A lightweight deep learning approach for detecting electrocardiographic lead misplacement.

OBJECTIVE: Electrocardiographic (ECG) lead misplacement can result in distorted waveforms and amplitudes, significantly impacting accurate interpretation. Although lead misplacement is a relatively low-probability event, with an incidence ranging from 0.4% to 4%, the large number of ECG records in clinical practice necessitates the development of an effective detection method. This paper aimed to address this gap by presenting a novel lead misplacement detection method based on deep learning models. APPROACH: We developed two novel lightweight deep learning model for limb and chest lead misplacement detection, respectively. For limb lead misplacement detection, two limb leads and V6 were used as inputs, while for chest lead misplacement detection, six chest leads were used as inputs. Our models were trained and validated using the Chapman database, with an 8:2 train-validation split, and evaluated on the PTB-XL, PTB, and LUDB databases. Additionally, we examined the model interpretability on the LUDB databases. Limb lead misplacement simulations were performed using mathematical transformations, while chest lead misplacement scenarios were simulated by interchanging pairs of leads. The detection performance was assessed using metrics such as accuracy, precision, sensitivity, specificity, and Macro F1-score. MAIN RESULTS: Our experiments simulated three scenarios of limb lead misplacement and nine scenarios of chest lead misplacement. The proposed two models achieved Macro F1-scores ranging from 93.42% to 99.61% on two heterogeneous test sets, demonstrating their effectiveness in accurately detecting lead misplacement across various arrhythmias. SIGNIFICANCE: The significance of this study lies in providing a reliable open-source algorithm for lead misplacement detection in ECG recordings. The source code is available at https://github.com/wjcai/ECG_lead_check.

Prognostic Impact of Left Atrial Appendage Patency After Device Closure.

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.

Coptisine inhibits neointimal hyperplasia through attenuating Pak1/Pak2 signaling in vascular smooth muscle cells without retardation of re-endothelialization.

BACKGROUND AND AIMS: Vascular injury-induced endothelium-denudation and profound vascular smooth muscle cells (VSMCs) proliferation and dis-regulated apoptosis lead to post-angioplasty restenosis. Coptisine (CTS), an isoquinoline alkaloid, has multiple beneficial effects on the cardiovascular system. Recent studies identified it selectively inhibits VSMCs proliferation. However, its effects on neointimal hyperplasia, re-endothelialization, and the underlying mechanisms are still unclear. METHODS: Cell viability was assayed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cell counting kit-8 (CCK-8). Cell proliferation and apoptosis were measured by flow cytometry and immunofluorescence of Ki67 and TUNEL. Quantitative phosphoproteomics (QPP) was employed to screen CTS-responsive phosphor-sites in the key regulators of cell proliferation and apoptosis. Neointimal hyperplasia was induced by balloon injury of rat left carotid artery (LCA). Adenoviral gene transfer was conducted in both cultured cells and LCA. Re-endothelialization was evaluated by Evan's blue staining of LCA. RESULTS: 1) CTS had strong anti-proliferative and pro-apoptotic effects in cultured rat VSMCs, with the EC50 4∼10-folds lower than that in endothelial cells (ECs). 2) Rats administered with CTS, either locally to LCA's periadventitial space or orally, demonstrated a potently inhibited balloon injury-induced neointimal hyperplasia, but had no delaying effect on re-endothelialization. 3) The QPP results revealed that the phosphorylation levels of Pak1S144/S203, Pak2S20/S197, Erk1T202/Y204, Erk2T185/Y187, and BadS136 were significantly decreased in VSMCs by CTS. 4) Adenoviral expression of phosphomimetic mutants Pak1D144/D203/Pak2D20/D197 enhanced Pak1/2 activities, stimulated the downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189/pBadS136, attenuated CTS-mediated inhibition of VSMCs proliferation and promotion of apoptosis in vitro, and potentiated neointimal hyperplasia in vivo. 5) Adenoviral expression of phosphoresistant mutants Pak1A144/A203/Pak2A20/A197 inactivated Pak1/2 and totally simulated the inhibitory effects of CTS on platelet-derived growth factor (PDGF)-stimulated VSMCs proliferation and PDGF-inhibited apoptosis in vitro and neointimal hyperplasia in vivo. 6) LCA injury significantly enhanced the endogenous phosphorylation levels of all but pBadS136. CTS markedly attenuated all the enhanced levels. CONCLUSIONS: These results indicate that CTS is a promising medicine for prevention of post-angioplasty restenosis without adverse impact on re-endothelialization. CTS-directed suppression of pPak1S144/S203/pPak2S20/S197 and the subsequent effects on downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189 and pBadS136 underline its mechanisms of inhibition of VSMCs proliferation and stimulation of apoptosis. Therefore, the phosphor-sites of Pak1S144/S203/Pak2S20/S197 constitute a potential drug-screening target for fighting neointimal hyperplasia restenosis.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.

Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling.

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy: The change of the paradigm.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

Incidence, impact and predictors of residual device patency after left atrial appendage closure with the LACbes device.

BACKGROUND: The residual device patency (RDP) after left atrial appendage closure (LAAC) with the LACbes device has not been specifically explored in atrial fibrillation (AF) patients. This study aims to explore the incidence, impact and predictors of RDP detected by cardiac computed tomography angiography (CCTA) post LAAC. METHODS: AF patients implanted with the LACbes device were prospectively enrolled. CCTA device surveillance was performed at 3 months post-procedure. Major adverse events (MAEs), including stroke/transient ischemic attack, major bleeding and all-cause death, were evaluated. RESULTS: Among 141 patients with CCTA surveillance, 56 (39.7%) showed no visible leak and 85 (60.3%) showed RDP. During the median follow-up of 443 [232, 706] days, the presence of RDP was not associated with an increased risk of MAEs (adjusted hazard ratio [HR]: 4.07, 95% confidence interval [CI]: 0.49-34.24, p = 0.196), while peri-device leak (PDL) at the lobe was associated with heightened risks of MAEs (adjusted HR: 6.85, 95% CI: 1.62-28.89, p = 0.009). In patients with PDL at the lobe, antiplatelet after 6 months (HR: 0.20, 95% CI: 0.05-0.91, p = 0.038) was independent protective predictor of MAEs. Besides, current smoking (odds ratio [OR]: 7.52, 95% CI: 2.68-21.08, p < 0.001) and maximum diameter of LAA orifice (OR: 1.16, 95% CI: 1.00-1.34, p = 0.048) were independent predictors of PDL at the lobe. CONCLUSIONS: Presence of PDL at the device lobe detected by CCTA at 3-month post LAAC with LACbes is associated with unfavorable prognosis in AF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03788941.

Auxin response factors fine-tune lignin biosynthesis in response to mechanical bending in bamboo.

Lignin contributes to plant mechanical properties during bending loads. Meanwhile, phytohormone auxin controls various plant biological processes. However, the mechanism of auxin's role in bending-induced lignin biosynthesis was unclear, especially in bamboo, celebrated for its excellent deformation stability. Here, we reported that auxin response factors (ARF) 3 and ARF6 from Moso bamboo (Phyllostachys edulis (Carrière) J. Houz) directly regulate lignin biosynthesis pathway genes, and affect lignin biosynthesis in bamboo. Auxin and lignin exhibited asymmetric distribution patterns, and auxin promoted lignin biosynthesis in response to bending loads in bamboo. Employing transcriptomic and weighted gene co-expression network analysis approach, we discovered that expression patterns of ARF3 and ARF6 strongly correlated with lignin biosynthesis genes. ARF3 and ARF6 directly bind to the promoter regions of 4-coumarate: coenzyme A ligase (4CL3, 4CL7, and 4CL9) or caffeoyl-CoA O-methyltransferase (CCoAOMT2) genes, pivotal to lignin biosynthesis, and activate their expressions. Notably, the efficacy of this binding hinges on auxin levels. Alternation of the expressions of ARF3 and ARF6 substantially altered lignin accumulation in transgenic bamboo. Collectively, our study shed light on bamboo lignification genetics. Auxin signaling could directly modulate lignin biosynthesis genes to impact plant lignin content.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial.

