Disordered gut microbiota promotes atrial fibrillation by aggravated conduction disturbance and unbalanced linoleic acid/SIRT1 signaling.

Emerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.

The Impact of Sleep Disturbance on Gut Microbiota, Atrial Substrate, and Atrial Fibrillation Inducibility in Mice: A Multi-Omics Analysis.

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography−mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

Commensal microbe-derived SCFA alleviates atrial fibrillation via GPR43/NLRP3 signaling.

Rationale: Dysbiotic gut microbiota (GM) and NLRP3 inflammasome are proarrhythmic factors in atrial fibrillation (AF). Herein, whether short-chain fatty acid (SCFA) produced from GM fermentation of dietary fiber serving as invisible mediators is yet unclear. Thus, the current study aimed to determine whether SCFA alleviated from NLRP3 signaling-mediated atrial remodeling protects AF development. Methods: First, a cross-sectional study based on the GC-MS metabolomics was performed to explore the association between fecal SCFA levels and AF traits in a cohort consisted of 48 individuals. Then, a well-established mice model fed diet deficient or enriched in dietary fiber was established to elucidate the pathophysiological role of SCFA involved in AF susceptibility, atrial remodeling, and G-protein-coupled receptor 43 (GPR43)/NLRP3 signaling. Finally, the effects of SCFA were verified on HL-1 cells. Results: Fecal SCFA levels were remarkably reduced in AF patients with a declining trend from paroxysmal to persistent AF. Prolonged P wave duration based on surface ECG and increased left atrial diameter gained from echocardiography was identified in low-fiber diet mice but lost in SCFA-supplemented group. Lack of dietary fiber enhanced susceptibility to AF under burst pacing, whereas SCFA might exert a protective effect. The supplementation of SCFA prevented dietary fiber deficiency-upregulated phosphorylation of calmodulin-dependent protein kinase II and ryanodine receptor 2, the disarray fibrosis, collagen expression, and NLRP3 inflammasome activation in atrial tissue. Finally, the AF protective roles of SCFA were identified through GPR43 mediated deactivation of NLRP3 by GPR43 knockdown in HL-1 cells. Conclusions: SCFA derived from dietary fiber fermentation by gut commensals alleviates AF development via GPR43/NLRP3 signaling.

Use of a coronary guidewire to facilitate transseptal puncture: A randomized comparison with a conventional technique.

INTRODUCTION: Transseptal puncture (TSP) is routinely performed for left heart intervention, but it can sometimes be complex and life-threatening. This study introduced a safe and effective method to facilitate TSP for left atrial access. METHODS AND RESULTS: A total of 200 patients (190 with atrial fibrillation, 10 with a left accessory pathway) were prospectively analyzed. In the guidewire group, TSP was performed using a SWARTZ sheath and a Brockenbrough needle with a 0.014-inch coronary guidewire instead of an inner stylet. The needle tip position was confirmed by pushing the guidewire into the left superior pulmonary vein after initial puncture in 100 patients. In the contrast group, TSP was performed in 100 patients using standard devices by injecting contrast to confirm needle-tip position. Left atrial access was achieved successfully in all patients in the two groups without serious complications. The guidewire group showed a higher first-pass rate for left atrial access compared with the contrast group (81.1% vs. 75% p < .001, respectively). CONCLUSION: Coronary guidewire TSP is safe and is associated with a high success rate, and it is thus a useful alternative to conventional TSP. This method is useful for patients with septal aneurysms and contrast allergies.

The efficacy and safety of radiofrequency ablation on the platelet activation and the inflammatory response in elderly atrial fibrillation patients.

BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. AF is more common in the elderly population than in the young population. Radiofrequency ablation (RA) is the treatment option for drug-naïve AF; however, previous studies have focused on the young population. Therefore, it would be clinically valuable to compare the efficacy and safety of RA in both elderly and young patients with AF. OBJECTIVE: This study intended to compare the efficacy and safety of RA in elderly and young patients with AF. METHODS: Forty patients with drug-naïve AF who underwent RA at our hospital were retrospectively evaluated, of whom 20 were < 65 years old (group 1) and 20 were ≥ 65 years old (group 2). The treatment efficacy was evaluated by comparing the durations of the surgical procedures, the postoperative platelet activation, and the inflammatory factor levels. RESULTS: The total operation times for RA (160.64 ± 7.25 vs. 160.64 ± 7.25 min, P = 0.341) and the fluoroscopy times (40.82 ± 5.93 vs. 39.89 ± 6.35 min, P = 0.636) did not differ between the elderly (74.1 ± 6.7 years) and the young (54.6 ± 7.9 years) groups. The postoperative platelet activation levels (6.90% ± 0.64% vs. 6.90% ± 0.70%, P = 0.991), the P-selectin expression levels (4.5 ± 1.3 vs. 4.9 ± 1.3, P = 0.333) and the activated glycoprotein IIb/IIIa (0.5 ± 1.0 vs. 0.4 ± 1.1, P = 0.649), and the inflammatory factor levels (C-reactive protein: 26.45 ± 6.66 vs. 25.72 ± 7.78 mg/L, P = 0.750) were elevated in both groups but did not differ between the two groups. CONCLUSION: RA is a safe and effective procedure in elderly and young patients with medically refractory AF.

Altered synthesis of genes associated with short-chain fatty acids in the gut of patients with atrial fibrillation.

BACKGROUND: The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients. RESULTS: Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001). CONCLUSIONS: The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.

Low-Voltage Zones as the Atrial Fibrillation Substrates: Relationship With Initiation, Perpetuation, and Termination.

Background: Low-voltage zones (LVZs) were usually targeted for ablation in atrial fibrillation (AF). However, its relationship with AF initiation, perpetuation, and termination remains to be studied. This study aimed to explore such relationships. Methods: A total of 126 consecutive AF patients were enrolled, including 71 patients for AF induction protocol and 55 patients for AF termination protocol. Inducible and sustainable AF were defined as induced AF lasting over 30 and 300 s, respectively. Terminable AF was defined as those that could be terminated into sinus rhythm within 1 h after ibutilide administration. Voltage mapping was performed in sinus rhythm for all patients. LVZ was quantified as the percentage of the LVZ area (LVZ%) to the left atrium surface area. Results: The rates of inducible, sustainable, and terminable AF were 29.6, 18.3, and 38.2%, respectively. Inducible AF patients had no significant difference in overall LVZ% compared with uninducible AF patients (10.2 ± 11.8 vs. 8.5 ± 12.6, p = 0.606), while sustainable and interminable AF patients had larger overall LVZ% than unsustainable (16.2 ± 11.5 vs. 0.5 ± 0.7, p < 0.001) and terminable AF patients (44.6 ± 26.4 vs. 26.3 ± 22.3, p < 0.05), respectively. The segmental LVZ distribution pattern was diverse in the different stages of AF. Segmental LVZ% difference was initially observed in the anterior wall for patients with inducible AF, and the septum was further affected in those with sustainable AF, and the roof, posterior wall, and floor were finally affected in those with interminable AF. Conclusions: The associations between LVZ with AF initiation, perpetuation, and termination were different depending on its size and distribution.

A modified percutaneous atrial balloon septoplasty for difficult transseptal puncture.

ABSTRACT: Catheter ablation of atrial fibrillation sometimes encounters difficulty in passing the interatrial septum. This study reports a modified percutaneous atrial balloon septoplasty with short balloon to gain access to left atrium (LA) during challenging transseptal puncture (TSP).We retrospectively analyzed 20 patients (61.75 ±â€Š7.31 years, 45% male) who received modified percutaneous atrial balloon septoplasty from August 2015 to October 2018. Soft-headed balance middle weight (BMW) guidewire was inserted into left superior pulmonary vein (LSPV) and short non-compliant balloon (15 mm in length and 4.0 or 5.0 mm in diameter) was used for atrial balloon septoplasty (ABS). Interatrial septum was located with inflated balloon and contrast "Hitting Wall" sign. All patients were followed-up for iatrogenic atrial septal defect (iASD) and other related complications.ABS and LA access were performed successfully without complications in all 20 patients. Time needed for ABS was correlated to the number of prior TSP (P = .007). During the 6-month follow-up, no remaining iASD was found by echocardiography.For atrial fibrillation patients with difficulty in passing the interatrial septum, this modified percutaneous ABS might be an alternative strategy which is safe to obtain transseptal access without short or long term complications.

Role of the notched unipolar electrogram in guiding catheter ablation of frequent premature ventricular contractions originating from the ventricular outflow tract.

