Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers.Methods and Results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Quantifying spatiotemporal dynamics in the Kolonnawa marsh of Colombo, Sri Lanka.

Kolonnawa marsh (KM) is an important wetland ecosystem in Colombo district, Sri Lanka that provides essential ecosystem services, and has undergone significant changes over recent decades due to continuous exploitation and reclamation. The values of wetlands are disregarded by decision-makers, despite the fact that they are crucial for improving the quality of water and offer chances for relaxation and amusement in metropolitan areas. Underestimation of the value of wetlands contributes to their continuing deterioration and inevitable loss. Investigating the changes in wetlands can provide crucial information for decision-making. This study aimed to monitor the spatiotemporal land-cover dynamics of KM with the prospect prediction as reduced total extent of KM gradually with time and marsh area being transformed into terrestrial vegetation with time. The collective images from Google Earth (2000 to 2021) and drone data (2022) were analyzed with the GIS application. Subsequently, 50-m2 grid squares with unique cell IDs are designed to link among land cover maps for spatiotemporal land-cover change analysis. Then, we calculate land cover category: surface water, marsh, and terrestrial vegetation proportions for each map in 50-m2 grid cells. Statistical comparison of the land cover changes in grid square cells shows that each land cover category has significant change with the time. The results showed that the reduction of KM marsh resulting in land cover changes has a positive implication on wetland degradation. Thus, interventions should be made for the restoration and sustainable management of KM.

Ripple map delineation of the reentrant circuit in a tricuspid annular atrial tachycardia mimicking focal activity.

A 70-year-old man with hypertensive heart disease underwent catheter ablation of persistent atrial fibrillation. After completing the pulmonary vein isolation, atrial burst pacing induced an annular atrial tachycardia (AT). Overdrive pacing exhibited constant fusion, indicating a macroreentrant mechanism of the AT. However, the CARTO3 activation map created using the Octaray catheter (both Biosense Webster, Irvine, CA) exhibited a centrifugal spread with the earliest activation site at the 4 o'clock position of the tricuspid annulus. In contrast, the Ripple map revealed a clear reentrant circuit with its isthmus located at the 4-6 o'clock position of the tricuspid annulus. The local electrograms in these areas recorded systolic and diastolic potentials simultaneously, and the misannotation of the large far-field potentials caused this discrepant result. Handling low-amplitude complex fractionated electrograms remains a challenge in creating a precise activation mapping. The Ripple map, especially when combined with the Octaray catheter, was effective in dynamically visualizing all these electrograms and accurately delineating the reentrant circuit.

Nonsynaptic Transmission Mediates Light Context-Dependent Odor Responses in Drosophila melanogaster.

Recent connectome analyses of the entire synaptic circuit in the nervous system have provided tremendous insights into how neural processing occurs through the synaptic relay of neural information. Conversely, the extent to which ephaptic transmission which does not depend on the synapses contributes to the relay of neural information, especially beyond a distance between adjacent neurons and to neural processing remains unclear. We show that ephaptic transmission mediated by extracellular potential changes in female Drosophila melanogaster can reach >200 µm, equivalent to the depth of its brain. Furthermore, ephaptic transmission driven by retinal photoreceptor cells mediates light-evoked firing rate increases in olfactory sensory neurons. These results indicate that ephaptic transmission contributes to sensory responses that can change momentarily in a context-dependent manner.SIGNIFICANCE STATEMENT Although extracellular field potential activities are commonly observed in many nervous systems, this activity has been generally considered as a side effect of synchronized spiking of neurons. This study, however, shows that field potential changes in retinae evoked by a sensory stimulus can control the excitability of distant neurons in vivo and mediates multimodal sensory integration in Drosophila melanogaster As such ephaptic transmission is more effective at a short distance, the ephaptic transmission from the retinae may contribute significantly to firing rate changes in downstream neurons of the photoreceptor cells in the optic lobe.

Catheter Ablation for Paroxysmal Atrial Fibrillation With Sick Sinus Syndrome: Insights From the Kansai Plus Atrial Fibrillation Registry.