Background: Cryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). Objectives: This study sought to assess the performance of a novel liquid nitrogen-driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). Methods: This was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen-driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. Results: A total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. Conclusions: This premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

Electrically Tunable Two-Color Cholesteric Laser.

Two-color lasing emission from an asymmetric structure, consisting of two dye-doped cholesteric liquid crystal (DD-CLC) layers separated by a transparent interlayer, is demonstrated. The DD-CLC mixtures have different reflection bands with long-wavelength band edges located at the green and red wavelengths of the visible spectrum, respectively. For the laser action, the CLC hosts provide the feedback, and the fluorescent laser dyes represent the active medium. When the stacked structure is optically pumped above the threshold, two simultaneous laser lines separated by 123 nm are observed at the long-wavelength band edges of the DD-CLC mixtures. The influence of an electric field on lasing behavior is also analyzed and discussed in terms of the reflection spectrum and laser action. The results show a reversible tuning of the reflection band, accompanied by a modification of the lasing characteristics under the application of an external field. Above a specific threshold voltage, one of the emission lines is suppressed and the other is conserved. With a further increase in the voltage, both laser emissions are entirely inhibited. The investigated structure demonstrates a simple technique to obtain an electrically tunable multi-wavelength laser, which might pave the way for a new generation of organic laser sources.

Combined Radiofrequency Ablation and Left Atrial Appendage Closure in Atrial Fibrillation and Systolic Heart Failure.

BACKGROUND: Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. METHODS: AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. RESULTS: Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores. CONCLUSIONS: Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Multiple flatbands and localized states in photonic super-Kagome lattices.

We demonstrate multiple flatbands and compact localized states (CLSs) in a photonic super-Kagome lattice (SKL) that exhibits coexistence of singular and nonsingular flatbands within its unique band structure. Specifically, we find that the upper two flatbands of an SKL are singular-characterized by singularities due to band touching with their neighboring dispersive bands at the Brillouin zone center. Conversely, the lower three degenerate flatbands are nonsingular and remain spectrally isolated from other dispersive bands. The existence of such two distinct types of flatbands is experimentally demonstrated by observing stable evolution of the CLSs with various geometrical shapes in a laser-written SKL. We also discuss the classification of the flatbands in momentum space, using band-touching singularities of the Bloch wave functions. Furthermore, we validate this classification in real space based on unit cell occupancy of the CLSs in a single SKL plaquette. These results may provide insights for the study of flatband transport, dynamics, and nontrivial topological phenomena in other relevant systems.

Cancer and Atrial Fibrillation Comorbidities Among 25 Million Citizens in Shanghai, China: Medical Insurance Database Study.

BACKGROUND: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China. OBJECTIVE: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations. METHODS: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed. RESULTS: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001). In the population with AF, the most prevalent cancer type was lung cancer, followed by colorectal, male genital organ, stomach, breast, liver, bladder, thyroid, leukemia, and esophageal cancers. AF was associated with an average of nearly 1.4-fold (prevalence ratio [PR] 1.37, 95% CI 1.35-1.38) increased prevalence of cancer after adjusting for age and sex. For site-specific analyses, an increased prevalence of cancer in the population with AF was observed in 20 of 21 cancer sites. This increased prevalence was most prominent for nonsolid tumors, including multiple myeloma (PR 2.56, 95% CI 2.28-2.87), leukemia (PR 1.73, 95% CI 1.57-1.90), and non-Hodgkin lymphoma (PR 1.59, 95% CI 1.43-1.77); intrathoracic malignancies, including mediastinum (PR 2.34, 95% CI 1.89-2.90), lung (PR 1.64, 95% CI 1.59-1.69), and esophageal cancers (PR 1.41, 95% CI 1.28-1.56); bone and soft tissue neoplasms (PR 1.56, 95% CI 1.37-1.77); and kidney cancer (PR 1.53, 95% CI 1.36-1.72). Cancer prevalence in the population with AF relative to that in the population without AF was higher in men than in women in 14 of 18 cancer sites, and female predominance was only observed for thyroid cancer. The peak age of index cancer diagnosis was lower in the population with AF (age group: 70-74 years) than in that without AF (age group: 75-79 years), especially for specific cancer types, including thyroid, central nervous system, mediastinum, esophageal, bladder, and biliary cancers. CONCLUSIONS: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.

