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Chen-Hung Lee,1 Ming-Jer Hsieh,1 Shang-Hung Chang,1 Kuo-Chun Hung,1 Chao-Jan Wang,2 Ming-Yi Hsu,2 Jyuhn-Huarng Juang,3 I-Chang Hsieh,1 Ming-Shien Wen,1 Shih-Jung Liu4,5 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Linkou, Taiwan; 2Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 4Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 5Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan 33305, TaiwanCorrespondence: Shih-Jung LiuBiomaterials Lab, Department of Mechanical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, TaiwanTel +886 3 211 8166Fax +886 3 211 8558Email profsjliu5347@gmail.comBackground: The high lifetime risk of vascular disease is one of the important issues that plague patients with diabetes mellitus. Systemic oral vildagliptin administration favors endothelial recovery and inhibits smooth muscle cell (SMC) proliferation. However, the localized release of vildagliptin in the diabetic vessel damage has seldom been investigated.Research design and methods: In this work, nanofiber-eluting stents that loaded with vildagliptin, a dipeptidyl peptidase-4 enzyme (DPP-4) inhibitor, was fabricated to treat diabetic vascular disease. To prepare nanofibers, the poly (D,L)-lactide-co-glycolide (PLGA) and vildagliptin were mixed using hexafluoroisopropanol and electrospinning process. In vitro and in vivo release rates of the vildagliptin were characterized using high-performance liquid chromatography.Results: Effective vildagliptin concentrations were delivered for more than 28 days from the nanofibrous membranes coating on the surface of the stents in vitro and in vivo. The vildagliptin-eluting PLGA membranes greatly accelerated the recovery of diabetic endothelia and reduced SMC hyperplasia. The type I collagen content of the diabetic vascular intimal area that was treated by vildagliptin-eluting stents was lower than that of the non-vildagliptin-eluting group.Conclusion: The experimental results revealed that stenting with vildagliptin-eluting PLGA membranes could potentially promote healing for diabetic arterial diseases.Keywords: re-endothelialization, neointimal hyperplasia, vildagliptin, biodegradable drug-eluting nanofibers

Cheng-Hung Lee,1 Ming-Jer Hsieh,1 Kuo-Sheng Liu,2,3 Che-Wei Cheng,3 Shang-Hung Chang,1 Shih-Jung Liu,3,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Kuo-Chun Hung,1 Yung-Hsin Yeh,1 Wei-Jan Chen,1 I-Chang Hsieh,1 Jyuhn-Huarng Juang,6 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Chang Gung University College of Medicine, Tao-Yuan, Taiwan; 2Department of Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan; 5Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, Tao-Yuan, Taiwan Objective: The current treatment of atherosclerotic coronary heart disease with limus-eluting stents can lead to incomplete endothelialization and substantial impairment of arterial healing relative to treatment with bare-metal stents. The sustained and local delivery of ticagrelor, a reversibly binding P2Y12 receptor inhibitor, using hybrid biodegradable nanofibers/stents, was developed to reduce neointimal formation and endothelial dysfunction.Methods: In this investigation, a solution of ticagrelor, poly(D,L)-lactide-co-glycolide, and hexafluoro isopropanol was electrospun to fabricate ticagrelor-eluting nanofibrous drug-eluting stents. The in vitro and in vivo ticagrelor concentrations were measured using a high-performance liquid chromatography assay. The effectiveness of ticagrelor-eluting stents was examined relative to that of sirolimus-eluting stents. Results: Adequate ticagrelor levels were detected for four weeks in vitro. Less HES5-positive labeling was found near the ticagrelor-eluting stented vessels (0.33±0.12) than close to the sirolimus-eluting stented vessels (0.57±0.15) (p

Cheng-Hung Lee,1,2 Chia-Ying Yu,2 Shang-Hung Chang,1 Kuo-Chun Hung,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 I-Chang Hsieh,1 Wei-Jan Chen,1 Yu-Shien Ko,1 Ming-Shien Wen1 1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan Introduction: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.Methods: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning.Results: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels.Conclusion: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries. Keywords: sequential-like and sustainable release, biodegradable drug-eluting stents, poly-L-lactide, polylactide-polyglycolide, mechanical properties

Cheng-Hung Lee,1,2 Yu-Huang Lin,3 Shang-Hung Chang,1 Chun-Der Tai,3 Shih-Jung Liu,2 Yen Chu,4 Chao-Jan Wang,5 Ming-Yi Hsu,5 Hung Chang,6 Gwo-Jyh Chang,7 Kuo-Chun Hung,1 Ming-Jer Hsieh,1 Fen-Chiung Lin,1 I-Chang Hsieh,1 Ming-Shien Wen,1 Yenlin Huang81Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Linkou, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, Chang Gung University, 4Laboratory of Cardiovascular Physiology, Division of Thoracic and Cardiovascular Surgery, 5Department of Medical Imaging and Intervention, 6Hematology-Oncology Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, 7Graduate Institute of Clinical Medicinal Sciences, Chang Gung University College of Medicine, Linkou, 8Department of Anatomical Pathology, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, TaiwanAbstract: Incomplete endothelialization, blood cell adhesion to vascular stents, and inflammation of arteries can result in acute stent thromboses. The systemic administration of acetylsalicylic acid decreases endothelial dysfunction, potentially reducing thrombus, enhancing vasodilatation, and inhibiting the progression of atherosclerosis; but, this is weakened by upper gastrointestinal bleeding. This study proposes a hybrid stent with biodegradable nanofibers, for the local, sustained delivery of acetylsalicylic acid to injured artery walls. Biodegradable nanofibers are prepared by first dissolving poly(D,L)-lactide-co-glycolide and acetylsalicylic acid in 1,1,1,3,3,3-hexafluoro-2-propanol. The solution is then electrospun into nanofibrous tubes, which are then mounted onto commercially available bare-metal stents. In vitro release rates of pharmaceuticals from nanofibers are characterized using an elution method, and a high-performance liquid chromatography assay. The experimental results suggest that biodegradable nanofibers release high concentrations of acetylsalicylic acid for three weeks. The in vivo efficacy of local delivery of acetylsalicylic acid in reducing platelet and monocyte adhesion, and the minimum tissue inflammatory reaction caused by the hybrid stents in treating denuded rabbit arteries, are documented. The proposed hybrid stent, with biodegradable acetylsalicylic acid-loaded nanofibers, substantially contributed to local, sustained delivery of drugs to promote re-endothelialization and reduce thrombogenicity in the injured artery. The stents may have potential applications in the local delivery of cardiovascular drugs. Furthermore, the use of hybrid stents with acetylsalicylic acid-loaded nanofibers that have high drug loadings may provide insight into the treatment of patients with high risk of acute stent thromboses.Keywords: biodegradable drug-eluting nanofibers, acetylsalicylic acid, release characteristics, cell adhesion to vascular stents