BACKGROUND: Coexisting sick sinus syndrome (SSS) is associated with both electrical and structural atrial remodelling in patients with atrial fibrillation (AF). Limited data are available concerning catheter ablation (CA) for AF in this condition. This study investigated the efficacy of CA as a curative therapy for AF and SSS in a large-scale prospective multicentre registry. METHODS: The Kansai Plus Atrial Fibrillation (KPAF) registry enrolled 5,010 consecutive patients who underwent CA for AF; this included 3,133 patients with paroxysmal AF (mean age, 66 years; male, 69.3%; mean CHA2DS2-VASc score, 2.05±1.50; SSS, n=315 [tachy-brady syndrome, n=285]). The endpoints included the recurrence of AF with a blanking period of 90 days after CA, and de novo pacemaker implantation during the follow-up period (median duration, 2.93 years). RESULTS: The AF-free survival did not significantly differ between patients with and those without SSS (n=2,818) after the initial (log-rank p=0.864) and final sessions (log-rank p=0.268). Pacemakers were implanted in 48 patients with SSS, and implantation in this group was significantly associated with AF recurrence, including early recurrence (adjusted odds ratio, 3.57; 95% confidence interval, 1.67-7.64; p=0.002). The remaining 85.3% of patients with SSS did not require pacemaker implantation at 3 years after CA. CONCLUSIONS: Coexisting SSS did not adversely affect recurrence-free survival after CA for paroxysmal AF. Pacemaker implantation was not required in most patients with SSS, with AF recurrence serving as a strong predictor for this.

Factors influencing the difference in dissolved ion inputs to the forest floor between deciduous and coniferous stands: comparison under high and low atmospheric deposition conditions.

It is necessary to clear the relationship between physical and vegetation factors on the processes governing dissolved ion inputs to the forest floor to estimate correctly the values of atmospheric input to the forest. This study identified the factors influencing the differences in dissolved ion inputs to the forest floor between coniferous evergreen and broad-leaved deciduous species by analyzing the phenological variations of dry deposition and canopy exchange calculated by the canopy budget model under a high-deposition site near the city of Tokyo and a low-deposition site 84 km further away. At low-deposition site, vegetation factors such as capture efficiency did not explain the differences in Na+ or Cl- dry deposition. Leaf physiological characteristics influenced the differences in the Mg2+ and Ca2+ canopy leaching values, and phenology, leaf wettability, and diffusion processes from water film into leaves influenced the differences in NH4+ and NO3- input processes between tree types. At the high-deposition site, differences in the dry deposition of Na+, SO42-, Cl-, Mg2+, Ca2+, NH4+, and NO3- between tree types were influenced by differences in capture efficiency between coniferous and broad-leaved canopies in the leafed period and by the absence of leaves in deciduous species after leaf fall. These results indicated that atmospheric deposition affected the capture efficiency of coniferous trees for dry deposition and enhanced the difference of dissolved ion inputs to the forest floor between coniferous and deciduous species.

A Sexually Dimorphic Olfactory Neuron Mediates Fixed Action Transition during Courtship Ritual in Drosophila melanogaster.

