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.

His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study.

BACKGROUND: His bundle pacing (HBP) is a physiological pacing strategy to preserve the electrical synchrony of ventricular conduction and left ventricular (LV) function. Left bundle branch pacing (LBBP) has emerged as an alternative physiological pacing technique. OBJECTIVE: To evaluate cardiac electrical and mechanical synchrony comparing LBBP and HBP in patients with permanent atrial fibrillation (AF). METHODS: Consecutive patients with symptomatic bradycardia and AF were enrolled from January to June of 2019. The cardiac electrical and mechanical synchrony in different pacing mode were evaluated at baseline and after implantation. RESULTS: Both HBP and LBBP were performed in 20 patients. LBBP significantly widened the QRS duration compared with the intrinsic conduction (113.2 ± 14.5  vs. 96.5 ± 16.2 ms; p = .01), while HBP did not (104.5 ± 22.3  vs. 96.5 ± 16.2 ms; p = .12). Both LBBP and HBP patients had similar LV myocardial strain measurements for the mechanical synchrony evaluation without significant change compared with baseline. There was no significant difference in right ventricular synchrony measurement between LBBP and HBP. Compared to HBP, LBBP had less interventricular synchrony (IMVD, 14.7 ± 9.2  vs. 3.1 ± 12.7 ms, p < .01; Ts-LV-RV, 37.9 ± 10.7  vs. 18.5 ± 10.8 ms, p < .001). CONCLUSIONS: Although LBBP's a physiological pacing mode can achieve a similar cardiac electrical and mechanical synchronization when compared to HBP, LBBP results in modest delay in RV activation, and the clinical implication remains to be studied.

Solvothermal Synthesis of Multiple Dihydropyrimidinones at a Time as Inhibitors of Eg5.

Solvothermal synthesis of multiple dihydropyrimidinones at a time has been developed in inexpensive and green bio-based solvent lactic acid without any additional catalysts or additives. By this method, thirty new dihydropyrimidinone derivatives were synthesized in two batches and characterized. All of the compounds were screened by Eg5 motor protein ATPase assay, and the positive compounds were tested against the Caco-2 cell line, HeLa cell line, L929 cell line and T24 cell line in vitro. Among them, compound C9 exhibited the best inhibitory activity against motor protein ATPase with an IC50 value of 30.25 µM and significant cytotoxic activity in the micromolar range against the cells above. The Lineweaver-Burk plot revealed that compound C9 was a mixed-type Eg5 inhibitor. A molecular modeling study using the Discovery Studio program was performed, where compound C9 exhibited good binding interaction with Eg5 motor protein ATPase, and this was consistent with the attained experimental results.

[A river stretch scale assessment of urban river habitat in the Taihu Lake Basin]. / 基于河段尺度的太湖流域城市河流生境评价.

Under the background of rapid urbanization, the degradation of urban river water environment and ecological function in the Taihu Lake Basin has become increasingly prominent. Consequently, it is particularly important to systematically assess urban river habitat. This study referred to and corrected the British Urban River Survey evaluation system. Based on the characte-ristics of urban rivers in the Taihu Lake Basin, we established the evaluation system of stretch habitat quality index (SHQI) of urban river stretches and analyzed the urban river habitat status and spatial variation in the Taihu Lake Basin. The results showed that the SHQI values of the 50 river stretches ranged between 8 and 21, with 3 river stretches classified as "excellent" habitat level, 6 as "good", 27 as "moderate", 9 as "poor", and 5 as "very poor". The vegetation index in urban river habitats in the Taihu Lake Basin was good, whereas that of the physical habitat and material index were bad. The overall ranking of habitats was Zhenjiang: Huzhou: Hangzhou: Jiaxing: Suzhou: Wuxi: Changzhou. There were significant differences in physical habitats, material indices and pollution indices among different cities. The main stream and the tributary section significantly differed in the material index and pollution index, but not significant for SHQI. The evaluation system constructed in this study reflected the current situation of urban river habitats in the Taihu Lake Basin, and could provide guidance for ecological restoration of urban rivers.

Risk of esophageal thermal injury during catheter ablation for atrial fibrillation guided by different ablation index.

BACKGROUND: During ablation for atrial fibrillation (AF), energy delivery toward the left atrial posterior wall may cause esophageal injury (EI). Ablation index (AI) was introduced to estimate ablation lesion size, however, the impact of AI technology on the risk of EI has not been explored. METHOD: From March 2019 to December 2019, 60 patients with paroxysmal AF undergoing first-time ablation were prospectively enrolled. The first 30 consecutive patients were ablated with the AI target value of 400 (AI-400 group), and the later 30 consecutive patients were ablated with the AI target value of 350 at the posterior wall (AI-350 group). Endoscopic ultrasonography was used to evaluate EI postablation. EI was classified as a category 1 (erythema or erosion) or a category 2 (hematoma or ulceration). RESULTS: Compared with the AI-400 group (59.9 ± 8.4 years; male, 60%), the AI-350 group (59.1 ± 9.9 years; male, 50%) had a lower incidence of EI (3.3% vs 26.7%, P = .03). There was no significant difference in the percentage of first-pass PVI between the AI-400 group and the AI-350 group (left PVI: 80% vs 73.4%, P = .54; right PVI: 80% vs 60%, P = .1). Neither ablation time nor fluoroscopy time was significantly different between the AI-400 group and the AI-350 group. CONCLUSIONS: AF ablation guide by AI target value of 350 may reduce esophageal thermal injury and has a similar efficiency on the acute success rate of first-pass PVI compared with an AI target value of 400 at the posterior wall.