OBJECTIVE: To investigate the value of a notched unipolar electrogram (N-uniEGM) in confirming the origin of premature ventricular contractions originating from the ventricular outflow tract (VOT-PVC) during mapping and ablation procedures. METHODS: This retrospective study enrolled consecutive patients with symptomatic idiopathic frequent VOT-PVCs that underwent radiofrequency ablation. The characteristics of the uniEGM of the successful ablation targets were analysed. N-uniEGM was defined as the uniEGM presenting a QS morphology with ≥1 steep notches on the downstroke deflection. All patients were followed-up for 3 months post-ablation. RESULTS: The study enrolled 190 patients with a mean ± SD age of 49.0 ± 15.3 years. N-uniEGMs were recorded in 124 of 190 (65.3%) patients. The N-uniEGM distribution area was limited to a mean ± SD of 0.8 ± 0.4 cm2. N-uniEGM showed consistency with the outcomes of activation mapping and pace mapping. Patients with an N-uniEGM had an ablation success rate of 98.4% (122 of 124) and their ablation times were significantly shorter than those without an N-uniEGM (7.6 ± 3.8 s versus 15.8 ± 8.8 s, respectively). The sensitivity and specificity of N-uniEGM in predicting successful ablation of VOT-PVCs were 72.6% and 91.7%, respectively. CONCLUSION: N-uniEGM was a highly specific and moderately sensitive predictor of successful radiofrequency ablation in patients with VOT-PVCs.

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation.

Alternations of gut microbiota (GM) in atrial fibrillation (AF) with elevated diversity, perturbed composition and function have been described previously. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation based on metagenomic sequencing and metabolomic analyses and to construct a GM-based predictive model for RAF. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter and the species Faecalibacterium spCAG:82, Bacillus gobiensis and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. After incorporating the clinical factors of RAF, taxonomic score retained a significant association with RAF incidence (HR = 2.647, P = .041). An elevated AUC (0.954) and positive NRI (1.5601) for predicting RAF compared with traditional clinical scoring (AUC = 0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance, and the nomogram and decision curve analysis validated the clinical value of the predicting model. These data provide novel possibility that incorporating the GM factor into future recurrent risk stratification.

Metagenomic data-mining reveals enrichment of trimethylamine-N-oxide synthesis in gut microbiome in atrial fibrillation patients.

BACKGROUND: The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. RESULTS: Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. CONCLUSIONS: The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.

Myofibroblast-Derived Exosomes Contribute to Development of a Susceptible Substrate for Atrial Fibrillation.

OBJECTIVE: Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome (Exo)-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. METHODS: Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymatic digestion. The activation of FBs into MFBs was induced by angiotensin II. Co-culture assay and in vitro Exo treatment were used to determine the effect of MFB-derived Exos on Cav1.2 expression. Confocal Ca2+ imaging was performed to examine the adrenergic stimulation-elicited Ca2+ influx signals. The levels of potential Cav1.2-inhibitory microRNAs (miRNAs) were measured by qRT-PCR. RESULTS: Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. More importantly, treatment with MFB-derived Exos caused repression of Cav1.2 expression in CMs. Additionally, the adrenergic receptor agonist-elicited Ca2+ influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. CONCLUSION: We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.

Different Types of Atrial Fibrillation Share Patterns of Gut Microbiota Dysbiosis.

Dysbiotic gut microbiota (GM) and disordered metabolic patterns are known to be involved in the clinical expression of atrial fibrillation (AF). However, little evidence has been reported in characterizing the specific changes in fecal microbiota in paroxysmal AF (PAF) and persistent AF (psAF). To provide a comprehensive understanding of GM dysbiosis in AF types, we assessed the GM signatures of 30 PAF patients, 20 psAF patients, and 50 non-AF controls based on metagenomic and metabolomic analyses. Compared with control subjects, similar changes of GM were identified in PAF and psAF patients, with elevated microbial diversity and similar alteration in the microbiota composition. PAF and psAF patients shared the majority of differential taxa compared with non-AF controls. Moreover, the similarity was also illuminated in microbial function and associated metabolic alterations. Additionally, minor disparity was observed in PAF compared with psAF. Several distinctive taxa between PAF and psAF were correlated with certain metabolites and atrial diameter, which might play a role in the pathogenesis of atrial remodeling. Our findings characterized the presence of many common features in GM shared by PAF and psAF, which occurred at the self-terminating PAF. Preventative and therapeutic measures targeting GM for early intervention to postpone the progression of AF are highly warranted.IMPORTANCE Atrial fibrillation has been identified to be associated with disordered gut microbiota. Notably, atrial fibrillation is a progressive disease and could be categorized as paroxysmal and persistent based on the duration of the episodes. The persistent atrial fibrillation patients are accompanied by higher risk of stroke and lower success rate of rhythm control. However, the microbial signatures of different categories of atrial fibrillation patients remain unknown. We sought to determine whether disordered gut microbiota occurs in the self-terminating PAF or intestinal flora develops dynamically during atrial fibrillation progression. We found that different types of atrial fibrillation show a limited degree of gut microbiota shift. Gut microbiota dysbiosis has already occurred in mild stages of atrial fibrillation, which might act as an early modulator of disease, and therefore may be regarded as a potential target to postpone atrial fibrillation progression.

