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.

A Mobile-Based Nutrition Tracker App Enhanced Dietitian-Guided 2:1:1 Diet-Induced Weight Loss: An 8-Week Retrospective Cohort Study in Taiwan.

Effective weight management interventions involve a combination of behavioral strategies focusing on dietary changes. Tracing the change through mobile apps has been proven to be a valuable platform for facilitating weight management in many countries. However, the effectiveness of mobile app-based dietary intervention on weight management in Taiwan remains to be determined. By using the designated mobile app, this study aimed to assess the efficacy of the diet intervention, which is based on a 2:1:1 portion control plate and a flexible low-carbohydrate (FLC) diet. This 8-week retrospective cohort study involved 10,297 participants who were divided into two groups: the intervention group (joined an 8-week diet intervention program with the daily diet record assessed by registered dietitians) and the control group (voluntarily using the app without instructional materials or coaching). After eight weeks of intervention, the intervention group showed a higher weight loss percentage (-4.78% vs. -1.54%), body mass index (BMI) (-1.26 kg/m2 vs. 0.69 kg/m2), and diet record completeness (73.52% vs. 28.91%) compared with the control group. With respect to gender, male participants showed higher baseline weight and higher weight loss (-6.02%) in the intervention group. In the intervention group, 2871 participants (33.4%) lost less than 4% of their weight, 5071 participants (58.9%) lost 4-8% of their body weight, and 662 participants (7.7%) lost >8% of their weight. Compared to the low-effectiveness group (weight lost <4%), the high-effectiveness group (weight lost >8%) had a significantly higher diet record completeness (91.61 ± 15.99 vs. 55.81 ± 32.92), dietary compliance (green light %) (88.93 ± 9.9 vs. 77.75 ±17.5), protein intake % (26.34 ± 2.85 vs. 23.49 ± 3.56), and fat intake % (49.66 ± 6.36 vs. 44.05 ± 7.37). Most importantly, the high-effectiveness group had a lower carbohydrate intake % (24.1 ± 7.86 vs. 32.46 ± 9.61). The results remained significant after being stratified by gender. This study found that the use of online applications plus the intervention of dietitians is beneficial for short-term weight loss. The composition of nutrients and dietary compliance also significantly impacted weight loss.

Cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus and cancer: a systematic review and meta-analysis.

BACKGROUND: Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer. METHODS: We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity. RESULTS: Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I2 = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I2 = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I2 = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I2 = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I2 = 0%). CONCLUSIONS: SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Effects of canagliflozin on cardiac remodeling and hemodynamic parameters in patients with type 2 diabetes mellitus.

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e', left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.

Reduced-Dose Rivaroxaban Is Associated with Lower All-Cause Mortality in Older Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Reduced-dose rivaroxaban (10 mg) was used in the J-ROCKET AF trial, demonstrating safety in the Asian population. It remains unclear whether treatment with reduced-dose versus full-dose rivaroxaban (20 mg/15 mg) is associated with all-cause mortality in older patients with nonvalvular atrial fibrillation. Proposed: To evaluate the effects of reduced-dose rivaroxaban on all-cause mortality in patients over 85. METHODS: We retrospectively enrolled medical records representing the period from October 2012 to November 2016. The 2 × 2 factorial design incorporated age (≥85 vs. <85) and rivaroxaban use (reduced vs. full dose). The primary study outcomes were all-cause and cardiac-related mortality. RESULTS: The study enrolled 2386 patients with a mean age of 76.6 ± 10.4 years; 51.8% were male. In the ≥85 group (n = 593), the reduced-dose subgroup had lower all-cause (5.3% vs. 10.6%, p = 0.02) and cardiac-related mortality (1.9% vs. 5.1%, p = 0.04), whereas the younger patients receiving reduced-dose rivaroxaban had higher all-cause mortality (3.7% vs. 1.8%, p = 0.01) but no difference in cardiac-related mortality (1.2% vs. 0.7%, p = 0.33). The rate of hospitalization for heart failure was significantly lower in the elderly group with reduced-dose rivaroxaban (7.2% vs. 15.7%, p < 0.01) but not in the younger group. After adjusting for confounders in the older group, treatment with reduced-dose rivaroxaban was associated with lower risk of all-cause mortality (adjusted HR (aHR): 0.40, 95% CI: 0.21-0.74, p < 0.01) and hospitalization for heart failure (aHR: 0.54, 95% CI: 0.29-0.99, p = 0.05). No associations were found between rivaroxaban dose and cardiac-related mortality in either group, nor between younger age and any outcome. CONCLUSIONS: Reduced-dose rivaroxaban was associated with lower risks of all-cause mortality and hospitalization for heart failure in older patients with nonvalvular atrial fibrillation. Future studies can investigate the effect of reduced-dose rivaroxaban on prognoses in elderly individuals ≥85 years in the west.