Objective 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. Methods Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. Results Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy ( P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III ( P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR

The well-known mediation-moderation model of subjective well-being has been criticized because it oversimplified the concept of culture. This study aimed to explore whether the family culture, as supplement of social culture, has significant impacts on subjective well-being. The intellectual-cultural orientation subscale (ICO) of family environment scale-CV (FES-CV), Eysenck personality questionnaire for adult (EPQA), and index of well-being (IWB) were used to test 340 college students from China. Results showed that the extraversion and neuroticism of personality traits have great influences on subjective well-being, and intellectual-cultural orientation as family culture, to represent characteristic of family culture, serves as a moderating variable for the 2 components of subjective well-being. And all these findings revealed that the trait of family culture should be considered as a supplement of the social culture and a critical complementary moderating influenced factor for subjective well-being. Together with personality traits, it can explain the variance of subjective well-being to some extent. The family cultural has an important influence on college students’ personality and subjective well-being. It is important to provide a high quality family cultural environment for college students.

Implantation of an intraocular lens (IOL) after combined vitrectomy and cataract surgery is usually required to reduce postoperative refraction errors. However, because of the severe fibrosis of the anterior capsule and the adhesion between the anterior and posterior capsules, it is difficult to reopen the capsular bag to complete the secondary IOL implantation. In this study, a surgical approach is described for reopening the severe adhesion between capsules and removing the significant fibroproliferative membranous material by injecting ophthalmic viscosurgical device into the periphery of the capsular bag to separate the anterior and posterior capsules. The IOL was implanted into the capsular bag without any zonular rupture or posterior capsule tear. The position of the IOL was stable during postoperative follow-up up to 3 months. This procedure to open a severely fibrosis capsule was safe and effective. [ABSTRACT FROM AUTHOR]

Lactococcus garvieae is an important pathogen in aquaculture, outbreaks of which significantly affect production. It is a rare pathogen with a low virulence in human infection. The relation between the aquaculture outbreak and the human infection has not been clarified. Prospective and retrospective epidemiologic surveillance of the four patients with L. garvieae infection between 2000 and 2003 and their relations to the aquaculture outbreaks of L. garvieae were conducted. All the four patients with L. garvieae infection were associated with gastrointestinal disorders. Three of the four patients gave a history of consuming raw fish and in three of the four patients, the infection occurred in summer between June and August while there is a decrease of fisheries production and an increase in L. garvieae infection in aquaculture farms. There was a 100% identity of 16S rDNA sequence of L. garvieae isolates from patient 1 and from the squid muscle obtained from the restaurant where patient 1 consumed the raw fish. Sporadic occurrence of L. garvieae infection in human appears to correlate with the seasonal aquaculture outbreaks of L. garvieae infection. The presence of gastro-intestinal disorder may facilitate L. garvieae infection. [ABSTRACT FROM AUTHOR]

Abstract. Objective:. To explore the correlation between ischiocavernosus muscle injury (ICMI) with different types of pelvic fractures and erectile dysfunction (ED) after pelvic fracture. Design:. Retrospective analysis of a prospective database. Setting:. The study was carried out at the affiliated hospital of Zunyi Medical University. Patients/participants:. A total of 776 male patients with pelvic fracture, aged 18 to 67 years, were recruited for this study by retrospective analysis, and based on the diagnosis of ED and the presence of ICMI, the participants were divided into ED and non-ED groups as well as ICMI and non-ICMI groups. Intervention:. No. Main outcome measurements:. ICMI, the type of pelvic fracture, International Index of Erectile Function-5 scores. Computed tomography/magnetic resonance imaging scans, electromyography (motor unit potential) was used to diagnose ICMI. Results:. The International Index of Erectile Function-5 score was 19.7 ± 5.9. The incidence of ED was 27.3%, the duration time of ED was 30 ± 23 months, and the incidence of reversible ED was 39.6% and of irreversible ED was 60.4%. The incidence of ICMI was 29.4%, among which the incidence of unilateral injury was 57.9%, and the incidence of bilateral injury was 42.1%. Among all pelvic fractures, the incidence of pubic ramus fracture was 88.1%. Bilateral pubic ramus fractures, bilateral fractures of the ischial ramus, and ICMI were independent risk factors for ED after pelvic fracture. Bilateral pubic ramus fractures and pubic symphysis separation were independent risk factors for ICMI. Unilateral ICMI was an independent risk factor for reversible ED, while bilateral ICMI was an independent risk factor for irreversible ED. Conclusions:. ICMI is associated with ED and may be a cause for ED, while pubic ramus fracture, ischial ramus fracture, and pubic symphysis separation may be the main causes of ICMI. Unilateral ICMI may be the main risk factor for transient ED, and bilateral ICMI may be the main risk factor for permanent ED.

Background: The 12-lead electrocardiogram (ECG) is an established modality for cardiovascular assessment. While deep learning algorithms have shown promising results for analyzing ECG data, the limited availability of labeled datasets hinders broader applications. Self-supervised learning can learn meaningful representations from the unlabeled data and transfer the knowledge to downstream tasks. This study underscores the development and validation of a self-supervised learning methodology tailored to produce universal ECG representations from longitudinally collected ECG data, applicable across a spectrum of cardiovascular assessments., Methods: We introduced a pre-trained model that utilizes contrastive self-supervised learning to universal ECG representations from 4,932,573 ECG tracing from 1,684,298 adult patients on 7 campuses of Chang Gung Memorial Hospital. We extensively evaluated the proposed model using an internal dataset collected from diverse healthcare establishments and an external public dataset encompassing varied cardiovascular conditions and sample magnitudes., Results: The pre-trained model showed the equivalent performance to the conventionally trained models, which solely rely on supervised learning in both internal and external datasets, to assess atrial fibrillation, atrial flutter, premature rhythm abnormalities, first-degree atrioventricular block, and myocardial infarction. When applied to small sample sizes, it was observed that the learned ECG representations enhanced the classification models, resulting in an improvement of up to 0.3 of the area under the receiver operating characteristic (AUROC)., Conclusions: The ECG representations learned from longitudinal ECG data are highly effective, particularly with small sample sizes, and further enhance the learning process and boost robustness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug., Methods and Results: Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P =0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P =0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding., Conclusions: Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.

