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The article presents a case study of a woman with hyperthyroidism and heart problems who was admitted to a hospital with cardiac abnormalities. A discussion of diagnostic testing which was conducted on the woman, and which resulted in her receiving a diagnosis of atrial fibrillation originating from superior vena cava which presented as typical atrial flutter, is presented.

Background: With emerging evidence on the efficacy of adding dapagliflozin to standard care for patients with heart failure with reduced ejection fraction (HFrEF), this study assessed the cost-effectiveness of add-on dapagliflozin to standard care versus standard care alone for HFrEF from the perspective of healthcare systems in the Asia–Pacific region. Methods: A Markov model was applied to project the outcomes of treatment in terms of lifetime medical cost and quality-adjusted life-years. The transition probabilities between health states in the model were obtained from the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction trial. Country-specific costs and utilities were extracted for modeling. The incremental cost-effectiveness ratio against a country-specific willingness-to-pay threshold was applied to determine the cost-effectiveness of treatment. A series of sensitivity analyses were performed to ensure the robustness of the study results. Costs are presented in 2020 United States dollars. Results: The incremental cost-effectiveness ratios for add-on dapagliflozin versus standard care alone were $5277, $9980, $12,305, $16,705, and $23,227 per quality-adjusted life-year gained in Korea, Australia, Taiwan, Japan, and Singapore, respectively. When using add-on dapagliflozin to standard care versus standard care alone, ~ 100% of simulations were cost-effective at a willingness-to-pay threshold of one gross domestic product per capita of the given Asia–Pacific country; however, the probability of being cost-effective for using add-on dapagliflozin decreased when the time horizon for simulation was restricted to 18 months and when the cardiovascular mortality for the two treatments (43.8% and 33.0%, respectively) was assumed to be the same. The cost-effectiveness results were most sensitive to cardiovascular mortality of treatment. Conclusions: Adding dapagliflozin to standard care is cost-effective for HFrEF in healthcare systems in the Asia–Pacific region, which supports the rational use of dapagliflozin for HFrEF in this region. [ABSTRACT FROM AUTHOR]

Background and aims Statin is not beneficial for dialysis patients but moderate to high intensity statin is beneficial for patients after acute myocardial infarction (MI). The aim of this study was to evaluate the effect of moderate to high intensity statin on mortality, cardiovascular outcomes in dialysis patients after acute MI. Methods Data on dialysis patients were retrieved from the National Health Insurance Research Database in Taiwan. Dialysis patients admitted for MI were selected and divided into two groups according to statin prescription or not after MI. All-cause mortality and cardiovascular outcomes after a 4-year follow-up were analyzed after propensity score matching (PSM). Results We identified 790 patients who received moderate to high intensity statin therapy and 1788 patients who did not receive any statins after acute MI and clinical outcomes were analyzed after 1:1 PSM. The benefit of statin on mortality therapy appeared from 1 year to the end of the 4-year follow-up period after hospitalization (statin group versus non-statin group: 22.9% vs . 31.1% at 1 year (HR: 0.70; 95% CI: 0.58–0.85); 48.0% vs. 55.1% at the end of the 4 years (HR: 0.76; 95% CI: 0.67–0.88)). In addition, the impact of statin therapy was stronger in patients with shock at admission ( p = 0.035). There were no differences in any individual cardiovascular outcome or adverse event. Conclusions Moderate to high intensity statin therapy might lower all-cause mortality in dialysis patients after acute MI, especially those with shock, but not influence cardiovascular outcomes and any adverse events. [ABSTRACT FROM AUTHOR]

The article discusses the nationwide population- based cohort study using retrospective data from the National Health Insurance Research Database in Taiwan. Topics include the evidence pertains to patients with established cardiovascular diseases or at high risk; the occurrence of cardiovascular or renal outcomes, and study demonstrating that administration of SGLT2 inhibitors.

Substrate Properties Between Vagal and Sympathetic Types of AF Introduction Autonomic modulation of the cardiac activity plays an important role in the pathogenesis of atrial fibrillation (AF). The aim of this study was to assess the differences in the atrial electrical and structural properties between patients with vagal and sympathetic AF. Methods The study included 30 patients (53 ± 12 years old, male 26) with frequent attacks of symptomatic paroxysmal AF. All cases underwent 24-hour ambulatory Holter monitoring before the catheter ablation. The onset of AF accompanied with an increased HF component and decreased L/H ratio was designated as a vagal type (group 1, n = 12), whereas a decreased HF component and increased L/H ratio was classified as a sympathetic type (group 2, n = 18). Electrical and structural properties were evaluated during the ablation procedure. Results All patients had AF originating from PVs. There was a higher incidence of non-PV triggers in group 2 patients than that in group 1 (44% vs 8%, P = 0.04). Group 1 had a higher bipolar peak-to-peak voltage and mean DF of the global left atrium (LA), shorter total activation time, and smaller LA volume than group 2, whereas the electrical and structural properties in the right atrium were similar. After a follow-up of 15 ± 7 months, there was a lower incidence of AF recurrence in group 1 than that in group 2 (0% vs 28%, P = 0.02). Conclusion There are better electrical properties and a smaller LA volume in patients with vagal-type AF. In contrast, the LA substrate is worse, and coexisting non-PV triggers and recurrence following ablation are more prevalent in patients with the sympathetic-type AF. [ABSTRACT FROM AUTHOR]

