ObjectiveTo evaluate the prognostic value of the combined neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) for adverse outcomes in Taiwanese patients with acute coronary syndrome (ACS).MethodsThis retrospective, single-center, observational cohort study analyzed 653 ACS patients from the Tri-Service General Hospital-coronary artery disease registry (Jan 2016-Aug 2018). NLR and MLR were calculated at presentation. The primary endpoint was a composite of in-hospital mortality and stroke. Optimal cut-off values were determined using receiver operating characteristic curve analysis (NLR > 5.22, MLR > 0.76). Univariable and multivariable logistic regression were used to assess the association of both elevated NLR/MLR with the primary endpoint.ResultsPatients with both elevated NLR and MLR (NLR > 5.22 and MLR > 0.76) demonstrated a significantly higher risk of the primary endpoint compared to the group with no elevation (OR = 7.16) in univariable analysis. This group also experienced longer hospital stays and higher non-cardiovascular mortality. However, this association became non-significant after multivariable adjustment for confounders.ConclusionsConcurrent elevation of both NLR and MLR at presentation is associated with increased in-hospital morbidity and prolonged hospitalization in ACS patients, although this did not remain an independent predictor in multivariable analysis. Ongoing statin therapy demonstrated a protective association in this cohort. These readily available markers may facilitate early risk stratification.

Background: Pre-existing atrial fibrillation (AF) and postoperative new-onset AF (NOAF) are independent perioperative risk factors associated with increased short-term mortality and adverse events. This study aimed to develop and validate an artificial intelligence (AI) model capable of detecting hidden AF, including both pre-existing AF and NOAF, from sinus rhythm electrocardiograms, to improve perioperative risks assessment. Methods: We trained and validated an AI model to detect hidden AF. Subsequent analysis confirmed the prognostic relevance of both pre-existing AF and NOAF in patients receiving non-cardiac surgery. The AI model was applied to patients without known AF to evaluate its predictive capability for NOAF and to stratify short-term clinical outcomes. Results: The AI model demonstrated an area under the receiver operating characteristic curve of 0.87 during the development phase for predicting AF. In an independent validation cohort, pre-existing AF and postoperative NOAF were significantly correlated with increased 30-day all-cause mortality. Patients without pre-existing AF who were classified as high-risk by the AI model had substantially higher 30-day all-cause mortality than their low-risk counterparts (HR 17.33, 95% CI 5.29-56.75). Furthermore, the model scores surpassed conventional clinical risk scores in predicting NOAF and 30-day all-cause mortality. Conclusions: This AI-based approach facilitated the accurate identification of patients with elevated perioperative AF-related risk. It will facilitate focused interventions that may enhance clinical outcomes.

AbstractBackgroundThe non‐vitamin K oral anticoagulant (NOAC), edoxaban, is approved for stroke prevention in patients with atrial fibrillation (AF) in many Asian countries. Nonetheless, data on its long‐term effectiveness and safety in routine clinical practice are limited in Taiwan.MethodsThe Global ETNA‐AF (Edoxaban Treatment in routiNe clinical prActice) registry is an observational study that integrates data of AF patients receiving edoxaban from multiple regional registries. Here, we report the subgroup analysis of two‐year outcomes in Taiwan (N = 973) and three Asian countries (South Korea, Hong Kong, Thailand; N = 2326).ResultsCompared with other Asian ethnicities, edoxaban users in Taiwan were older and had lower creatinine clearance levels. The incidence of clinical events was low and comparable in four Asian countries. Upon 2 years of observation, the annualized rates of cardiovascular death and ischemic stroke/systemic embolic event were 0.50% and 0.90% in Taiwan and 0.33% and 0.91% in other Asian ethnicities, respectively. The annualized rates of major/clinically relevant non‐major bleeding and major gastrointestinal bleeding were 2.06% and 0.39% in Taiwan and 2.06% and 0.49% in other Asian ethnicities, respectively. Intracranial hemorrhage was rarely reported in four Asian countries (annualized rate: 0.35%).ConclusionsAlthough some differences in patient characteristics were observed among Asian ethnicities, the low clinical event rates in two‐year ETNA‐AF data reassure the effectiveness and safety of edoxaban in routine care for AF patients in Taiwan, South Korea, Hong Kong, and Thailand.