Iron deficiency in Taiwanese patients with heart failure and reduced ejection fraction.

BACKGROUND: Iron deficiency (ID) is a common comorbidity among patients with heart failure and reduced ejection fraction (HFrEF), and is associated with poorer outcomes independent of anemia. This study aimed to evaluate the prevalence and prognostic significance of ID in Taiwanese patients with HFrEF. METHODS: We included HFrEF patients from two multicenter cohorts at different periods. The multivariate Cox regression analysis was applied to assess the risk of outcomes associated with ID, accounting for the varying risk of death. RESULTS: Of the 3612 patients with HFrEF registered from 2013 to 2018, 665 patients (18.4%) had available baseline iron profile measurements. Of these, 290 patients (43.6%) were iron deficient; 20.2% had ID+/anemia+, 23.4% ID+/anemia-, 21.5% ID-/anemia+, and 34.9% ID-/anemia-. Regardless of anemia status, patients with coexisting ID had a higher risk than those without ID (all-cause mortality: 14.3 vs 9.5 per 100 patient-years, adjusted hazard ratio [HR] 1.33; 95% confidence interval [CI], 0.96-1.85; p = 0.091; cardiovascular mortality: 10.5 per 100 patient-years vs 6.1, adjusted HR 1.54 [95% CI, 1.03-2.30; p = 0.037]; cardiovascular mortality or first unplanned hospitalization for HF: 36.7 vs 19.7 per 100 patient-years, adjusted HR 1.57 [95% CI, 1.22-2.01; p < 0.001]). Among patients eligible for treatment in the IRONMAN trial design (43.9%), parenteral iron therapy was estimated to reduce heart failure hospitalizations and cardiovascular deaths by 13.7 per 100 patient-years. CONCLUSION: Iron profiles were tested in less than one-fifth of the Taiwanese HFrEF cohort. ID was present in 43.6% of tested patients and was independently associated with poor prognosis in these patients.

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.

Early detection of myocardial ischemia in resting ECG: analysis by HHT.

BACKGROUND: Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert-Huang transformation (HHT) in patients with angina pectoris. METHODS: Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect. RESULTS: After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test. CONCLUSIONS: Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

Risks and outcomes of critical limb ischemia in hemodialysis patients: a prospective cohort study.