Electromechanical Interval and Strokes After Ablations of AF. Introduction: Atrial fibrillation (AF) is associated with increased risk of embolic stroke. Catheter ablation of AF provides an effective therapy for patients with symptomatic and drug-refractory AF. The aim of this study was to evaluate whether the atrial electromechanical interval is useful in identifying patients at risk of stroke after successful catheter ablation. Methods and Results: A total of 279 AF patients who received catheter ablation and showed no evidence of recurrences were enrolled. Electromechanical interval (PA-PDI) was determined as the time interval from the initiation of P wave deflection to the peak of mitral inflow A wave on pulse wave Doppler imaging. The PA-PDI interval was measured for each patient after the 3-month blanking period of catheter ablation. The clinical endpoint was the occurrence of ischemic stroke. During the follow-up of 46.5 ± 17.2 months, 6 patients suffered from ischemic strokes. Patients with strokes had higher CHA2DS2-VASc scores and longer PA-PDI intervals (138.7 ± 12.4 ms vs 161.2 ± 7.7 ms, P value < 0.001) compared to those without strokes. At a cutoff point of 150 ms identified by ROC curve, the positive and negative predictive values of the PA-PDI interval to predict stroke were 86.7% and 100%, respectively. The PA-PDI interval improved the predictive performance of the CHA2DS2-VASc score, and the area under the ROC curve increased from 0.75 to 0.85. Conclusions: Our results suggest that the PA-PDI interval is a useful tool to identify patients with high risk of stroke after successful catheter ablation of AF. (J Cardiovasc Electrophysiol, Vol. 24, pp. 375-380, April 2013) [ABSTRACT FROM AUTHOR]

Nonlinear Analysis of Atrial Fibrillation. Introduction: Currently, the identification of complex fractionated atrial electrograms (CFEs) in the substrate modification is mostly based on cycle length-derived algorithms. The characteristics of the fibrillation electrogram morphology and their consistency over time are not clear. The aim of this study was to optimize the detection algorithm of crucial CFEs by using nonlinear measure electrogram similarity. Methods and Results: One hundred persistent atrial fibrillation patients that underwent catheter ablation were included. In patients who required CFE ablation (79%), the time-domain fibrillation signals (6 seconds) were acquired for a linear analysis (mean fractionation interval and dominant frequency [DF]) and nonlinear-based waveform similarity analysis of the local electrograms, termed the similarity index (SI). Continuous CFEs were targeted with an endpoint of termination. Predictors of the various signal characteristics on the termination and clinical outcome were investigated. Procedural termination was observed in 39% and long-term sinus rhythm maintenance in 67% of the patients. The targeted CFEs didn't differ based on the linear analysis modalities between the patients who responded and did not respond to CFE ablation. In contrast, the average SI of the targeted CFEs was higher in termination patients, and they had a better outcome. Multivariate regression analysis showed that a higher SI independently predicted sites of termination (≥0.57; OR = 4.9; 95% CI = 1.33-18.0; P = 0.017). Conclusions: In persistent AF patients, a cycle length-based linear analysis could not differentiate culprit CFEs from bystanders. This study suggested that sites with a high level of fibrillation electrogram similarity at the CFE sites were important for AF maintenance. (J Cardiovasc Electrophysiol, Vol. 24, pp. 280-289, March 2013) [ABSTRACT FROM AUTHOR]

The present study investigated the incidence and predictors of permanent pacemaker (PPM) implantation for late atrioventricular block (AVB) in patients with atrioventricular nodal reentrant tachycardia (AVNRT) who received ablation. The data from 3,442 patients with AVNRT who received ablation were analyzed. Those who developed late AVB (>1 month after ablation) and received a PPM were identified. The incidence of PPM implantation in 1,148 matched patients with Wolff-Parkinson-White syndrome and in the whole population of Taiwan were compared. Of the patients with AVNRT receiving ablation (mean follow-up duration 128.3 ± 62.5 months), 15 (0.4%) received PPM implantation for late AVB (mean interval after catheter ablation 95.4 ± 55.0 months). Only age (odds ratio 1.05, p = 0.02) and transient AVB (odds ratio 8.55, p [ 0.01) during the procedure were independently associated with PPM implantation for late AVB. The patients with AVNRT had a greater incidence of PPM implantation due to late AVB compared to the matched patients with Wolff-Parkinson-White syndrome. The annual incidence of PPM implantation for AVB was also greater in the patients with AVNRT than in the general population. In conclusion, the incidence of PPM implantation for late AVB in patients with AVNRT who received catheter ablation was low but still greater than that in patients with Wolff-Parkinson-White syndrome and the general population in Taiwan. [ABSTRACT FROM AUTHOR]