Introduction: Eleclazine is a highly selective late sodium current inhibitor, possibly effective in reducing ventricular fibrillation (VF) in heart failure (HF) with ischemia-reperfusion (IR) injury. The electrophysiological effects of eleclazine at therapeutic hypothermia (TH) are unknown. We investigated the effects of eleclazine in suppressing VF in failing rabbit hearts with IR injury undergoing TH., Method: HF was induced by right ventricular pacing. An IR model was created using coronary artery ligation for 60 min, followed by reperfusion for 30 min. Hearts were excised and Langendorff-perfused for optical mapping and electrophysiological studies. Electrophysiological studies were repeated after TH (33°C) for 30 min or eleclazine (1 μm) infusion for 20 min., Results: In failing IR-injured hearts, eleclazine reduced action potential duration (APD) dispersion and accelerated intracellular Ca2+ uptake to suppress arrhythmogenic alternans but also exacerbated rate-dependent conduction slowing, resulting in neutral effects on VF inducibility at normothermia. TH increased VF severity. Eleclazine after TH ameliorated TH-induced APD dispersion and further depressed conduction to reduce VF inducibility and severity. TH after eleclazine also slowed conduction to a greater extent to reduce VF inducibility and severity by extrastimulus pacing. In control IR-injured hearts, eleclazine increased VF severity by dynamic pacing at normothermia, which was counteracted by TH., Conclusions: Eleclazine does not prevent VF at normothermia but reduces VF inducibility and severity by extrastimulus pacing at TH in isolated failing hearts with regional IR injury., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aims: The PIONEER-HF and PARAGLIDE-HF trials aimed to determine the efficacy and safety of the in-hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real-world routine care is unclear. This study aimed to investigate the applicability of the PIONEER-HF and PARAGLIDE-HF trials to real-world AHF patients., Methods and Results: We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER-HF eligible (n = 3683) and non-eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE-HF eligible (n = 5191) and non-eligible (n = 5832) patients with an LVEF >40%. Over a mean follow-up of 3.5 years, the PIONEER-HF non-eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88-1.04). No significant difference was found in the composite outcome between PARAGLIDE-HF non-eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90-1.04)., Conclusions: Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril-valsartan. Yet, non-eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril-valsartan benefits in non-eligible AHF patients., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Electrocardiogram (ECG) abnormalities have demonstrated potential as prognostic indicators of patient survival. However, the traditional statistical approach is constrained by structured data input, limiting its ability to fully leverage the predictive value of ECG data in prognostic modeling., Methods: This study aims to introduce and evaluate a deep-learning model to simultaneously handle censored data and unstructured ECG data for survival analysis. We herein introduce a novel deep neural network called ECG-surv, which includes a feature extraction neural network and a time-to-event analysis neural network. The proposed model is specifically designed to predict the time to 1-year mortality by extracting and analyzing unique features from 12-lead ECG data. ECG-surv was evaluated using both an independent test set and an external set, which were collected using different ECG devices., Results: The performance of ECG-surv surpassed that of the Cox proportional model, which included demographics and ECG waveform parameters, in predicting 1-year all-cause mortality, with a significantly higher concordance index (C-index) in ECG-surv than in the Cox model using both the independent test set (0.860 [95% CI: 0.859- 0.861] vs. 0.796 [95% CI: 0.791- 0.800]) and the external test set (0.813 [95% CI: 0.807- 0.814] vs. 0.764 [95% CI: 0.755- 0.770]). ECG-surv also demonstrated exceptional predictive ability for cardiovascular death (C-index of 0.891 [95% CI: 0.890- 0.893]), outperforming the Framingham risk Cox model (C-index of 0.734 [95% CI: 0.715-0.752])., Conclusion: ECG-surv effectively utilized unstructured ECG data in a survival analysis. It outperformed traditional statistical approaches in predicting 1-year all-cause mortality and cardiovascular death, which makes it a valuable tool for predicting patient survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI)., Methods: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 μmol/L., Results: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits., Conclusions: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The role of P-wave in identifying left atrial enlargement (LAE) with the use of artificial intelligence (AI)-enabled electrocardiography (ECG) models is unclear. It is also unknown if AI-enabled single-lead ECG could be used as a diagnostic tool for LAE surveillance. We aimed to build AI-enabled P-wave and single-lead ECG models to identify LAE using sinus rhythm (SR) and non-SR ECGs, and compare the prognostic ability of severe LAE, defined as left atrial diameter ≥ 50 mm, assessed by AI-enabled ECG models vs echocardiography., Methods: This retrospective study used data from 382,594 consecutive adults with paired 12-lead ECG and echocardiography performed within 2 weeks of each other at Chang Gung Memorial Hospital. UNet++ was used for P-wave segmentation. ResNet-18 was used to develop deep convolutional neural network-enabled ECG models for discriminating LAE. External validation was performed with the use of data from 11,753 patients from another hospital., Results: The AI-enabled 12-lead ECG model outperformed other ECG models for classifying LAE, but the single-lead ECG models also showed excellent performance at a left atrial diameter cutoff of 50 mm. AI-enabled ECG models had excellent and fair discrimination on LAE using the SR and the non-SR data set, respectively. Severe LAE identified by AI-enabled ECG models was more predictive of future cardiovascular disease than echocardiography; however, the cumulative incidence of new-onset atrial fibrillation and heart failure was higher in patients with echocardiography-severe LAE than with AI-enabled ECG-severe LAE., Conclusions: P-Wave plays a crucial role in discriminating LAE in AI-enabled ECG models. AI-enabled ECG models outperform echocardiography in predicting new-onset cardiovascular diseases associated with severe LAE., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With the coming of a rapidly aging society, individuals born in the baby boom era after World War II are now facing the challenges of aging. From late middle age to successful aging, what are the perceptions and responses of these quasi-seniors? With this in mind, referring to Phelan's successful aging scale, the researchers developed the 4P Strategies (Physical, Psychological, Prospect, and Place and Relationships) tailored for quasi-seniors. Based on grounded theory, the results of 12 sessions of focused interviews (involving a total of 93 interviewees between the ages of 55 and 75; 41 males and 52 females; 48 not retired and 45 retired) were matched with the 4P Strategies. The results were the following: (1) regarding the Physical factor, the interviewees were shocked by their physical decline, and they had begun to devise strategies for health preservation and exercise; (2) regarding the Psychological factor, in order to mentally adapt, the interviewees agreed that moderate stress relief was absolutely necessary; (3) regarding the Prospect factor: the interviewees felt that one should make financial plans early, contemplate the value of life, and more actively learn and realize one's dreams; and (4) regarding the Place and Relationships factor, the interviewees aimed to rebuild their close relationships with their spouses, family members, and old friends and had polarized views regarding where to live in their old age. On the whole, the most discussed issue among the interviewees was where to live in their old age. Many had their own views and plans and did not stick to traditional views; however, they took the opinions of their significant others into account. During the interviews, interviewees wished to understand the responses of their peers to serve as a reference for their own decisions, and they realized that successful aging also required learning. This study aimed to encourage quasi-seniors about to enter their old age and help them to learn how to positively respond to aging as well as work towards a happy life with successful aging. This study could fill in gaps in research involving individuals in this age group and provide a reference for relevant policies.

