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.

The significance of heart rate variability in patients with frequent premature ventricular complex originating from the ventricular outflow tract.

BACKGROUND: As an indicator of cardiac autonomic nervous activity, heart rate variability (HRV) is closely linked to premature ventricular complexes (PVCs). However, its role in patients with frequent PVCs originating from the ventricular outflow tract remains unclear. HYPOTHESIS: Here, we hypothesize that there may be alterations in HRV among patients with frequent PVCs originating from the ventricular outflow tract, which could play significant roles in the management of such patients. METHODS: A retrospective study was conducted, including 106 patients with frequent outflow tract PVCs and 106 healthy participants as controls. HRV was assessed based on the 24-hour Holter recording. The originating foci of PVCs were identified during radiofrequency catheter ablation. RESULTS: Patients with frequent outflow tract PVCs exhibited decreased levels of high frequency (HF), standard deviation of all NN intervals, and standard deviation of the average NN intervals, but increased ratios of low frequency to HF (LF/HF ratio), even after propensity score-matched analysis. Further investigation revealed that patients with PVCs originating from right ventricular outflow tract (RVOT) had much higher LF/HF ratios. Multivariate logistic regression analysis demonstrated that the LF/HF ratio was independently associated with PVCs originating from RVOT. Receiver operating characteristics curve indicated that the LF/HF ratio effectively determined the origin of PVCs (the area under the curve = 0.75, p < .001). CONCLUSIONS: Patients with frequent outflow tract PVCs exhibited impaired HRV. Additionally, the LF/HF ratio played a significant role in determining the origin of outflow tract PVCs.

Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease.

BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.

Association between urinary metabolites of volatile organic compounds and cardiovascular disease in the general population from NHANES 2011-2018.

BACKGROUND: Volatile organic compounds (VOCs) contain hundreds of chemicals and human exposure to VOCs is pervasive. However, most studies have considered only a single chemical or a class of similar chemicals. OBJECTIVE: We aimed to investigate the association between urinary volatile organic compound metabolites (mVOCs) and the risk of cardiovascular disease (CVD) in the general population. METHODS: The data in this study were collected from the National Health and Nutrition Examination Survey in 2011-2018. Eligible patients were aged ≥20 years for whom complete data for 20 types of urinary mVOCs and CVD outcomes were available. Multivariate logistic regression models were used to elucidate the association between mVOCs and CVD. Generalized additive models were used to examine the nonlinear relationships between mVOCs and CVD. RESULTS: 6814 indiviuals were included in the final analysis, of whom 508 had CVD. Higher urinary concentrations of N-acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA) and N-Acetyl-S-(2-cyanoethyl)-l-cysteine (CYMA) and a lower urinary concentration of 2-aminothiazoline-4-carboxylic acid (ATCA) were associated with CVD outcomes after the adjustment for potential confounding factors. A nonlinear relationship and a threshold effect were only observed between N-acetyl-S-(N-methylcarbamoyl)-l-cysteine (AMCC) and CVD among 20 types of mVOCs. There was a significantly positive correlation between AMCC and CVD when AMCC concentration was >2.32 g/mL. CONCLUSION: The findings of this study suggested a significant correlation between urinary VOC metabolites and CVD. Urinary mVOCs may indicate hazardous exposure or distinct metabolic traits in patients with CVD.

Effect of Prolonged Use of Dronedarone on Recurrence in Patients with Non-Paroxysmal Atrial Fibrillation After Radiofrequency Ablation (DORIS): Rationale and Design of a Randomized Multicenter, Double-Blinded Placebo-Controlled Trial.