Accuracy of the Injection-Based Occlusion Tool Utilizing Saline and Glucose Solution in Cryoballoon Ablation Guided by a Novel Dielectric Imaging System.

Introduction: The aim of this study is to assess the accuracy of the injection-based occlusion (IBO) tool utilizing saline and glucose solution in verifying pulmonary vein (PV) occlusion during cryoballoon ablation guided by a novel dielectric system (KODEX-EPD system). Methods: In this retrospective study, we enrolled 34 consecutive patients with paroxysmal atrial fibrillation (AF) who underwent their initial cryoballoon ablation procedure guided by the KODEX-EPD system. PV occlusion was firstly assessed by the IBO tool utilizing saline or glucose solution and then verified by direct contrast angiography. Patients were divided into two groups according to the fluid used in the IBO tool: the Saline Group and the Glucose Group. Results: The overall procedure time and fluoroscopy time were comparable between the Saline Group and the Glucose Group (113.7 ± 18.3 vs. 108.4 ± 15.9 min; p = 0.375 and 10.1 ± 3.7 vs. 9.3 ± 3.5 min; p = 0.559). The IBO tool was utilized a total of 138 times in the Saline Group and 135 times in the Glucose Group. When assessing PV occlusion, the IBO tool using saline demonstrated a sensitivity of 92.6% and a specificity of 95.2% compared to angiography. Similarly, the IBO tool utilizing glucose solution showed a sensitivity of 93.2% and a specificity of 96.1%. Conclusions: The IBO tool utilizing non-contrast fluid, saline and glucose solution, demonstrates a high level of sensitivity and specificity in accurately predicting PV occlusion during cryoablation procedures. Both the saline and glucose solutions used in the IBO tool show promising results in effectively assessing PV occlusion.

Gain optimization of an erbium-ytterbium co-doped amplifier via a Si3N4 photonic platform.

Erbium-doped waveguide amplifiers enable the integration of various active functions on a silicon platform. Er3+ can provide the basis for efficient optical amplification of photonic integrated circuits, but the gain is limited by cooperative upconversion leading to doping concentration limitations and insufficient optimization of the waveguide structure. In this paper, an erbium-ytterbium co-doped Al2O3 amplifier has been innovatively implemented on a low loss Si3N4 waveguide by careful design and optimization with the finite difference method. A more accurate and comprehensive theoretical model of erbium-ytterbium co-doping is established, with consideration of upconversions, energy transfer, amplified spontaneous radiation and propagation loss to perform optimization of the high-gain erbium-ytterbium co-doped waveguide amplifier. The optimized waveguide amplifier achieves a small-signal gain of more than 36 dB at 1550 nm under Er3+ concentration of 3 × 1020 cm-3 and Yb3+ concentration of 3 × 1021 cm-3. Endowing Si3N4 photonic integrated circuits with gain can enable the miniaturization of various on-chip based active devices.

Higher Sodium Channel Excitability in Cardiac Purkinje Fibers: Implications for Multifocal Ectopic Purkinje-Related Premature Contractions.