Duration of Persistent Atrial Fibrillation Is Associated with Alterations in Human Gut Microbiota and Metabolic Phenotypes.

Atrial fibrillation (AF) has been shown to be associated with disordered gut microbiota (GM). The underlying factors governing persistent AF (psAF) are not well understood, and the association between AF duration and GM profiles remains to be characterized. Thus, the present study aimed at investigating the dysbiosis of GM in patients with short and long psAF duration and illuminating the relationship between the GM and psAF maintenance. Based on metagenomic sequencing and metabolomic analyses, we assessed the metabolic and GM signature in 12 patients with psAF of <12 months (Pers<12m), eight patients with psAF of >12 months (Pers>12m), and 20 controls. We found that the GM in patients with both Pers<12m and Pers>12m was significantly perturbed, with an elevated microbial diversity, distinct structure, and discrepant composition. Although Pers<12m and Pers>12m patients shared a large number of common bacteria with controls, including 84 genera and 404 species, certain bacteria were differently enriched at different AF durations. Furthermore, disturbance in gut microbial function and GM-linked metabolic alterations were detected in both the Pers<12m and Pers>12m groups. The connection of GM and metabolites with psAF is consistent with interaction and potential modulation of host metabolic pathways due to GM dysbiosis with AF persistence. Our results showed that patients of the Pers<12m and Pers>12m groups shared many common disordered GM and metabolic features, which might occur in early disease, while prolonged psAF duration was related to certain unique alterations. Preventative strategies targeting GM and microbial metabolites for early intervention to treat AF patients are highly warranted.IMPORTANCE Atrial fibrillation was associated with a disordered gut microbiota in previous research. However, the gut microbiota signature of patients at different stages of atrial fibrillation remains largely unknown. We sought to determine whether the shift in the gut microbiota and metabolic profiles occurs early and remains stable or develops gradually during atrial fibrillation. We found that patients with persistent atrial fibrillation of <12 months and persistent atrial fibrillation of >12 months shared most of the common features of gut microbiota dysbiosis. However, some distinctive and progressive alterations in the gut microbiota and metabolic structure, which may contribute to the progression of atrial fibrillation, were identified. The present study provides a comprehensive description of the dysbiotic gut microbiota and metabolic profiles in patients of short and long persistent atrial fibrillation, and our findings may help identify therapeutic strategies targeting the gut microbiota to treat atrial fibrillation at an early stage.

Study on the relationship between telomere length changes and recurrence of atrial fibrillation after radiofrequency catheter ablation.

INTRODUCTION: Advanced age is the foremost risk factor for atrial fibrillation (AF). Telomere length is a surrogate for biological aging, but the association between shortened leukocyte telomere length (LTL) and recurrence of AF (RAF) after ablation remains inconclusive. METHODS: In this prospective analysis, 282 patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between RAF and LTL was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier analysis. RESULTS: After a mean follow-up of 14.20 ± 5.04 months, RAF was documented in 78 of the 277 patients who completed the study (28.16%). In Cox proportional hazards models, LTL, age, diagnosis to ablation time (DTAT), N-terminal pronatriuretic peptide, and CHA2DS2-VASc score were significantly associated with RAF. After multivariable adjustment, LTL and DTAT were predicted as independent risk factors for RAF with hazard ratio (HR) of 3.17 (95% confidence interval [CI]: 1.23-8.15, P = 0.017) and 1.43 (95% CI: 1.10-1.86, P = 0.007), respectively. In addition, ROC analysis indicated the potential diagnostic value of LTL with an area under the curve of 0.64 (P < 0.001; sensitivity = 60.3%, specificity = 57.8%), and an optimum cut-off value of 1.040. LTL less than or equal to 1.040 was defined as shortened LTL, while LTL greater than 1.040 nonshortened LTL. Kaplan-Meier analysis showed RAF rate curve was separated significantly between two groups (21.2% vs 35.9%, log-rank test result P = 0.007). Patients with shortened LTL might have a higher risk for RAF with HR = 1.84 (P = 0.008). CONCLUSIONS: Shortened LTL is an independent risk factor for AF recurrence. Shortened LTL could be a potential biomarker in predicting RAF after ablation.

