. Both registries recorded the ASCVD outcomes of the patients. Ten-fold validation and temporal validation methods were used to evaluate the performance of the binary classification analysis [prediction of major adverse cardiovascular (CV) events in one year]. Time-to-event analyses were also performed. Results: In the binary classification analysis, eXtreme Gradient Boosting (XGBoost) and random forest had the best performance, with areas under the receiver operating characteristic curve (AUC-ROC) of 0.72 (0.68-0.76) and 0.73 (0.69-0.77), respectively, although it was not significantly better than other models. Temporal validation was also performed, and the data showed significant differences in the distribution of various features and event rate. The AUC-ROC of XGBoost dropped to 0.66 (0.59-0.73), while that of random forest dropped to 0.69 (0.62-0.76) in the temporal validation method, and the performance also became numerically worse than that of the logistic regression model. In the time-to-event analysis, most models had a concordance index of around 0.70. Conclusions: Machine learning models with appropriate transfer learning may be a useful tool for the development of CV risk prediction models and may help improve patient care in the future.

Inflammation and renal function decline in chronic coronary syndrome: a prospective multicenter cohort study.

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 < 0.001), but not hs-CRP (P = 0.092), and eGFR decline. The aggregative effect of these biomarkers was also distinctly correlated with renal events (score 2: P = 0.042; score 3: P < 0.001). CONCLUSIONS: Inflammatory burden was associated with eGFR decline in patients with chronic coronary syndrome.

Effect of Limb Salvage by Excimer Laser Angioplasty Plus Low-Pressure Balloon Inflation in Chronic Limb-Threatening Ischemia Patients with Infrapopliteal Vessel Disease.

Background: Patients with chronic limb-threatening ischemia (CLTI) often exhibit long, diffuse, totally occluded and heavily calcified infrapopliteal (IP) lesions. This study evaluated limb salvage after peripheral excimer laser atherectomy (PELA) plus low-pressure balloon inflation (LPBI) without stent deployment in CLTI patients with severe IP disease. Methods: We retrospectively evaluated 70 consecutive patients with 109 IP vessels who underwent PELA plus LPBI from 2010 to 2013. Technical success was defined as at least one IP straight-line flow being achieved below the malleolus. Binary logistic regression was performed to identify factors associated with 6-month limb salvage. Results: Of the 109 IP vessels, 100 (91.7%) were totally occluded, and none of the patients received a stent. Of the 70 patients, 20% were octogenarians, and 85.8% had a Rutherford-Becker class 5 and 6. The technical success rate was 87.1% and 6-month limb salvage rate was 78.6%. Rutherford score was negatively correlated with clinical success (adjusted odds ratio 0.24; p = 0.028). No immediate major cardiovascular events were recorded during admission. Conclusions: PELA plus LPBI may be a treatment option for complex IP lesions in patients with CLTI. Higher Rutherford class was correlated with a lower 6-month limb salvage rate. However, a large-scale study with a control group is needed to clarify our results.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

The Incident Ocular Diseases Related to Chemotherapy in Cancer Patients are Associated with Increasing Risk of Incident Stroke.

Background: In addition to cardiotoxicity, ocular toxicity induced by chemotherapeutic agents is not uncommon. Objective: This study aimed to explore the association between ocular adverse events and major adverse cardiovascular events (composite endpoint) caused by chemotherapy, and whether specific ocular events could be potential predictors of some specific components of the composite endpoint. Methods: A total of 5378 newly diagnosed patients (age > 18 y/o) with any malignancy or metastatic solid tumors who received chemotherapy from January 1997 to December 2010 were enrolled from the Taiwan National Health Insurance Research Database. Patients who developed new incident ocular diseases were classified as the study group, and those who did not develop incident ocular diseases as the control group. Results: After propensity score matching, there was a significant increase in the incidence of stroke in the ocular diseases group compared to the no ocular diseases group (13.4% vs. 4.5%, p < 0.0001). Tear film insufficiency, keratopathy, glaucoma, and lens disorders were associated with a significantly higher risk of stroke. A longer duration of methotrexate and a longer duration with higher total amount of tamoxifen were associated with both incident ocular diseases and incident stroke. Cox proportional hazards regression showed that the only independent risk factor for stroke was incident ocular diseases [Adjusted relative risk (95% confidence interval): 2.96 (1.66-5.26), p = 0.0002]. In addition, incident ocular disease was the most significant risk factor compared with other traditional cardiovascular risk factors. Conclusions: Incident ocular diseases related to chemotherapy were associated with a significantly higher risk of stroke.

Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor Ameliorate Metabolic Disorder and Obesity Induced Cardiomyocyte Injury and Mitochondrial Remodeling.