BACKGROUND: Prolonged use of anti-arrhythmic drugs (AAD) beyond the post-ablation blanking period to maintain sinus rhythm has been adopted in clinical practice but without sufficient evidence. Dronedarone is an AAD valid for maintaining sinus rhythm with fewer side effects than other AAD for long-term use. OBJECTIVE: We sought to investigate the effect of prolonged use of dronedarone on the recurrence of non-paroxysmal AF patients beyond 3 months within the first year after ablation. METHODS: Non-paroxysmal AF patients will receive dronedarone for 3 months after radiofrequency ablation. Patients without drug side effects and atrial tachyarrhythmia (AT) recurrence will then be randomly divided into dronedarone and placebo groups and followed up until 1 year after ablation. The primary endpoint is the cumulative nonrecurrence rate post 3 months to 1 year after ablation. Patients will receive 7-day Holter monitoring (ECG patch) at 6, 9, and 12 months after ablation to evaluate AT recurrence. Secondary endpoints include dronedarone withdrawal due to side effects or intolerance of AT recurrence, time to the first recurrence, repeat ablation, electrical cardioversion, unscheduled emergency room visit, or re-hospitalization. CONCLUSION: This trial will evaluate whether prolonged use of dronedarone effectively reduces the recurrence rate after ablation in non-paroxysmal AF patients. The result of this trial will provide evidence for optimizing post-ablation anti-arrhythmic therapy. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT05655468, 19-December-2022.

An analysis of antithrombotic therapy in elderly patients with atrial fibrillation undergoing percutaneous coronary interventions.

As a result of large, randomized trials and updates to clinical guidelines, antithrombotic therapy following percutaneous coronary intervention (PCI) has changed in recent years for patients with nonvalvular atrial fibrillation (NVAF). The purpose of this study was to investigate the real-world data of antithrombotic regimens at discharge and their evolving trends, as well as compare the effect of different therapies on the incidence of major cardiovascular and cerebrovascular ischemic events (MACCEs) and bleeding events in elderly patients. An analysis of 6298 stent implantation patients from 2016 to 2018 was carried out retrospectively. Atrial fibrillation (AF) patients ages 65 and older were divided into two groups according to the antithrombotic regimens prescribed at hospital discharge: dual antiplatelet aggregation treatment group (DAPT) and anticoagulant treatment and antiplatelet aggregation treatment group (ATT). Baseline characteristics, efficacy endpoints (MACCEs/cerebrovascular ischemic events) and safety endpoints (bleeding events) were analysed and compared between the different antithrombotic regiments. During 2016 to 2018, the use of oral anticoagulants (OAC) increased from 16.3% to 54.1% (p trend <0.01). Since the introduction of non-vitamin K antagonist oral anticoagulants (NOACs), warfarin usage has decreased from 100% to 41.7%, and NOACs have rapidly replaced warfarin. The rate of persistent AF in the ATT group was significantly higher than the rate in the DAPT group (79.6% vs 59.7%, p = 0.01), and the ATT group used more proton pump inhibitors (PPI) than the DAPT group (23.3% vs 11.8%, p = 0.01). A significant decrease was observed in MACCEs (10.7% vs 26.0%, p < 0.01) and cerebrovascular ischemic events (2.9% vs 11.8%, p = 0.01) in the ATT group compared with the DAPT group. According to the ATT subgroup analysis, there was a significant difference in the incidence of overall bleeding between the triple anticoagulant therapy group and the dual anticoagulant therapy group (DT) (18.0% vs 2.4%, p = 0.02). MACCEs were predicted independently by ATT and CHA2 DS2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category) scores, whereas bleeding was predicted independently by PPI use and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol) scores. As a result of NOAC introduction and use, the combination of antithrombotic regimens at discharge for elderly patients with AF after PCI has changed rapidly over the past few years toward a higher use of ATTs, whereas patients with AF undergoing PCI still rarely receive an appropriate antithrombotic regimen. It is essential to conduct ATT in elderly patients who are undergoing PCI, and further DT may be more appropriate.

Novel algorithm for diagnosis of Arrhythmogenic cardiomyopathy and dilated cardiomyopathy: Key gene expression profiling using machine learning.