BACKGROUND: Multifocal ectopic Purkinje-related premature contractions (MEPPCs) are associated with SCN5A variants. However, it is not well understood why Purkinje fibers, but not ventricular myocardium, play a predominant role in arrhythmogenesis. OBJECTIVES: This study sought to explore the underlying mechanisms of MEPPC. METHODS: Whole-cell patch-clamp and molecular biology techniques were used in the present study. RESULTS: Clinical data from one patient with R814W variant showed MEPPC syndrome, which is well responsive to amiodarone. Compared with canine ventricular myocytes, Purkinje cells (PCs) had significantly larger sodium current (INa), leftward shift of INa activation and inactivation curves, suggesting higher sodium channel excitability in PCs. Real-time polymerase chain reaction and Western blot analysis showed that the mRNA and protein expression of NaVß1 and NaVß3 was higher in canine Purkinje fibers than in ventricular myocardium. INa in heterologous Chinese hamster ovary cell expression system co-expressing NaV1.5 and NaVß1/NaVß3 exhibited similar biophysical properties of INa in PCs. R814W variant shifted INa activation in a hyperdepolarized direction, caused a larger window current, and generated an outward-gating pore current at depolarized voltages. Coexpression of NaVß1/NaVß3 with Nav1.5-R814W further left-shifted INa activation and caused an even larger window current and gating pore current, suggesting higher susceptibility of Purkinje fibers to R814W variant. Amiodarone inhibited INa, shifted its inactivation to more negative voltages, and significantly decreased the window current. CONCLUSIONS: A higher expression of ß1 and ß3 subunits contributes to higher sodium channel excitability in cardiac Purkinje fibers, making them more susceptible to MEPPC.

Multimodality imaging in diagnosing lipomatous atrial septal hypertrophy with atrial septal defect: a case report.

Background: Lipomatous atrial septal hypertrophy (LASH) with atrial septal defect (ASD) is a rare congenital anomaly. Although LASH is a histologically benign cardiac lesion characterized by excessive fat deposition in the interatrial septum that spares the fossa ovale, it has been associated with supraventricular arrhythmias or sick sinus syndrome. Application of multimodal imaging is crucial for accurate diagnosis, appropriate treatment of LASH with ASD, and follow-up. Case summary: A 68-year-old female patient presented with recurrent chest tightness and palpitation. Multimodal imaging revealed the characterizations of LASH and ASD. Two-dimensional transesophageal echocardiography showed a "dumbbell"-shaped involvement of the cephalad and caudal regions with sparing of a single secundum ASD. The septum with a brightness feature is an uncommon condition characterized by the deposition of unencapsulated fat cells in the atrial septum. Real-time four-dimensional transesophageal echocardiography reflected the lipomatous hypertrophy of the atrial septum and an oval-shaped ASD. Cardiac computer tomography angiography later confirmed this finding. The patient achieved a good clinical response with an ASD percutaneous occlusion guided by intracardiac echocardiography (ICE). Conclusion: This case demonstrates a LASH combined with ASD. Multimodality imaging can provide an accurate diagnosis and may guide the procedure for precise occlusion.

Efficacy of Left Atrial Appendage Closure and Oral Anticoagulation After Atrial Fibrillation Catheter Ablation.

Left atrial appendage closure (LAAC) proved to be noninferior to oral anticoagulation (OAC) in nonablated patients with atrial fibrillation (AF). This study aimed to compare the efficacy and safety of LAAC with those of OAC therapy in patients after AF ablation. This study included patients who underwent catheter ablation (CA) of AF between January 2016 and December 2020. The cohort was divided into CA + LAAC and CA + OAC, where propensity score matching was used to select controls, and each group contained 682 subjects. The enrolled patients' mean age was 70.34 ± 8.32 years, and 47.3% were female; their CHA2DS2-VASc score was 3.48 ± 1.17. Baseline characteristics were similar between groups. After a 3-year mean follow-up, the incidence of thromboembolic events was 1.25 and 1.10 and that of major bleeding events was 0.65 and 1.72 per 100 patient-years in the CA + LAAC, and CA + OAC groups, respectively. The rate of thromboembolisms and major adverse cardiovascular events was similar between the 2 groups (hazard ratio [HR] 1.162, 95% confidence interval [CI] 0.665 to 2.030, p = 0.598, HR 0.711, 95% CI 0.502 to 1.005, p = 0.053); however, that of major bleeding and all-cause death was significantly reduced with LAAC (HR 0.401, 95% CI 0.216 to 0.746, p = 0.004, HR 0.528, 95% CI 0.281 to 0.989, p = 0.046). There was no significant difference in periprocedural complications (p >0.05) and the rate of AF recurrence (OAC vs LAAC: 39.44% vs 40.62%, p = 0.658). LAAC is a reasonable and safer alternative to OAC therapy in high-risk patients after AF ablation.