Intracardiac echocardiography guided electrified J-wire trans-septal puncture: A prospective randomized controlled trial.

BACKGROUND: Application of electrocautery to a J-wire is used to perform transseptal puncture (TSP), but with limited evidence supporting safety and efficacy. We conducted a prospective randomized controlled trial to evaluate the safety and efficacy of this technique. METHODS: Two hundred consecutive patients were randomized in a 1:1 fashion to either the ICE-guided electrified J-wire TSP group or a conventional Brockenbrough (BRK) needle TSP group. The TSP was performed with a 0.032″ guidewire under 20 W, "coag" mode and was compared to TSP using the BRK needle. The primary safety endpoints were complications related to TSP. The primary efficacy endpoints included the TSP success rate, the total TSP time, and the total procedure time. RESULTS: All patients complete the procedure safely. The electrified J-wire TSP group had a significantly shorter TSP time than BRK needle TSP group. The total procedure time, number of TSP attempts required to achieve successful LA access, width of the intra-atrial shunt at the end of ablation were similar between the two groups. The incidence of new cerebral infarction detected by MRI were similar between the two groups (3/32 patients in the J-wire TSP group and 2/26 patients in conventional BRK TSP group, p = .82). And no difference in the incidence of residual intra-atrial shunt (4.3% vs. 6%, p = .654) during the 3-month's follow up. CONCLUSION: Using an electrified J-wire for TSP under the guidance of ICE appears to be as safe as and more efficient than conventional BRK needle TSP, which may be especially useful in the era of non-fluoroscopy AF ablation.

Fecal calprotectin: A novel predictor of ulcerated esophageal injury after atrial fibrillation catheter ablation.

BACKGROUND: Atrial esophageal fistula (AEF) is a lethal complication that can occur post atrial fibrillation (AF) ablation. Esophageal injury (EI) is likely to be the initial lesion leading to AEF. Endoscopic examination is the gold standard for a diagnosis of EI but extensive endoscopic screening is invasive and costly. This study was conducted to determine whether fecal calprotectin (Fcal), a marker of inflammation throughout the intestinal tract, may be associated with the existence of esophageal injury. METHODS: This diagnostic study was conducted in a cohort of 166 patients with symptomatic AF undergoing radiofrequency catheter ablation from May 2020 to June 2021. Fcal tests were performed 1-7 days after ablation. All patients underwent endoscopic ultrasonography 1 or 2 days after ablation. RESULTS: The levels of Fcal were significantly different between the EI and non-EI groups (404.9 µg/g (IQR 129.6-723.6) vs. 40.4 µg/g (IQR 15.0-246.2), p < .001). Analysis of ROC curves revealed that a Fcal level of 125 µg/g might be the optimal cut-off value for a diagnosis of EI, giving a 78.8% sensitivity and a 65.4% specificity. The negative predictive value of Fcal was 100% for ulcerated EI. CONCLUSIONS: The level of Fcal is associated with EI post AF catheter ablation. 125 µg/g might be the optimal cut-off value for a diagnosis of EI. Negative Fcal could predict the absence of ulcerated EI, which could be considered a precursor to AEF.

Use of intracardiac echocardiography in vein of Marshall ethanol infusion for ablation of persistent atrial fibrillation.