BACKGROUND: It is difficult to distinguish between arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM) because of their similar clinical manifestations. This study aimed to develop a novel diagnostic algorithm for distinguishing ACM from DCM. METHODS: Two public datasets containing human ACM and DCM myocardial samples were used. Consensus clustering, non-negative matrix factorization and principal component analysis were applied. Weighted gene co-expression network analysis and machine learning methods, including random forest and the least absolute shrinkage and selection operator, were used to identify candidate genes. Receiver operating characteristic curves and nomograms were performed to estimate diagnostic efficacy, and Spearman's correlation analysis was used to assess the correlation between candidate genes and cardiac function indices. RESULTS: Both ACM and DCM showed highly similar gene expression patterns in the clustering analyses. Hub gene modules associated with cardiomyopathy were obtained using weighted gene co-expression network analysis. Thirteen candidate genes were selected using machine learning algorithms, and their combination showed a high diagnostic value (area under the ROC curve = 0.86) for distinguishing ACM from DCM. In addition, TATA-box binding protein associated factor 15 showed a negative correlation with cardiac index (R = -0.54, p = 0.0054) and left ventricular ejection fraction (R = -0.48, p = 0.0015). CONCLUSIONS: Our study revealed an effective diagnostic model with key gene signatures, which indicates a potential tool to differentiate between ACM and DCM in clinical practice. In addition, we identified several genes that are highly related to cardiac function, which may contribute to our understanding of ACM and DCM.

Impaired heart rate variability in patients with arrhythmogenic cardiomyopathy: A multicenter retrospective study in China.

Background: Cardiac sympathetic nerve system (SNS) might play an important role in arrhythmogenesis of arrhythmogenic cardiomyopathy (ACM). This study aims to assess the activity of cardiac SNS in ACM patients by heart rate variability (HRV), and to investigate its predictive value for sustained ventricular tachycardia (sVT). Methods: A total of 88 ACM patients and 65 sex- and age- matched healthy participants were enrolled. The time domain measures were used to evaluate the activity of cardiac SNS. An independent cohort with 48 ACM patients was as the validation cohort. Results: ACM patients had lower levels of standard deviation of all NN intervals (SDNN) [118.0 (90.3, 136.8) vs. 152.0 (132.5, 174.5) ms, p < 0.001] compared with healthy participants. Further analysis showed ACM patients with sVT had lower levels of SDNN than those without sVT (105.0 ± 28.1 vs. 131.8 ± 33.1 ms, p < 0.001). Multivariate logistic regression analysis showed SDNN was independently associated with sVT in ACM patients [odds ratio (OR) 0.59, 95% confidence interval (CI) (0.45-0.78), p < 0.001]. Receiver operating characteristics curve demonstrated SDNN had clinical values in predicting sVT in ACM patients [area under the curve (AUC) = 0.73, 95% CI (0.63-0.84), p < 0.001], which was verified in the validation cohort. Conclusion: The present study suggests that HRV is impaired in patients with ACM, and the SDNN level has a moderate value in risk stratification for sVT in ACM patients. In addition, the finding might provide new target for the further management of ACM with integrated traditional Chinese and western medicine.

Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury.

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.

Case report: Artery of Percheron infarction as a rare complication during atrial fibrillation ablation.

The incidence of stroke or transient ischemic attacks (TIA) in atrial fibrillation (AF) catheter ablation procedures is around 1% and may be unnoted under anesthesia. The artery of Percheron (AOP) infarction is a rare kind of stroke with heterogeneity in manifestation, which further makes the perioperative early detection and diagnosis a challenge. Herein, we present one patient who underwent AF ablation and presented mental status alteration after withdrawing anesthetics. An emergency head CT was obtained, which revealed no apparent pathological changes. A late MRI test confirmed the diagnosis of AOP infarction. With oral anticoagulants and rehabilitation therapies, the patient's awareness improved and fully recovered on the sixth-month follow-up. Variability in manifestation, no positive radiological finding on initial CT, and a low incidence has made few clinicians to gain much experience with this type of infarct, which delays the diagnosis and initiation of appropriate treatment.

B cell-mediated regulatory mechanisms control tumor-promoting intestinal inflammation.

