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A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group.Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 P P P

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA2DS2-VASc scores differed significantly between DOAC dosing regimens, with patients given an appropriate standard-dose being significantly younger (63.3 ± 9.4 versus 64.8 ± 9.5 versus 73.2 ± 6.8 years, P < 0.0001) and lower (2.1 ± 1.5 versus 2.4 ± 1.6 versus 3.4 ± 1.4, P < 0.0001) than those given an off-label under-dose or an appropriate low-dose. During the median 19.0-month follow-up period, the AF recurrence rate was similar between the appropriate standard-dose and off-label under-dose groups but relatively low in the appropriate low-dose group (42.5% versus 41.2% versus 35.4%, P = 0.08). Annualized rates of thromboembolic events, major bleeding, and death from any cause were 0.47%, 0.70%, and 0.23% in the off-label under-dose group, while those rates were 0.74%, 0.73%, and 0.65% in the appropriate standard-dose, and 1.58%, 2.12%, and 1.57% in the appropriate low-dose groups.In conclusion, the clinical adverse event rates for patients on an off-label under-dose DOAC regimen after ablation, predicated on careful patient evaluations, was not high as seen with that of patients on a standard DOAC dosing regimen.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71–1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49–0.94) and had a CHA2DS2-VASc score

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance > 60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.

Background Relations between characteristics and outcomes of patients in Japan with atrial fibrillation (AF) and the type of medical facility providing their outpatient care are unclear. Methods and results We compared patient characteristics and outcomes between 2 university hospitals (n = 1178), 20 general hospitals (n = 1308), and 41 private clinics (n = 751) (follow-up: 39.3 months) in the prospective SAKURA AF Registry. Private clinic patients were significantly older than university hospital and general hospital patients (73.4 ± 9.2 vs. 70.3 ± 9.8 and 72.6 ± 8.9 years; p Conclusions Adverse clinical events at small to large hospitals appear to be higher than those at private clinics, suggesting that careful attention for preventing stroke/SE and cardiovascular events should be paid to patients at a university or general hospital.

IntroductionData are lacking on the extent to which patients with non-valvular atrial fibrillation (AF) who are aged ≥80 years benefit from ablation treatment. The question pertains especially to patients’ postablation quality of life (QoL) and long-term clinical outcomes.Methods and analysisWe are initiating a prospective, registry-based, multicentre observational study that will include patients aged ≥80 years with non-valvular AF who choose to undergo treatment by catheter ablation and, for comparison, such patients who do not choose to undergo ablation (either according to their physician’s advice or their own preference). Study subjects are to be enrolled from 52 participant hospitals and three clinics located throughout Japan from 1 June 2022 to 31 December 2023, and each will be followed up for 1 year. The planned sample size is 660, comprising 220 ablation group patients and 440 non-ablation group patients. The primary endpoint will be the composite incidence of stroke/transient ischaemic attack (TIA) or systemic embolism (SE), another cardiovascular event, major bleeding and/or death from any cause. Other clinical events such as postablation AF recurrence, a fall or bone fracture will be recorded. We will collect standard clinical background information plus each patient’s Clinical Frailty Scale score, AF-related symptoms, QoL (Five-Level Version of EQ-5D) scores, Mini-Mental State Examination (optional) score and laboratory test results, including measures of nutritional status, on entry into the study and 1 year later, and serial changes in symptoms and QoL will also be secondary endpoints. Propensity score matching will be performed to account for covariates that could affect study results.Ethics and disseminationThe study conforms to the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies issued by the Ministry of Health, Labour and Welfare, Japan. Results of the study will be published in one or more peer-reviewed journals.Trial registration numberUMIN000047023.

