ABSTRACT
Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Subject(s)
Aged , Humans , Male , Middle Aged , Atrial Fibrillation/complications , Cross-Sectional Studies , Gastrointestinal Microbiome , Lipopolysaccharides , Prospective StudiesABSTRACT
<p><b>BACKGROUND</b>It is unclear whether a history of paroxysmal atrial fibrillation (PAF) would impact the effect of catheter ablation on persistent atrial fibrillation (AF). This study aimed to compare the effect of catheter ablation on persistent AF with and without a history of PAF.</p><p><b>METHODS</b>One hundred and eighty-three patients underwent catheter ablation of persistent AF lasting for > 1 month and were reviewed. Patients were divided into two groups according to whether they had a history of PAF or not. Group I consisted of persistent AF patients with a history of PAF, and group II consisted of persistent AF patients without such a history. All patients received catheter ablation focused on pulmonary vein isolation and were observed for arrhythmia recurrences, which were defined as documented episodes of AF or atrial tachycardia after a blanking period of 3 months.</p><p><b>RESULTS</b>One hundred and three patients (60.9%) in group I and sixty-six patients (39.1%) in group II were successfully followed and included in analysis. There were no significant differences in clinical and echocardiographic characteristics between both groups except for a younger age and more male patients in group II. After (15.5 ± 10.7) months of follow-up, 59 (57.3%) patients in group I and 49 (74.2%) patients in group II maintained sinus rhythm free of anti-arrhythmia drugs (P = 0.025). Multivariate analyses found left atrial anteroposterior diameter (P = 0.006) and persistent AF with a history of PAF (OR 1.792, 95%CI 1.019 - 3.152; P = 0.043) as the only independent statistical predictors of arrhythmia recurrences.</p><p><b>CONCLUSION</b>The arrhythmia recurrence rate of catheter ablation based on pulmonary vein isolation in persistent AF with a history of PAF was higher than those without a history of PAF.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Atrial Fibrillation , General Surgery , Catheter Ablation , Proportional Hazards Models , Pulmonary Veins , General Surgery , RecurrenceABSTRACT
<p><b>BACKGROUND</b>Radiofrequency (RF) ablation has become a widely accepted treatment for atrial fibrillation (AF). This study aimed to identify the efficacy and safety of pulmonary vein (PV) ablation with ethanol and to explore an alternative energy source for catheter ablation of AF.</p><p><b>METHODS</b>Twelve open-chest mongrel dogs were randomized into ethanol ablation group and control group. Both the injections and electrophysiological mapping procedures were performed epicardialy. In ethanol ablation group (n = 6), injections were performed to circumferentially ablate the root of each PV (0.2 ml each site, 3 mm apart) with 95% ethanol using an 1 ml injector. In control group (n = 6), saline was injected other than ethanol. PV isolation was confirmed with a circular catheter immediately after the procedure and at follow up of 30 days. PV isolation was defined as the absence of PV potentials at each electrode of the circular catheter positioned at the PV side of the lesions, as well as complete conduction block into left atrium (LA) during PV pacing.</p><p><b>RESULTS</b>PV electrical isolation with complete bidirectional conduction block was achieved with ethanol immediately and at 30 days in 95% of PVs, while saline injection caused only transient conduction changes between LA and PVs. In ethanol group, histologic analysis showed transmural lesions at 30 days. And there was no evidence of PV stenosis or thrombus formation. Mean LA diameter was not significantly different between baseline and 30 days.</p><p><b>CONCLUSION</b>Ethanol is a safe energy source to effectively isolate PV in canine model and may be promising in endocardial ablation procedure of AF patients in the future.</p>