BACKGROUND: Few methods have been reported to demonstrate real-time effects during vein of Marshall (VOM) ethanol infusion in persistent atrial fibrillation (PeAF). OBJECTIVE: This study was to evaluate the impact of left atrial (LA) monitoring using intracardiac echocardiography (ICE) during VOM ethanol infusion. METHODS: Seventy-four consecutive patients with PeAF who underwent VOM ethanol infusion followed by radiofrequency (RF) ablation were included. Patients with findings on ICE consistent with echogenic streaming in the LA and with increased myocardial local echogenicity along the VOM area were placed into one group (group A) and those without into the other group (group B). Outcomes between the 2 groups were compared. RESULTS: Forty-six patients (62%) were placed into group A. A new ethanol-induced low-voltage area in group A was larger than that in group B (8.5 cm2 [5.5-10.2 cm2] and 4.0 cm2 (2.4-6.3 cm2]; P < .001). The RF ablation time required to achieve MI block was reduced in group A patients (263.0 seconds [196.0-351.0 seconds] vs 417.0 seconds [315.0-709.5 seconds] in group B patients; P < .001). MI block was achieved in 46 patients (100%) via an endocardial approach in group A and 27 patients (96.4%) in group B (extra coronary sinus ablation in 4 patients). One patient developed clinically significant pericardial effusions and required pericardiocentesis in group B. CONCLUSION: Presence of increased myocardial local echogenicity at the ridge and consistent echogenic streaming in the LA detected by ICE-based imaging during VOM ethanol infusion suggests increased ablated tissue in that region and lower RF ablation time during ablation for PeAF.

Left atrial appendage occlusion using the LAmbre device in atrial fibrillation patients with a history of ischemic stroke: 1-Year outcomes from a multicenter study in China.

BACKGROUND: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke have a significantly higher risk of stroke recurrence. This study aimed to examine the safety and efficacy of the LAmbre left atrial appendage occlusion device in NVAF patients with a history of stroke. METHODS: We examined 103 consecutive NVAF patients in 11 Chinese medical centers who had a history of stroke or transient ischemic attacks (TIA) and underwent placement of the LAmbre device. Follow-up was conducted 1, 3, 6, and 12 months after the procedure. The primary endpoints were the incidence of new ischemic or hemorrhagic stroke, TIA, systemic embolism, or cardiac death. Secondary endpoints were serious perioperative or device-related complications and cerebral, gastrointestinal, or other bleeding events requiring transfusion of at least 2 units of packed red blood cells. RESULTS: Mean patient age was 67.63 ± 7.14 years; mean CHA2DS2-VASc score was 4.72 ± 1.18 and mean HAS-BLED score was 1.90 ± 1.00. LAmbre device placement was successful in 101 patients (98.05%). Mean follow-up was 12.2 months. Five patients (4.95%) developed a new pericardial effusion after the procedure; none required treatment. Eighty-six patients (85.15%) exhibited no peri-device leak (PDL). However, 13 (12.8%) had a small (0-3 mm) PDL and two (2.3%) had a moderate PDL (3-5 mm). One recurrent stroke occurred during follow-up (1.1%). No other complications occurred. CONCLUSIONS: This multicenter study shows the safety and efficacy of LAmbre left atrial appendage occlusion for NVAF patients with a history of stroke or TIA.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

False Tendons in the Left Ventricle: Implications for Successful Ablation of Left Posterior Fascicular Tachycardias.

BACKGROUND: The anatomical substrate for left posterior fascicular ventricular tachycardia (LPF-VT) is still unclear. OBJECTIVES: The purpose of this study is to describe the endocavitary substrate of the re-entrant loop of LPF-VT. METHODS: A total of 26 consecutive patients with LPF-VT underwent an electrophysiology study and radiofrequency ablation. RESULTS: Intracardiac echocardiography imaging observed a 100% prevalence of false tendons (FTs) at the left posterior septal region in all patients, and 3 different types of FTs could be classified according to their location. In 22 patients, a P1 potential could be recorded via the multielectrode catheter from a FT. In 4 patients without a recorded P1 during LPF-VT, the earliest P2 potentials were recorded from a FT in 3 patients, and from a muscular connection between 2 posteromedial papillary muscles in 1 patient. Catheter ablation focused on the FTs with P1 or earliest P2 (in patients without P1) was successful in all 26 patients. After 19 ± 8.5 months of follow-up, no patients had recurrence of LPF-VT. CONCLUSIONS: FTs provide an electroanatomical substrate for LPF-VT and a "culprit FT" may be identified as the critical structure bridging the macro-re-entrant loop. Targeting the "culprit FT" is a novel anatomical ablation strategy that results in long-term arrhythmia-free survival.