Mechanisms underlying tumor-promoting inflammatory processes in colitis-associated colorectal cancer (CAC) remain largely elusive. Here, we provide genetic evidence for distinct B cell-mediated immunoregulatory mechanisms that protect from chronic colitis versus CAC. We demonstrate an inherent capacity of interleukin-10 (IL-10)-producing B cells to differentiate into immunoglobulin A (IgA) plasma cells (PCs) upon Toll-like receptor (TLR) activation. Our data show that B cell-derived IL-10 is essential to limit pathogenic T helper type 1 (Th1)/Th17 T cell responses during chronic colitis, while IgA PCs derived from IL-10+ B cells are being implicated in restraining tumorigenesis during CAC. Formation of a tumor-protective intestinal environment was associated with clonal expansion of specific types of colonic IgA PCs and development of an altered microbiota that attenuated CAC. We thus propose that regulatory B cell-mediated immunomodulation entails temporal release of IL-10, which is superseded by the generation of specific IgA affecting the microbial community, thereby controlling chronic inflammation and tumorigenesis in a distinctive but interrelated manner.

Berberine treats atherosclerosis via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway in gut microbiota.

Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR's metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.

Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction.

Purpose: Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Salvia miltiorrhiza Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury. Methods: Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI. Results: Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression. Conclusion: These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.

Bipolar catheter ablation strategies for outflow tract ventricular arrhythmias refractory to unipolar ablation.

INTRODUCTION: Conventional unipolar catheter ablation (UA) is generally effective for the treatment of outflow tract ventricular arrhythmias (OT-VAs). However, deep foci refractory to UA remains a clinical challenge. The present study evaluated the efficacy and safety of bipolar ablation (BA) in the treatment of OT-VAs refractory to UA. METHODS: A total of 1022 consecutive patients with antiarrhythmic drugs resistant OT-VAs were screened for inclusion in this study, from 1643 VAs cases who underwent catheter ablation in two centers from October 2014 to May 2019. BA was performed after failed sequential UA. The pair of catheters used for BA was positioned on opposing surfaces of the earliest activation (EA) sites or on adjacent anatomical structures. RESULTS: Twelve patients (seven males, mean age 33.3 ± 16.2 years) who met the inclusion criteria were recruited: one patient suffered sustained monomorphic ventricular tachycardia (VT), six patients had frequent premature ventricular contractions (PVCs), and nonsustained VT (NSVT), and five patients had PVCs only. The 24-hPVC/NSVT burden was 36.9 ± 21.7%. The mean distance between two ablation catheters during BA was 11.1 ± 4.3 mm (range 6.5-23.9 mm). The "rS" morphology of the unipolar electrogram was recorded simultaneously in both EA regions in seven cases (58.3%). Acute eradication of VAs was obtained in 10 (83.3%) cases. At a median follow-up of 58 months, 10 patients (83.3%) remained free from VAs. CONCLUSION: BA was highly effective and safe for the treatment of OT-VAs refractory to UA.

Severe coronary artery spasm during left atrial appendage closure plus catheter ablation for atrial fibrillation: case presentation.

BACKGROUND: Left atrial appendage closure (LAAC) combined with radiofrequency catheter ablation (RFCA) as a hybrid procedure is commonly performed to treat atrial fibrillation (AF). Although this treatment carries a low risk of coronary artery spasm (CAS), and has never been observed in LAAC procedure, caution still needed to be taken. We presented a case of CAS that occurred in an AF patient during the hybrid procedure. CASE PRESENTATION: The patient was a 65-year-old man with paroxysmal AF who developed CAS during RFCA and LAAC. In this case, LAAC was performed ahead of RFCA. After atrial septal puncture, the occluder was advanced into left atrium through delivery sheath, and successfully deployed in the LAA. After verifying the assessment of "PASS" criteria, we decided to release the device. However, before releasing the occluder in LAAC, the patient's blood pressure (BP) fell to 70/45 mmHg with heart rate (HR) drop and ST-segment elevation in II, III, and aVF and reciprocal ST-segment depression in I and aVL. Isotonic sodium chloride load was administered. After 3 min, the BP and HR raised, and ST-segment returned to normal. The occluder was successfully released after the stable condition of the patient. Then, RFCA was sequentially performed. When isolating the right pulmonary veins, the patient's BP and HR fell again with ST-segment elevation in inferior leads. Spontaneous ventricular tachycardia and fibrillation developed rapidly and defibrillation was performed immediately with success. Coronary angiography revealed the obstruction of the right coronary artery which disappeared completely after intracoronary nitroglycerin injection (1 mg). Under systemic diltiazem infusion, the RFCA procedure was accomplished. After the procedure, the patient recovered without any neurologic deficit, and CAS has never recurred with isosorbide mononitrate treatment during follow-up. CONCLUSIONS: CAS is a rare complication associated with AF hybrid procedure. Attention should be paid to this rare but potentially life-threatening complication.