BACKGROUND It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Introduction: The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. Methods and Results: We investigated 2737 consecutive patients (25.6% female, mean age 63.4 ± 10.3 years) who underwent a first catheter ablation for AF from the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 25.2 months, 2070 (75.6%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 122 (4.5%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.7 per 100 person-years) compared with the AF recurrence group (3.2 per 100 person-years; P = 0.001). The multivariate analysis revealed that freedom from AF (hazard ratio 0.57; 95% confidence interval 0.39–0.83; P = 0.003) was independently associated with the incidence of the composite event.¬¬ Conclusion: In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Direct oral anticoagulants (DOACs) are sometimes prescribed at off-label under-doses for patients who have undergone ablation for atrial fibrillation (AF). This practice may be an attempt to balance the risk of bleeding against that of stroke or AF recurrence.We examined outcomes of 1163 patients who continued use of a DOAC after ablation. The patients were enrolled in a large (3530 patients) multicenter registry in Japan. The study patients were classified as 749 (64.4%) appropriate standard-dose DOAC users, 216 (18.6%) off-label under-dose DOAC users, and 198 (17.0%) appropriate low-dose DOAC users.Age and CHA

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.

Entrainment is a useful method for locating reentrant atrial tachycardia (AT) circuits, but alterations or termination of the AT can derail this process. We assessed whether resetting an upstream site of a neighboring electrode by a scanned extrastimulus at a downstream site (when the upstream tissue was refractory) could diagnose that site within the AT circuit. The procedure was applied to 48 ATs with a cycle length (CL) of 238 ± 42 ms (26 common flutters, 8 perimitral flutters, 7 left atrial [LA] roof-dependent AT, 3 LA scar-related macroreentrant ATs, 2 pulmonary vein-gap reentry tachycardias, 1 right atrial scar-related macroreentrant AT, and 1 with an unidentified circuit). Entrainment and scanned extrastimulation were attempted at the cavotricuspid isthmus, LA roof, and mitral isthmus and/or critical AT isthmus. Within the circuit, the post-pacing interval minus the ATCL after entrainment was < 30 ms for all ATs and resetting of the AT cycle by ≥ 5 ms occurred in 94% of the ATs. No ATs were reset by extrastimulation outside the circuit. The positive predictive value of both maneuvers for locating the circuit was 100%, and the negative predictive value of the extrastimulation was similar to that of entrainment (96% vs. 100%, P = 0.25). The incidence of an AT alteration was lower with extrastimulation than with entrainment (1% vs. 9%, P = 0.01). For ATs with a CL < 210 ms, extrastimulation yielded a good diagnostic performance without any AT alterations. AT resetting by a scanned extrastimulus is diagnostic and avoids AT alterations.

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index &lt, 1.75, n = 1022), second tertile (1.75 &le, FIB4 index &lt, 2.51, n = 1022), and third tertile (FIB4 index &ge, 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p &lt, 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p &lt, 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72, 95% CI 1.31&ndash, 2.25) and all-cause mortality (HR 1.43, 95% CI 1.06&ndash, 1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p &lt, 0.05), net reclassification improvement (all p &lt, 0.001), and integrated discrimination improvement (all p &lt, 0.001). A FIB4 index &ge, 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p &lt, 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.

Objective Despite use of provocation testing to unmask dormant left atrium (LA)-PV conduction after index pulmonary vein isolation (PVI) for atrial fibrillation (AF), AF recurrence still occurs, with PV reconnection as the main cause. In an effort to answer the question whether freedom from AF recurrence can be achieved by ablation that targets sites of dormant conduction, we compared sites of dormant conduction against sites of PV reconnection identified at the time of repeat ablation for AF recurrence. Materials and methods The study group comprised 46 patients (30 men/16 women, aged 58.7 ± 10.3 years) with AF (paroxysmal: n = 37, persistent: n = 9) who underwent repeat ablation for AF recurrence 12.3 (7.4–29.7) months after the index ablation procedure. Ipsilateral PVs were divided into 8 segments each (736 total segments), and the relation between dormant conduction sites and PV reconnection sites was determined per segment. Results Dormant LA-PV conduction was unmasked and ablated in 22 (47.8%) of the 46 patients at sites within 43 (5.8%) of the 736 PV segments. Late PV reconnection was found within 122 (17%) of the 736 PV segments at the time of re-ablation for AF recurrence. Only 22 (18%) of these 122 PV segments corresponded to dormant conduction sites identified during the index procedure. Conclusion Although additional ablation to eliminate dormant PV conduction unmasked during the index ablation procedure is performed, the majority of PVs that show reconduction at the time of treatment for clinical AF recurrence are PVs that have not shown dormant conduction.