The regulation of adipose tissue metabolism by irisin involves modulating gene expressions related to energy metabolism and insulin sensitivity via miRNA-mediated signaling pathways within adipose tissue. Understanding the molecular mechanisms behind the role of irisin is vital for addressing obesity and related metabolic complications. In this study, we undertook an extensive miRNA transcriptomic approach to identify differentially expressed miRNAs following irisin exposure in adipocytes and murine white adipose tissue. Our findings spotlighted two miRNAs, miRNA-758 and miRNA-668, as being influenced by irisin. To understand the impact of the modulations of these miRNAs by irisin, we performed a signaling pathway and network analysis. After irisin exposure, both, miRNA-758 and miRNA-668, emerged as key regulators in leptin and CDK5 signaling pathways. Leptin, a hormone originating from adipose tissue, is primarily produced by adipocytes, and its effects are known to be mediated by CDK5. In essence, this study identifies pivotal genes and miRNAs in irisin-driven mechanisms in adipose tissue, offering valuable insights for crafting novel therapeutic strategies for metabolic and associated disorders.

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

Background: The risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients., Methods: The database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death., Results: Patients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20-8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30-3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases., Conclusions: The machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction., 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., (© 2023 Chang, Liu, Huang, Hsu, Chen, Lin, Tsai, Chou, Wen, Wo, Lee, Liu, Wang and Kuo.)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce new-onset atrial fibrillation (AF) in patients with type 2 diabetes mellitus (T2DM). We aimed to determine the long-term effects of SGLT2i on atrial tachyarrhythmia recurrence after catheter ablation (CA) in T2DM patients., Methods: This retrospective study enrolled consecutive patients with T2DM undergoing CA for AF between January 2016 and December 2021. Patient baseline demographic characteristics and use of anti-diabetic and anti-arrhythmic medications were analyzed. Echocardiographic parameters were obtained one day and 6 months after CA., Results: Our study population comprised 122 patients (70% paroxysmal AF). The baseline patient characteristics were similar between the SGLT2i-treated group (n = 45) and the non-SGLT2i-treated group (n = 77) except for stroke. At 6-month follow-up, body-mass index (BMI) was significantly decreased and left ventricular ejection fraction (LVEF) was significantly increased only in the SGLT2i group. E/e' was decreased 6 months after CA in both groups. During a mean follow-up of 33.7 ± 21.6 months, 22 of 122 patients had atrial tachyarrhythmia recurrence. The long-term atrial tachyarrhythmia-free survival rate was significantly higher in the SGLT2i-treated patients, and multivariate analysis revealed that AF type and SGLT2i use were independently associated with atrial tachyarrhythmia recurrence after CA., Conclusion: The use of SGLT2i and AF type were independent risk factors associated with atrial tachyarrhythmia recurrence after CA in T2DM patients with AF. This result was at least partly due to the pleiotropic effects of SGLT2i on BMI reduction and left ventricular function improvement., Competing Interests: All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis., Methods: This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF <40%, using original ECG signals or transformed images from 190,359 patients with paired ECG and echocardiogram within 14 days. The 190,359 patients were divided into a training set of 133,225 and a validation set of 57,134. The accuracy of recognizing LVSD and subsequent mortality predictions were tested using ECGs from 190,316 patients with paired data. Of these 190,316 patients, we further selected 49,564 patients with multiple echocardiographic data to predict LVSD incidence. We additionally used data from 1,194,982 patients who underwent ECG only to assess mortality prognostication. External validation was performed using data of 91,425 patients from Tri-Service General Hospital, Taiwan., Results: The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% women), and 8,216 patients (4.3%) had LVSD. The median follow-up period was 3.9 years (interquartile range 1.5-7.9 years). The area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity of the signal-based DNN (DNN-signal) to identify LVSD were 0.95, 0.91, and 0.86, respectively. DNN signal-predicted LVSD was associated with age- and sex-adjusted hazard ratios (HRs) of 2.57 (95% confidence interval [CI], 2.53-2.62) for all-cause mortality and 6.09 (5.83-6.37) for cardiovascular mortality. In patients with multiple echocardiograms, a positive DNN prediction in patients with preserved LVEF was associated with an adjusted HR (95% CI) of 8.33 (7.71 to 9.00) for incident LVSD. Signal- and image-based DNNs performed equally well in the primary and additional datasets., Conclusion: Using DNNs, ECG becomes a low-cost, clinically feasible tool to screen LVSD and facilitate accurate prognostication., 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 © 2023 Huang, Hsu, Liu, Lin, Tsai, Chen, Chang, Liu, Lee, Wo, Chou, Wang, Wen and Kuo.)