Animals perform a series of actions in a fixed order during ritualistic innate behaviors. Although command neurons and sensory pathways responding to external stimuli that trigger these behaviors have been identified, how each action is induced in a fixed order in response to multimodal sensory stimuli remains unclear. Here, the sexually dimorphic lateral antennal lobe tract projection neuron 4 (lPN4) in male Drosophila melanogaster mediates the expression of a fixed behavioral action pattern at the beginning of the courtship ritual, in which a male taps a female body and then extends a wing unilaterally to produce a courtship song. We found that blocking the synaptic output of lPN4 caused an increase in the ratio of male flies that extended a wing unilaterally without tapping the female body, whereas excitation of lPN4 suppressed the transition from the tapping phase to the unilateral wing extension phase. Real-time calcium imaging showed that lPN4 is activated by a volatile pheromone, palmitoleic acid, whose responses were inhibited by simultaneous gustatory stimulation with female cuticular hydrocarbons, showing the existence of an "AND-gate" for multimodal sensory inputs during male courtship behaviors. These results suggest that the function of lPN4 is to suppress unilateral wing extension while responding to a female smell, which is released by appropriate contact chemosensory inputs received when tapping a female. As the female smell also promotes male courtship behaviors, the olfactory system is ready to simultaneously promote and suppress the progress of courtship actions while responding to a female smell.SIGNIFICANCE STATEMENT Although it has been 80 years since Konrad Lorenz and Niko Tinbergen introduced how multiple acts comprising separate innate behaviors are released in a fixed order according to external stimuli, the neural circuits responsible for such fixed action patterns remain largely unknown. The male courtship behavior of Drosophila melanogaster is a good model to investigate how such a fixed behavioral sequence is determined in the brain. Here, we show that lateral antennal lobe tract projection neuron 4 (lPN4) in D. melanogaster functions as an "AND-gate" for volatile and contact chemosensory inputs, mediating the expression of tapping behaviors before unilateral wing extension during male courtship rituals.

Sex Differences in the Efficacy of Pulmonary Vein Isolation Alone vs. Extensive Catheter Ablation in Patients With Persistent Atrial Fibrillation.

BACKGROUND: Women experience more severe arrhythmogenic substrates. This study hypothesized that an extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might be effective for women, whereas the PVI alone strategy (PVI-alone) might be sufficient for men to maintain sinus rhythm. The aim of this study was to test this hypothesis.Methods and Results: This study is a post-hoc subanalysis of the EARNEST-PVI trial focusing on sex differences in the efficacies of different ablation strategies. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial in patients with persistent AF. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia. The EARNEST-PVI trial randomized 376 (76%) men (PVI-alone 186, PVI-plus 190) and 121 (24%) women (PVI-alone 63, PVI-plus 58). The event rate was significantly lower for men and numerically lower for women in the PVI-plus than the PVI-alone group, and there was no interaction between men and women (hazard ratio, 0.641; 95% confidence interval, 0.417-0.985; P value, 0.043 for men vs. hazard ratio, 0.661; 95% confidence interval, 0.352-1.240; P value, 0.197 for women; P value for interaction, 0.989). CONCLUSIONS: The superiority of the extensive ablation strategy vs. the PVI-alone strategy for persistent AF was consistent across both sexes.

Post-ablation left atrial function impacts long-term recurrence of atrial fibrillation after ablation.

Left atrial (LA) function can help predict various cardiovascular events. Catheter ablation for atrial fibrillation (AF) modifies baseline LA function through the maintenance of sinus rhythm and myocardial injury. We investigated the impact of post-ablation LA function on recurrence of AF after ablation and identified the predictors of reduced post-ablation LA function. A total of 616 patients who underwent AF ablation (paroxysmal, N = 310; non-paroxysmal, N = 306) were retrospectively examined with cardiac computed tomography at baseline and 3 months after the final ablation procedure. Post-ablation LA emptying fraction (LAEFpost) was calculated. We evaluated the association between LAEFpost and recurrence of AF after the final ablation procedure. Further, we assessed the predictors of reduced LAEFpost. The recurrence rate of AF was 72.7% after the final ablation procedure [median follow-up 48 months (48.0, 48.0), total number of ablation sessions: 1.4 ± 0.7]. Multivariate analysis revealed that LAEFpost was associated with the recurrence of AF (hazard ratio/10% increase: 0.62, 95% confidence interval: 0.51-0.75, P < 0.0001). LAEFpost had a mild predictive power for recurrence of AF (c-statistics: 0.670, optimal cutoff: 26.36%, P < 0.0001). The recurrence-free proportion among patients with reduced LAEFpost (< 26.36%, N = 100) and those with preserved LAEFpost (≥ 26.36%, N = 516) was 40% and 79%, respectively (P < 0.0001). The predictors of reduced LAEFpost were low pre-ablation LAEF, high pre-ablation LA volume, low body mass index (BMI), and female sex. Further, reduced LAEFpost was associated with the total number of ablation sessions and extra-pulmonary vein LA ablation. In conclusion, reduced LAEFpost was associated with recurrence of AF after ablation. Advanced LA remodeling, low BMI, and female sex could predict reduced LAEFpost. Although additional ablation was associated with reduced LAEFpost, it remains unclear whether reduced LAEFpost resulted from the additional ablation. Reduced LAEFpost might help stratify patients with ablation-refractory AF.