Background Limited data exist on indicators of durable pulmonary vein isolation (PVI) undergoing cryoballoon ablation (CBA) for atrial fibrillation (AF). We investigated whether balloon temperature and time to PVI can be used to predict early PV reconduction (EPVR), including residual PV conduction and adenosine triphosphate‐induced dormant conduction and the relation between touch‐up ablation of EPVR sites and mid‐term recurrence of AF. Methods We obtained procedural and outcome data from the records of 130 consecutive patients who underwent CBA and followed up for 13.4 months. Results EPVR was identified in 86 (17%) PVs of 61 (47%) patients. Balloon temperatures during 30 seconds (−27 ± 5.7°C vs −31 ± 5.5°C), 60 seconds (−36 ± 5.6°C vs −41 ± 5.4°C), and at the nadir point (−41 ± 7.4°C vs −49 ± 7.0°C) were significantly higher, and the time to PVI was longer (90 ± 50 seconds vs 52 ± 29 seconds) in PVs with EPVR than in those without (P

Atrial electrical and structural remodeling is related to the perpetuation of atrial fibrillation (AF) subsequent to sinus node dysfunction. We investigated the relationship between AF recurrence after catheter ablation and sinus node dysfunction in long-standing persistent AF patients using the sinus node recovery time (SNRT) after defibrillation.Fifty-one consecutive patients who underwent a first ablation for long-standing persistent AF were enrolled. Intracardiac cardioversion was applied before ablation in the absence of any antiarrhythmic drugs, and the power required to defibrillate, number, and SNRT after defibrillation were measured. All patients underwent the same designed radiofrequency catheter ablation procedure.No patient required permanent pacemaker implantation due to sinus dysfunction after the ablation. During the follow-up period of 28.4 months (3.6-43.7), 35 out of 51 patients (69%) experienced an AF recurrence. The AF recurrence was significantly associated with an older age (60 ± 11 versus 52 ± 12 years in the non-recurrence group, P = 0.0196), longer SNRT after defibrillation (1722 [1410-2656] versus 1295 [676-1651] msec, P = 0.0125), and larger left atrial (LA) volume (59 ± 25 versus 41 ± 15 mL, P = 0.0119). There were no significant differences in the AF duration, AF cycle length, and right and total atrial conduction times between the 2 groups. A longer SNRT after defibrillation (adjusted HR 2.13, 95%CI 1.16-3.71, P = 0.0152) and larger LA volume (adjusted HR 1.03, 95%CI 1.01-1.04, P = 0.0054) were independent predictors of AF recurrence after ablation.Assessment of the SNRT after defibrillation may help to predict a successful ablation in patients with long-standing persistent AF.

Background: Ablation targeting complex fractionated atrial electrograms (CFAEs) or high dominant frequency (DF) sites is generally effective for persistent atrial fibrillation (AF). CFAEs and/or high DF sites may exist in low-voltage regions, which theoretically represent abnormal substrates. However, whether CFAEs or high DF sites reflect low voltage substrates during sinus rhythm (SR) is unknown. Methods: Sixteen patients with AF (8 with paroxysmal AF; 8, persistent AF) underwent high-density mapping of the left atrium (LA) with a 3-dimensional electroanatomic mapping system before ablation. The LA was divided into 7 segments and the mean bipolar voltage recorded during AF and SR, CFAEs (cycle lengths of 50–120 ms), and DF sites were assessed in each segment with either a duo-decapolar ring catheter (n=10) or a 64-pole basket catheter (n=6). Low-voltage areas were defined as those of 8 Hz) did not correlate with % low-voltage sites during SR; however, CFAEs sites were located in high-voltage regions during AF and high DF sites were located in low voltage regions during AF. Conclusions: CFAEs and high DF areas during AF do not reflect damaged atrial myocardium as shown by the SR voltage. However, CFAEs and high DF sites may demonstrate different electrophysiologic properties because of different voltage amplitude during AF.