Prevalence and Predictors of Additional Ablation Beyond Pulmonary Vein Isolation in Patients With Paroxysmal Atrial Fibrillation.

Background: Pulmonary vein isolation (PVI) is an effective strategy in the treatment of paroxysmal atrial fibrillation (PAF). Yet, there are limited data on additional ablation beyond PVI. In this study, we sought to assess the prevalence, predictors, and outcomes of additional ablation in PAF patients. Methods: A total of 537 consecutive patients with PAF were retrospectively evaluated for the index procedure. PVI was successfully conducted in all patients, after which electrophysiological study and drug provocation were performed, and additional ablations were delivered for concomitant arrhythmias, non-PV triggers, and low voltage zone (LVZ). The prevalence, predictors, and outcomes of additional ablation were analyzed. Results: Among 537 consecutive patients, 372 addition ablations were performed in 241 (44.88%) patients, including 252 (67.74%) concomitant arrhythmias in 198 (36.87%) patients, 56 (15.05%) non-PV triggers in 52 (9.68%) patients and 64 (17.20%) LVZ modification in 47 (8.75%) patients. Lower LVEF (OR = 0.937, p = 0.015), AF episode before procedure (OR = 2.990, p = 0.001), AF episode during procedure (OR = 1.998, p = 0.002) and AF episode induced after PVI (OR = 15.958, p < 0.001) were independent predictors of additional ablation. Single-procedure free from atrial arrhythmias at 58.36 ± 7.12 months post-ablation was 70.48%. Conclusions: Additional ablations were common in patients with PAF for index procedure. Lower LVEF and AF episodes before, during the procedure, and induced after PVI predicts additional ablation.

Determination and Application of Nineteen Monoamines in the Gut Microbiota Targeting Phenylalanine, Tryptophan, and Glutamic Acid Metabolic Pathways.

It has been reported that monoamine neurotransmitters can be produced by gut microbiota, and that several related metabolites of amino acids in these pathways are associated with nervous system (NVS) diseases. Herein, we focused on three pathways, namely, phenylalanine (Phe), tryptophan (Trp), and glutamic acid (Glu), and established an underivatized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of nineteen monoamine neurotransmitters and related metabolites in the gut microbiota. The neurotransmitters and related metabolites included Phe, tyrosine (Tyr), l-dopa (Dopa), dopamine (DA), 3-methoxytyramine, Trp, hydroxytryptophan, 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), kynurenine (KN), kynurenic acid (KYNA), melatonin, tryptamine (TA), indole-3-lactic acid (ILA), indole-3-acetic acid (IAA), indolyl-3-propionic acid (IPA), Glu, gamma-aminobutyric acid (GABA), and acetylcholine (Ach). A fluoro-phenyl bonded column was used for separation, and the mobile phase consisted of methanol:acetonitrile (1:1) and water, with 0.2% formic acid in both phases. The compounds exhibited symmetric peak shapes and sufficient sensitivity under a total analysis time of 8.5 min. The method was fully validated with acceptable linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The results showed that neurotransmitters, such as Dopa, DA, 5-HT, GABA, and Ach, were present in the gut microbiota. The metabolic pathway of Trp was disordered under depression, with lower levels of 5-HT, 5-HIAA, KN, KYNA, TA, ILA, IAA, IPA, and Glu, and a higher ratio of KYNA/KN. In addition, some first-line NVS drugs, such as sertraline, imipramine, and chlorpromazine, showed regulatory potential on these pathways in the gut microbiota.