Bidirectional associations have been demonstrated between negative emotions, such as anxiety and depression, and hypertension, which can lower quality of life and increase mortality. Eye movement desensitization and reprocessing (EMDR) has been recognized as a successful intervention for individuals experiencing significant psychological distress. This study aimed to investigate the impact of an eye movement desensitization and reprocessing intervention for patients with hypertension on improving symptoms of anxiety and depression, blood pressure, and heart rate variability (HRV). This longitudinal randomized controlled trial consecutively enrolled patients with hypertension. Patients were randomly divided into two groups: one group received the EMDR intervention (n = 50); the control group received routine care (n = 52). Data were collected at four different time points: pre-intervention (T0), immediately post-intervention (T1), and at one-month and three-month follow-ups (T2 and T3, respectively). Data were analysed using the generalized estimating equation. At T1, when compared with the control group, patients in the intervention group showed substantial improvements in systolic blood pressure and measures of HRV such as low frequency, high frequency, and ratios of low frequency/high frequency (all p < .01). Symptoms of anxiety were also significantly more decreased compared with controls (p < 0.001). Improvements in symptoms of anxiety and hypertension following EMDR suggest this should be considered as a clinical treatment option for this at-risk group of patients.

BACKGROUND:The prevalence and incidence of non-valvular atrial fibrillation (NVAF) in Taiwan increase with age. Low adherence to oral anticoagulants heightens stroke risk. This study evaluated whether advanced educational intervention could enhance dabigatran adherence in Taiwanese patients with NVAF. METHODS:This multicenter clinical trial in Taiwan enrolled 873 patients aged 20-74 years and newly diagnosed with NVAF. Patients were randomized to receive advanced educational intervention or standard care only. Dabigatran adherence at 12 months was evaluated using the Morisky Medication Adherence Scale (MMAS-8), along with the proportion of subjects reporting "never/rarely forgetting to take dabigatran" at 3, 6, and 9 months, dabigatran discontinuation rate, and the safety outcomes in both groups. RESULTS:Both groups reached the maximum MMAS-8 median score at all visits, showing no significant differences. Adverse event rates were 3.9 % (17/441) in the standard care group, including four stroke and thromboembolic events, versus 4.2 % (18/432) in the advanced educational intervention group, with one stroke and thromboembolic event. Subgroup analysis of patients with initial MMAS-8 scores below 8 points showed a significant difference at sixth month (6 vs. 7, P = 0.011). Over 3, 6, 9, and 12 months, MMAS-8 scores improved in both groups, with the advanced educational intervention group achieving a perfect adherence by 12 months (routine group: 6, 6, 7, 7; advanced group: 6, 7, 7, 8). CONCLUSION:Advanced educational intervention significantly improved dabigatran adherence in younger patients with low initial adherence, demonstrating its potential in managing NVAF in Taiwan. TRIAL REGISTRATION NUMBER:NCT04532528.

Ventricular arrhythmias (VAs) are major causes of sudden cardiac death in chronic kidney disease (CKD) patients. Indoxyl sulfate (IS) is one common uremic toxin found in CKD patients. This study investigated whether IS could induce VAs via increasing right ventricular outflow tract (RVOT) arrhythmogenesis. Using conventional microelectrodes and whole-cell patch clamps, we studied the action potentials (APs) and ionic currents of isolated rabbit RVOT tissue preparations and single cardiomyocytes before and after IS (0.1 and 1.0 µM). Calcium fluorescence imaging was performed in RVOT cardiomyocytes treated with and without IS (1.0 µM) to evaluate the calcium transient and the calcium leak. In rabbit RVOT tissues, IS (0.1 and 1.0 µM) attenuated the contractility and shortened the AP durations in a dose-dependent manner. In addition, IS (0.1 and 1.0 µM) enhanced the pro-arrhythmia effects of isoproterenol (ISO, 1.0 µM) and rapid ventricular pacing (20 Hz) in RVOT (before versus after ISO, 25% versus 83%, N = 12). In RVOT cardiomyocytes, IS (1.0 µM) significantly decreased the sodium currents and L-type calcium currents but increased the sodium-calcium exchanger currents. Cardiomyocytes treated with IS (1.0 µM) had lower calcium transients but higher calcium leak than those without IS treatment. Pretreatment with secretoneurin (SN, 30 nM, a potent neuropeptide, suppressing CaMKII) prevented IS-induced ionic current changes and arrhythmogenesis. In conclusions, IS modulates RVOT electrophysiology and arrhythmogenesis via enhanced CaMKII activity. SN attenuates the effects of IS, leading to a novel therapeutic target for CKD arrhythmias.