Background The mechanisms underlying self-perpetuation of persistent atrial fibrillation (AF) are not well understood. To gain insight into these mechanisms, we conducted a study comparing left atrial (LA) electroanatomic maps obtained during sinus rhythm between patients with paroxysmal AF (PAF) and patients with persistent AF (PerAF). Methods The study included 23 men with PAF (age, 56.3±12.1 years) and 13 men with PerAF (age, 54.3±13.4 years). LA voltage mapping was performed during sinus rhythm. The clinical and electroanatomic characteristics of the two groups were evaluated and analyzed statistically. Results The bipolar voltages at the LA septum, roof, and posterior wall, right superior pulmonary vein (PV) and its antrum, right superior PV carina, and right inferior PV antrum were significantly lower in patients with PerAF than in those with PAF. The bipolar voltages in other parts of the LA did not differ statistically between the two groups. Conclusion PAF and PerAF seem to be characterized by differences in the regional voltage in the LA and PVs. The LA structural remodeling of PerAF may initiate from the right PVs and their antra and LA septum, roof, and posterior wall.

Background The safety of discontinuing oral anticoagulant (OAC) after ablation for atrial fibrillation (AF) in Japanese patients has not been clarified.Methods and Results:A study based on the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) was conducted. Data were collected from 3,451 consecutive patients (74.1% men; age, 63.3±10.3 years) who had undergone AF ablation at any of 24 cardiovascular centers in Japan between August 2011 and July 2017. During a 20.7-month follow-up period, OAC therapy was discontinued in 1,836 (53.2%) patients; 51 patients (1.5%) suffered a stroke/transient ischemic attack (TIA), 71 (2.1%) suffered major bleeding, and 36 (1.0%) died. Patients in whom OAC therapy was discontinued were significantly younger than those in whom OACs were continued, and their CHA2DS2-VASc scores were significantly lower. The incidences of stroke/TIA, major bleeding, and death were significantly lower among these patients. Upon multivariate adjustment, stroke events were independently associated with relatively high baseline CHA2DS2-VASc scores but not with OAC status. Conclusions Although the incidences of stroke/TIA, major bleeding, and death were relatively low among patients for whom OAC therapy was discontinued, stroke/TIA occurrence was strongly associated with a high baseline stroke risk rather than with OAC status. Thus, discontinuation of OAC therapy requires careful consideration, especially in patients with a high baseline stroke risk.

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD a...

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Objective: To explore factors related to changing renal function and the prognostic effect of worsening renal function in patients with atrial fibrillation (AF). Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter prospective observational registry that includes 3267 AF patients from 63 institutions in the Tokyo area. Worsening renal function was defined as an estimated glomerular filtration rate (eGFR) decrease equaling more than 20% of the patient’s baseline eGFR. Results: During a median 39.3 month follow-up period, patients’ eGFR decreased annually by a mean value of 1.07 mL/min/1.73 m2. Multivariable analysis showed that age ≥75 years, body weight ≤50 kg, a history of heart failure and initially preserved renal function (creatinine clearance [CrCl] ≥ 60 mL/min) were significantly associated with a decrease in eGFR, whereas a history of AF ablation was associated with a maintain in eGFR. The 194 patients with worsening renal function were at significantly increased risk of death, stroke and major bleeding (adjusted hazard ratios [HRs]: 2.06, 1.97 and 2.23, respectively). Conclusion: Age ≥75 years, body weight ≤50 kg, a history of heart failure and initially preserved renal function appear to promote renal dysfunction in patients with AF, but a history of AF ablation seems to have a favorable effect. Worsening renal function seems to increase AF patients’ risk of adverse clinical events. Renal function can decline quickly; thus, early intervention including AF ablation is warranted.

