Spread of plasmids carrying antibiotic resistance genes in soil-lettuce-snail food chain.

Fertilization can change the composition of antibiotic resistance genes(ARGs) and their host bacteria in agricultural fields, while complex microbial activities help ARGs into crops and transmit them to humans through agricultural products.Therefore, this study constructed a farmland food chain with soil-lettuce-snail as a typical structure, added genetically engineered Pseudomonas fluorescens containing multidrug-resistant plasmid RP4 to track its spread in the farmland food chain, and used different fertilization methods to explore its influence on the spread and diffusion of ARGs and intl1 in the farmland food chain. It was found that exogenous Pseudomonas can enter plants from soil and pass into snails' intestines, and there is horizontal gene transfer phenomenon of RP4 plasmid in bacteria. At different interfaces of the constructed food chain, the addition of exogenous drug-resistant bacteria had different effects on the total abundance of ARGs and intl1. Fertilization, especially manure, not only promoted the spread of Pseudomonas aeruginosa and the transfer of RP4 plasmid levels, but also significantly increased the total abundance of ARGs and intl1 at all interfaces of the constructed food chain. The main ARGs host bacteria in the constructed food chain include Proteobacteria, Bacteroides, and Firmicutes, while Flavobacterium of Bacteroides is the unique potential host bacteria of RP4 plasmid. In conclusion, this study provides a reference for the risk assessment of ARGs transmitted to the human body through the food chain, and has important practical significance to reduce the antibiotic resistance contamination of agricultural products and ensure the safety of vegetable basket.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Effects of earthworms on antibiotic resistance genes in different soil-plant systems.

Earthworms play an important role in the soil environment. To explore the difference in earthworms influence on various media in different soil-plant systems, the abundance of tetracycline, sulfonamide and quinolone resistance genes and the structure of the bacterial community were analysed from five different media including non-rhizosphere soil, rhizosphere soil, phyllosphere, root endophytes and earthworm intestine by real-time quantitative PCR and high-throughput 16S rRNA sequencing. Studies have shown that earthworms can reduce the absolute abundance of antibiotic resistance genes (ARGs) in non-rhizosphere soil. Root endophytes in the soil-cabbage system and rhizosphere soil in the soil-setaria system had the same findings. Earthworms can change the bacterial community structure, especially that of Proteobacteria and Cyanobacteria in the phyllosphere and root endophytes. Redundancy analysis (RDA) results that bacterial community change was the main factor affecting ARGs. In addition, earthworms increased the proportion of Cyanobacteria in root endophytes, and Cyanobacteria was significantly positively correlated with sul3. This study provides a scientific basis for controlling the migration and diffusion of ARGs and reducing environmental risks in soil-plant systems in the future.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society (HRS), the Asia Pacific HRS, and the Latin American HRS.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

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.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair.

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.

Beyond conduction impairment: Unveiling the profound myocardial injury in left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. OBJECTIVE: This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. METHODS: LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. RESULTS: LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. CONCLUSION: LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM.

RV1+RV3 Index to Differentiate Idiopathic Ventricular Arrhythmias Arising From Right Ventricular Outflow Tract and Aortic Sinus of Valsalva: A Multicenter Study.

BACKGROUND: This study aimed to investigate the predictive value of parameters of every precordial lead and their combinations in differentiating between idiopathic ventricular arrhythmias (IVAs) from the right ventricular outflow tract and aortic sinus of Valsalva (ASV). METHODS AND RESULTS: Between March 1, 2018, and December 1, 2021, consecutive patients receiving successful ablation of right ventricular outflow tract or ASV IVAs were enrolled. The amplitude and duration of the R wave and S wave were measured in every precordial lead during IVAs. These parameters were either summed, subtracted, multiplied, or divided to create different indexes. The index with the highest area under the curve to predict ASV IVAs was developed, compared with established indexes, and validated in an independent prospective multicenter cohort. A total of 150 patients (60 men; mean age, 45.3±16.4 years) were included in the derivation cohort. The RV1+RV3 index (summed R-wave amplitude in leads V1 and V3) had the highest area under the curve (0.942) among the established indexes. An RV1+RV3 index >1.3 mV could predict ASV IVAs with a sensitivity of 95% and a specificity of 83%. Its predictive performance was maintained in the validation cohort (N=109). In patients with V3 R/S transition, an RV1+RV3 index >1.3 mV could predict ASV IVAs, with an area under the curve of 0.892, 93% sensitivity, and 75% specificity. CONCLUSIONS: The RV1+RV3 index is a simple and novel criterion that accurately differentiates between right ventricular outflow tract and ASV IVAs. Its performance outperformed established indexes, making it a valuable tool in clinical practice.

Anticoagulation Intensity during Appendage Occlusion:Lessons from Silent Cerebral Embolism.

INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolisms (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study is to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging (MRI) before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 seconds could decrease the risk of the SCE without increasing the major bleeding events.

A Simple Score to Predict New-onset Atrial Fibrillation After Ablation of Typical Atrial Flutter.