Background: The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors., Methods: Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components., Results: At the end of maximal 5-year follow-up (median 22.18 months with interquartile range 7.20-49.08 months for MACE in protocol 1 and 23.46 months with interquartile range 8.15-49.02 months for MACE in protocol 2), compared with an E/e' value of <8, an intermediate value of E/e' 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P < .0001). In protocol 2, an intermediate E/e' value of 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P < .05), except an intermediate value E/e' 8 to 15 was not associated with AF., Conclusions: In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with CV events and is a useful marker of risk., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Introduction: Central sleep apnea (CSA) is a common and serious comorbidity mainly occurring in patients with heart failure (HF), which tends to be underdiagnosed and has not been widely studied. Overnight polysomnography (PSG) is the gold standard for diagnosing CSA; however, the time and expense of the procedure limit its applicability. Portable monitoring (PM) devices are convenient and easy to use; however, they have not been widely studied as to their effectiveness in detecting CSA in patients with HF. In the current study, we examined the diagnostic value of PM as a screening tool to identify instances of CSA among patients with HF., Methods: A total of 22 patients under stable heart failure conditions with an ejection fraction of <50% were enrolled. All patients underwent PM and overnight PSG within a narrow time frame. The measurements of the apnea-hypopnea index (AHI), hypopnea index (HI), central apnea index (CAI), and obstructive apnea index (OAI) obtained from PSG, automatic scoring, and manual scoring of PM were recorded. The results obtained from PSG and those from PM (automatic and manual scoring) were compared to assess the accuracy of PM., Results: Among the patients, CSA in 11 patients was found by PSG. The AHI measurements performed using manual scoring of PM showed a significant correlation with those performed using PSG (r = 0.69; P = 0.01). Nonetheless, mean AHI measurements showed statistically significant differences between PSG and automatic scoring of PM (40.0 vs. 23.7 events/hour, respectively; P < 0.001), as well as between automatic and manual scoring of PM (23.7 vs. 29.5 events/hour; P < 0.001). Central sleep apnea was detected by PM; however, the results were easily misread as obstructive apnea, particularly in automatic scoring., Conclusion: PM devices could be used to identify instances of central sleep apnea among patients with HF. The results from PM were well-correlated with standard PSG results, and manual scoring was preferable to automated scoring., 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 © 2022 Tung, Hsieh, Chuang, Lin, Hung, Lu, Lee, Hu, Wen and Chen.)

Exosome-based regenerative therapies are potentially easier to manufacture and safer to apply compared to cell-based therapies. However, many questions remain about how to bio-manufacture reproducible and potent exosomes using animal-free reagents. Here we evaluate the hypothesis that designer biomaterial substrates can be used to alter the potency of exosomes secreted by human induced pluripotent stem cells (iPSCs). Two animal-free designer matrices were fabricated based on recombinant elastin-like polypeptides (ELPs): one including a cell-adhesive RGD ligand and a second with a non-adhesive RDG peptide. While iPSCs cultured on these two substrates and Matrigel-coated controls had similar levels of proliferation, the RDG-ELP substrate significantly increased protein expression of stemness markers OCT4 and SOX2 and suppressed spontaneous differentiation compared to those on RGD-ELP. The pro-survival potency of iPSC-derived exosomes was evaluated using three distinct stress tests: serum starvation in murine fibroblasts, hypoxia in human endothelial cells, and hyperosmolarity in canine kidney cells. In all three cases, exosomes produced by iPSCs grown on RDG-ELP substrates had similar pro-survival effects to those produced using iPSCs grown on Matrigel, while use of RGD-ELP substrates led to significantly reduced exosome potency. These data demonstrate that recombinant substrates can be designed for the robust bio-manufacturing of iPSC-derived, pro-survival exosomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Uncontrolled post-traumatic hemorrhage is an important cause of traumatic mortality that can be avoided. This study intends to use machine learning (ML) to build an algorithm based on data collected from an electronic health record (EHR) system to predict the risk of delayed bleeding in trauma patients in the ICU. We enrolled patients with torso trauma in the surgical ICU. Demographic features, clinical presentations, and laboratory data were collected from EHR. The algorithm was designed to predict hemoglobin dropping 6 h before it happened and evaluated the performance with 10-fold cross-validation. We collected 2218 cases from 2008 to 2018 in a trauma center. There were 1036 (46.7%) patients with positive hemorrhage events during their ICU stay. Two machine learning algorithms were used to predict ongoing hemorrhage events. The logistic model tree (LMT) and the random forest algorithm achieved an area under the curve (AUC) of 0.816 and 0.809, respectively. In this study, we presented the ML model using demographics, vital signs, and lab data, promising results in predicting delayed bleeding risk in torso trauma patients. Our study also showed the possibility of an early warning system alerting ICU staff that trauma patients need re-evaluation or further survey.

Background: Patients admitted with acute decompensated heart failure (ADHF) have a poor prognosis and poor quality of life due to dyspnea and edema. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective water diuretic. This study aimed to evaluate the efficacy and safety of a short course of tolvaptan to treat volume overload in patients with ADHF., Methods: We conducted a phase III, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a short course of tolvaptan (15 mg/day for 4 days) in hospitalized ADHF patients with volume overload despite the use of conventional diuretics. The primary end-point was the change in body weight after 4 days of treatment. The secondary end-points were the change in intake/output balance, change in serum sodium/potassium concentrations, physician/patient assessed signs and symptoms of heart failure after 4 days of treatment, and all-cause mortality in 1 month., Results: A total of 110 patients were screened, and 91 were randomized to receive 15 mg/day of tolvaptan for 4 days (n = 46) or matching placebo (n = 45). Compared to the placebo-treated patients, tolvaptan significantly reduced body weight (-1.36 ± 2.13 kg in the tolvaptan group vs. -0.59 ± 1.27 kg in the placebo group, p = 0.0394). The tolvaptan group also had a negative intake/urine volume balance compared to the placebo group (-509.3 ± 2788.2 ml vs. 975.5 ± 1903.1 ml, p = 0.0059). The safety profile of tolvaptan was acceptable., Conclusions: Tolvaptan significantly reduced volume overload in hospitalized ADHF patients with volume overload despite the use of conventional diuretics.

Background: Atrial fibrillation (AF)-associated embolic stroke is preventable, and AF detection may help to prevent stroke in subjects with paroxysmal AF. We aimed to evaluate the AF detection performance of smartwatch photoplethysmography (PPG) and the feasibility of ambulatory monitoring for AF detection in the daily life., Design and Methods: Consecutive subjects who underwent ambulatory Holter electrocardiogram (ECG) monitoring for AF detection or AF burden evaluation were enrolled. The participants underwent 24 hours of simultaneous Holter ECG monitoring and continuous PPG recording using a Garmin smartwatch. The PPG signals were processed for noise rejection, beat detection, beat labeling, and rhythm labeling for each 5-minute segment. The accuracy of the PPG AF detection was calculated using the corresponding simultaneous Holter ECG as the AF diagnostic standard., Results: Among the 200 available participants, 112 participants (56%) developed AF (the AF group). The sensitivity, specificity, and positive predicted value of AF detection in participants were 97.3%, 88.6%, and 91.6%, respectively. The area under the receiver operating characteristic curve was 0.90. When the performance was analyzed in these 5-minute segments, the sensitivity, specificity, and positive predicted values of AF detection were 97.1%, 86.8%, and 89.7%, respectively., Conclusions: This study demonstrated the feasibility of ambulatory monitoring for AF detection using a commercial smartwatch in daily life. A smartwatch may be an alternative screening tool to standard ambulatory Holter monitoring., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Objectives: Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR., Methods: From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months., Results: The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels., Conclusions: Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia., Citation: Chuang L-P, Pang J-HS, Lin S-W, et al. Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration. J Clin Sleep Med . 2022;18(5):1365-1373., (© 2022 American Academy of Sleep Medicine.)