BACKGROUND:Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and the pulmonary vein (PV) is the most important AF trigger. Neuregulin 1β (NRG1β), which is elevated in patients with paroxysmal AF, may activate signalling pathways that mediate cellular adaptations and subsequent stress in the myocardium. The objectives of this study were to study the effects of NRG1β on the PVs and explore the underlying mechanisms. METHODS:A conventional microelectrode, a whole-cell patch clamp, Western blotting and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, reactive oxygen species and cytosolic sodium ([Na+]i) in isolated rabbit PV tissue and single cardiomyocytes with or without NRG1β (10 nM) incubation for 4 h. RESULTS:NRG1β-treated PVs had faster beating rates and a higher incidence of triggered activity than control PVs. The increased PV spontaneous beating rate induced by NRG1β could be mitigated by ranolazine (a late Na+ current inhibitor, 10 μM), KN93 (1 μM) and AIP (1 μΜ) (CaMKII inhibitors) and AKTi (AKT-1/2 inhibitor, 10 μM). NRG1β-treated PV cardiomyocytes demonstrated larger late Na+ and Na+-Ca2+ exchanger current than control PV cardiomyocytes. AIP decreased late Na+ current in NRG1β-treated PV cardiomyocytes. Furthermore, NRG1β-treated PV cardiomyocytes had smaller intracellular Ca2+ transients and reduced sarcoplasmic reticulum Ca2+ contents, but higher levels of [Na+]i, oxidative stress and RyR-dependent SR Ca2+ leak than control PV cardiomyocytes. The increased RyR-dependent SR Ca2+ leak by NRG1β could be alleviated by KN93. Additionally, NRG1β-treated PV cardiomyocytes exhibited upregulated AKT, pAKT, ERK, pERK, CaMKII and pCaMKII, while SERCA2a and PLB were downregulated. AKTi can downregulate oxi-CaMKII and CaMKII in NRG1β-treated PV cardiomyocytes. CONCLUSION:By modulating electrophysiological characteristics, Ca2+ homeostasis, and enhancing oxidative stress through AKT/CaMKII signalling, NRG1β increased PV arrhythmogenesis with increasing RyR-dependent SR Ca2+ leak of PV cardiomyocytes.

BACKGROUND:Atrial fibrillation (AF) is often underdiagnosed and undertreated by noncardiologists. This study evaluated whether artificial intelligence-enabled ECG (AI-ECG) alerts could improve AF diagnosis and non-vitamin K antagonist oral anticoagulant prescriptions by noncardiologists. METHODS:In this open-label, cluster randomized controlled trial (NCT05127460) at 2 hospitals in Taiwan, noncardiologists were randomized to an intervention group (AI-ECG alerts) or control group (usual care). Alerts were sent to physicians when AI-ECG identified AF in emergency or hospitalized patients at risk of stroke (CHA₂DS₂-VASc ≥1 for men, ≥2 for women), excluding those with prior AF or oral anticoagulant use. Primary end points included a non-vitamin K antagonist oral anticoagulant prescription within 90 days after discharge, new AF diagnosis, echocardiogram arrangements, and cardiologist visits. Secondary end points were ischemic stroke, cardiovascular death, and all-cause death. RESULTS:A total of 8857 and 8960 patients were treated by 120 and 113 noncardiologists in the intervention and control groups, respectively; 275 and 245 patients had AI-detected AF. The non-vitamin K antagonist oral anticoagulant prescription rate was significantly higher in the intervention group (23.3% versus 12.0%; hazard ratio [HR], 1.85 [95% CI, 1.11-3.07]). The intervention group also had a higher rate of AF diagnosis (HR, 1.40 [95% CI, 1.03-1.90]). No significant differences were observed in echocardiogram arrangements, cardiologist visits, or the rates of ischemic stroke, cardiovascular death, and all-cause death. CONCLUSIONS:An AI-ECG alert for AF identification promoted non-vitamin K antagonist oral anticoagulant prescriptions among noncardiologists, thus reducing the disparity in AF care quality between cardiologists and noncardiologists. REGISTRATION:URL: https://clinicaltrials.gov/; Unique identifier: NCT05127460.