Selective anatomical catheter ablation of left atrial ganglionated plexus for vasovagal syncope: Left superior and right anterior ganglionated plexus ablation.

BACKGROUND: Vasovagal syncope (VVS) is one of the most common causes of syncope. Traditional treatment has not achieved satisfactory results. The purpose of this study was to assess the feasibility and efficacy of selective anatomical catheter ablation of left atrial ganglionated plexus (GP) as a therapeutic strategy for the patients of symptomatic VVS. METHODS: A total of 70 patients with at least once recurrent syncopal episode of VVS with a positive head-up tilt test were enrolled. They were divided into GP ablation group and control group. Patients in GP ablation group received anatomical catheter ablation of left superior ganglionated plexus (LSGP) and right anterior ganglionated plexus (RAGP). Patients in the control group were guideline-directed conventional therapy. The primary endpoint was VVS recurrences. The secondary endpoint was the recurrence of syncope and prodrome events. RESULTS: There were no statistical differences in clinical characteristics between the ablation group (n = 35) and the control group (n = 35). Over a follow-up of 12 months, the ablation group had significantly lower syncope recurrence compared with the control group (5.7% vs. 25.7%, p = .02), and the ablation group had significantly lower syncope and prodrome recurrence compared with the control group (11.4% vs. 51.4%, p < .001). In GP ablation, 88.6% of the patients showed significant vagal response during LSGP ablation, and 88.6% of the patients showed significantly increased heart rate during RAGP ablation. CONCLUSIONS: For patients with recurrent VVS, selective anatomical catheter ablation of LSGP and RAGP is superior to conventional therapy in reducing syncope recurrence.

Colchicine attenuates the electrical remodeling of post-operative atrial fibrillation through inhibited expression of immune-related hub genes and stabilization of microtubules.

Rationale: Acute inflammation is a major risk factor for post-operative atrial fibrillation (POAF), and epicardial adipose tissue (EAT) is considered as a source of inflammatory mediators. However, underlying mechanisms and pharmacological targets of POAF are poorly understood. Methods: Integrative analysis of array data from EAT and right atrial appendage (RAA) samples was conducted to identify potential hub genes. Lipopolysaccharide (LPS)-stimulated inflammatory models in mice and in induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs) were used to examine the exact mechanism underlying POAF. Electrophysiological analysis, multi-electrode array, and Ca2+ imaging was employed to explore the alterations of electrophysiology and Ca2+ homeostasis under inflammation. Flow cytometry analysis, histology and immunochemistry were performed to investigate immunological alterations. Results: We observed electrical remodeling, enhanced atrial fibrillation (AF) susceptibility, immune cell activation, inflammatory infiltration, and fibrosis in LPS-stimulated mice. LPS-stimulated iPSC-aCMs showed arrhythmias, abnormal Ca2+ signaling, reduced cell viability, disrupted microtubule network and increased α-tubulin degradation. VEGFA, EGFR, MMP9 and CCL2 were identified as hub genes simultaneously targeted in the EAT and RAA of POAF patients. Notably, treatment of colchicine in LPS-stimulated mice resulted in a U-shape dose-response curve, where greatly improved survival rates were observed only at doses between 0.10-0.40 mg/kg. At this therapeutic dose level, colchicine inhibited the expression of all the identified hub genes and effectively rescued the pathogenic phenotypes observed in LPS-stimulated mice and iPSC-aCM models. Conclusions: Acute inflammation promotes α-tubulin degradation, induces electrical remodeling, and both recruits and facilitates the infiltration of circulating myeloid cells. A certain dose of colchicine attenuates electrical remodeling and decreases the recurrence of AF.