Atrial Substrate Properties in Chronic AF Patients with LASEC. Background: The atrial substrate in chronic atrial fibrillation (AF) patients with a left atrial spontaneous echo contrast (LASEC) has not been previously reported. The aim of this study was to investigate the atrial substrate properties and long-term follow-up results in the patients who received catheter ablation of chronic AF. Methods: Of 36 consecutive patients with chronic AF who received a stepwise ablation approach, 18 patients with an LASEC (group I) were compared with 18 age-gender-left atrial volume matched patients without an LASEC (group II). The atrial substrate properties including the weighted peak-to-peak voltage, total activation time during sinus rhythm (SR), dominant frequency (DF), and complex fractionated electrograms (CFEs) during AF in the bi-atria were evaluated. Result: The left atrial weighted bipolar peak-to-peak voltage (1.0 ± 0.6 vs 1.6 ± 0.7 mV, P = 0.04), total activation time (119 ± 20 vs 103 ± 13 ms, P < 0.001) and DF (7.3 ± 1.3 vs 6.6 ± 0.7 Hz, P < 0.001) differed between group I and group II, respectively. Those parameters did not differ in the right atrium. The bi-atrial CFEs (left atrium: 89 ± 24 vs 92 ± 25, P = 0.8; right atrium: 92 ± 25 vs 102 ± 3, P = 0.9) did not differ between group I and group II, respectively. After a mean follow-up of 30 ± 13 month, there were significant differences in the antiarrhythmic drugs (1.1 ± 0.3 vs 0.7 ± 0.5, P = 0.02) needed after ablation, and recurrence as persistent AF (92% vs 50%, P = 0.03) between group I and group II, respectively. After multiple procedures, there were more group II patients that remained in SR, when compared with group I (78% vs 44%, P = 0.04). Conclusion: There was a poorer atrial substrate, lesser SR maintenance after catheter ablation and need for more antiarrhythmic drugs in the chronic AF patients with an LASEC when compared with those without an LASEC. (J Cardiovasc Electrophysiol, Vol. pp. 1-8) [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate whether CHADS2 and CHA2DS2-VASc scores are useful for risk stratification in patients after catheter ablation of atrial fibrillation (AF). Background: AF is associated with increased risk of cardiovascular events. However, limited data are available on the predictors of adverse events in patients with AF after catheter ablation. Methods: A total of 565 patients with AF who underwent catheter ablation were enrolled in the study. The clinical endpoint was occurrence of thromboembolic events (ischemic stroke, transient ischemic attack, peripheral embolism, or pulmonary embolisms) or death during follow-up after catheter ablation. Results: During a follow-up of 39.2 ± 22.6 months, 27 patients (4.8%) experienced adverse events. Both the CHADS2 and CHA2DS2-VASc scores were useful predictors of events in separate multivariate models. The areas under the receiver-operator characteristic curves based on the CHADS2 and CHA2DS2-VASc scores in predicting events were 0.785 and 0.830, respectively. Although the difference did not reach statistical significance (p = 0.116), the CHA2DS2-VASc score could be used to further stratify the patients with CHADS2 scores of 0 or 1 into 2 groups with different event rates (7.1% vs. 1.1%, p = 0.003) at a cutoff value of 2. Conclusions: The CHADS2 and CHA2DS2-VASc scores are useful predictors of adverse events after catheter ablation of AF. [Copyright &y& Elsevier]

The article examines the use of Vancomycin as an antibiotic treatment for Staphylococcus aureus infections in diabetic foot in Taiwan. It states that a study was conducted to test the efficacy of the modified protocol of Vancomycin. Furthermore, the details of the study involving diabetis patients, administration of vancomycin dosage, and results are discussed.

Introduction: Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia-Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia-Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval., Methods: The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2)., Results: Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2 mmol/L (123.7 mg/dL), patients had a median percent change in LDL-C of - 60.8% at 1-6 months. Goal achievement increased from 7.9% to 69.8% for < 1.8 mmol/L (< 70 mg/dL) and 4.4% to 57.8% for < 1.4 mmol/L (< 55 mg/dL) from baseline to 12 months. In the one-time data collection, more patients had ≥ 1.8 mmol/L (≥ 70 mg/dL) baseline LDL-C in the evolocumab vs non-PCSK9i group (95.2% and 48.5%, respectively). Surveys found that physicians applied guideline-recommended treatment targets, and patients demonstrated gaps in understanding cardiovascular risk., Conclusion: Real-world, Asia-Pacific data showed that LDL-C reduction after initiating evolocumab was consistent with that observed in other clinical trials and patient populations. Graphical abstract available for this article.·., (© 2024. The Author(s).)