Sodium-glucose transporter 2 inhibitors (SGLT2is) exert significant cardiovascular and heart failure benefits in type 2 diabetes mellitus (DM) patients and can help reduce cardiac arrhythmia incidence in clinical practice. However, its effect on regulating cardiomyocyte mitochondria remain unclear. To evaluate its effect on myocardial mitochondria, C57BL/6J mice were divided into four groups, including: (1) control, (2) high fat diet (HFD)-induced metabolic disorder and obesity (MDO), (3) MDO with empagliflozin (EMPA) treatment, and (4) MDO with glibenclamide (GLI) treatment. All mice were sacrificed after 16 weeks of feeding and the epicardial fat secretome was collected. H9c2 cells were treated with the different secretomes for 18 h. ROS production, Ca2+ distribution, and associated proteins expression in mitochondria were investigated to reveal the underlying mechanisms of SGLT2is on cardiomyocytes. We found that lipotoxicity, mitochondrial ROS production, mitochondrial Ca2+ overload, and the levels of the associated protein, SOD1, were significantly lower in the EMPA group than in the MDO group, accompanied with increased ATP production in the EMPA-treated group. The expression of mfn2, SIRT1, and SERCA were also found to be lower after EMPA-secretome treatment. EMPA-induced epicardial fat secretome in mice preserved a better cardiomyocyte mitochondrial biogenesis function than the MDO group. In addition to reducing ROS production in mitochondria, it also ameliorated mitochondrial Ca2+ overload caused by MDO-secretome. These findings provide evidence and potential mechanisms for the benefit of SGLT2i in heart failure and arrhythmias.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan.

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

An open-label randomized noninferior study of generic name and brand name of propafenone for rhythm control in patients with paroxysmal atrial fibrillation.

BACKGROUND: Propafenone is a class IC antiarrhythmic agent that is commonly used as the first-line therapy for patients with paroxysmal atrial fibrillation (AF) in Taiwan. This study compared the efficacy and safety of generic (Rhynorm) and brand name (Rytmonorm) propafenone for rhythm control of paroxysmal AF in Taiwan. METHODS: This was an open-label randomized multicenter noninferior study conducted in Taiwan. We enrolled 76 patients with AF. To investigate the efficacy of propafenone, we used a wearable electrocardiogram (ECG) event recorder to evaluate the daily burden of AF episodes in patients for 24 weeks. The primary efficacy endpoint was the frequency of AF with clinical significance, which was indicated by AF duration ≥30 seconds. The safety endpoints included proarrhythmic or hemodynamic adverse events. RESULT: To analyze the efficacy and safety of these agents, 71 patients (five patients with screen failure) were randomized to two groups, specifically a Rhynorm group (n = 37) and a Rytmonorm group (n = 34), for 24 weeks of the treatment period. The baseline patient characteristics were comparable between the groups. However, the Rhynorm group was older (65.4 ± 8.40 vs 59.8 ± 10.8 years; p = 0.02). The primary efficacy endpoint at week 24 decreased by 4.76% ± 18.5% (from 24.3% ± 33.9% to 19.0% ± 28.7%; p = 0.13) in the Rhynorm group and by 3.27% ± 15.2% (from 16.9% ± 26.4% to 13.6% ± 19.2%; p = 0.22) in the Rytmonorm group, with an intergroup difference of 1.5% ± 17.0%; p = 0.71. This finding indicates that Rhynorm is not inferior to Rytmonorm ( p = 0.023 for noninferiority). The safety profile of the agents was comparable between the two groups. CONCLUSION: Our results verified that Rhynorm was noninferior to Rytmonorm in terms of efficacy and safety for treating paroxysmal AF in Taiwan ( ClinicalTrials.gov Identifier: NCT03674658).

Prescription Pattern in Angiotensin Receptor Neprilysin Inhibitor is Associated with Heart Failure Events.

Background: Angiotensin receptor neprilysin inhibition (ARNI) is superior to enalapril in reducing the risk of cardiovascular death and heart failure hospitalization (HFH). However, whether prescription pattern is associated with heart failure outcome is unknown. Methods: This is a retrospective study of 153 patients who received ARNI in a tertiary medical center in Taiwan. We analyzed the impact of dose up-titration and prescription timing including during initial admission, within 3 months after initial HFH discharge, and at outpatient clinics without prior HFH. The primary endpoint was the composite of cardiovascular death and HFH. Results: After a mean follow-up period of 287 ± 197 days, the primary endpoint occurred in 43 (28.1%) subjects. Patients without and with a primary endpoint significantly differed in terms of history of valvular heart disease (VHD, p = 0.006), ventricular tachyarrhythmia (VT, p = 0.043), percutaneous coronary intervention (p = 0.007), coronary artery bypass grafting (p = 0.002), chronic kidney disease (p = 0.002), age (p = 0.002), diastolic blood pressure (p = 0.025), and prescription timing (p = 0.002). Kaplan-Meier analysis showed ARNI up-titration and prescription timing had a significant association with primary endpoint-free survival (Breslow test; p = 0.032, and log-rank test; p = 0.001, respectively). Cox regression analysis showed that independent predictors for the primary endpoint were ARNI up-titration [hazard ratio (HR): 0.41, p = 0.024], non-hospital ARNI versus hospital ARNI (HR: 0.41, p = 0.009), VHD (HR: 2.71, p = 0.013), VT (HR: 3.09, p = 0.02), and age (HR: 1.03, p = 0.033). Conclusions: The prescription pattern of ARNI could be associated with heart failure events.

2023 Guidelines of the Taiwan Society of Cardiology on the Diagnosis and Management of Chronic Coronary Syndrome.

Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of "stable CAD" may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.