Decrease in red cell distribution width as a useful predictor of success after catheter ablation for atrial fibrillation: a retrospective multi-center study.

Red cell distribution width (RDW) is reportedly associated with cardiovascular events, including atrial fibrillation (AF). We investigated whether the RDW values were associated with the outcomes of catheter ablation for AF. This retrospective multicenter study included 501 patients with AF (239 paroxysmal AF cases, 196 persistent AF cases, and 66 long-standing persistent AF cases) who underwent initial AF ablation between March 2017 and May 2018. The RDW values were evaluated before and at 1-3 months after the procedure. The patients were stratified based on the recurrence of AF within 1 year after the index procedure with a blanking period of 3 months into recurrence group (107 patients, 21.4%) and no-recurrence group (394 patients, 78.6%). There were no significant differences in preoperative RDW values between the groups (p = 0.37). The RDW value did not change significantly after the ablation in the recurrence group (13.55-13.60%, p = 0.37), although it decreased significantly in the no-recurrence group (13.64-13.37%, p < 0.001). Multivariate Cox proportional hazards regression analyses revealed that a postoperative change in RDW (ΔRDW) was independently associated with AF recurrence (hazard ratio 2.00, 95% confidence interval 1.42-2.76, p < 0.001). Receiver operating characteristic curve analysis revealed that a ΔRDW cut-off value of - 0.1% provided a c-statistic of 0.65 for predicting AF recurrence. Decrease in RDW during the blanking period after ablation independently predicted the 1-year success of AF ablation.

Echocardiographic features of acute-phase microscopic polyangiitis in Japanese patients: A single-centre retrospective study.

OBJECTIVES: Microscopic polyangiitis (MPA) affects various organs. However, echocardiographic findings of MPA are unclear. We aimed to evaluate the echocardiographic features of acute-phase MPA in Japanese patients. METHODS: This single-centre retrospective study included 15 patients with MPA who underwent echocardiography within 2 weeks of commencing steroid therapy for induction or reinduction. The echocardiography parameters of thetients were compared with those of 30 age- and sex-matched controls. RESULTS: No significant differences in left ventricular (LV) diameter, LV ejection fraction, or e' were observed between the two groups. However, the MPA group showed a significantly higher left atrial (LA) diameter and LA volume index, as well as higher early diastolic filling velocity, diastolic pulmonary venous flow velocity, and trans-tricuspid pressure gradient, and a shorter deceleration time (DCT). Serum C-reactive protein levels were positively correlated with E wave, E/A, and DCT. These results may indicate that increased LV stiffness, rather than impairment of LV relaxation, contributed to LV diastolic function, resulting in LA enlargement. CONCLUSIONS: Patients with acute-phase MPA had LA dilatation associated with LV diastolic dysfunction. This finding indicates the importance of cardiac assessment in patients with MPA, especially in patients with a strong inflammatory reaction.

The color pattern inducing gene wingless is expressed in specific cell types of campaniform sensilla of a polka-dotted fruit fly, Drosophila guttifera.