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan's National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this article, the TiN sensitive film as a sensing membrane was deposited onto n + -type Si substrate by a DC sputtering technique for extended-gate field-effect transistor (EGFET) pH sensors and detection of cardiac troponin-I (cTn-I) in the patient sera for the first time. The crystal structure, Raman spectrum, element profile, surface roughness, and surface morphology of the TiN sensitive film were characterized by X-ray diffraction, Raman spectroscopy, secondary ion mass spectroscopy, atomic force microscopy, and scanning electron microscopy, respectively. The sensing performance of the TiN sensitive film is correlated with its relative structural feature. A high sensitivity of 57.49 mV/pH, a small hysteresis voltage of ∼1 mV, and a low drift rate of 0.31 mV/h were obtained in the TiN sensitive film. In addition, the pH sensitivity of this TiN EGFET sensor was preserved approximately 57 mV/pH after operation time of 180 days. Subsequently, the cTn-I antibodies with carboxyl groups activated by 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) along with N-hydroxysuccinimide (NHS) were immobilized on the TiN sensitive film functionalizing with 3-aminopropyl triethoxysilane (APTES). After obtaining the successful immobilization of cTn-I antibodies on the TiN EGFET biosensor, the cTn-I antigen specifically binds with its relative antibody. The cTn-I EGFET biosensor showed a high sensitivity of 21.88 mV/pC cTn-I in a wide dynamic range of 0.01-100 ng/mL. Furthermore, the concentrations of cTn-I in patient sera measured by our TiN EGFET biosensors are comparable to those determined by commercial enzyme-linked immuno-sorbent assay kits., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coronary computed tomography angiography (CCTA) is a widely used imaging modality for diagnosing coronary artery disease (CAD) but is limited by a high false positive rate when evaluating coronary arteries with stents and heavy calcifications. Virtual intravascular endoscopy (VIE) images generated from CCTA can be used to qualitatively assess the vascular lumen and might be helpful for overcoming this challenge. In this study, one hundred subjects with coronary stents underwent both CCTA and invasive coronary angiography (ICA). A total of 902 vessel segments were analyzed using CCTA and VIE. The vessel segments were first analyzed on CCTA alone. Then, using VIE, the segments were classified qualitatively as either negative or positive for in-stent restenosis (ISR) or CAD. These results were compared, using ICA as the reference, to determine the added diagnostic value of VIE. Of the 902 analyzed vessel segments, CCTA/VIE had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (shown in %) of 93.9/90.2, 96.2/98.2, 96.0/97.7, 70.0/83.1, and 99.4/99.0, respectively, in diagnosing ISR or CAD, with significantly improved specificity ( p = 0.025), accuracy ( p = 0.046), and positive predictive value ( p = 0.047). VIE can be a helpful addition to CCTA when evaluating coronary arteries.

Objective: The weight losses after bariatric surgery are modulated by multiple factors in people with obesity. MicroRNAs (miRNAs) have been reported to show significant regulatory roles in adipose tissue. However, a serum miRNA signature to serve as a biomarker of sustained weight losses following bariatric surgery has not yet been established., Methods: MiRNA microarray was used to identify differentially expressed miRNAs in the serum of patients with an effective response after bariatric surgery compared with those without. Excess weight loss > 55% at 6 months after surgery was defined as an effective response., Results: Three miRNAs were shown to have a significantly differential expression between patients with or without an effective response following bariatric surgery. The miR-31-5p was downregulated, whereas miR-328-3p and miR-181a-5p were upregulated in the patients with effective responses compared with those without effective responses. Panels of the serum ratios of miR-328-3p/miR-31-5p or miR-181a-5p/miR-31-5p and individual BMI value exhibited good performance in preoperative prediction of treatment effectiveness. Bioinformatic analysis depicted that predicted targets of these miRNAs were involved in the regulation of the AMP-activated protein kinase signaling pathway., Conclusions: A circulating miRNA signature with clinical variables (BMI) can be a clinical biomarker to predict effectiveness following bariatric surgery., (© 2022 The Obesity Society.)

Background: Patients with active peptic ulcer (PU) were excluded from direct oral anticoagulant (DOAC) trials for stroke prevention in patients with atrial fibrillation (AF). This study evaluated the safety and effectiveness of DOACs in AF patients with active, inactive and no peptic ulcer (PU). Methods: This study accessed electronic medical records from January 1, 2009 to May 31, 2019 at a multi-center healthcare provider in Taiwan and involved 2,955 AF patients who had undergone esophagogastroduodenoscopy ≤ 1 year before anticoagulation. Subjects were classified into 3 groups: active ( n = 237), inactive ( n = 828) and no-PU ( n = 1,890) groups. We compared the risks of major bleeding, gastrointestinal bleeding, and ischemic stroke/systemic embolism (IS/SE) between DOACs and warfarin among the 3 groups. Results: In the active PU group, there were no significant differences in the risks of major bleeding [hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.08-4.98, p = 0.676], gastrointestinal bleeding (HR = 0.65, 95% CI 0.08-4.98, p = 0.676) and IS/SE (HR = 2.58; 95% CI 0.53-12.70, p = 0.243) between DOAC and warfarin (as the reference). In the inactive PU group, there were no significant differences in the risks of major bleeding (HR = 0.36, 95% CI 0.09-1.39, p = 0.138), gastrointestinal bleeding (HR = 0.21, 95% CI 0.02-1.80, p = 0.153), and IS/SE (HR = 1.04, 95% CI 0.39-2.82, p = 0.934) between DOAC and warfarin (as the reference). In the no-PU group, DOACs were associated with lower risk of major bleeding (HR = 0.26, 95% CI 0.12-0.53, p < 0.001), gastrointestinal bleeding (HR = 0.25, 95% CI 0.01-0.59, p = 0.002), and similar risk of IS/SE (HR = 0.92, 95% CI 0.55-1.54, p = 0.757) compared to warfarin. Conclusions: DOACs were as effective as warfarin in preventing IS/SE irrespective of PU status and safer than warfarin in reducing major bleeding in the no-PU group. In patients with active or inactive PUs, DOAC and warfarin were not significantly different in their effects on major bleeding or gastrointestinal bleeding., 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 Wang, Huang, Wu, Huang, Wang, Kuo, Chu, Wen, Chen, Huang and Chang.)