Background: Peripheral arterial disease (PAD) is more common in patients receiving maintenance hemodialysis than in the general population. Critical limb ischemia (CLI), the most severe form of PAD, is associated with high amputation and mortality risk. However, few prospective studies are available evaluating this disease's presentation, risk factors and outcomes for patients receiving hemodialysis. Methods: The Hsinchu VA study, a prospective multicentre study, investigated the impact of clinical factors on cardiovascular outcomes of patients receiving maintenance hemodialysis from January 2008 until December 2021. We evaluated the presentations and outcomes of patients with newly diagnosed PAD and the correlations of clinical variables with newly diagnosed CLI. Results: Of 1136 study participants, 1038 had no PAD on enrolment. After a median follow-up period of 3.3 years, 128 had newly diagnosed PAD. Of these, 65 presented with CLI, and 25 underwent amputation or died from PAD. Patients presenting with CLI had more below-the-knee (52%) and multi-level (41%) disease, and completely occluded segments (41%), and higher risk for amputation or PAD-related death compared with patients without CLI (27.7% vs 9.5%, P = .01). After multivariate adjustment, disability, diabetes mellitus, current smoking and atrial fibrillation were significantly associated with newly diagnosed CLI. Conclusions: Patients undergoing hemodialysis had higher rates of newly diagnosed CLI than the general population. Those with disabilities, diabetes mellitus, smoking and atrial fibrillation may require careful examination for PAD. Trial registration: Hsinchu VA study, ClinicalTrials.gov identifier: NCT04692636.

The Removal, Excision, Sterilization, and Quarantine (RESQ) Method is a Feasible Alternative Treatment for Cardiac Implantable Electronic Device Infections.

Background: Current guidelines recommend that all infected cardiac implantable electronic devices (CIEDs) should be removed. However, financial or anatomical concerns can lead to management of infection with simple debridement, as opposed to complete removal. In this observational study, we report the outcomes of our modified procedure for this real-world dilemma. Methods and Results: The Quarantine (RESQ) method is characterized as follows: the removal (R) of all non-essential foreign materials, including old sutures and leads; the excision (E) of all non-viable, chronically inflamed, granulation, or scar tissue; the sterilization (S) of the remaining generator; and the quarantine (Q) of a new pocket in the sub-muscular layer for reimplantation. From a review of electronic medical records, 30 patients were selected and divided into three groups according to the intervention used: RESQ (n = 9) in group A, simple debridement (n = 16) in group B, and guideline-recommended replacement (n = 5) in group C. Patient baseline characteristics were similar between the groups. After analyzing the proportion of patients that were free from infection one year following their respective interventions, we found that group A performed better than group B (100% and 31.2% infection-free, respectively, p = 0.001), and was comparable to group C (both 100% infection-free, p = not applicable). Conclusions: The RESQ method is a feasible and beneficial alternative for selected patients with CIED infections who are unable to receive a generator replacement according to the recommended guideline.

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.

Real-World Analyses of the Treatment Conditions in Patients Initiating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor in Taiwan.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan. METHODS: This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan. RESULTS: A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HIS＋ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (p＜0.01), corresponding to a 49.6%±31.8% LDL-C reduction. CONCLUSIONS: In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.

The Autonomic Imbalance of Myocardial Ischemia during Exercise Stress Testing: Insight from Short-Term Heart Rate Variability Analysis.

Exercise stress testing (EST) has limited power in diagnosing obstructive coronary artery disease (CAD). The heart rate variability (HRV) analysis might increase the sensitivity of CAD detection. This study aimed to evaluate the correlation between short-term HRV and myocardial ischemia during EST, including the acceleration, maximum, and recovery stages of heart rate (HR). The HRV during EST from 19 healthy (RHC) subjects and 35 patients with CAD (25 patients with insignificant CAD (iCAD), and 10 patients with significant CAD (sCAD)) were compared. As a result, all HRV indices decreased at the maximum stage and no significant differences between iCAD and sCAD were found. The low-frequency power of heart rate signal (LF) of the RHC group recovered relatively quickly from the third to the sixth minutes after maximum HR, compared with that of the sCAD group. The relative changes of most HRV indices between maximum HR and recovery stage were lower in the sCAD group than in the RHC group, especially in LF, the standard deviation of all normal to normal intervals (SDNN), and the standard deviation in the long axis direction of the Poincaré plot analysis (SD2) indices (p < 0.05). The recovery slope of LF was significantly smaller in the sCAD group than in the RHC group (p = 0.02). The result suggests that monitoring short-term HRV during EST provides helpful insight into the cardiovascular autonomic imbalance in patients with significant CAD. The relative change of autonomic tone, especially the delayed sympathetic recovery, could be an additional marker for diagnosing myocardial ischemia.