Pace capture and adenosine triphosphate provocation are complementary rather than mutually exclusive methods to ensure durable pulmonary vein isolation.

INTRODUCTION: Adenosine triphosphate (ATP)-provoked dormant conduction (DC) and pacing for unexcitability are used to identify conduction gaps along the ablation lines after circumferential pulmonary vein isolation (CPVI). We aim to determine whether ATP provocation and pacing are interchangeable as endpoints for ablation of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: A total of 107 patients with PAF were randomly divided into two groups after completion of CPVI. In group I (A-P group, n = 53), ATP was administered first. If DC was uncovered, additional ablation was performed until ATP tests were negative. Bipolar pacing along the ablation line was performed subsequently. In group II (P-A group, n = 54), the same protocol was used, but the pacing and the ATP tests were performed in the opposite sequence. The 12-month ablation outcomes of all patients were compared with those of a historical control group of 107 patients with PAF in whom only ATP test was performed. Regardless of which test was performed first, the other modality still identified conduction gaps. In group I, pacing maneuvers identified gaps in 49% (n = 26) of patients who had negative ATP tests. In group II, ATP tests uncovered DC in 18.5% (n = 10) of patients in whom pacing identified no gaps. After 12 months, a higher proportion of patients (91.6%) were free from atrial tachyarrhythmias compared with the historical control group (81.3%; P = 0.031). CONCLUSION: Pacing along the ablation lines and ATP provocation are complementary tests for evaluating the durability of CPVI and can lead to better long-term outcomes when used in combination.

Low-Dose Ibutilide Combined with Catheter Ablation of Persistent Atrial Fibrillation: Procedural Impact and Clinical Outcome.

BACKGROUND: In patients with persistent atrial fibrillation (AF), the procedural and clinical outcomes of ablation combined with infusion of antiarrhythmic drug are unknown. OBJECTIVES: To determine the impact of low-dose ibutilide after circumferential pulmonary vein isolation (CPVI) and/or left atrial (LA) substrate modification on acute procedural and clinical outcome of persistent AF. METHODS: In a prospective cohort of 135 consecutive patients with persistent AF, intravenous 0.25 mg ibutilide was administered 3 days before the procedure and intraprocedurally, if required, after CPVI and/or additional LA substrate modification of sites with continuous, rapid or fractionated, and low-voltage (0.05-0.3 mv) atrial activity. RESULTS: Persistent AF was terminated by CPVI alone (n=15) or CPVI + ibutilide (n=32) in 47 (34.8%) patients (CPVI responders). Additional LA substrate modification without (n=33) or with subsequent administration of 0.25 mg ibutilide (n=19) terminated AF in another 52 (38.5%) patients (substrate modification responders). Sinus rhythm was restored by electrical cardioversion in the remaining 36 (26.7%) patients (nonresponders). The mean LA substrate ablation time was 14 ± 6 minutes. At follow-up of 24 ± 10 months, the rates of freedom from atrial tachyarrhythmias among the responders in CPVI and substrate modification groups were mutually comparable (66.0% and 69.2%) and higher than among the nonresponders (36.1%; P < 0.01). Among the responders, there was no difference in clinical outcome between patients whose persistent AF was terminated without or with low-dose ibutilide. CONCLUSION: Administration of low-dose ibutilide during ablation of persistent AF may allow select patients wherein substrate ablation is not or minimally required to optimize procedural and clinical outcomes.

The safety and efficacy of hybrid ablation for the treatment of atrial fibrillation: A meta-analysis.

