Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

The BTB-BACK-TAZ domain protein MdBT2 reduces drought resistance by weakening the positive regulatory effect of MdHDZ27 on apple drought tolerance via ubiquitination.

Drought stress is one of the dominating challenges to the growth and productivity in crop plants. Elucidating the molecular mechanisms of plants responses to drought stress is fundamental to improve fruit quality. However, such molecular mechanisms are poorly understood in apple (Malus domestica Borkh.). In this study, we explored that the BTB-BACK-TAZ protein, MdBT2, negatively modulates the drought tolerance of apple plantlets. Moreover, we identified a novel Homeodomain-leucine zipper (HD-Zip) transcription factor, MdHDZ27, using a yeast two-hybrid (Y2H) screen with MdBT2 as the bait. Overexpression of MdHDZ27 in apple plantlets, calli, and tomato plantlets enhanced their drought tolerance by promoting the expression of drought tolerance-related genes [responsive to dehydration 29A (MdRD29A) and MdRD29B]. Biochemical analyses demonstrated that MdHDZ27 directly binds to and activates the promoters of MdRD29A and MdRD29B. Furthermore, in vitro and in vivo assays indicate that MdBT2 interacts with and ubiquitinates MdHDZ27, via the ubiquitin/26S proteasome pathway. This ubiquitination results in the degradation of MdHDZ27 and weakens the transcriptional activation of MdHDZ27 on MdRD29A and MdRD29B. Finally, a series of transgenic analyses in apple plantlets further clarified the role of the relationship between MdBT2 and MdHDZ27, as well as the effect of their interaction on drought resistance in apple plantlets. Collectively, our findings reveal a novel mechanism by which the MdBT2-MdHDZ27 regulatory module controls drought tolerance, which is of great significance for enhancing the drought resistance of apple and other plants.

Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro.

This study aimed to clarify the role of glutamine in atherosclerosis and its participating mechanism. Forty C57BL/6J mice were divided into wild control (wild Con), ApoE- /- control (ApoE- /- Con), glutamine + ApoE- /- control (Glut + ApoE- /- Con), ApoE- /- high fat diet (ApoE- /- HFD), and glutamine + ApoE- /- HFD (Glut + ApoE- /- HFD) groups. The degree of atherosclerosis, western blotting, and multiomics were detected at 18 weeks. An in vitro study was also performed. Glutamine treatment significantly decreased the degree of aortic atherosclerosis (p = 0.03). O-GlcNAcylation (O-GlcNAc), IL-1ß, IL-1α, and pyruvate kinase M2 (PKM2) in the ApoE- /- HFD group were significantly higher than those in the ApoE- /- Con group (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05), and aggravated by O-GlcNA transferase (OGT) overexpression in the in vitro study (p < 0.05). Multiomics showed that the ApoE- /- HFD group had higher levels of oxidative stress regulatory molecules (guanine deaminase [GUAD], xanthine dehydrogenase [XDH]), proinflammatory regulatory molecules (myristic acid and myristoleic acid), and stress granules regulatory molecules (caprin-1 and deoxyribose-phosphate aldolase [DERA]) (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05). We conclude that glutamine supplementation might alleviate atherosclerosis through downregulation of O-GlcNAc, glycolysis, oxidative stress, and proinflammatory pathway.

An ITO-Free Kesterite Solar Cell.

Photovoltaic thin film solar cells based on kesterite Cu2 ZnSn(S, Se)4 (CZTSSe) have reached 13.8% sunlight-to-electricity conversion efficiency. However, this efficiency is still far from the Shockley-Queisser radiative limit and is hindered by the significant deficit in open circuit voltage (VOC ). The presence of high-density interface states between the absorber layer and buffer or window layer leads to the recombination of photogenerated carriers, thereby reducing effective carrier collection. To tackle this issue, a new window structure ZnO/AgNW/ZnO/AgNW (ZAZA) comprising layers of ZnO and silver nanowires (AgNWs) is proposed. This structure offers a simple and low-damage processing method, resulting in improved optoelectronic properties and junction quality. The ZAZA-based devices exhibit enhanced VOC due to the higher built-in voltage (Vbi ) and reduced interface recombination compared to the usual indium tin oxide (ITO) based structures. Additionally, improved carrier collection is demonstrated as a result of the shortened collection paths and the more uniform carrier lifetime distribution. These advances enable the fabrication of the first ITO-free CZTSSe solar cells with over 10% efficiency without an anti-reflective coating.

Development of two novel on-site detection visualization methods for murine hepatitis virus based on the multienzyme isothermal rapid amplification.