Characteristics of immune clusters and cell abundance in patients with different subtypes of nonparoxysmal atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Inflammation plays an important role in the initiation and perpetuation of AF. The present study was conducted to characterize immune clusters in nonparoxysmal AF and to distinguish immune subtypes of nonparoxysmal AF. Immune-related algorithms (CIBERSORT, ESTIMATE, and ssGSEA) were used to evaluate the immune cluster characterization and cell abundance, and multivariable logistics analysis was performed to determine the most relevant immune cells. We identified differentially expressed genes (DEGs) and used consensus clustering analysis to identify nonparoxysmal AF subtypes. Weighted gene coexpression network analysis (WGCNA) was used for finding highly correlated gene sets and attach to external sample traits. And it was conducted twice to identify the immune- and subtype- related modules. Finally, Metascape was used to compare the biological functions of the two nonparoxysmal AF subtypes we obtained. CytoHubba was used to identify the hub genes of these two subtypes. Based on the results of bioinformatics analysis, regulatory T cells, resting NK cells, active mast cells and neutrophils were considered to be closely related to nonparoxysmal AF. The brown module was identified as the most relevant module to the above immune cells by WGCNA. We identified two major nonparoxysmal AF subtypes by consensus clustering analysis and their enriched biological functions by Metascape. The hub genes are TYROBP, PTPRC, ITGB2, SPI1, PLEK, and CSF1R in permanent AF and JAM3, S100P, ARPC5, TRIM34, and GREB1L in persistent AF. This study revealed two major nonparoxysmal AF subtypes and eleven hub genes, which provide potential therapeutic targets for anti-inflammatory treatments of nonparoxysmal AF.

Intracardiac echocardiography is a safe and effective alternative to transesophageal echocardiography for left atrial appendage thrombus evaluation at the time of atrial fibrillation ablation: The ICE-TEE study.

BACKGROUND: Intracardiac echocardiography (ICE) technology has been increasingly accepted as an integral part of atrial fibrillation (AF) ablation procedures. It is still unknown whether ICE can routinely replace transesophageal echocardiography (TEE) for routine thrombus screening in non-selective AF patients. OBJECTIVE: To assess whether ICE can routinely replace TEE in screening for left atrial (LA)/left atrial appendage (LAA) thrombus in general patients undergoing catheter ablation for AF. METHODS: A total of 2003 consecutive patients undergoing AF ablation were included. 1155 patients (ICE group) received intra-procedural ICE examination for LA/LAA thrombus screening, while 848 patients (TEE group) received pre-procedure TEE examination. The incidence of thrombus, peri-procedure complications, and hospital efficiency were assessed. RESULTS: The LA and LAA were adequately visualized in all patients. Five patients in the ICE group and 15 patients in the TEE group were found to have LAA thrombus. The incidence of major periprocedural thrombo-embolic events was comparable between two groups (0.2% vs. 0.1%, p = .76), none were due to undetected LA/LAA thrombus. Other major periprocedural complications occurred at similar rates in both groups, while post-procedure fever was less common in the ICE group (12.7% vs. 17.4%, p < .001). Procedure times and hospital length of stay were both shorter in the ICE group (142 min [87-197 min] vs. 150 min [95-205 min], and 3[2-4] day vs. 4[3-5] day, respectively, both p < .001). CONCLUSIONS: ICE can replace TEE for atrial thrombus screening in AF patients undergoing ablation without increased complications. An "ICE replacing TEE" workflow can also reduce the incidence of postoperative fever and improve hospital efficiency.

Respiratory control minimizes diaphragmatic contraction and dry cough during pulsed-field ablation of atrial fibrillation.