BACKGROUND: New-onset atrial fibrillation (NeAF) is common after cavotricuspid isthmus-dependent counterclockwise atrial flutter (CCW-AFL) ablation. This study aimed to investigate a simple predictive model of NeAF after CCW-AFL ablation. METHODS: From January 2013 to December 2017, consecutive patients receiving CCW-AFL ablation were enrolled from three centers. Clinical, echocardiographic, and electrocardiographic data were collected and followed. Patients from two centers and another center were assigned into the derivation and validation cohorts, respectively. In the derivation cohort, logistic regression was performed to evaluate the ability of parameters to discriminate those with and without NeAF. A score system was developed and then validated. RESULTS: Two hundred seventy-one patients (mean 59.7±13.6 age; 205 male) were analyzed. During follow-up (73.0±6.5 months), 107 patients (39.5%) had NeAF. 190 and 81 patients were detected in the derivation and validation cohorts, respectively. Hypertension, age ≥70 years, left atrial diameter ≥42 mm, P wave duration ≥120 ms and the negative component of flutter wave in lead II ≥120 ms were selected as the final parameters. A weighted score was used to develop the HAD-AF score ranging from 0 to 9. In the derivation cohort, area under the receiver operating characteristic curve (AUC) was 0.938 (95% CI 0.902-0.974), superior to those of currently used CHA2DS2-VASC (0.679, 95% CI 0.600-0.757) and HATCH scores (0.651, 95% CI 0.571-0.730) (P<0.001). Performance maintained in the validation cohort. CONCLUSIONS: 39.5% of patients developed NeAF in 6 years after CCW-AFL ablation. HAD-AF score can reliably identify patients likely to develop NeAF after CCW-AFL ablation.

General anesthesia enhances lesion quality and ablation efficiency of circumferential pulmonary vein isolation.

Background: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. General anesthesia (GA) resolves the problem of pain intolerability and provides regular respiratory mode which might improve the catheter maneuverability of AF ablation. This study aims to compare the procedural performance of PVI under GA versus conscious sedation (CS) from multiple perspectives. Methods: A total of 36 consecutive patients undergoing first AF ablation under GA were enrolled in GA group. Another 109 patients receiving AF ablation under CS in the same period were selected as the control group. After propensity score matching, 29 matched pairs with similar baseline characteristics were available for further analysis. The AIFV (using AI to analyze the raw data from CARTO3 system) system was used to evaluate six procedural parameters in each PVI procedure. Results: Compared with CS, PVI under GA had a significantly shorter total PVI time (51.4 min vs. 67.8 min; p = .003) and higher radiofrequency ratio (62.6% vs. 55.8%; p = .032). The number of gaps (1.0 vs. 3.0; p < .001) and the rate of break point were significantly lower in the GA group. GA was also associated with a higher effective ablation-index ratio (87.5% vs. 74.1%; p < .001) and effective force-over-time ratio (85.3% vs. 69.2%; p = .001). After a medium follow-up time of 24 months, 12/29 (41.4%) patients in the CS group and 6/29 (20.7%) patients in the GA group suffered from AF recurrence (p = .156). Conclusions: GA improves the lesion quality and procedural efficiency of PVI from multiple perspectives evaluated by the AIFV system.

Sex difference in atrial scar prevalence: What can we learn from the STABLE-SR-III trial?

BACKGROUND: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown. OBJECTIVE: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups. METHODS: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure. RESULTS: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003). CONCLUSION: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men.

Cardiac-specific overexpression of CREM-IbΔC-X via CRISPR/Cas9 in mice presents a new model of atrial cardiomyopathy with spontaneous atrial fibrillation.

Atrial cardiomyopathy (ACM) forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately replicate the entire progression of atrial lesions, particularly the onset of AF, presents significant challenges. In the present study, we found that the isoform of CRE-binding protein modulator (CREM-IbΔC-X), which is involved in the regulation of cardiac development and atrial rhythm, was highly expressed in atrial biopsies from patients with AF. Building upon this finding, we employed CRISPR/Cas9 technology to create a mouse model with cardiac-specific overexpression of CREM-IbΔC-X (referred to as CS-CREM mice). This animal model effectively illustrated the development of ACM through electrophysiological and structural remodelings over time. Proteomics and Chip-qPCR analysis of atrial samples revealed significant upregulation of cell-matrix adhesion and extracellular matrix structural components, alongside significant downregulation of genes related to atrial functions in the CS-CREM mice. Furthermore, the corresponding responses to anti-arrhythmia drugs, i.e., amiodarone and propafenone, suggested that CS-CREM mice could serve as an ideal in vivo model for drug testing. Our study introduced a novel ACM model with spontaneous AF by cardiac-specifically overexpressing CREM-IbΔC-X in mice, providing valuable insights into the mechanisms and therapeutic targets of ACM.

Mid-term outcome of catheter ablation of idiopathic non-outflow tract ventricular arrhythmias.

BACKGROUND: Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. METHOD AND RESULTS: From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). CONCLUSION: Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Stretchable, Self-Rolled, Microfluidic Electronics Enable Conformable Neural Interfaces of Brain and Vagus Neuromodulation.

Implantable neuroelectronic interfaces have gained significant importance in long-term brain-computer interfacing and neuroscience therapy. However, due to the mechanical and geometrical mismatches between the electrode-nerve interfaces, personalized and compatible neural interfaces remain serious issues for peripheral neuromodulation. This study introduces the stretchable and flexible electronics class as a self-rolled neural interface for neurological diagnosis and modulation. These stretchable electronics are made from liquid metal-polymer conductors with a high resolution of 30 µm using microfluidic printing technology. They exhibit high conformability and stretchability (over 600% strain) during body movements and have good biocompatibility during long-term implantation (over 8 weeks). These stretchable electronics offer real-time monitoring of epileptiform activities with excellent conformability to soft brain tissue. The study also develops self-rolled microfluidic electrodes that tightly wind the deforming nerves with minimal constraint (160 µm in diameter). The in vivo signal recording of the vagus and sciatic nerve demonstrates the potential of self-rolled cuff electrodes for sciatic and vagus neural modulation by recording action potential and reducing heart rate. The findings of this study suggest that the robust, easy-to-use self-rolled microfluidic electrodes may provide useful tools for compatible neuroelectronics and neural modulation.