Association of N-Terminal Pro-brain Natriuretic Peptide With Volume Status and Cardiac Function in Hemodialysis Patients.

Introduction: N-terminal-pro-brain natriuretic peptide (NT-pro BNP) is secreted by cardiomyocytes in cases of cardiac structure disorder and volume overload. However, the relationship between NT-pro BNP level and body fluid status in dialysis patients with reduced cardiac ejection function (EF) is uncertain. Therefore, we aimed to investigate this relationship. Methods: We enrolled patients who had been receiving hemodialysis for >3 months. Blood sample, transthoracic echocardiographic, and bioimpedance spectroscopy measurements were performed during a midweek non-dialysis day. The predictive value of NT-pro BNP in hemodialysis patients with volume overload was analyzed. Results: A total of 129 hemodialysis patients (74 men and 55 women; mean age: 59.4 ± 13.0 years) were recruited. The average hemodialysis duration was 55.5 (23.9-93.4) months, the NT-pro BNP level was 4992 (2,033-15,807) pg/mL, and the value of overhydration was 2.68 ± 0.19 (-1.9 to 12.2) L. The NT-pro BNP level was independently correlated with overhydration in both the LVEF ≥ 60% (ß = 0.236, P = 0.044) and LVEF <60% (ß = 0.516, P = 0.032) groups, even after adjustments for potentially confounding variables. In receiver operating characteristic curves of NT-pro BNP for predicting volume overload, the area under the curve was 0.783 [95% CI (0.688-0.879), P < 0.001) and 0.788 [95% CI (0.586-0.989), P < 0.001] in the LVEF ≥ 60% and LVEF < 60% groups, respectively. Conclusions: NT-pro BNP is a predictive factor for volume overload in hemodialysis patients with or without EF declines.

Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson's disease by regulating gut microbiota.

The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (L-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of L-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The L-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut-brain dialog activated by BBR's effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson's disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal L-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of L-dopa in the gut microbiota through a vitamin-like effect.

Paradoxical Association Between Intradialytic Blood Pressure Change and Long-Term Mortality with Different Levels of Interdialytic Weight Gain.

BACKGROUND: A greater interdialytic weight gain (IDWG) implies a greater ultrafiltration rate, which might lead to hemodynamic instability and intradialytic blood pressure (BP) change in hemodialysis patients. However, current studies have not explicated the impact of IDWG on the association between intradialytic BP changes and prognosis, especially in patients without cardiac dysfunction and diabetes. In this study, we aimed to explore the relationship between absolute intradialytic BP changes and mortality with different IDWG levels. METHODS: A total of 204 hemodialysis patients (without cardiac dysfunction and diabetes) were included in this prospective observation study, with a mean follow-up of 55.32±20.99 months. Initially, we collected IDWG, IDWG% (percentages according to dry weight), and pre-/post-BPs of 36 consecutive dialysis sessions during three months enrollment. And the average value of them was defined as baseline value. Patients were divided into 3 cohorts according to IDWG% tertiles (<3.3%, 3.3%-4.6%, ≥4.6%). Comparisons between different tertiles were analyzed. RESULTS: Compared to the low IDWG% group (tertile 1, T1), patients of high IDWG% group (tertile 3, T3) were younger, had higher ultrafiltration rate, less residual kidney function, lower BMI and dry weight, longer dialysis vintage and higher N terminal pro B type natriuretic peptide levels (P<0.05). Correlations were found between IDWG% and intradialytic BP changes. Kaplan-Meier analysis and multivariate Cox regression model adjusted for demographic data, dialysis information and predialysis BPs indicated that greater absolute intradialytic BP changes were associated with worse prognosis in T1 group (P<0.05). While in T3 group, less absolute intradialytic BP changes were associated with higher mortality (P<0.05). CONCLUSION: There is a paradoxical association between absolute intradialytic BP changes and long-term mortality with different IDWG levels. Both BP stability and volume balance are crucial to patients' prognosis.