Real-World Investigation on Anticoagulation Management Before and After Catheter Ablation for Atrial Fibrillation in Japan　- Periprocedural and Long-Term Outcomes.

BACKGROUND: Optimal periprocedural oral anticoagulant (OAC) therapy before catheter ablation (CA) for atrial fibrillation (AF) and the safety profile of OAC discontinuation during the remote period (from 31 days and up to 1 year after CA) have not been well defined.Methods and Results: The RYOUMA registry is a prospective multicenter observational study of Japanese patients who underwent CA for AF in 2017-2018. Of the 3,072 patients, 82.3% received minimally interrupted direct-acting OACs (DOACs) and 10.2% received uninterrupted DOACs. Both uninterrupted and minimally interrupted DOACs were associated with an extremely low thromboembolic event rate. Female, long-standing persistent AF, low creatinine clearance, hepatic disorder, and high intraprocedural heparin dose were independent factors associated with periprocedural major bleeding. At 1 year after CA, DOAC was continued in 55.9% of patients and warfarin in 56.4%. The incidence of thromboembolic and major bleeding events for 1 year was 0.3% and 1.2%, respectively. Age ≥73 years, dementia, and AF recurrence were independently associated with major bleeding events. Univariate analyses revealed that warfarin continuation and off-label overdose of DOACs were risk factors for major bleeding after CA. CONCLUSIONS: High intraprocedural dose of heparin was associated with periprocedural major bleeding events. At 1 year after CA, over half of the patients had continued OAC therapy. Thromboembolic events were extremely low; however, major bleeding occurred in 1.2%. Age ≥73 years, dementia, and AF recurrence were independently associated with major bleeding after CA.

Impact of Box Isolation on Rotors and Multiple Wavelets in Persistent Atrial Fibrillation.

BACKGROUND: Additional benefits of posterior left atrial (LA) box isolation (BOXI) over pulmonary vein isolation (PVI) in persistent atrial fibrillation (perAF) have been reported, but the mechanism is still unclear. We evaluated the effects of BOXI on rotors and multiple wavelets in the whole LA.Methods and Results:Twenty patients with perAF (including 12 cases of longstanding perAF) underwent PVI. Real-time phase mapping (ExTRa Mapping) was performed in the whole LA during AF. Subsequently, BOXI was added and re-ExTRa Mapping was performed again at the same site. The nonpassively activated ratio (%NP), the ratio of the form of rotors and multiple wavelets to the recording time, was compared before and after BOXI. After BOXI, the %NP significantly decreased in the anterior wall (from 53±22% to 39±23%, P=0.010), inferior wall (from 51±16% to 34±19%, P=0.001), and LA appendage (from 23±27% to 16±19%, P=0.049). However, there were no significant differences in the septum (49±19% vs. 49±18%, P=0.562) or lateral wall (41±19% vs. 38±15%, P=0.526). CONCLUSIONS: BOXI not only reduced the critical mass for maintenance of AF, but also decreased the rotors and multiple wavelets in the anterior wall, inferior wall and LA appendage during perAF.

Effects and Risks of Heparin Bridging and Different Modes of Interruption/Resumption of Rivaroxaban on Perioperative Complications of Catheter Ablation for Atrial Fibrillation　- Another Analysis of the JACRE-R Registry.

BACKGROUND: The JACRE-R Registry, in which 42 Japanese institutions participated, monitored the efficacy and safety of rivaroxaban in catheter ablation (CA) of atrial fibrillation (AF). In the present analysis, we sought to elucidate the effects and risks of heparin bridging and different patterns of interruption/resumption of rivaroxaban on complications of CA.Methods and Results:We administered rivaroxaban during the perioperative period and recorded the incidence of complications up to 30 days after CA. A total of 1,118 patients were registered; 546 received heparin bridging and 572 did not. The bridging group showed a significantly higher incidence of non-major bleeding than the no-bridging group (4.03% vs. 0.87%; P=0.001). In the group receiving their last dose of rivaroxaban at 8-28 h before CA, neither thromboembolism nor major bleeding was observed during or after CA and the incidence of non-major bleeding was low (4/435, 0.92%). The incidence of non-major bleeding was significantly higher in the group resuming rivaroxaban ≥12 h after CA than in the group resuming <12 h (1.79% vs. 0.27%, P=0.045). CONCLUSIONS: Heparin bridging increased the risk of non-major bleeding perioperatively. It was safe to stop rivaroxaban 8-28 h before the CA procedure, whereas resumption of the drug within 12 h of CA was associated with a lower incidence of non-major bleeding.