Background: The therapeutic effect of low-voltage area (LVA)-guided left atrial (LA) linear ablation for non-paroxysmal atrial fibrillation (non-PAF) is uncertain. We aimed to investigate the efficacy of LA linear ablation based on the preexisting LVA and its effects on LA reverse remodeling in non-PAF patients., Methods: We retrospectively evaluated 145 consecutive patients who underwent radiofrequency catheter ablation for drug-refractory non-PAF. CARTO-guided bipolar voltage mapping was performed in atrial fibrillation (AF). LVA was defined as sites with voltage ≤ 0.5 mV. If circumferential pulmonary vein isolation couldn't convert AF into sinus rhythm, additional LA linear ablation was performed preferentially at sites within LVA., Results: After a mean follow-up duration of 48 ± 33 months, 29 of 145 patients had drugs-refractory AF/LA tachycardia recurrence. Low LA emptying fraction, large LA size and high extent of LVA were associated with AF recurrence. There were 136 patients undergoing LA linear ablation. The rate of linear block at the mitral isthmus was significantly higher via LVA-guided than non-LVA-guided linear ablation. Patients undergoing LVA-guided linear ablation had larger LA size and higher extent of LVA, but the long-term AF/LA tachycardia-free survival rate was higher than the non-LVA-guided group. The LA reverse remodeling effects by resuming sinus rhythm were noted even in patients with a diseased left atrium undergoing extensive LA linear ablation., Conclusions: LVA-guided linear ablation through targeting the arrhythmogenic LVA and reducing LA mass provides a better clinical outcome than non-LVA guided linear ablation, and outweighs the harmful effects of iatrogenic scaring in non-PAF patients., Competing Interests: The authors have declared that no competing interests exist.

Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32-4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64-4.70, P < 0.001), cardiovascular diseases (OR 2.97, 95% CI = 1.73-5.11, P < 0.001), and atrial fibrillation (AF) (OR 2.36, 95% CI = 1.17-4.76, P = 0.017) were independent risk factors for VT/VF OHCA (n = 81) compared with non-VT/VF OHCA (n = 380). A composite SACAF score was developed (male Sex, Age ≤ 65 years, Cardiovascular diseases, and AF) and compared with the performance of a modified CHA 2 DS 2 -VASc score (Cardiovascular diseases, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65-74 years, female Sex category). The area under the receiver operating characteristic curve (AUC) of the SACAF was 0.739 (95% CI = 0.681-0.797, P < 0.001), whereas the AUC of the modified CHA 2 DS 2 -VASc was 0.474 (95% CI = 0.408-0.541, P = 0.464). A SACAF score of ≥ 2 was useful in discriminating VT/VF from non-VT/VF OHCAs with a sensitivity of 0.75 and a specificity of 0.60. In conclusion, the simple SACAF score appears to be useful in discriminating VT/VF from non-VT/VF bystander-witnessed OHCAs and the findings may also shed light on future mechanistic evaluation., (© 2021. The Author(s).)

Coronary computed tomography angiography (CCTA) is routinely used for anatomical assessment of coronary artery disease (CAD). However, invasive measurement of fractional flow reserve (FFR) is the current gold standard for the diagnosis of hemodynamically significant CAD. CT-derived FFRCT and CT perfusion are two emerging techniques that can provide a functional assessment of CAD for risk stratification and clinical decision making. Several clinical studies have shown that the diagnostic performance of concomitant CCTA and functional CT assessment for detecting hemodynamically significant CAD is at least non-inferior to that of other routinely used imaging modalities. This article aims to review the current clinical evidence and recent developments in functional CT techniques., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Background: It remains unknown whether P wave duration (PWD) ≥ 150 ms measured after extensive radiofrequency catheter ablation (RFCA) can identify non-paroxysmal atrial fibrillation (non-PAF) patients at increased risk of atrial tachyarrhythmia recurrence. We investigated the predicting power of PWD and its association with left atrial (LA) reverse remodeling in patients with non-PAF undergoing pulmonary vein isolation with LA linear ablation., Methods: We retrospectively evaluated 136 patients who underwent RFCA for drug-refractory non-PAF. Electroanatomic mapping was acquired during AF. Low-voltage area (LVA) was defined as an area with bipolar voltage ≤0.5 mV. Electrocardiography and echocardiography were performed during sinus rhythm 1 day and 3 months after RFCA. PWD was measured using amplified 12‑lead electrocardiography. Prolonged PWD was defined as maximum PWD ≥ 150 ms., Results: Over a mean follow-up duration of 48 ± 35 months, 28 patients experienced atrial tachyarrhythmia recurrence. PWD was positively correlated with LVA (r = 0.527, p < 0.001) and inversely correlated with LA emptying fraction (r = -0.399, p < 0.001). PWD was shortened and LA emptying fraction (LAEF) was increased in patients without atrial tachyarrhythmia recurrence during follow-up. Atrial tachyarrhythmia-free survival was significantly more likely in patients without a prolonged PWD (83.5% vs 60.7%, p = 0.002). Multivariate analysis showed that LAEF and PWD were independent predictors of atrial tachyarrhythmia recurrence., Conclusions: PWD ≥ 150 ms measured after RFCA can identify patients with non-PAF at increased risk of atrial tachyarrhythmia recurrence. PWD is correlated with LVA and LAEF and reflects LA reverse remodeling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The effectiveness and safety of initiating sacubitril/valsartan therapy among patients who are hospitalized for acute heart failure (HF) is unclear., Methods: A cohort of 3736 patients with HF with reduced ejection fraction (HFrEF) hospitalized for acute HF was identified from Chang Gung Research Database between January 1, 2016 and August 31, 2019. The risks of rehospitalization for HF and death associated with sacubitril/valsartan therapy compared to angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy were evaluated. We used stabilized inverse probability of treatment weighting to balance the baseline covariates. The risks of fatal and non-fatal outcomes between the groups were compared using a Cox proportional hazard model and Fine and Gray subdistribution hazard model, respectively., Findings: The composite of rehospitalization for HF and death occurred in 22.9% of the patients in the sacubitril/valsartan group compared to 32.6% in the ACEI/ARB group (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52-0.97) after a mean follow-up period of 11.8 months. The sacubitril/valsartan group had a lower risk of rehospitalization for HF (subdistribution HR 0.83, 95% CI 0.74-0.92) and all-cause death (HR 0.51, 95% CI 0.27-0.94). There were no significant differences in the rates of worsening renal function or severe hyperkalemia between the two groups., Interpretation: In real-world practice, initiating sacubitril/valsartan therapy among patients with HFrEF who were hospitalized for acute HF was associated with a lower rate of rehospitalization for HF and death compared with ACEI/ARB therapy., Funding: This study was supported by Novartis Pharmaceuticals., Competing Interests: The authors declare that there is no conflict of interest., (© 2021 The Authors.)