Murine hepatitis virus (MHV) infection is one of the most prevalent types of mice infection in laboratory. MHV could cause death in mice and even interfere with the results in animal experiments. Herein, we developed two isothermal approaches based on the Multienzyme Isothermal Rapid Amplification (MIRA), for rapid detection of MHV in conserved M gene. We designed and screened several pairs of primers and probes and the isothermal fluorescence detector was applied for the exonuclease Ⅲ reverse transcription MIRA (exo-RT-MIRA) assay. To further simplify the workflow, the portable fluorescence visualization instrument, also as a palm-sized handheld system, was used for the naked-eye exo-RT-MIRA assay. The amplification temperature and time were optimized. The assay could be processed well at 42°C 20 min for the exo-RT-MIRA and the naked-eye exo-RT-MIRA assay. The limit of detection (LoD) of the exo-RT-MIRA assay was 43.4 copies/µL. The LoD of the naked-eye exo-RT-MIRA assay was 68.2 copies/µL. No nonspecific amplifications were observed in the two assays. A total of 107 specimens were examined by qPCR and two assays developed. The experimental results statistical analysis demonstrated that the exo-RT-MIRA assay with the qPCR yielded sufficient agreement with a kappa value of 1.000 (p<0.0001). The results also exhibited a good agreement (kappa value, 0.961) (p<0.0001) between the naked-eye exo-RT-MIRA assay and the qPCR assay. In our study, the exo-RT-MIRA assay and the naked-eye exo-RT-MIRA assay presented the possibility of new methods in MHV point-of-testing diagnosis.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Irradiance uniformity reshaping method for solar simulators based on computer-generated spatial filter films.

Irradiance uniformity is critical to the accuracy of photovoltaic device test results. Therefore, to post-correct the irradiance uniformity inherent in artificial lighting systems, a spatial irradiance filter scheme for film patterns is proposed based on the physical phenomenon of a positively related relationship between inkjet concentration and the transparency of the flexible film. The scheme first establishes the characteristic equation between the irradiance absorption and pattern grayscale values and then generates the spatial filtering pattern by utilizing the light intensity distribution to be calibrated, matrix operations, and bilinear interpolation. To evaluate its performance, an STM32 microprocessor-based irradiance distribution measurement system was developed and used to test and verify single lamp, planar array, and curved surface array light sources. The results reveal that the corrected irradiance uniformity improves by 15.5%, 24.01 %, and 13.11%, all of which achieve the Class A irradiance uniformity of the IEC 60904-9 standard.

Interval estimation of relative risks for combined unilateral and bilateral correlated data.

Measurements are generally collected as unilateral or bilateral data in clinical trials, epidemiology, or observational studies. For example, in ophthalmology studies, the primary outcome is often obtained from one eye or both eyes of an individual. In medical studies, the relative risk is usually the parameter of interest and is commonly used. In this article, we develop three confidence intervals for the relative risk for combined unilateral and bilateral correlated data under the equal dependence assumption. The proposed confidence intervals are based on maximum likelihood estimates of parameters derived using the Fisher scoring method. Simulation studies are conducted to evaluate the performance of proposed confidence intervals with respect to the empirical coverage probability, the mean interval width, and the ratio of mesial non-coverage probability to the distal non-coverage probability. We also compare the proposed methods with the confidence interval based on the method of variance estimates recovery and the confidence interval obtained from the modified Poisson regression model with correlated binary data. We recommend the score confidence interval for general applications because it best controls converge probabilities at the 95% level with reasonable mean interval width. We illustrate the methods with a real-world example.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

Prospective randomized comparison between upgraded '2C3L' vs. PVI approach for catheter ablation of persistent atrial fibrillation: PROMPT-AF trial design.

BACKGROUND: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion. OBJECTIVE: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF. STUDY DESIGN: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months). CONCLUSIONS: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation.

Low temperature compensates for defective tapetum initiation to restore the fertility of the novel TGMS line ostms15.