The benefits of rapidly up-titrating evidence-based treatments following heart failure (HF) hospitalizations were demonstrated in the The Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies (STRONG-HF) trial and emphasized in contemporary HF guidelines. We aimed to assess up-titration patterns of guideline-directed medical treatments in the Taiwanese HF population. Combining data from the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry and the Treatment with Angiotensin Receptor neprilysin inhibitor for Taiwan Acute Heart Failure (TAROT-AHF) study cohort, we formed the "Taiwan real-world cohort". We compared these data with subgroups of patients with left ventricular ejection fraction ≤40% in the STRONG-HF trial. Patients in the Taiwan cohort exhibited similar blood pressure, heart rate and N-terminal pro B-type natriuretic peptide levels at discharge compared with those in the STRONG-HF trial. A higher proportion of patients in the STRONG-HF high-intensity care group received up-titrations compared with those in the usual care group and the Taiwan cohort. Composite all-cause mortality or HF hospitalization at 180 days for patients in the high-intensity care group, usual care group, and Taiwan cohort were 17.4%, 23.7%, and 31.9%, respectively, with differences largely contributed by HF hospitalization (10.1%, 17.9%, and 27.6%, respectively), whereas all-cause mortality rates were similar (11.0%, 9.6%, and 9.3%, respectively). Gender did not affect this trend. In conclusion, our data highlights a treatment gap between the STRONG-HF trial and real-world practices in Taiwan, urging prompt optimization of HF therapy., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials., Patients and Methods: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis., Results: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting., Conclusion: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: This study investigated whether initial SGLT2 (sodium-glucose cotransporter 2) inhibitor-based treatment is superior to metformin-based regimens as a primary prevention strategy among low-risk patients with diabetes., Methods and Results: In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors-based and metformin-based regimens were 1:2 matched by propensity score. Study outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end-stage renal disease. Compared with 1928 patients receiving metformin-based regimens, 964 patients receiving SGLT2 inhibitor-based regimens had similar all-cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51-1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25-1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59-1.92]), stroke (HR, 0.78 [95% CI, 0.48-1.27]), and progression to end-stage renal disease (HR, 0.88 [95% CI, 0.32-2.39]). However, SGLT2 inhibitors were associated with a lower risk of all-cause mortality (HR, 0.47 [95% CI, 0.23-0.99]; P for interaction=0.008) and progression to end-stage renal disease (HR, 0.22 [95% CI, 0.06-0.82]; P for interaction=0.04) in patients under the age of 65., Conclusions: In comparison to metformin-based regimens, SGLT2 inhibitor-based regimens showed a similar risk of all-cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first-line therapy in select low-risk patients, for example, younger patients with diabetes.

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., Competing Interests: All the authors declare no conflict of interest.

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., Competing Interests: All the authors declare no conflict of interest.

Competing Interests: Declaration of competing interest The authors have no competing interest to declare.

Background: In the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients., Methods: Between 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system., Results: Among the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71-0.78 and 0.69-0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment., Conclusions: This study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Type 2 diabetes is associated with an increased risk of herpes zoster and postherpetic neuralgia. However, the association of type 1 diabetes with herpes zoster or postherpetic neuralgia remains unclear. This retrospective cohort study using Taiwan's Health Insurance Research Database included 199,566 patients with type 1 diabetes and 1,458,331 with type 2 diabetes, identified during the period 2000 to 2012. Patients with type 1 diabetes had a significantly higher risk of developing herpes zoster than those with type 2 diabetes (p < 0.001). Across all age groups, the impact of diabetes on herpes zoster was greater in type 1 than in type 2 diabetes. Patients with both type 1 and type 2 diabetes had a 1.45-fold higher risk of post-herpetic neuralgia than those without diabetes (hazard ratio 1.45, 95% confidence interval 1.28-1.65; hazard ratio 1.45, 95% confidence interval 1.37-1.52, respectively), and there was no difference between the 2 types of diabetes (hazard ratio 1.06; 95% confidence interval 0.93-1.21). The results recommend consideration of herpes zoster vaccination at an earlier age in patients with type 1 diabetes.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P <0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.

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., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

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., Competing Interests: All authors declare no conflict of interest.

Objective: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m 2 ), which have been excluded from the landmark trials., Patients and Methods: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m 2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints., Results: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m 2 ) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m 2 vs 21.4±17.5 mL/min per 1.73 m 2 ; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users., Conclusion: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