Aims: Whether therapeutic hypothermia (TH) is proarrhythmic in preexisting failing hearts with acute ischemia-reperfusion (IR) injury is unknown. Additionally, the effectiveness of rotigaptide on improving conduction slowing in hearts with IR injury is ambiguous. We investigated the electrophysiological effects of TH and rotigaptide in failing rabbit hearts with acute IR injury and determined the underlying molecular mechanisms. Methods and Results: Heart failure was induced by right ventricular pacing (320 beats/min, 4 weeks). Rabbits with pacing-induced heart failure were randomly divided into TH ( n = 14) and non-TH ( n = 7) groups. The IR rabbit model was created by ligating the coronary artery for 60 min, followed by reperfusion for 15 min in vivo . Then, the hearts were excised quickly and Langendorff-perfused for simultaneous voltage and intracellular Ca 2+ (Ca i ) optical mapping. Electrophysiological studies were conducted, and vulnerability to ventricular fibrillation (VF) was evaluated using pacing protocols. TH (33°C) was instituted after baseline studies, and electrophysiological studies were repeated. Rotigaptide (300 nM) was infused for 20 min, and electrophysiological studies were repeated under TH. Cardiac tissues were sampled for Western blotting. TH increased the dispersion and beat-to-beat variability of action potential duration (APD), aggravated conduction slowing, and prolonged Ca i decay to facilitate spatially discordant alternans (SDA) and VF induction. Rotigaptide reduced the dispersion and beat-to-beat variability of APD and improved slowed conduction to defer the onset of arrhythmogenic SDA by dynamic pacing and elevate the pacing threshold of VF during TH. However, the effect of rotigaptide on TH-enhanced VF inducibility was statistically insignificant. TH attenuated IR-induced dysregulation of protein expression, but its functional role remained uncertain. Conclusion: Therapeutic hypothermia is proarrhythmic in failing hearts with acute IR injury. Rotigaptide improves TH-induced APD dispersion and beat-to-beat variability and conduction disturbance to defer the onset of arrhythmogenic SDA and elevate the VF threshold by dynamic pacing, but these beneficial electrophysiological effects are unable to suppress TH-enhanced VF inducibility significantly., 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 Lee, Chang, Wo, Liu, Wen and Chou.)

Abstract: Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders caused by enzyme deficiencies in glycogen catabolism. The more common type, GSD type Ia, is caused by glucose-6-phosphatase deficiency and often complicated by gout from hyperuricemia. Here, the authors report a rare case of a tophi wound caused by GSD type Ia in a Chinese patient. Difficulties in this case included the control of abnormal blood markers, especially uric acid; removal of tophi deposited in the tissues; restoration of hand function after wound healing; and patient adherence to treatment and follow-up. A multidisciplinary team was set up consisting of experts from the authors' wound care center and the departments of endocrinology, orthopedics, and rehabilitation. The wound healed in 53 days and was followed up for about 7 months. During follow-up, the patient's hand function returned to normal, and no new tophi formed. Because GSDs are a congenital lifelong condition, regular follow-ups are especially important., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To evaluate the performance of a single‑lead, 14-day continuous electrocardiogram (ECG) patch for the detection of arrhythmias compared to conventional 24-h monitoring., Methods: This prospective clinical trial enrolled patients suspected of arrhythmias but not diagnosed by 12‑lead ECGs. Each patient underwent a 24-h Holter and 14-day ECG patch simultaneously. Seven types of arrhythmias were classified: supraventricular tachycardia (SVT, repetitive atrial beats >4 beats), irregular SVT without P wave (>4 beats), AF/AFL (irregular SVT without P wave ≥30 s), pause ≥3 s, atrioventricular block (AVB; Mobitz type II, third-degree, two to one or high degree AVB), ventricular tachycardia (VT), and polymorphic VT., Results: A total of 158 patients were recruited (mean wear time:12.3 ± 3.2 days). The overall arrhythmia detection rate was higher with 14-day ECG patches (59.5%) compared to 24-h Holter (19.0%, P < 0.001). Up to 87.2% of arrhythmias recorded with 14-day ECG patches were not associated with symptoms. The 14-day ECG patch was associated with higher detection rates compared to the 24-h Holter in patients with SVT (52.5% versus 15.8%, P < 0.001), irregular SVT without P wave (12.7% versus 4.4%, P = 0.002), AF/AFL (9.5% versus 3.8%, P = 0.042), and critical arrhythmias (pause ≥3 s, AVB, VT, polymorphic VT) (16.5% versus 2.5%, P < 0.001). The 14-day ECG patch detected more than 2 types of arrhythmias in 5.1% of patients. No serious adverse events in patients wearing the 14-day ECG patch were reported., Conclusions: The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: The coprescription of an angiotensin-converting enzyme inhibitor (ACEi) with clopidogrel reportedly increases bleeding risk. However, studies have not described such an increase in cases of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI)., Methods: We analyzed electronic medical records of patients with discharge records of having undergone DAPT after PCI from a national health insurance claims database for January 1, 2006 to December 31, 2014. The date of PCI was the index date, and the primary outcome was major bleeding. The unit of analysis was one person-quarter. We compared patients who were prescribed with those not prescribed an ACEi in the cohort. A Poisson model with inverse probability of treatment weighting was fitted using generalized estimating equations to measure the risk of outcomes., Results: In total, 193,258 patients underwent DAPT after PCI; 46% had a coprescription of an ACEi. After screening, 170,775 patients (479,263 person-quarters) remained for analysis. The mean patient age was 65 ± 13 years, and 73.43% were men. In total, 79,739 prescriptions of an ACEi were written: 57%, 14.21%, 8.88%, 7.17%, and 4.68% were for captopril, ramipril, enalapril, perindopril, and imidapril, respectively. A concomitant prescription of an ACEi with clopidogrel was not associated with increased bleeding risk (adjusted rate ratio: 1.08, 99% confidence interval: 0.99-1.17)., Conclusions: The coadministration of an ACEi with clopidogrel after PCI is common. In this real-world cohort study, such coadministration was not associated with an increased risk of major bleeding in patients undergoing DAPT after PCI., (Copyright © 2021 Elsevier B.V. All rights reserved.)