In rice breeding, thermosensitive genic male sterility (TGMS) lines based on the tms5 locus have been extensively employed. Here, we reported a novel rice TGMS line ostms15 (Oryza sativa ssp. japonica ZH11) which show male sterility under high temperature and fertility under low temperature. Field evaluation from 2018 to 2021 revealed that its sterility under high temperature is more stable than that of tms5 (ZH11), even with occasional low temperature periods, indicating its considerable value for rice breeding. OsTMS15 encodes an LRR-RLK protein MULTIPLE SPOROCYTE1 (MSP1) which was reported to interact with its ligand to initiate tapetum development for pollen formation. In ostms15, a point mutation from GTA (Val) to GAA (Glu) in its TIR motif of the LRR region led to the TGMS phenotype. Cellular observation and gene expression analysis showed that the tapetum is still present in ostms15, while its function was substantially impaired under high temperature. However, its tapetum function was restored under low temperature. The interaction between mOsTMS15 and its ligand was reduced while this interaction was partially restored under low temperature. Slow development was reported to be a general mechanism of P/TGMS fertility restoration. We propose that the recovered protein interaction together with slow development under low temperature compensates for the defective tapetum initiation, which further restores ostms15 fertility. We used base editing to create a number of TGMS lines with different base substitutions based on the OsTMS15 locus. This work may also facilitate the mechanistic investigation and breeding of other crops.

Risk Factors for Left Ventricular Thrombus Formation in Patients with Dilated Cardiomyopathy.

BACKGROUND: Left ventricular thrombus (LVT) is a common complication of dilated cardiomyopathy (DCM), causing morbidity and mortality. METHODS: This study retrospectively analyzed patients with DCM from January 2002 to August 2020 in Beijing Anzhen Hospital. Clinical characteristics were compared between the LVT group and the age and sex 1:4 matched with the LVT absent group. The receiver operator characteristic (ROC) curve was plotted to evaluate the diagnostic value of D-dimer predicting LVT occurrence in DCM. RESULTS: A total of 3,134 patients were screened, and LVT was detected in 72 (2.3%) patients on echocardiography. The patients with LVT had higher D-dimer, fibrinogen, and lower systolic blood pressure than those without LVT. The ejection fraction (EF) was lower and left ventricular end-systolic diameter was larger in the LVT group. Severe mitral regurgitation (MR) was more common in the LVT absent groups. The prevalence of atrial fibrillation was lower in the LVT group. The ROC curve analysis yielded an optimal cut-off value of 444 ng/mL DDU (D-dimer units) for D-dimer to predict the presence of LVT. Multivariable binary logistic regression analysis revealed that EF (OR = 0.90, 95% CI = 0.86-0.95), severe MR (OR = 0.19, 95% CI = 0.08-0.48), and D-dimer level (OR = 15.4, 95% CI = 7.58-31.4) were independently associated with LVT formation. CONCLUSION: This study suggested that elevated D-dimer levels (>444 ng/mL DDU) and reduced EF were independently associated with increased risk of LVT formation. Severe MR could decrease the incidence of LVT.

The adjunctive effect for left pulmonary vein isolation of vein of Marshall ethanol infusion in persistent atrial fibrillation.

OBJECTIVE: This study sought to assess the effect of ethanol infusion into the vein of Marshall (EIVOM) on the acute success of left pulmonary vein (LPV) isolation in persistent atrial fibrillation (PeAF). METHODS AND RESULTS: A total of 313 patients with drug-resistant PeAF were enrolled (135 in Group 1 and 178 in Group 2). In Group 1, EIVOM was firstly performed, followed by radiofrequency ablation (RFA) including bilateral pulmonary vein isolation (PVI) and linear ablation at roofline, cavotricuspid isthmus, and mitral isthmus (MI). In Group 2, PVI and linear ablations were completed with RFA. First-pass isolation of the LPV was achieved in 119 (88.1%) and 132 (74.2%) patients in Groups 1 and 2, respectively (P = 0.002). The rate of acute pulmonary vein reconnection (PVR) was significantly lower in Group 1 (9.6% vs. 22.5%, P = 0.003). About half of acute PVR occurred in the carina with or without EIVOM. CONCLUSION: EIVOM is effective in achieving a higher first-pass isolation and a lower acute PVR of LPV in PeAF.

Fascicular ventricular tachycardia arising from the left side His and its adjacent region: a subset of upper septal idiopathic left ventricular tachycardia.