Direct-acting oral anticoagulants (DOACs) are widely used in aged Japanese patients with atrial fibrillation (AF), but outcome data for such patients are limited. We compared outcomes between 1895 (58.5%) patients aged

Background Although a ventriculoatrial interval (VAI) of ≤70 ms is used to distinguish atrioventricular nodal reentrant tachycardia from orthodromic atrioventricular reciprocating tachycardia (AVRT), a VAI of ≤70 ms is sometimes observed in cases of AVRT. The study aimed to evaluate the short VAI that is seen in AVRT and to understand its underlying mechanism. Methods Electrophysiologic studies of 46 consecutive patients with AVRT involving an accessory pathway (AP) were examined retrospectively. Results AP was right sided in seven patients and left sided in 39. A VAI (interval from QRS onset to the earliest intracardiac atrial electrogram recorded by any mapping catheter during AVRT) ≤70 ms during AVRT (short VAI) was observed in eight patients: six with a left lateral AP and two with a left posteroseptal AP. During AVRT involving a left-sided AP, the QRS-V interval (from the earliest QRS onset to the local ventricular electrogram at a site which showed earliest atrial electrogram recorded from the coronary sinus catheter) was significantly shorter (37 ± 7 ms vs 54 ± 13 ms, P = 0.001) and supernormal conduction (QRS duration or the QRS-V interval shortening by ≥10 ms during AVRT) was more frequently seen (63% vs 6%, P = 0.02) in the short VAI group than in the normal VAI group. Furthermore, these parameters were shown to be determinants for short VAI. Conclusions A short VAI is sometimes observed during AVRT involving a left-sided AP. The short VAI may be caused by rapid propagation or supernormal conduction between the proximal Purkinje-muscle junction and basal left ventricular myocardium.

The clinical utility of an automated lesion tagging module based on catheter stability information (VisiTag) with the CARTO system during atrial fibrillation (AF) ablation remains to be established. We investigated whether VisiTag-guided extensive encircling pulmonary vein isolation (EEPVI) produces durable lesions.The study involved 54 patients undergoing EEPVI for paroxysmal AF. We performed EEPVI guided by the module-generated ablation tags, i.e., "VisiTags," which are point-by-point ablation tags placed on 3D maps. The patients were divided into two groups: those treated under a moderate catheter stability VisiTag setting, i.e., a 3-mm distance limit for at least 5 s and a minimum contact force (CF) of 8 g over 25 % of the set time period with a target force-time integral (FTI) ≥300 g*s (n = 27), and those treated under a strict catheter stability setting, i.e., a 3-mm distance limit for at least 10 s and a minimum CF of 10 g over 50 % of the set time period with a target FTI ≥400 g*s (n = 27).After EEPVI, adenosine triphosphate-provoked dormant PV conduction was observed in six (22 %) patients in the moderate catheter stability group and in one (4 %) patient in the strict catheter stability group (p = 0.1003); the 12.9-month success rate was 81 % in both groups.The strict catheter stability setting for automated lesion tagging together with a target FTI of400 g*s, vs. the moderate catheter stability setting with a target FTI of300 g*s, produces less frequent ATP-provoked PV conduction and yields a comparably high mid-term success rate.

We sought to better understand the association between and clinical implications of ganglionated plexi (GPs), epicardial adipose tissue (EAT) in the left atrium (LA), and the initiation and maintenance of atrial fibrillation (AF). Three-dimensional (3D) computed tomography (CT) reconstruction images of the LA, PVs, and LA-EAT were merged with the LA geometry for 25 with paroxysmal AF (PAF) and 15 with persistent AF (PerAF) scheduled for ablation. High-frequency stimulation (20 Hz, 25 mA, 10 ms) was performed at three sites within each of the five major anatomical LA GPs (superior left, inferior left, anterior right, inferior right, and Marshall tract GPs) to elicit vagal responses. Correspondence between the five GP areas and vagal response sites, LA-EAT, and complex fractionated atrial electrograms (CFAEs) was examined. The long-term outcomes of adjuvant LA-EAT-based ablation were assessed in 31 patients with PAF and 102 with PerAF. LA-EAT overlapped 93 ± 14 % of five major anatomical GP areas, and the vagal response sites and CFAE sites corresponded to 77 ± 23 and 76 ± 25 %, respectively (p