PV isolation guided by esophageal visualization with a tailored ablation strategy for the avoidance of esophageal thermal injury: a randomized trial.

PURPOSE: Radiofrequency ablation along the posterior wall of the left atrium may lead to atrioesophageal fistula due to esophageal thermal injury. The purpose of our study was to prospectively investigate whether ablation guided by soluble contrast esophageal visualization (SCEV) reduces injury during atrial fibrillation (AF) ablation. METHODS: Seventy-eight patients with paroxysmal AF undergoing circumferential pulmonary vein isolation (PVI) were randomized to a SCEV group (n = 39) and control group without visualization (n = 39). Cine imaging of the esophagus was performed during soluble contrast swallowing at the beginning of ablation, after adjacent ipsilateral PVI and at the end of the procedure. The ablation lesion set was modified to avoid radiofrequency delivery within the contrast esophagram boundaries. In the control group, a single final ingestion was performed at the end of the procedure. Esophageal injury was assessed by esophagogastroscopy within 24 h in all patients. RESULTS: In the control group, the ablation lesion crossed over the esophagus in 46.2% of patients, whereas in SCEV group, the ablation line violated the boundaries of the esophagus unavoidably in 15.4% of patients (confidence interval (CI); 1.61-13.98, p = 0.003). The incidence of esophageal injury was significantly lower in patients that underwent ablation with SCEV (5.1% vs. 20.5%, CI; 0.04-1.06, p = 0.042). Regardless of randomization group, patients who received ablation which overlapped the esophagus had a higher incidence of esophageal injury compared with those without overlap (37.5 vs. 1.9%, CI; 3.73-271.37, p = 0.000). CONCLUSIONS: Esophageal contrast visualization helps to reduce the potential for esophageal injury during paroxysmal AF ablation. This simple procedural adjunct has important implications to improve safety of paroxysmal AF ablation procedures globally.

Adjunctive percutaneous ablation targeting epicardial arrhythmogenic structures in patients of atrial fibrillation with recurrence after multiple procedures.

INTRODUCTION: Repeat ablation strategy for atrial fibrillation (AF) recurrence after multiple ablation procedures is known to be challenging. This study evaluated the insights of adjunctive ablation for epicardial arrhythmogenic substrates in those patients via a percutaneous epicardial approach. METHODS AND RESULTS: Thirty-five consecutive patients with AF/atrial tachycardia (AT) recurrence, who had two or more prior ablation procedures, were enrolled from September 2016 to December 2018. In addition to a standard endocardial approach, epicardial mapping and ablation were performed via a percutaneous subxiphoid access in the electrophysiology lab. Adjunctive epicardial ablations for left lateral ridge (LLR) were performed in 31 of 35 patients (88.6%) for efficient transmural lesions with pacing capture loss. Marshall Bundle (MB) potentials were documented on epicardial LLR in three patients and abolished by direct epicardial ablation. Bachmann's bundle (BB) was ablated as an epicardial conduction gap in four patients with a refractory anterior wall line. Two epicardial AT/AF triggers were detected followed by successful termination with epicardial ablation. No periprocedural complications occurred. About 23 of 35 patients (65.7%) remained free from AF/AT after 23.2 ± 9 months of the procedure. CONCLUSIONS: Patients with multiple failed prior AF procedures refractory to antiarrhythmic therapy might warrant a percutaneous epicardial mapping and ablation strategy, with adjunctive therapy for targeting LLR/MB, BB, and underlying epicardial triggers in addition to a standard endocardial approach.

Anthocidins A⁻D, New 5-Hydroxyanthranilic Acid Related Metabolites from the Sea Urchin-Associated Actinobacterium, Streptomyces sp. HDa1.