AIMS: Pulsed-field ablation (PFA) is a promising new ablation modality to treat atrial fibrillation. However, PFA can cause varying degrees of diaphragmatic contraction and dry cough, especially under conscious sedation. This prospective study presents a method to minimize the impact of PFA on diaphragmatic contraction and dry cough during the procedure. METHODS AND RESULTS: Twenty-eight patients underwent PFA for pulmonary vein (PV) and superior vena cava isolation under conscious sedation. Each patient received two groups of ablations in each vein: the control group allowed PFA application during any phase of respiratory cycle, while the test group used respiratory control, delivering PFA energy only at the end of expiration. A rating score system was developed to assess diaphragmatic contraction and dry cough. A total of 1401 control ablations and 4317 test ablations were performed. The test group had significantly lower scores for diaphragmatic contraction (P < 0.01) and dry cough (P < 0.001) in all PVs compared to the control group. The average relative reductions in scores for all PVs were 33-47% for diaphragmatic contraction and 67-83% for dry cough. The percentage of ablations with scores ≧2 for diaphragmatic contraction decreased significantly from 18.5-28.0% in the control group to 0.4-2.6% in the test group (P < 0.001). For dry cough, the percentage decreased from 11.9-43.7% in the control group to 0.7-2.1% in the test group. CONCLUSION: Pulsed-field ablation application at the end of expiration can reduce the severity of diaphragmatic contraction and eliminate moderate and severe dry cough during PV isolation performed under conscious sedation.

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF). METHODS: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications. RESULTS: Two hundred twenty five patients were randomized (AI group [n = 149] and CF group [n = 76]). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = .035). After a median follow-up of 12.2 months, 154/225 (68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = .253). The incidence of peri-procedural complications is low and without difference between two groups. CONCLUSIONS: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance.

Challenges and opportunities when transitioning from in vivo gene replacement to in vivo CRISPR/Cas9 therapies - a spotlight on hemophilia.

INTRODUCTION: Currently, a few in vivo gene replacement therapies are commercially available, with many in clinical development for the treatment of some inherited monogenic diseases. These disorders arise from mutations in genes encoding essential proteins with a well understood biological function. Wide adoption of gene replacement therapies requires solid safety and efficacy profiles with demonstrable long-term durability and cost-benefit advantages vs standard therapies. AREAS COVERED: This expert review outlines the challenges and opportunities in treating hemophilia, including the progression from in vivo gene therapies toward in vivo gene editing, focusing on pre-clinical and emerging clinical data for gene editing and addressing the need for sustained and durable gene expression during hepatocyte proliferation when the liver is unable to maintain steady gene expression and protein production. EXPERT OPINION: In vivo gene editing in liver tissues may be able to rescue patients younger than 18 years who are not eligible for gene replacement therapies, with hemophilia as a prime example.

Left Atrial Appendage Mechanical Dispersion Assessed by Speckle-Tracking Echocardiography as a Determinant of Left Atrial Appendage Blood Stasis in Patients With Atrial Fibrillation.

Aims: We sought to investigate the relationship of left atrial appendage (LAA) mechanical dispersion (MD) with LAA dense spontaneous echo contrast (SEC) or thrombus, and to compare its usefulness in the identification of thrombogenesis with left atrial (LA) MD or LA/LAA strain parameters in patients with atrial fibrillation (AF). Methods: We conducted a cross-sectional study of 493 consecutive patients with AF [65(58.5-71.0) years, male 66.9%] who underwent echocardiography prior to catheter ablation. We measured the LAA and LA global longitudinal strain (GLS) using speckle-tracking echocardiography (STE). LAA MD and LA MD was defined as the standard deviation (SD) of time to peak positive strain corrected by the R-R interval. Results: Patients with LAA dense SEC/thrombus (n = 70) had significantly higher LAA MD than controls (n = 423) [median 14.2(11.6-16.8)% vs 9.4(6.2-12.1)%, p < 0.01]. Multivariable analysis showed that LAA MD was independently associated with LAA dense SEC/thrombus in four different models (Odds ratio, 1.23-1.24; p < 0.01), and provided additional diagnostic value over clinical and standard echocardiographic parameters. Whereas, LA MD was not independently associated with LAA dense SEC/thrombus and had no incremental value over other LA/LAA mechanical parameters. Conclusion: LAA mechanical dispersion was an independent determinant of LAA dense SEC/thrombus in AF patients, incremental to conventional risk factors and superior to LA mechanical dispersion.

First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice.