Phosphodiesterase inhibitors regulate intracellular Ca2+ of cardiomyocytes through enhancing second messenger signalling. This study aimed to investigate whether TP-10, a selective phosphodiesterase10A inhibitor, modulates Ca2+ cycling, attenuating arrhythmogenesis in the right ventricular outflow tract (RVOT). Right ventricular tissues from New Zealand white rabbits were harvested, and electromechanical analyses of ventricular tissues were conducted. Intracellular Ca2+ was monitored using Fluo-3, and ionic current was recorded using patch-clamp in isolated cardiomyocytes. Tissues from RVOT exhibited a reduction in action potential duration at both 50% and 90% repolarisation following treatment with TP-10. This treatment also inhibited burst firing induced by isoproterenol (ISO) in RVOT tissues, an effect that was nullified by thapsigargin. The protein kinase G inhibitor KT5823, whether used alone or in conjunction with TP-10, also suppressed ISO-induced burst firing in these tissues. Compared to the control group, RVOT cardiomyocytes treated with TP-10 demonstrated enhanced amplitudes of Ca2+ transients and increased stores of Ca2+ in the sarcoplasmic reticulum. Although the L-type Ca2+ current was diminished in TP-10-treated cardiomyocytes, the current from the Na+-Ca2+ exchanger was elevated. Furthermore, the density of late Na+ current was significantly reduced in these treated cardiomyocytes. TP-10 administration also resulted in increased levels of calcium regulatory proteins, specifically phosphorylated phospholamban at Thr17 and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a. Our findings indicate that TP-10 attenuates ISO-induced arrhythmic events in RVOT tissues via cGMP-mediated modulation of intracellular Ca2+ regulation.

Catheter ablation for tachyarrhythmia via superior approach has been used in patients without possible inferior vena cava access such as in cases of venous occlusion or complex anomaly. Difficulty in catheter manipulation, instability, number of required vascular access, and radiation exposure of operator had been described in the procedure. Application of three-dimensional (3-D) mapping system in catheter ablation via superior approach could navigate the guiding catheter and provide more precise ablation. We reported four cases receiving catheter ablation due to atrioventricular nodal reentry tachycardia, atrial fibrillation, and right ventricular arrhythmia via superior approach facilitated by 3-D mapping system with fewer vascular access and catheters.

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital -Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (>= 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in -hospital mortality, and secondary endpoints were post -discharge mortality and post -discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non -cardiovascular causes. In -hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in -hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusion: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in -hospital mortality, post -discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

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

IntroductionUnsuccessful endocardial ablation for perimitral atrial flutter (AFL) could be attributed by the epicardial bridging.ObjectiveThis study aimed to investigate the electrophysiological characteristics of epicardial breakthrough during catheter ablation of perimitral AFL.Materials and methodsThis retrospective study recruited 40 patients who received successful catheter ablation of perimitral AFL from January 2016 to June 2021. The patients were divided into two groups: group 1 (n = 18) successful endocardial ablation, and group 2 (n = 22) successful epicardial ablation following unsuccessful endocardial ablation owing to incomplete mitral block or unachievable termination AFL. The local electrogram (EGM) interval of coronary sinus (CS) duration perimitral AFL was measured before catheter ablation.ResultsThere was no significant difference in the baseline characteristics between the two groups. In group 2, 60% of successful epicardial ablation was performed in intra-CS ablation and 40% in VOM ethanol infusion. Group 2 patients had a longer EGM interval of distal CS than that in group 1 (CS1-2: 64.2 17.5 vs. 42.4 0.09 ms, P = 0.008, CS3-4: 57.13 19.4 vs. 43.8 7.5 ms; P = 0.001). The conduction velocity at successful site was slower in group 2 compared to group 1 (0.18 0.05 vs. 0.75 0.19 m/s, P = 0.040). In the multivariate analysis, distal EGM interval (CS1-2) was identified as independent predictor of the need of epicardial ablation with the optimal cutoff of 49 ms.ConclusionLonger EGM interval in distal CS during perimitral AFL was observed in perimitral AFL patients with epicardial breakthrough following endocardial-failed ablation, which may be associated with the need of epicardial ablation.

BACKGROUND:Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with electrocardiography (ECG) and chest x-ray (CXR) features to detect AD and evaluate their performance.METHODS:This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD type A and 64 AD type B) was used to train DLMs for ECG and CXR, and 9904 independent ED records (40 AD type A and 34 AD type B) were used to validate DLM performance. Human-machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits.RESULTS:The area under the curves (AUCs) of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human-machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD type A, and AD type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation.CONCLUSIONS:DLMs may serve as decision-supporting tools for identification of AD and facilitate differential diagnosis in patients with acute chest pain.