AIMS: Fascicular ventricle tachycardia (FVT) arising from the proximal aspect of left His-Purkinje system (HPS) has not been specially addressed. Current study was to investigate its clinical, electrocardiographic, and electrophysiological characteristics. METHODS AND RESULTS: Eighteen patients who were identified as this rare FVT were consecutively enrolled, and their scalar electrocardiogram and electrophysiological data were collected and analysed. The ventricular tachycardia (VT) morphology was similar to sinus rhythm (SR) in eight patients, left bundle branch block type in one patient, right bundle branch block type in seven patients, and both narrow and wide QRS type in two patients. During VT, right-sided His potential preceded the QRS with His-ventricle (H-V) interval of 36.3 ± 12.4 ms, which was shorter than that during SR (-51.4 ± 8.6 ms) (P = 0.002). The earliest Purkinje potentials (PPs) were recorded within 7 ± 3 mm of left-side His and preceded the QRS by 49.1 ± 14.0 ms. Mapping along the left anterior fascicle and left posterior fascicle revealed an antegrade activation sequence in all with no P1 potentials recorded. In the two patients with two VT morphologies, the earliest PP was documented at the same site, and the activation sequence of HPS remained antegrade. Ablation at the earliest PP successfully eliminated the tachycardia, except one patient who developed complete atrial-ventricular block and two patients who abandoned ablations. After at least 12 months follow-up, 15 patients were free from any recurrences. CONCLUSIONS: Fascicular ventricle tachycardia arising from the proximal aspect of left HPS was featured by recording slightly shorter H-V interval and absence of P1 potentials. Termination of VT requires ablation at the left-sided His or its adjacent region.

Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation.

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

Impact of pre-ablation left appendage flow velocities on long term recurrence of catheter ablation for paroxysmal atrial fibrillation.

BACKGROUND: Despite undergoing a single ablation, many patients with paroxysmal atrial fibrillation (PAF) experience a gradually increasing recurrence rate. This study aims to examine the relationship between left atrial appendage emptying velocity (LAAeV) and filling velocity (LAAfV) profiles and 3-year recurrence of AF after ablation. METHODS: We conducted a prospective study of 658 consecutive PAF patients who underwent their first ablation between January 2018 and December 2019. We collected the clinical and echocardiographic characteristics of the patients. LAAeV and LAAfV were obtained from a transesophageal echocardiogram (TEE) before catheter ablation. Patients were followed at regular intervals to monitor for the primary outcome of AF recurrence. RESULTS: After a median follow-up period of 35.3 months (range, 10.7-36.3), 288 patients (43.8%) experienced AF recurrence after catheter ablation. Patients who experienced AF recurrence had decreased LAAeV and LAAfV (LAAeV: 56.5 ± 21.2 vs. 59.6 ± 20.7 cm/s, p = .052; LAAfV: 47.5 ± 17.9 vs. 51.7 ± 18.2, p = .003). Kaplan-Meier analysis showed that patients in the low LAAeV (<55 cm/s) group had a poorer event-free survival rate than those in the high LAAeV (≥55 cm/s) group (log-rank p = .012). Patients with LAAfV <48 cm/s had a significantly higher risk of AF recurrence than those with LAAfV ≥48 cm/s (log-rank p = .003). In the multivariable model, low LAAfV pre-ablation in TEE-guided was significantly independently associated with 3-year recurrence after single radiofrequency ablation in patients with PAF, along with LA dimension and duration of AF. CONCLUSION: This study found an independent association between low LAAfV pre-ablation in TEE-guided and 3-year recurrence after single radiofrequency ablation in patients with PAF.

Vein of Marshall ethanol infusion: First-step or adjunctive choice for perimitral atrial tachycardia?

BACKGROUND: Perimitral atrial tachycardia (PMAT) is the most frequent type of iatrogenic atrial tachycardia (AT) after atrial fibrillation (AF) ablation. Vein of Marshall ethanol infusion (EIVOM) is a promising technique in mitral isthmus (MI) ablation. METHODS: A total of 165 patients with PMAT were divided into three groups according to ablation strategies, including RF only group (n = 89), RF-EIVOM group (initial RF ablation with adjunctive EIVOM, n = 28), and EIVOM-RF group (first-step EIVOM with touch-up RF ablation, n = 48). Acute and follow-up procedure outcomes were evaluated. RESULTS: PMAT terminated in 89.9%, 89.3%, and 93.7% of patients in RF only, RF-EIVOM and EIVOM-RF groups, respectively (p = .715), with complete MI block achieved in 80.9%, 89.3%, and 95.8% of patients (EIVOM-RF vs. RF only, p = .012). First-step utilization of EIVOM was associated with a significant shortening of RF ablation time at MI (EIVOM-RF 2.1 ± 1.3 min, RF only 7.9 ± 5.9 min, RF-EIVOM 6.8 ± 5.8 min; p < .001) and a decrease in the proportion of patients need ablation within coronary sinus (CS, EIVOM-RF 14.6%, RF only 61.8%, RF-EIVOM 64.3%; p < .001). After a mean follow-up of 12.1 ± 6.2 months, AF/AT recurred in 39 (43.8%), 6 (21.4%), and 12 (25.0%) patients in RF only, RF-EIVOM, and EIVOM-RF group (RF-EIVOM vs. RF only, p = .026; EIVOM-RF vs. RF only, p = .022). CONCLUSIONS: EIVOM was associated with an enhanced acute MI block rate as well as reduced AF/AT recurrence. First-step utilization of EIVOM promises to significantly simplify the RF ablation process. CONDENSED ABSTRACT: PMAT is the most common type of iatrogenic AT after AF ablation procedures. EIVOM contributed to a higher acute MI block rate and lower arrhythmia recurrence risk during follow-up. First-step utilization of EIVOM significantly reduced the need for radiofrequency ablation at MI and inside CS with the advantage of creating a homogenous, transmural lesion and eliminating epicardial connections.