CONTEXT: Post-sepsis cognitive impairment is one of the major sequelae observed in survivors of sepsis. Astragalus injection is the normally preferred treatment in sepsis in clinical settings. OBJECTIVE: This study evaluated the benefits and related mechanism of Astragalus injection on post-sepsis cognitive impairment. MATERIALS AND METHODS: C57BL/6J mice were divided into three groups: Control, LPS (2.5 mg/kg, i.p.), and LPS + Astragalus injection (5.0 mL/kg). The surviving mice from sepsis were injected with material named Astragalus injection continuously for 13 days. Behavioural tests were first conducted to evaluate the benefits. Second, inflammatory cytokines secretion, BBB integrity, neurodegeneration, and protein expression was evaluated in vivo and in vitro. RESULTS: Compared with the LPS group, mice in Astragalus injection group exhibited shorter escape latency (34.6 s versus 24.5 s) in the Morris water maze test. Treatment with Astragalus injection could reverse LPS-induced neuroinflammation in mice and BV2 cells. Continuous Astragalus injection treatment not only prevented blood-brain barrier dysfunction, but also prevented neurodegeneration. Further molecular docking tests and western blot results reflected that the main constituents of Astragalus injection could interact with TrkB (the estimated binding energy values were -7.0 to -5.0 kcal/mol) and upregulate the protein expression of BDNF/TrkB/CREB signalling pathway during the chronic stage in mice. DISCUSSION: Astragalus injection treatment could reduce neuroinflammation, reverse BBB dysfunction, prevent neurodegeneration, and upregulate BDNF-CREB pathway during LPS-induced sepsis, ultimately preventing the development of cognitive decline. CONCLUSION: Astragalus injection could be a potential preventive and therapeutic strategy for sepsis survivors in clinical settings.

Catheter ablation for persistent atrial fibrillation with left ventricular systolic dysfunction: Who is the best candidate?

BACKGROUND: Tachycardia-induced cardiomyopathy is poorly recognized pre-ablation. It remains unclear of better patient selection and timing for catheter ablation in persistent atrial fibrillation (PerAF) with heart failure (HF). METHODS: Consecutive patients with PerAF and left ventricular ejection fraction (LVEF) <50% referred for AF ablation were retrospectively included. The impact of LV size, heart rate (HR), and LVEF pre-ablation were analyzed for assessing LV systolic function recovery, defined as LVEF increase of ≥20% or to a value ≥55% after ablation. RESULTS: A total of 120 patients (2017-2020) were included. After 19 ±14 months post ablation, LVEF improvement was similar in patients with normal or dilated LV (18.3 ± 9.4% vs. 16.1 ± 10.8%, P = .25), rapid or controlled HR (19.5 ± 10% vs. 16.1 ± 10%, P = .09), but higher in HFrEF (HF with reduced EF) than HFmrEF (HF with midrange EF) (21.6 ± 10.3% vs. 14.9 ± 9.3%, P < .01). There was more LV systolic function recovery in those with normal to moderate LV dilation (80%, odds ratio [OR] 15.22, P < .01), HR ≥80 bpm (79%, OR 5.38, P < .01) and HFmrEF (80%, OR 4.03, P < .01). The overall AF freedom was similar between normal and dilated LV (59% vs. 62%, P = .95), rapid and controlled HR (67% vs. 56%, P = .18), and HFmrEF and HFrEF (65% vs. 50%, P = .19). CONCLUSION: Catheter ablation is effective independent of LV dilation, rate control or HFrEF. Patients with normal to moderate LV dilation, resting HR ≥80 bpm and HFmrEF may be candidates for early PerAF ablation to achieve LVEF normalization.

Selective Interventricular Septal Radiofrequency Ablation in Patients With Hypertrophic Obstructive Cardiomyopathy: Who Can Benefit?