INTRODUCTION: Hybrid ablation, an emerging therapy that combines surgical intervention and catheter ablation, has become a viable option for the treatment of persistent atrial fibrillation. In this analysis, we aimed to evaluate the safety and efficacy of hybrid ablation, as well as compare the outcomes of one-step and staged approaches. METHODS: We conducted a search in major online databases and selected the studies that met the inclusion criteria. The primary endpoint was defined as no episode of atrial fibrillation or atrial tachycardia lasting longer than 30 seconds without administration of antiarrhythmic drugs. RESULTS: Sixteen studies including 785 patients (paroxysmal atrial fibrillation, n = 83; persistent atrial fibrillation, n = 214; long-standing persistent atrial fibrillation, n = 488) were selected. Average history of atrial fibrillation was (5.0±1.6) years. The pooled proportion of patients who were arrhythmia-free at the primary endpoint was 73% (95% CI, 64%-81%, Cochran's Q, P<0.001; I2 = 81%). The pooled rate of severe short-term complications was 4% (95% CI, 2%-7%, Cochran's Q, P = 0.01; I2 = 51%). The success rate after one-step procedures (69%) was lower than that after staged procedures (78%). The staged approach could ultimately prove to be safer, although complication rates were relatively low for both approaches (2% and 5%, respectively). CONCLUSIONS: Hybrid ablation is an effective and generally safe procedure. The current data suggest that staged hybrid ablation could be the optimal approach, as it is associated with a higher success rate and a seemingly lower complication rate. Additional randomized controlled trials are necessary to confirm these results.

Effect of remote ischemic preconditioning on left atrial remodeling and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is known to induce left atrial remodeling and prothrombotic response. AIMS: This study aimed to evaluate the effect of remote ischemic preconditioning (RIPC) on left atrial remodeling and prothrombotic response induced by RFCA of AF. METHODS: Forty-four patients with drug-refractory paroxysmal AF undergoing RFCA were randomized into RIPC (four short episodes of forearm ischemia) and control groups before the procedure. Blood samples were collected before RIPC/sham RIPC, and 24 and 72 hours later after the procedure. The atrial remodeling marker matrix metalloproteinase-9 (MMP-9) and endothelial damage marker von Willebrand factor (vWF) were measured using enzyme-linked immunosorbent assay. Platelet activation was evaluated by flow cytometric measurements of the expression of platelet P-selectin (CD62P) and active glycoprotein IIb/IIIa receptor (PAC-1). The early recurrence of atrial fibrillation (ERAF) in the two groups was observed over the subsequent 3 months. RESULTS: RFCA resulted in a significant increase in MMP-9 and vWF in both the groups, which persisted for 72 hours. However, the expression of CD62P and PAC-1 showed less increase during RFCA in either group. The RIPC group showed a lower increase in MMP-9 and vWF compared with the control group. In contrast, no significant differences were found in the trend of expression of CD62P and PAC-1 during RFCA between the two groups. The AF recurrence in the 3 months after the ablation was significantly lower in the RIPC group than in the control group. CONCLUSIONS: RIPC before RFCA for paroxysmal AF significantly reduces the increase in markers of left atrial remodeling and endothelial damage associated with the procedure, and results in a lower ERAF.

Recurrence after successful catheter ablation for ventricular arrhythmia from the aortic root.

OBJECTIVE: The mechanism underlying recurrence after successful ablation of ventricular arrhythmias (VAs) was unclear. Spectrum analysis can help to identify near-field activation. The purpose of this study was to quantify the changes of near-field activation in response to ablation at the VAs origin in the aortic root (AR-VAs) and to assess its relationship with late ablation outcome. METHODS AND RESULTS: Patients who underwent acutely successful ablation for AR-VAs were analysed. Ventricular electrograms acquired before and after ablation at VAs origin were subjected to spectrum analysis. The area under the curve of the high frequency component (HFC, 50-200 Hz) and the low frequency component (LFC, 0-50 Hz) was measured. The proportion of HFC to the frequency spectrum of 0-200 Hz was defined as the HFC ratio (HFCR). The reduction of HFC and HFCR in response to ablation was defined as HFC pre-post and HFCR pre-post, respectively. Documentation of VAs with the same morphology after an acute successful procedure was defined as recurrence. Fifty-six patients were analysed, and VAs recurred in 17 patients. HFCR pre-post, HFC pre-post, and HFC pre-ablation were significantly higher in patients without recurrence. And HFCR pre-post has the highest predictive value (area under the receiver-operating characteristic curve: 0.975). A HFCR pre-post of 1.0% differentiated two groups (sensitivity = 84.6%, specificity = 100%). Higher HFCR pre-post was correlated with shorter VAs termination time (correlation coefficient = -0.399, p = .009). CONCLUSIONS: HFCR pre-post can quantify the near-field activation change during ablation. Incomplete destruction to the VAs foci could underlie recurrence after successful ablation.