Background Cryoballoon catheter ablation was developed to simplify ablation for atrial fibrillation (AF). Initial enthusiasm for its widespread use has been dampened by phrenic nerve (PN) injury (PNI). Objective The purpose of this study was to assess the effect of cryoballoon inflation at the right superior pulmonary vein (RSPV) orifice on PN location and to elucidate the potential mechanism of PNI. Methods Twenty patients with paroxysmal atrial fibrillation underwent ablation performed with a second-generation 28-mm cryoballoon catheter. Before ablation, the pacing-determined PN course was delineated along the right atrium. PN location and its relation to the RSPV as well as RSPV surface distortions after balloon inflation were established with a NavX mapping system. Results During RSPV ablation, the inflated balloon surface extended anteriorly 6.3 ± 1.8 mm outside the RSPV. This narrowed the distance between the PN capture points in the RSPV vs PN location from 11.4 ± 5.0 mm to 7.5 ± 5.0 mm ( P = .0002) and increased the PN capture area from 1.9 ± 1.3 cm 2 to 3.2 ± 1.8 cm 2 ( P = .0004). Furthermore, the PN capture points shifted toward the orifice within the RSPV and after balloon inflation were located significantly closer to the orifice in the 3 patients with transient PNI than in those without PNI. Conclusion Cryoballoon inflation at the RSPV orifice alters PV/left atrial surface geometry, reducing the distance between the energy delivery source and the PN and increasing PN area, possibly explaining the mechanism of PNI. PN pacing within the RSPV after balloon inflation may be useful for preventing PNI.

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, but the real-world data after approval of direct oral anticoagulants (DOACs) are still lacking in Japan. We investigated the association of the baseline renal function and adverse clinical events and risk of adverse clinical events with DOACs compared to warfarin for each renal functional level in Japanese AF patients. Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter observational registry (median follow-up period: 39 months). The creatinine clearance (CrCl) values were estimated by the Cockcroft–Gault formula, and divided into normal renal function, and mild and moderate-severe CKD (CrCl ≥ 80, 50–79, &lt, 50 mL/min). Results: In the SAKURA AF Registry, the baseline CrCl data were available for 3242 patients (52% for DOAC and 48% for warfarin user). The relative risk of adverse clinical events was significantly higher in the patients with a CrCl &lt, 50 mL/min as compared to those with a CrCl ≥ 80 mL/min (adjusted HRs: 2.53 for death, 2.53 for cardiovascular [CV] events, 2.13 for strokes, and 1.83 for major bleeding). Risks of all adverse clinical events were statistically even between DOAC and warfarin users for each renal function level. Conclusion: Moderate–severe CKD was associated with a higher mortality, CV events, strokes, and major bleeding than normal renal function. The safety and effectiveness of DOACs over warfarin were similar for each renal function level. By a worsening renal function, the incidence of adverse clinical events increased, especially deaths and CV events as compared to strokes and major bleeding.

Background: Complex fractionated atrial electrograms (CFAEs) and high dominant frequency (DF) are targets for atrial fibrillation (AF) ablation. Although adenosine triphosphate (ATP) is known to promote AF by shortening the atrial refractory period, its role in the pathogenesis of CFAEs and DF during AF is not fully understood. Methods: We recorded electrical activity from a 64-electrode basket catheter placed in the left atrium (LA) of patients with paroxysmal AF (PAF, n=18) or persistent AF (PerAF, n=19) before ablation. Atrial electrogram fractionation intervals (FIs) and DFs were measured from bipolar electrograms of each adjacent electrode pair. Offline mean atrial FIs and DFs were obtained before bolus injection of 30 mg ATP. Peak effect was defined as an R–R interval >3 s. Results: With ATP, the mean FI decreased (from 110.4±29.1 ms to 90.5±24.7 ms, P