With the promising cardiovascular benefits in the STEP and SPRINT trials, the 2022 Taiwan's hypertension guidelines redefined the hypertension threshold as 130/80 mmHg and a universal blood-pressure target of <130/80 mmHg. This study's objective was to examine the cost-effectiveness of the intensive blood-pressure target for hypertensive patients using estimated lifetime medical costs and quality-adjusted life years (QALY) from the Taiwan national payer's perspective. We developed a lifetime Markov model comparing the intensive and conservative blood-pressure targets. Incremental cost-effectiveness ratio (ICER) against the willing-to-pay thresholds at the one-time [US$34,000(NT$1,020,000)] and three-time [US$100,000(NT$3,000,000)] gross domestic product per capita were defined as very cost-effect and only cost-effective. The cost-effectiveness in different age stratifications and cardiovascular risks treated with a more intensive target (120 mmHg) were examined in the subgroup analyses. The new blood-pressure treatment target produced more lifetime medical costs [US$31,589(NT$947,670) versus US$26,788(NT$803,640)] and QALYs (12.54 versus 12.25), and the ICER was US$16,589(NT$497,670), which was 99.1% and 100% probability of a very cost-effective and cost-effective strategy. The ICERs in all age stratifications had more than a 90% probability of being very cost-effective, and ICERs decreased with age. More intensive control in patients with high cardiovascular risks produced a lower ICER [US$14,547(NT$436,410)]. In conclusion, Taiwan's new blood-pressure treatment target can prevent more cardiovascular events with acceptable costs per QALY below the willing-to-pay thresholds. The cost-effectiveness of intensive control is consistent across different ages and more pronounced with the increase in age and cardiovascular risk., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Some sodium-glucose co-transporter-2 (SGLT2) inhibitors showed benefits on heart failure (HF), but different SGLT2/SGLT1 selectivity might influence the treatment effect. This study aimed to meta-analyze the treatment effects of SGLT2 inhibitors and the diversity of receptor selectivity for patients with and without HF., Methods: Randomized controlled trials were searched in PubMed, Embase, Cochrane databases and ClinicalTrials.gov registry from inception to October 2020. The interest outcomes were analyzed with random-effects models and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup analyses examined the treatment effects among SGLT2 inhibitors with different SGLT2/SGLT1 selectivity., Results: The final analyses included 10 trials and 52,607 patients. The RR of total cardiovascular (CV) death or hospitalization for HF (HHF) between SGLT2 inhibitors and placebo was 0.79 (95% CI 0.74-0.84, I2 = 31%). With SGLT2 inhibitors, HF patients had reduced mortality risks (RR 0.89, 95% CI 0.80-0.99, I2 = 0), and non-HF patients had lower risks of major adverse CV events (RR 0.92, 95% CI 0.85-0.99, I2 = 0). The risk reduction of HHF was consistent in groups of HF (RR 0.72, 95% CI 0.64-0.80, I2 = 8%) and non-HF (RR 0.74, 95% CI 0.61-0.89, I2 = 0), but the effect of the low SGLT2/SGLT1 selectivity inhibitor was insignificant in non-HF patients., Conclusion: The efficacy of SGLT2 inhibitors on risk reduction of total CV death or HHF is consistent with the previous studies. The regimen is beneficial for reducing mortality in patients with HF and major adverse CV events in those without HF. Different SGLT2/SGLT1 selectivity may differ in the treatment effects in patients with and without HF., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

During the COVID-19 pandemic, reductions in heart failure (HF) hospitalizations have been widely reported, and there is an urgent need to understand how HF care has been reorganized in countries with different infection levels, vaccination rates and healthcare services. The OPTIMIZE Heart Failure Care program has a global network of investigators in 42 countries, with first-hand experience of the impact of the pandemic on HF management in different care settings. The national coordinators were surveyed to assess: 1) the challenges of the COVID-19 pandemic for continuity of HF care, from both a hospital and patient perspective; 2) the organizational changes enacted to ensure continued HF care; and 3) lessons learned for the future of HF care. Contributions were obtained from 37 national coordinators in 29 countries. We summarize their input, highlighting the issues raised and using the example of three very different settings (Italy, Brazil, and Taiwan) to illustrate the similarities and differences across the OPTIMIZE program., (Copyright © 2022. Published by Elsevier B.V.)

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 m 2 ), 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., (Copyright © 2022 Hsu, Chang, Chao, Chiou, Lin, Chung, Lin, Huang, Liang, Liao and Lee.)

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation., Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2)., Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001)., Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

Aims: Although the beneficial effect of sacubitril/valsartan (SAC/VAL) compared to enalapril was consistent across ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) groups, the PARADIGM-HF study did not analyse the effect of ventricular remodelling on patients with different aetiologies, which may affect clinical treatment outcomes. This study aimed to compare left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes., Methods and Results: A total of 1576 patients were analysed. Patients were grouped by LVEF changes following SAC/VAL treatment for 8-month period. LVEF improvement ≥15% was defined as 'significant improvement', and <5% or worse was classified as 'lack of improvement'. The primary outcome was a composite of cardiovascular death and unplanned hospitalization for heart failure. Patients with NICM had lower baseline LVEF but improvement was significantly greater comparing to those with ICM (baseline 28.0 ± 7.7% vs. 30.1 ± 7.1%, P < 0.001, LVEF increase of 11.1 ± 12.6% vs. 6.7 ± 10.2%, P < 0.001). The effect of functional improvement of SAC/VAL on NICM patients showed bimodal distribution. Primary endpoints were inversely associated with LVEF changes in NICM patients: adjusted hazard ratio was 0.42 [95% confidence interval (CI) 0.31-0.58, P < 0.001] for NICM patients with significant improvement, and was 1.73 (95% CI 1.38-2.16, P < 0.001) for NICM patients but lack of improvement. Primary endpoints of ICM patients did not demonstrate an association with LVEF changes., Conclusion: Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients indicates favourable outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90-95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.

A variety of feature extraction and classification approaches have been proposed using electrocardiogram (ECG) and ECG-derived signals for improving the performance of detecting apnea events and diagnosing patients with obstructive sleep apnea (OSA). The purpose of this study is to further evaluate whether the reduction of lower frequency P and T waves can increase the accuracy of the detection of apnea events. This study proposed filter bank decomposition to decompose the ECG signal into 15 subband signals, and a one-dimensional (1D) convolutional neural network (CNN) model independently cooperating with each subband to extract and classify the features of the given subband signal. One-minute ECG signals obtained from the MIT PhysioNet Apnea-ECG database were used to train the CNN models and test the accuracy of detecting apnea events for different subbands. The results show that the use of the newly selected subject-independent datasets can avoid the overestimation of the accuracy of the apnea event detection and can test the difference in the accuracy of different subbands. The frequency band of 31.25-37.5 Hz can achieve 100% per-recording accuracy with 85.8% per-minute accuracy using the newly selected subject-independent datasets and is recommended as a promising subband of ECG signals that can cooperate with the proposed 1D CNN model for the diagnosis of OSA.