A collaborative study to establish the national standard for SARS-CoV-2 RNA nucleic acid amplification techniques (NAAT) in Taiwan.

The conventional PCR remains a valuable method to detect the newly emergent coronavirus rapidly and accurately. Our investigation aimed to establish the standard materials of SARS-CoV-2 for NAAT detection. We provided formalin-inactivated SARS-CoV-2 and confirmed RNA copy numbers. In addition, the virus genome was confirmed with whole-genome sequencing and identified as Wuhan/WI04/2019. Seven laboratories were invited for this collaborative study, according to the reporting data, we determined the SARS-CoV-2 with the unit of 6.35 Log10 copies/mL as the national standard. The availability of the national standard (NS) of SARS-CoV-2 will facilitate the standardization and harmonization of SARS-CoV-2 NAAT assays.

Clinical impacts of sacubitril/valsartan on patients eligible for cardiac resynchronization therapy.

AIMS: Sacubitril/valsartan (SAC/VAL) has been used in patients with heart failure and reduced ejection fraction (HFrEF), and cardiac resynchronization therapy (CRT) could benefit the HFrEF patients with wide QRS durations. This study aimed to evaluate the clinical impacts of SAC/VAL on reverse cardiac remodelling in CRT-eligible and CRT-ineligible HFrEF patients with different QRS durations. METHODS AND RESULTS: The TAROT-HF study was a multicentre, observational study enrolling patients who initiated SAC/VAL from 10 hospitals since 2017. Patients with baseline left ventricular ejection fraction (LVEF) ≤ 35% were classified into two groups: (i) Group 1: CRT-eligible group, patients with left bundle branch block (LBBB) morphology plus QRS duration ≥130 ms or non-LBBB morphology plus QRS duration ≥150 ms; and (ii) Group 2: CRT-ineligible group. Propensity score matching was performed to adjust for confounders, and 1168 patients were analysed. Baseline characteristics were comparable between the two groups. The improvements in LVEF and left ventricular end-systolic volume index (LVESVi) were more significant in Group 2 than in Group 1 after 1 year SAC/VAL treatment (LVEF: 8.4% ± 11.3% vs. 4.5% ± 8.1%, P < 0.001; change percentages in LVESVi: -14.4% ± 25.9% vs. -9.6% ± 23.1%, P = 0.004). LVEF improving to ≥50% in Groups 1 and 2 constituted 5.2% and 20.2% after 1 year SAC/VAL treatment (P < 0.001). Multivariate analyses showed that wide QRS durations were negatively associated with the reverse cardiac remodelling in these HFrEF patients with SAC/VAL treatment. CONCLUSION: Despite SAC/VAL treatment, wide QRS durations are associated with lower degrees of left ventricular improvement than narrow ones in the HFrEF patients. Optimal intervention timing for the CRT-eligible patients requires further investigation.

Utility of PREDICT-HF score in high-risk Asian heart failure patients receiving sacubitril/valsartan.

Objective: The aim of this study was to investigate the application of sacubitril/valsartan in clinical practice and the utility of PREDICT-HF score for outcome prediction in Asian heart failure patients with difference risk profiles. Methods: The TAROT-HF study was a multicenter, single-arm, observational study. Totally 1,187 outpatients with HFrEF treated with sacubitril/valsartan were enrolled and categorized by: (1) high-risk group with ≥1 of the following three risk factors: old age (≥80 years), low baseline systolic blood pressure (<100 mmHg), and renal impairment (eGFR <30 ml/min/1.73 m2), and (2) standard-risk group, those who did not have any risk factors. Clinical outcomes were assessed using the PREDICT-HF risk model. Results: A total of 305 (25.7%) patients matched the criteria for the high-risk group. The event rates of cardiovascular death or first unplanned heart failure hospitalization (HFH) among the overall population, high-risk, and standard-risk groups were 13.7, 24.9, and 10.8 events per 100 patient-years, respectively. The C statistics for the PREDICT-HF model in the overall cohort and high-risk group for cardiovascular death or first unplanned HFH at 2 years were 0.73 (95% CI 0.70-0.76) and 0.71 (95% CI 0.65-0.76), respectively. The permanent discontinuation rate among the high-risk patients was significantly higher than that among the standard-risk patients (8.3 vs. 2.5 per 100 patient-years, p < 0.001). Conclusions: Real-world outcomes of the TAROT-HF study demonstrated that the PREDICT-HF model performed well in Asian HFrEF patients. Three easily detected clinical profiles of age, renal function, and systolic BP could help to identify patients at risk before initiating sacubitril/valsartan.