Introduction: Septal mass reduction is beneficial for hypertrophic obstructive cardiomyopathy (HOCM) patients with severe left ventricular outflow (LVOT) gradient and symptoms, with surgical myectomy or alcohol septal ablation (ASA) currently recommended in selected patients. Radiofrequency (RF) ablation of hypertrophied septum has been published as a novel method to alleviate LVOT obstruction in small populations. This study aims to investigate factors influencing clinical outcomes of radiofrequency septum ablation. Methods and Results: In this study, 20 patients with HOCM who underwent endocardial ablation were included. Echocardiography and cardiac MRI (CMR) data was collected and analyzed pre- and (or) post- procedure. Nineteen patients underwent ablation successfully, while ablation was aborted in one patient with prior RBBB due to transient complete atrioventricular block (AVB). After 6 months of follow-up, NYHA heart functional class improved from III (2 - 3) to II (1 - 2) (p < 0.001), and resting LVOT gradient was significantly reduced (87.6 ± 29.5 mmHg vs. 48.1 ± 29.7, p < 0.001). LVOT gradient reduction was significantly higher in patients with limited basal septal hypertrophy (60.9 ± 8.3 vs. 27.9 ± 7.1, p = 0.01), shorter anterior mitral leaflet (56.1 ± 6.4 vs. 20.4 ± 5.0, p < 0.01), and normally positioned papillary muscle (36.9 ± 7.1 vs. 75.0 ± 6.3, p < 0.05). Conclusions: Endocardial septal ablation appears to be a safe and effective procedure for alleviating LVOT gradient in patients with HOCM, especially in those with limited basal septal hypertrophy, shorter anterior mitral leaflet, and normal positioned papillary muscle.

ICE-Derived Left Atrial and Left Ventricular Endocardial and Myocardial Speckle Tracking Strain Patterns in Atrial Fibrillation at the Time of Radiofrequency Ablation.

Objectives: Intracardiac echocardiography(ICE) has excellent imaging resolution and border recognition which increase strain measurement accuracy. We hypothesized that left atrial(LA) substrate and functional impairment can be detected by measuring LA strain deformation in patients with persistent and paroxysmal atrial fibrillation(AF), as compared to those with no AF. Strain deformation changes in LA and left ventricle(LV) can also be assessed post-ablation to determine its effect. Methods: ICE-derived speckle tracking strain(STS) was prospectively performed in 96 patients, including 62 patients with AF(31 persistent and 31 paroxysmal AF) pre-/post-ablation, and 34 patients with no AF. We measured major strain parameters including longitudinal segmental(endo/myocardial) "average peak overall strain of all segments"(PkAll), peak strain rate(SR),and different time-to-peak strain in LA and LV images. Results: At baseline, persistent AF patients had significantly lower(p<0.01) LA endocardial(4.3±2.5 vs. 20.3±8.9 and 25.5±12.9 %) and myocardial PkAll(4.4±2.6 vs. 15.7±7.2 and 20.9±9.2 %), endocardial(0.9±0.4 vs. 1.8±0.7 and 2.2±0.6 1/s) and myocardial peak SR(0.7±0.4 vs. 1.5±0.6 and 1.9±0.5 1/s), as compared to paroxysmal AF and no AF patients. After successful ablation, endo-/myocardial LA PkAll and peak SR were significantly improved, most dramatically in patients with persistent AF. LV endocardial/myocardial strain and SR also improved in AF patients post-ablation. Conclusion: LA longitudinal strain(%)/SR(1/s) parameters in AF patients are more abnormal than those with no AF, suggesting LA substrate/functional damage. AF ablation improved LA strains/SR but with values in paroxysmal > persistent AF suggesting background LA damage in persistent AF.

Topological charge-density method of identifying phase singularities in cardiac fibrillation.

Spiral waves represent the key motifs of typical self-sustained dynamical patterns in excitable systems such as cardiac tissue. The motion of phase singularities (PSs) that lies at the center of spiral waves captures many qualitative and, in some cases, quantitative features of their complex dynamics. Recent clinical studies suggested that ablating the tissue at PS locations may cure atrial fibrillation. Here, we propose a different method to determine the location of PSs. Starting from the definition of the topological charge of spiral waves, we obtain the expression of the topological charge density in a discrete case. With this expression, we can calculate the topological charge at each grid in the space directly, so as to accurately identify the position of PSs.