Background/purpose: The present study was designed to evaluate the local cardiology infrastructure and services for heart failure (HF) care in Taiwan hospitals and to compare the HF care with the hospitals in European countries., Methods: Available data from a total of 98 medical centers and regional hospitals in Taiwan were analyzed. Each facility was given a single copy of the questionnaire between September and December 2019, and service records were extracted from the National Health Insurance Database. European data were adopted from the 2017 European Society of Cardiology Atlas., Results: The number of cardiologists per million populations in Taiwan was 57.4, and it was lower than the European median (72.8). The median percentages of interventional and electrophysiologists among cardiologists were 64% and 15% in Taiwan, which were both higher than the European median values (12% and 5%, respectively). The accessibility rates to implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Taiwan were both higher (3.4 and 3.0 centers per million populations) comparing to those in European countries (median 1.6 and 1.5 centers per million populations). Comparing to 67 hospitals without HF care teams in Taiwan, 31 hospitals (31.6%) with HF teams have significantly more cardiology staff, enhanced procedural capabilities with more alternatives on oral or intravenous HF relevant medications., Conclusion: Our analysis clearly demonstrated discrepancies in cardiology subspecialties and CRT/ICD accessibilities between European countries and Taiwan. Variations in HF-focused services and facilities plus HF-directed medications have demonstrated significant differences among Taiwanese hospitals with or without HF care team., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

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.

Background: EMPEROR-Reduced trial provides promising evidence on the efficacy of empagliflozin adding to the standard treatment in patients with heart failure and reduced ejection fraction (HFrEF). This study aimed to investigate the cost-effectiveness of add-on empagliflozin vs. standard therapy alone in HFrEF from the perspective of the Asia-Pacific healthcare systems. Methods: A Markov model was constructed to simulate HFrEF patients and to project the lifetime direct medical costs and quality-adjusted life years (QALY) of both therapies. Transitional probabilities were derived from the EMPEROR-Reduced trial. Country-specific costs and utilities were extracted from published resources. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was used to examine the cost-effectiveness. A series of sensitivity analyses was performed to ensure the robustness of the results. Results: The ICERs of add-on empagliflozin vs. standard therapy alone in HFrEF were US$20,508, US$24,046, US$8,846, US$53,791, US$21,543, and US$20,982 per QALY gained in Taiwan, Japan, South Korea, Singapore, Thailand, and Australia, respectively. Across these countries, the probabilities of being cost-effective for using add-on empagliflozin under the WTP threshold of 3-times country-specific gross domestic product per capita were 93.7% in Taiwan, 95.6% in Japan, 96.3% in South Korea, 94.2% Singapore, 51.9% in Thailand, and 95.9% in Australia. The probabilities were reduced when shortening the time horizon, assuming the same cardiovascular mortality for both treatments, and setting lower WTP thresholds. Conclusion: Adding empagliflozin to HFrEF treatment is expected to be a cost-effective option among the Asia-Pacific countries. The cost-effectiveness is influenced by the WTP thresholds of different countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liao, Yang, Kuo, Lee, Chang, Tang, Hua, Chang, Chen, Strong, Ou and Toh.)

Aims: Ivabradine has been used in patients who have chronic heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant sinus heart rate ≥70 bpm. This administration for acute HFrEF remains a concern. This study used a real-world multicentre database to investigate the effects of ivabradine among patients with acute decompensated HFrEF before discharge., Methods and Results: This study retrospectively identified patients with acute decompensated HFrEF who were administered ivabradine at discharge from two multicentre HF databases. Propensity score matching was performed to adjust for confounders. Cardiovascular mortality, all-cause mortality, and recurrent HF rehospitalization risks were then compared between those with and without ivabradine treatment. After 1:2 propensity score matching, 876 patients (age, 60.7 ± 14.6 years; female, 23.2%; left ventricular ejection fraction, 28.2% ± 7.8%; and heart rate at discharge, 84.3 ± 13.8 bpm) were included in the final analysis, including 292 and 584 patients with and without ivabradine treatment at discharge, respectively. No significant differences were observed in baseline characteristics between the two groups. At 1 year follow-up, patients in the ivabradine group had significantly lower heart rates (77.6 ± 14.7 vs. 81.1 ± 16.3 bpm; P = 0.005) and lower HF severity symptoms (New York Heart Association Functional class, 2.1 ± 0.7 vs. 2.3 ± 0.9; P < 0.001) than those from the non-ivabradine group. Ivabradine users had significantly lower risks of 1 year cardiovascular mortality (5.8 vs. 12.2 per 100-person year; P = 0.003), all-cause mortality (7.2 vs. 14.0 per 100-person year; P = 0.003), and total HF rehospitalization (42.3 vs. 72.6 per 100-person year; P < 0.001) than non-ivabradine users. Following multivariate analysis, the predischarge prescription of ivabradine remained independently associated with lower 1 year all-cause mortality (hazard ratio, 0.45; 95% confidence interval, 0.28-0.74; P = 0.002) and cardiovascular mortality (hazard ratio, 0.41; 95% confidence interval, 0.24-0.72; P = 0.002)., Conclusions: The current study findings suggest that ivabradine treatment is associated with reduced risks of cardiovascular mortality, all-cause mortality, and HF rehospitalization within 1 year among patients with acute decompensated HFrEF in real-world populations., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL. Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group ( n = 45) and an atypical AFL group ( n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence. Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence. Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chou, Chung, Chang, Lin, Lo, Hu, Chao, Liao, Tuan, Lin, Chang, Liu, Wu, Huang, Chen, Cheng, Liu, Lugtu, Jain, Feng, Chang and Chen.)