A novel esophageal retractor with eccentric balloon during atrial fibrillation ablation.

BACKGROUND: Due to the anatomically adjacent relationship between the left atrium (LA) and esophagus, energy delivery on the posterior wall of LA is limited. The aim of this study was to evaluate the feasibility of a novel esophageal retractor (SAFER) with an inflatable C-curve balloon during atrial fibrillation (AF) ablation. METHOD: Nine patients underwent AF ablation assisted with the SAFER. After inflation, the esophagus was deviated laterally away from the intended ablation site of the posterior wall under local anesthesia. The extent of mechanical esophageal deviation (MED) was evaluated under fluoroscopy, defined as the shortest distance from the trailing esophageal edge to the closest point of the ablation line. Gastroscopy was performed before and after ablation. The target ablation index used in all LA sites including the posterior wall was 400-450 after effective MED. All adverse events during the periprocedural period were recorded. RESULTS: The mean deviation distance achieved 16.2 ± 9.6 mm away from the closest ablation point of the pulmonary vein lesion set. With respect to the individual left and right pulmonary vein lesion sets, the deviation distance was 19.7 ± 11.5 and 12.7 ± 6.8 mm, respectively. The extent of deviation was 0 to 5 mm, 5.1 to 10 mm, or >10 mm in 0(0%), 7(38.9%), and 11(61.1%), respectively. Procedural success was achieved in all patients without acute reconnection. There was only one esophageal complication which manifested as esophageal erosion and this patient experienced throat pain possibly related to the SAFER retractor with no clinical sequelae. CONCLUSION: Esophageal deviation with the novel eccentric balloon is a novel feasible choice during AF ablation, enabling adequate energy delivery to the posterior wall of LA. Additional prospective randomized controlled studies are required for further validation.

Measurement of Serum Ultra-Sensitive Thyroid-Stimulating Hormone Levels to Determine the Risk for Recurrence of Atrial Fibrillation Following Catheter Ablation in 575 Patients from a Single Center.

BACKGROUND Thyroid dysfunction has been proved to contribute to the occurrence of atrial fibrillation (AF), leading to the development of AF in animal models and clinical populations. This single-center study investigated the relationship between ultra-sensitive thyroid-stimulating hormone (uTSH) levels and the recurrence of atrial fibrillation (AF) in 575 hospitalized patients who had undergone catheter ablation. MATERIAL AND METHODS The study enrolled 575 hospitalized patients with AF who needed catheter ablation, 105 were non-first catheter ablation patients, and 470 were first catheter ablation (CA) patients. Before ablation, fasting biochemical indexes, including uTSH, were detected. Patients were classified according to uTSH quartile. The presence of AF was confirmed by 12-lead electrocardiogram or 24-h ambulatory electrocardiogram. RESULTS A total of 105 (18.44%) patients had undergone catheter ablation of AF twice or more. Univariate logistic regression analysis showed no significant relationship between uTSH and AF recurrence (HR, 1.047; 95% CI 0.986-1.111; P=1.127). Multivariate logistic regression analysis indicated that compared with low quartiles (Q1 OR, 0.71, 95% CI: 0.35-1.46; P=0.36; Q2 OR 0.71, 95% CI 0.36-1.39; P=0.31;Q3 OR 0.22, 95% CI 0.09-0.53; P=0.001), high quartiles of uTSH had a higher risk of AF recurrence. After adjusting for sex, the risk of AF recurrence in the high quartile uTSH was higher in males than in the low quartile (Q1 OR, 0.60, 95% CI: 0.29-1.26; P=0.18;Q2 OR, 0.52, 95% CI, 0.24-1.13; P=0.09;Q3 OR, 0.42, 95% CI, 0.18-0.94; P=0.03), but not in women. CONCLUSIONS Serum TSH levels in male patients treated for AF with cardiac ablation were significantly associated with AF recurrence.