Duration of Heart Failure With Reduced Ejection Fraction Associated With Electrocardiographic Outcomes Before and After Sacubitril/Valsartan.

AIM: Changes in QRS duration in patients with heart failure with reduced ejection fraction (HFrEF) after sacubitril/valsartan therapy is not fully understood. This study aimed to assess the association of duration of HFrEF diagnosis with electrocardiographic and echocardiographic outcomes between before and after sacubitril/valsartan. METHODS: We included HFrEF patients who received naïve sacubitril/valsartan therapy for ≥3 months, between January 2016 and March 2018. All patients were divided into 2 groups based on their duration of HFrEF. Generalized linear models were analyzed the cardiac outcomes after sacubitril/valsartan therapy by HFrEF duration. RESULTS: Among these, 42 patients were HFrEF duration of <1 year and 47 patients were ≥1 year. The mean difference of QRS duration was lesser in the <1-year group than in the ≥1-year group (-2.3 msec vs 6.3 msec; P = .029). However, the mean difference of left ventricular ejection fraction (LVEF) was higher in the ≥1-year group (13.8% vs 5.8%; P = .008). After adjusting for patient demographics and clinical characteristics, the ≥1-year group had a significantly prolonged QRS duration (coefficient = 11; 95% confidence interval [CI], 0.3-21.7) and an unfavorable LVEF recovery (coefficient = -10.3; 95% CI -14.5 to -6.1) compared with the <1-year group. CONCLUSION: Prolonged QRS durations and unfavorable LVEF recoveries after sacubitril/valsartan therapy were observed in patients with HFrEF duration of ≥1 year. Earlier diagnosis of HFrEF and appropriate medication treatment may be beneficial in the improvement of QRS duration and LVEF recovery.

The autonomic balance of heart rhythm complexity after renal artery denervation: insight from entropy of entropy and average entropy analysis.

BACKGROUND: The current method to evaluate the autonomic balance after renal denervation (RDN) relies on heart rate variability (HRV). However, parameters of HRV were not always predictive of response to RDN. Therefore, the complexity and disorder of heart rhythm, measured by entropy of entropy (EoE) and average entropy (AE), have been used to analyze autonomic dysfunction. This study evaluated the dynamic changes in autonomic status after RDN via EoE and AE analysis. METHODS: Five patients were prospectively enrolled in the Global SYMPLICITY Registry from 2020 to 2021. 24-h Holter and ambulatory blood pressure monitoring (ABPM) was performed at baseline and 3 months after RDN procedures. The autonomic status was analyzed using the entropy-based AE and EoE analysis and the conventional HRV-based low frequency (LF), high frequency (HF), and LF/HF. RESULTS: After RDN, the ABPM of all patients showed a significant reduction in blood pressure (BP) and heart rate. Only AE and HF values of all patients had consistent changes after RDN (p < 0.05). The spearman rank-order correlation coefficient of AE vs. HF was 0.86, but AE had a lower coefficient of variation than HF. CONCLUSIONS: Monitoring the AE and EoE analysis could be an alternative to interpreting autonomic status. In addition, a relative change of autonomic tone, especially an increasing parasympathetic activity, could restore autonomic balance after RDN.