Background: This study used a real-world database to investigate the prescription patterns of sacubitril/valsartan (Sac/Val) among Taiwanese patients with heart failure with reduced ejection fraction (HFrEF)., Methods: The Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study is a principal investigator-initiated, multicenter, observational, retrospective study on Taiwanese HFrEF patients. A total of 1772 patients with HFrEF (mean age 62.5 years, 75.3% male, mean left ventricular ejection fraction [LVEF] 29.3%) who received Sac/Val at 10 hospitals between 2017 and 2018 were enrolled at the date of Sac/Val initiation. Among these patients, 585 (33%) initially received Sac/Val during acute decompensated heart failure (HF) hospitalization (TAROT-AHF arm), whereas 1187 (67%) initially received the same at the outpatient clinic (TAROT-CHF arm)., Results: A total of 1343 (75.8%) patients received an initial dose of 50 mg twice daily or fewer, whereas 422 (23.8%) received the standard initiation dose (100 mg twice daily). During outpatient Sac/Val initiation, the mean dosages were significantly higher than that following hospitalization (117 ± 55 mg vs 109 ± 57 mg; p = 0.014). Multivariate analysis identified younger age, higher systolic blood pressure, higher LVEF, prior use of renin-angiotensin system inhibitors, use of ivabradine, and a history of diabetes mellitus as independent factors for initiating a standard Sac/Val dose. Over a follow-up period of 18 months, incidences of cardiovascular death or first unplanned HF hospitalization were 18.69 and 33.11 per 100-person years for the TAROT-CHF and TAROT-AHF arms, respectively., Conclusion: The TAROT-HF study provided an opportunity to describe the clinical features of patients with HFrEF who received Sac/Val, assess the real-world utilization and efficacy of Sac/Val, and compare these patients with those included in prior registries., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Since 1953, sinus tachycardia has been defined as a heart rate (HR) in sinus rhythm of >100 beats per minute (bpm). However, this number has never been formally evaluated, and no established threshold values for special groups, such as those with heart failure (HF) accompanied by a reduced ejection fraction (HFrEF). Herein, we provided evidence that lowering the HR of patients with HFrEF to <70 bpm with medications such as ivabradine improves outcomes. Numerous large-scale trials and smaller clinical studies have shown that reducing the HR in patients with HFrEF improves cardiovascular and overall outcomes. Evidence suggests that a HR of <70 bpm is appropriate for patients with HFrEF. Examination of HF registries indicates that in a large proportion of these patients the HR exceeds 80 bpm, and no consideration is given to lowering the HR, due in large part to lack of physician awareness of the benefits of a lower HR. Evidence indicates that the first-line medication for lowering HR in patients with HFrEF is ivabradine. In conclusion, the improved prognosis following appropriate HR management in patients with HFrEF suggest that the cut-off value for sinus tachycardia in these patients should be redefined as 75 bpm. Maintaining a HR of <70 bpm in patients with HFrEF is associated with improved cardiovascular and overall outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Renin-angiotensin system inhibitors and beta-blockers are the initial treatment of choice for heart failure with reduced ejection fraction (HFrEF), whereas sacubitril/valsartan (SAC/VAL) and ivabradine are considered to second-line therapies. The eligibility of SAC/VAL and ivabradine according to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) labels, Taiwan National Health Insurance (TNHI) reimbursement regulations, and European Society of Cardiology (ESC) heart failure (HF) guidelines are diverse, and they may not fulfill the needs of real-world HFrEF patients., Methods: Patients hospitalized for HF with left ventricular ejection fraction (LVEF) ≤ 40% were recruited from 21 hospitals in Taiwan between 2013 and 2014. The criteria for SAC/VAL and ivabradine according to the different regulations were applied., Results: Of 1,474 patients, 86.8%, 29.4%, and 9.5% met the EMA/FDA label criteria, TNHI-regulation, and ESC guidelines for SAC/VAL, compared to 47.1%, 37.2%, and 45.6% for ivabradine, respectively. Ineligible reasons for the TNHI regulations included LVEF > 35% (19.9%, for SAC/VAL and ivabradine) and sinus rate < 75 beats per minute (bpm) (29.9%, for ivabradine). Although not meeting the TNHI regulations, patients with LVEF 35-40% had a similar 1-year mortality rate (15.6% vs. 15.8%, p = 0.876) to those with LVEF ≤ 35%, whereas patients with a sinus rate 70-74 bpm had a similar 1-year mortality rate (15.3% vs. 16.1%, p = 0.805) to those with a sinus rate ≥ 75 bpm., Conclusions: Approximately 70% and 63% of TSOC-HFrEF registry patients were ineligible for SAC/VAL and ivabradine, respectively, according to current TNHI regulations. Regardless of the eligibility for novel HFrEF medications, the high incidence of adverse events suggests that all patients should be treated cautiously.