A polka-dotted fruit fly, Drosophila guttifera, has a unique pigmentation pattern on its wings and is used as a model for evo-devo studies exploring the mechanism of evolutionary gain of novel traits. In this species, a morphogen-encoding gene, wingless, is expressed in species-specific positions and induces a unique pigmentation pattern. To produce some of the pigmentation spots on wing veins, wingless is thought to be expressed in developing campaniform sensillum cells, but it was unknown which of the four cell types there express(es) wingless. Here we show that two of the cell types, dome cells and socket cells, express wingless, as indicated by in situ hybridization together with immunohistochemistry. This is a unique case in which non-neuronal SOP (sensory organ precursor) progeny cells produce Wingless as an inducer of pigmentation pattern formation. Our finding opens a path to clarifying the mechanism of evolutionary gain of a unique wingless expression pattern by analyzing gene regulation in dome cells and socket cells.

Pulmonary vein isolation alone vs. more extensive ablation with defragmentation and linear ablation of persistent atrial fibrillation: the EARNEST-PVI trial.

AIMS: Previous studies could not demonstrate any benefit of more intensive ablation in addition to pulmonary vein isolation (PVI) including complex fractionated atrial electrogram (CFAE) and linear ablation for recurrence in the initial catheter ablation of persistent atrial fibrillation (AF). This study aimed to establish the non-inferiority of PVI alone to PVI plus these additional ablation strategies. METHODS AND RESULTS: Patients with persistent AF who underwent an initial catheter ablation (n = 512, long-standing persistent AF; 128 cases) were randomly assigned in a 1:1 ratio to either PVI alone (PVI-alone group) or PVI plus CFAE and/or linear ablation (PVI-plus group). After excluding 15 cases who did not receive procedures, we analysed 249 and 248 patients, respectively. The primary endpoint was recurrence of AF, atrial flutter, and/or atrial tachycardia, and the non-inferior margin was set at a hazard ratio of 1.43. In the PVI-plus group, 85.1% of patients had linear ablation and 15.3% CFAE ablation. After 12 months, freedom from the primary endpoint occurred in 71.3% of patients in the PVI-alone group and in 78.3% in the PVI-plus group [hazard ratio = 1.56 (95% confidence interval: 1.10-2.24), non-inferior P = 0.3062]. The procedure-related complication rates were 2.0% in the PVI-alone group and 3.6% in the PVI-plus group (P = 0.199). CONCLUSION: This randomized trial did not establish the non-inferiority of PVI alone to PVI plus linear ablation or CFAE ablation in patients with persistent AF, but implied that the PVI plus strategy was promising to improve the clinical efficacy (NCT03514693).

Home Sleep Apnea Test to Screen Patients With Atrial Fibrillation for Sleep Apnea Prior to Catheter Ablation.

BACKGROUND: Whether all atrial fibrillation (AF) patients should be evaluated for sleep apnea before catheter ablation (CA) remains controversial. Watch-type peripheral arterial tonometry (W-PAT) is a home sleep testing device and an easier tool for diagnosing sleep apnea than polysomnography. We investigated the prevalence and predictors of sleep apnea using W-PAT in unscreened sleep apnea patients with AF before CA.Methods and Results:The study was conducted under a retrospective, single-center, observational design. We included 776 consecutive patients who underwent both W-PAT and AF ablation. Sleep apnea assessments were successfully performed in 774 patients (99.7%; age 65±11 years, 73.3% male; body mass index [BMI] 24.1±3.5, 56.8% paroxysmal AF). The mean apnea-hypopnea index (AHI) was 20.1±15.6. Although 81.7% of the patients had normal Epworth sleepiness scores (mean 6.5), only 88 (11.4%) had a normal AHI (AHI <5) and 412 (53.2%) had moderate-severe sleep apnea (AHI ≥15). Obesity, male sex, nonparoxysmal AF, hypertension, and a left atrial diameter (LAd) ≥40 mm were predictors of moderate-severe sleep apnea. However, the prevalence of moderate-severe sleep apnea in patients without those predictors (i.e., non-obesity (44.2%), female sex (43.0%), paroxysmal AF (43.9%), no hypertension (45.5%)), and LAd <40 mm (41.0%) was considerably high. CONCLUSIONS: Almost all patients successfully underwent W-PAT to diagnose sleep apnea. Patients undergoing AF ablation had a high prevalence of sleep apnea, and screening for sleep apnea was important in those patients even if they did not have sleepiness or risk factors.