Background: Although alteration of the amplitude and morphology of bipolar electrograms is used widely as a guide of the ablation effect, there is little information concerning unipolar electrograms. The amplitude and morphology of filtered bipolar (BP) and filtered unipolar (UP) electrograms were compared during pulmonary vein isolation in patients with atrial fibrillation. Methods: BP (30–250 Hz) and UP (30–100 Hz) signals from the ablation catheter were recorded before and after each ablation point at the pulmonary vein antrum in 6 patients with atrial fibrillation. Results: In the electrogram group with low-voltage amplitude in BP electrograms before ablation (

IntroductionHigh dominant frequency (DF) sites during atrial fibrillation (AF) play an important role in the perpetuation of AF. We investigated the relationship between the DFs from intracardiac electrograms (iEGM) and the surface electrocardiogram (ECG) during AF, and the relationship between the surface ECG DF and atrial remodeling.MethodsIn 48 patients (57±11 years, 47 males, 20 paroxysmal), the V1–6 precordial leads and specific V7–9 ECG leads were recorded for 8s for an off-line analysis before AF ablation. The QRS-T complex was canceled by a template subtraction algorithm using the CEPAS™ system (Cuoretech Pty Ltd, Sydney, Australia). The iEGM DF maps, reconstructed using the Ensite NavX (St. Jude Medical, Inc., St. Paul, MN, USA) system, were simultaneously created for the right atrium and left atrium (LA) during AF.ResultsThe DF in leads V8 and V9 correlated well with the DF in the LA floor (R=0.55, p

LA Wall Thickness, LA Electrogram, and Dormant PV Conduction Introduction Atrial remodeling plays a key role in development of the substrate for atrial fibrillation (AF). Whether the wall thicknesses of the left atrium (LA) and pulmonary vein (PV)–LA junction affect remodeling and AF ablation is unknown. We investigated the relationship between wall thicknesses, electrogram characteristics, and adenosine triphosphate (ATP)-provoked dormant PV conduction as they pertain to AF. Methods In 50 patients with AF and 25 patients without AF, wall thicknesses of the LA and PV–LA junction were measured on 320-slice computed tomography images. For the AF patients, NavX-based voltage maps generated during sinus rhythm were obtained, and ATP-provoked dormant PV conduction after PV isolation was evaluated. Results Walls of the LA and PV–LA junction were significantly thicker in the AF patients than in the control patients (1.83 ± 0.29 mm vs. 1.59 ± 0.28 mm, respectively; P = 0.0010; and 0.88 ± 0.14 mm vs. 0.65 ± 0.11 mm, P

Background: The presence of complex fractionated atrial electrograms (CFAEs) and high dominant frequencies (DFs) during atrial fibrillation (AF) have been demonstrated to be related to AF maintenance. Therefore, sequential mapping of CFAEs and DFs have been used for target sites of AF ablation. However, such mapping strategies are valid only if the CFAEs and DFs are spatiotemporally stable during the mapping procedure. We obtained spatially stable multi-electrode recordings to assess the spatiotemporal stability of CFAEs and DFs. Methods: We recorded electrical activity during AF for 10 min with a 64-electrode basket catheter (48 bipole electrode pairs) placed in the left atrium in 36 patients with AF (paroxysmal AF [PAF], n=16; persistent AF [PerAF], n=20). The spatial and temporal distribution of the CFAEs (fractionation interval 8 Hz) at 1-min intervals for 10 min were compared for each of the 48 bipoles. Results: The baseline CFAEs were located at 68.5±14.0% (32.9±6.7) of the 48 bipoles; however, the high DF sites were fewer (9.6±8.6% [4.6±4.1 bipoles]). The CFAEs sites did not change significantly during the 10-min recording period (kappa statistic: 0.71±0.24); however, the high DF sites changed significantly (kappa statistic: 0.07±0.19). These spatiotemporal changes in the CFAEs and high DFs did not differ between patients with PAF and PerAF. Conclusions: Regardless of the AF type, CFAEs sites, but not high DF sites, showed a high degree of spatial and temporal stability.