Background: Over recent years, new evolution in guideline-directed medical therapy (GDMT) contributes to clinical benefits in patients with heart failure and reduced ejection fraction (HFrEF). The additional medical expenditure may be a concern due to the current financial constraint. This study aimed to investigate the medical costs and clinical effectiveness of contemporary GDMT in recently hospitalized HFrEF patients., Methods: Acutely decompensated hospitalized HFrEF patients from two multicenter cohorts of different periods were retrospectively analyzed. A propensity score matching was performed to adjust the baseline characteristics. Annual medication costs, risks of mortality, and recurrent heart failure hospitalizations (HFH) were compared., Results: Following 1:2 propensity score matching, there were 426 patients from the 2017-2018 cohort using sacubitril/valsartan, while 852 patients from 2013 to 2014 did not use so at discharge. Baseline characteristics were similar, whereas the sacubitril/valsartan users were more likely to receive beta-blockers, ivabradine and mineralocorticoid receptor antagonists at discharge (79.3% vs 60.4%, 23.2% vs 0%, and 64.1% vs 49.8%, p < 0.001). The 2017-2018 cohort produced more medication costs by 1277 United States dollar (USD) per person per year, while it resulted in lower rates of HFH and all-cause mortality (10.3 vs 20.3 and 48.8 vs 79.9 per 100 person-year, p < 0.001). Costs of preventing a mortality event and a HFH event with contemporary treatments were 15 758 USD (95% confidence interval [CI] 10 436-29 244) and 5317 USD (95% CI 3388-10 098), respectively., Conclusion: The higher adoption of GDMT was associated with greater medical expenses but better clinical outcomes in recently decompensated HFrEF patients., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

We demonstrate residual channel attention networks (RCAN) for the restoration and enhancement of volumetric time-lapse (four-dimensional) fluorescence microscopy data. First we modify RCAN to handle image volumes, showing that our network enables denoising competitive with three other state-of-the-art neural networks. We use RCAN to restore noisy four-dimensional super-resolution data, enabling image capture of over tens of thousands of images (thousands of volumes) without apparent photobleaching. Second, using simulations we show that RCAN enables resolution enhancement equivalent to, or better than, other networks. Third, we exploit RCAN for denoising and resolution improvement in confocal microscopy, enabling ~2.5-fold lateral resolution enhancement using stimulated emission depletion microscopy ground truth. Fourth, we develop methods to improve spatial resolution in structured illumination microscopy using expansion microscopy data as ground truth, achieving improvements of ~1.9-fold laterally and ~3.6-fold axially. Finally, we characterize the limits of denoising and resolution enhancement, suggesting practical benchmarks for evaluation and further enhancement of network performance.

Aims: Ivabradine and sacubitril/valsartan are second-line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications., Methods and Results: Patients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine-first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan-first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re-hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine-first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan-first treatment (∆heart rate -9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P < 0.001; ∆SBP 4.6 ± 16.5 mmHg vs. -4.8 ± 17.2 mmHg, P < 0.001), whereas sacubitril/valsartan-first treatment showed a higher degree of LVEF improvement (∆LVEF 3.6 ± 7.8% vs. 0.7 ± 7.7%, P = 0.002) than ivabradine-first treatment. At the end of follow-up, SBP, LVEF, and left ventricular volume were comparable between two Sequential subgroups., Conclusions: Among patients with HFrEF, simultaneous rather than sequential treatment with sacubitril/valsartan and ivabradine was a better strategy to reduce adverse events and achieve left ventricular reverse remodelling. Ivabradine treatment had a more significant benefit on improving haemodynamic stability, whereas sacubitril/valsartan treatment showed a more significant effect on improving LVEF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Many works in recent years have been focused on developing a portable and less expensive system for diagnosing patients with obstructive sleep apnea (OSA), instead of using the inconvenient and expensive polysomnography (PSG). This study proposes a sleep apnea detection system based on a one-dimensional (1D) deep convolutional neural network (CNN) model using the single-lead 1D electrocardiogram (ECG) signals. The proposed CNN model consists of 10 identical CNN-based feature extraction layers, a flattened layer, 4 identical classification layers mainly composed of fully connected networks, and a softmax classification layer. Thirty-five released and thirty-five withheld ECG recordings from the MIT PhysioNet Apnea-ECG Database were applied to train the proposed CNN model and validate its accuracy for the detection of the apnea events. The results show that the proposed model achieves 87.9% accuracy, 92.0% specificity, and 81.1% sensitivity for per-minute apnea detection, and 97.1% accuracy, 100% specificity, and 95.7% sensitivity for per-recording classification. The proposed model improves the accuracy of sleep apnea detection in comparison with several feature-engineering-based and feature-learning-based approaches.