Efficacy of Extensive Ablation for Persistent Atrial Fibrillation With Trigger-Based vs. Substrate-Based Mechanisms　- A Prespecified Subanalysis of the EARNEST-PVI Trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) would be effective for modification of non-pulmonary vein (non-PV) substrates, whereas PVI might be sufficient for elimination of PV triggers. This study aimed to test the hypothesis that in patients with reproducible atrial fibrillation (AF) triggered by premature atrial contractions originating only from PVs, PVI alone can be sufficient to maintain sinus rhythm.Methods and Results:This study is a prespecified subanalysis of the EARNEST-PVI randomized controlled trial. This study investigated the efficacy of the PVI-alone strategy (PVI-alone) in comparison with the extensive strategy (PVI-plus) for persistent AF with a trigger-based mechanism vs. a substrate-based mechanism. Patients were stratified into 3 groups based on AF mechanisms: (1) Substrate group (N=236); (2) PV trigger group (N=236); and (3) non-PV trigger group (N=24). The hazard ratios for AF recurrence of the PVI-alone strategy with reference to the PVI-plus strategy were 1.456 (95% confidence interval [CI] [0.864-2.452]) in the substrate group, 1.648 (95% CI 0.969-2.801) in the PV trigger group, and 0.937 (95% CI 0.252-3.488) in the non-PV trigger group. No significant interaction between ablation strategy and AF mechanism was observed (P for interaction=0.748). CONCLUSIONS: This study indicated that the efficacies of the PVI-alone strategy compared with the PVI-plus strategy were consistent across persistent AF with trigger-based and substrate-based mechanisms.

Sex differences in atrial fibrillation ablation outcomes: insights from a large-scale multicentre registry.

AIM: The impact of sex differences on the clinical outcomes of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is controversial. We investigated the sex differences regarding the efficacy and clinical outcomes of RFCA of AF. METHODS AND RESULTS: We conducted a large-scale, prospective, multicentre, observational study (Kansai Plus Atrial Fibrillation Registry). We enrolled 5010 consecutive patients who underwent an initial RFCA of AF at 26 centres (64 ± 10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. Female patients (n = 1369, 27.3%) were older (female vs. male, 68 ± 9 vs. 63 ± 11 years, P < 0.0001) with a lower prevalence of non-paroxysmal AF (27.1% vs. 38.9%, P < 0.0001). Fewer females experienced time-dependent pulmonary vein (PV) reconnections and more females received a non-PV foci ablation than males in the index RFCA. The 3-year cumulative incidence of AF recurrences in the multivariate analysis after single procedures was significantly higher in females than males (43.3% vs. 39.0%, log rank P = 0.0046). Females remained an independent predictor of AF recurrence (hazard ratio 1.24; 95% confidence interval 1.12-1.38, P < 0.0001). The AF recurrence rates after multiple procedures were also higher in females, but fewer females experienced PV reconnections during second sessions. More females experienced de novo pacemaker implantations during the long-term follow-up. Females were associated with a higher risk of heart failure hospitalizations and major bleeding after RFCA in the multivariate analysis. CONCLUSIONS: Females experienced more frequent AF recurrences probably due to non-PV arrhythmogenicity and de novo pacemaker implantations than males during the long-term follow-up after RFCA of AF.

Burden and Long Firing of Premature Atrial Contraction Early After Catheter Ablation Predict Late Recurrence of Atrial Fibrillation.