Four new 5-hydroxyanthranilic acid related compounds, named anthocidins A⁻D (1⁻4), two known analogues n-lauryl 5-hydroxyanthranilate (5) and isolauryl 5-hydroxyanthranilate (6), together with benzamide (7), 3-hydroxy-4-methoxycinnamamide (8), and (3S-cis)-hexahydro-3-[(3,4-dihydroxyphenyl)methyl]pyrrolo[1,2-a]pyrazine-1,4-dione (9), were isolated from the fermentation broth of the marine-derived actinomycete, Streptomyces sp. HDa1, which was isolated from the gut of a sea urchin, Anthocidaris crassispina, collected from Hainan Island, China. The structures of these secondary metabolites were elucidated on the basis of their 1D and 2D-NMR and mass spectroscopic data, and anthocidin A was confirmed by single-crystal X-ray diffraction with Cu Kα radiation. Anthocidins A⁻D (1⁻4) feature an acetyl group substitution at the amino group and varying alkyl side chains at the carboxyl group of 5-hydroxyanthranilic acid, and compound 5 was isolated as a natural product for the first time. The cytotoxic and antibacterial activity of compounds 1⁻9 were evaluated.

Metabolic benefits of rivaroxaban in non-valvular atrial fibrillation patients after radiofrequency catheter ablation.

BACKGROUND AND OBJECTIVE: Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug-food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA). METHODS: From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure. RESULTS: Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79). CONCLUSIONS: Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.

Impact of Anatomically Guided Ganglionated Plexus Ablation on Electrical Firing from Isolated Pulmonary Veins.

BACKGROUND: The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI. METHODS: Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. RESULTS: In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. CONCLUSION: GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms.

Alendronate prevents angiotensin II-induced collagen I production through geranylgeranylation-dependent RhoA/Rho kinase activation in cardiac fibroblasts.

Collagen I is the main component of extracellular matrix in cardiac fibrosis. Our previous studies have reported inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis, while the exact molecular mechanism was still unclear. This paper was designed to investigate the effect of alendronate, a farnesylpyrophosphate synthase inhibitor, on regulating angiotensin II-induced collagen I expression in cultured cardiac fibroblasts and to explore the underlying mechanism. By measuring the mRNA and protein levels of collagen I, we found that alendronate prevented angiotensin II-induced collagen I production in a dose-dependent manner. The inhibitory effect on collagen I expression was reversed by geranylgeraniol, and mimicked by inhibitors of RhoA/Rho kinase pathway including C3 exoenzyme and GGTI-286. Thus we suggested geranylgeranylation-dependent RhoA/Rho kinase activation was involved in alendronate-mediated anti-collagen I synthetic effect. Furthermore, we accessed the activation status of RhoA in alendronate-, geranylgeraniol- and GGTI-286-treated cardiac fibroblasts and gave an indirect evidence for RhoA activation via geranylgeranylation. Then we came to the conclusion that in cardiac fibroblasts, alendronate could protect against angiotensin II-induced collagen I synthesis through inhibition of geranylgeranylation and inactivation of RhoA/Rho kinase signaling. Targeting geranylgeranylation and RhoA/Rho kinase signaling will hopefully serve as therapeutic strategies to reduce fibrosis in heart remodeling.

Non-pulmonary vein foci induced before and after pulmonary vein isolation in patients undergoing ablation therapy for paroxysmal atrial fibrillation: incidence and clinical outcome.

OBJECTIVE: To evaluate the incidence and clinical outcome of adenosine triphosphate (ATP) plus isoproterenol (ISP)-induced non-pulmonary vein (PV) foci before and after circumferential PV isolation (CPVI) during index ablation in patients with paroxysmal atrial fibrillation (PAF). METHODS: In 80 consecutive patients undergoing catheter ablation for drug-refractory, symptomatic PAF at our hospital from April 2010 to January 2011, atrial fibrillation (AF) was provoked with ATP (20 mg) and ISP (20 µg/min) administration before and after CPVI. The spontaneous initiation of AF was mapped and recorded. RESULTS: Before ablation, AF mostly originating from PVs (PV vs. non-PV, 36/70 vs. 3/70; P<0.01) was induced in 39 patients with sinus rhythm. CPVI significantly suppressed AF inducibility; however, more non-PV foci were provoked (post-CPVI vs. pre-CPVI, 13/76 vs. 3/70; P=0.016). Patients with pre- and post-CPVI induced AF (n=49) were divided according to non-PV foci being induced (group N, n=17) or not (group P, n=32). After mean (19.2±8.2) months follow-up, 88.2% (15/17) and 65.6% (21/32) of patients in groups N and P, respectively, were free from AF recurrence (P=0.088). CONCLUSIONS: ATP+ISP administration effectively provokes non-PV foci, especially after CPVI in PAF patients. Although in this study difference did not achieve statistical significance, supplementary ablation targeting non-PV foci might benefit clinical outcome.

Ethyl 3-methyl-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyridazine-2-carboxyl-ate.

The title compound, C(10)H(11)N(3)O(3), was synthesized by the reaction of 3,5-bis-(ethoxy-carbon-yl)-2-formyl-4-methyl-1H-pyrrole and hydrazine hydrate. The angle between the pyrrole ring and the pyridazinone ring is 0.93 (9)°. In the crystal, inter-molecular N-H⋯O and N-H⋯N hydrogen-bond inter-actions link the mol-ecules into a two-dimensional network.