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

To determine if an electrocardiogram-based artificial intelligence system can identify pneumothorax prior to radiological examination. This is a single-center, retrospective, electrocardiogram-based artificial intelligence (AI) system study that included 107 ECGs from 98 pneumothorax patients. Seven patients received needle decompression due to tension pneumothorax, and the others received thoracostomy due to instability (respiratory rate ≥ 24 breaths/min; heart rate, < 60 beats/min or > 120 beats/min; hypotension; room air O2 saturation, < 90%; and patient could not speak in whole sentences between breaths). Traumatic pneumothorax and bilateral pneumothorax were excluded. The ECGs of 132,127 patients presenting to the emergency department without pneumothorax were used as the control group. The development cohort included approximately 80% of the ECGs for training the deep learning model (DLM), and the other 20% of ECGs were used to validate the performance. A human–machine competition involving three physicians was conducted to assess the model performance. The areas under the receiver operating characteristic (ROC) curves (AUCs) of the DLM in the validation cohort and competition set were 0.947 and 0.957, respectively. The sensitivity and specificity of our DLM were 94.7% and 88.1% in the validation cohort, respectively, which were significantly higher than those of all physicians. Our DLM could also recognize the location of pneumothorax with 100% accuracy. Lead-specific analysis showed that lead I ECG made a major contribution, achieving an AUC of 0.930 (94.7% sensitivity, 86.0% specificity). The inclusion of the patient characteristics allowed our AI system to achieve an AUC of 0.994. The present AI system may assist the medical system in the early identification of pneumothorax through 12-lead ECG, and it performs as well with lead I ECG alone as with 12-lead ECG.

Background/Purpose: Pharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet.Methods: CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients.Results: Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel.Conclusion: Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.Copyright 2022, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: Atrial fibroblasts activation causes atrial fibrosis, which is one major pathophysiological contributor to atrial fibrillation (AF) genesis. Klotho is a pleiotropic protein with remarkable cardiovascular effects, including anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study investigated whether Klotho can modulate the activity of human atrial fibroblasts and provides an anti-fibrotic effect. Methods: Cell migration assay and proliferation assay were used to investigate fibrogenesis activities in single human atrial fibroblasts with or without treatment of Klotho (10 and 100 pM, 48 h). Calcium fluorescence imaging, the whole-cell patch-clamp, and Western blotting were performed in human atrial fibroblasts treated with and without Klotho (100 pM, 48 h) to evaluate the store-operated calcium entry (SOCE), transient receptor potential (TRP) currents, and downstream signaling. Results: High dose of Klotho (100 pM, 48 h) significantly reduced the migration of human atrial fibroblasts without alternating their proliferation; in addition, treatment of Klotho (100 pM, 48 h) also decreased SOCE and TRP currents. In the presence of BI-749327 (a selective canonical TRP 6 channel inhibitor, 1 μM, 48 h), Klotho (100 pM, 48 h) could not inhibit fibroblast migration nor suppress the TRP currents. Klotho-treated fibroblasts (100 pM, 48 h) had lower phosphorylated phospholipase C (PLC) (p-PLCβ3 Ser537) expression than the control. The PLC inhibitor, U73122 (1 μM, 48 h), reduced the migration, decreased SOCE and TRP currents, and lowered p-PLCβ3 in atrial fibroblasts, similar to Klotho. In the presence of the U73122 (1 μM, 48 h), Klotho (100 pM, 48 h) could not further modulate the migration and collagen synthesis nor suppress the TRP currents in human atrial fibroblasts. Conclusions: Klotho inhibited pro-fibrotic activities and SOCE by inhibiting the PLC signaling and suppressing the TRP currents, which may provide a novel insight into atrial fibrosis and arrhythmogenesis.

Background:A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).Objectives:This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI.Methods:Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel.Results:A HANC [H: low hemoglobin (< 13 g/dL for men and < 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate < 60 mL/min] risk stratification score was developed, and demonstrated optimal sensitivity and specificity at a cutoff score of ≥ 2. The HANC score compared favorably against the recently validated ABCD score in the full Switch Study cohort (n = 200), and the ABCD-GENE score in a genotyped cohort (n = 102).Conclusions:The HANC score may serve to alert clinicians to patients at potentially higher HPR risk on clopidogrel, but not prasugrel. Further research to validate this score and assess its correlation with clinical outcomes is warranted.