BACKGROUND: Associations between characteristics of premature atrial contraction (PAC) 6 months after catheter ablation (CA) and later recurrence are not known. We investigated the effects of PAC characteristics on long-term outcomes of initially successful atrial fibrillation (AF) ablation.Methods and Results:In all, 378 patients (mean age 61 years, 21% female, 67% paroxysmal AF) who underwent initial radiofrequency CA for AF without recurrence up to 24-h Holter monitoring 6 months after the procedure were reviewed retrospectively. The calculated number of PAC/24 h and the length of the longest PAC run during Holter recording were analyzed. After 4.3±1.2 years (mean±SD) follow-up, 123 (32.5%) patients experienced late recurrence. Patients with recurrence had significantly more PAC/24 h (median [interquartile range] 110 [33-228] vs. 42 [16-210]; P<0.01) and a longer longest PAC run (5 [2-8] vs. 3 [1-5]; P<0.01) than those without. Receiver operating characteristic curve analysis indicated 58 PAC/24 h and a longest PAC run of 5 were optimal cut-off values for predicting recurrence. After adjusting for previously reported predictors of late recurrence, frequent PAC (≥58/24 h) and longest PAC run ≥5 were found to be independent predictors of late recurrence (hazard ratios [95% confidence intervals] 1.93 [1.24-3.02; P<0.01] and 1.81 [1.20-2.76; P<0.01], respectively). CONCLUSIONS: Six months after successful AF ablation, both frequent PAC and long PAC run are independent predictors of late recurrence.

Comparison of the Safety and Efficacy of Automated Annotation-Guided Radiofrequency Ablation and 2nd-Generation Cryoballoon Ablation in Paroxysmal Atrial Fibrillation.

BACKGROUND: Automated ablation lesion annotation with optimal settings for parameters including contact force (CF) and catheter stability may be effective for achieving durable pulmonary vein isolation. Methods and Results: We retrospectively examined 131 consecutive patients who underwent initial catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) by automatic annotation system (VISITAG module)-guided radiofrequency CA (RFCA) (n=61) and 2nd-generation cryoballoon ablation (CBA) (n=70) in terms of safety and long-term efficacy. The automatic annotation criteria for the RFCA group were as follows: catheter stability range of motion ≤1.5 mm, duration ≥5 s, and CF ≥5 g. We ablated for >20 s with a force-time integral >150 gs at each site, before moving to the next site. Each interlesion distance was <6 mm. Procedural complications were more frequent in the CBA group (1.6% vs. 10.0%, P=0.034). Across a median follow-up of 2.98 years, 88.5% and 70.0% of patients in the RFCA and CBA groups, respectively, were free from recurrence (log-rank test, P=0.0039). There was also a significant difference in favor of RFCA with respect to repeat ablations (3.3% vs. 24.3%, log-rank test, P=0.0003). CONCLUSIONS: RF ablation guided by an automated algorithm that includes CF and catheter stability parameters showed better long-term outcomes than CBA in the treatment of patients with PAF without increasing complications.

Clinical experience of idarucizumab use in cases of cardiac tamponade under uninterrupted anticoagulation of dabigatran during catheter ablation of atrial fibrillation.

Anticoagulants are prescribed for prevention of thromboembolic events (TE) of atrial fibrillation (AF), however, their effects have a negative impact on disastrous bleeding outcomes. Idarucizumab was developed to reverse the anticoagulation effects of dabigatran. This study aimed to retrospectively investigate the clinical efficacy and safety of idarucizumab in the setting of progressive emergent bleeding events associated with catheter ablation (CA). Dabigatran is given uninterruptedly as an anticoagulant in patients undergoing CA of AF. The capacity of idarucizumab to reverse the anticoagulant effects of dabigatran in patients with cardiac tamponade associated with CA was examined by measuring the activated partial thromboplastin time (aPTT), active clotting time (ACT), and prothrombin international normalizing ratio (PT-INR). The primary endpoint was effective hemostasis. This analysis included 21 patients receiving idarucizumab, given for restoration of hemostasis. In all 21 patients, hemostasis was restored at a median of 205.6 ± 14.8 min. Normal intraoperative cessation of bleeding was reported in 16 patients, and completion of hemostasis was also ascertained in the remaining four within 5 h. No TEs occurred within 72 h after the idarucizumab administration. Despite a significant reduction in the aPTT and ACT, no significant change was observed in PT-INR after administering idarucizumab. In emergency situations, idarucizumab was able to reverse dabigatran within a relatively short period without any serious adverse events.