Efficacy and Safety of Rivaroxaban and Warfarin in the Perioperative Period of Catheter Ablation for Atrial Fibrillation　- Outcome Analysis From a Prospective Multicenter Registry Study in Japan.

BACKGROUND: Catheter ablation (CA) is a common treatment for atrial fibrillation (AF). Although rivaroxaban is increasingly used as a substitute for warfarin, its safety and efficacy during CA have not been established in Japanese patients. In the present study we explored the efficacy/safety of rivaroxaban during the CA perioperative period.Methods and Results:We prospectively enrolled Japanese AF patients scheduled for CA who had received either rivaroxaban (rivaroxaban cohort, JACRE-R) or warfarin (warfarin cohort, JACRE-W) during the perioperative period. Primary outcome was a composite of thromboembolism and major bleeding within 30 days after CA. In JACRE-R and JACRE-W, 1,118 (median age, 65 years) and 204 patients (median, 69 years) were enrolled from 42 and 22 institutions, respectively. In JACRE-R, the primary outcome occurred in 7 patients (0.6%), comprising thromboembolism in 2 and major bleeding in 5. Non-major bleeding occurred in 27 patients (2.4%), and the incidence was significantly lower in patients without heparin bridging (n=572) than in those with heparin bridging (n=546). In JACRE-W, the primary outcome occurred in 3 patients (1.5%), all of which were major bleeding. After adjustment for patients' characteristics, no significant difference was observed between the JACRE-R and JACRE-W cohorts for the primary outcome. CONCLUSIONS: The rates of thromboembolism and major bleeding events during the AF ablation perioperative period in Japanese patients treated with rivaroxaban was as low as in those treated with warfarin. (Circ J 2016; 80: 2295-2301).

Current status of catheter ablation for atrial fibrillation--updated summary of the Japanese Catheter Ablation Registry of Atrial Fibrillation (J-CARAF).

BACKGROUND: The purpose of this study was to provide precise data on the current status of catheter ablation for atrial fibrillation (AF) in Japan. METHODS AND RESULTS: The Japanese Heart Rhythm Society requested that members retrospectively register data for AF ablation performed in September 2011, March 2012, and September 2012. A total of 165 centers submitted data for 3,373 patients (age, 62±11 years; male, 76.1%; paroxysmal AF, 64.4%). Pulmonary vein isolation (PVI) and additional ablation were performed in 97.5% and 77.4% of patients, respectively. 3-D mapping systems and irrigated-tip catheters were used in 94.8% and 87.7% of the patients, respectively. Although the mean CHADS2 score was 1.0±1.0, the majority received oral anticoagulant (OAC) during and following the procedure (69.8% and 97%, respectively). Vitamin K antagonist (VKA) prescription, however, decreased (1st vs. 3rd survey, during and following the procedure, 59.3% vs. 47.8% and 81.7% vs. 55.2%, respectively, P<0.0001, both) and that of new OAC (NOAC) increased drastically (9.6% vs. 24.2% and 15.8% vs. 42.1%, respectively, P<0.0001). Early complications were reported in 4.5% of the patients, but no instance of early death was reported. CONCLUSIONS: In addition to PVI, additional ablation procedures are also performed very frequently. Although the mean CHADS2 score was low, peri-procedural OAC therapy was commonly performed, and NOAC drastically superseded VKA.

Nationwide survey of catheter ablation for atrial fibrillation: the Japanese Catheter Ablation Registry of Atrial Fibrillation (J-CARAF)--report of 1-year follow-up.

BACKGROUND: A nationwide survey of catheter ablation for atrial fibrillation (AF) was conducted in Japan to determine the mid-term performance of the therapy from analysis of the 1-year outcome of registered patients. METHODS AND RESULTS: A total of 2,137 patients who underwent AF ablation in September 2011 and March 2012 were initially registered. In 2013, the 1-year follow-up data of 1,208 patients (56.5% of 2,137) from 119 centers were collected. Average age was 61.9±10.7 years. Patients with paroxysmal AF (PAF) constituted 64.3%. Persistent AF (pAF) and long-standing pAF (LS-pAF) were 20.4% and 15.3%, respectively. For all patients, 76.7% underwent their first AF ablation. At 1 year after AF ablation, 70.9%, 61.4%, and 56.2% of PAF, pAF, and LS-pAF patients, respectively, were free from AF or clinical/partial success (PAF vs. pAF or LS-pAF: P<0.01). Re-ablation was performed in 11.3%, 16.3%, and 17.3%, respectively. Multivariate logistic regression analysis revealed that procedure time (odds ratio [OR] 0.82, P=0.000), and results of AF induction test (OR 1.36, P<0.02) were significantly related to successful outcome. CONCLUSIONS: Approximately 70% of PAF and 60% of nonPAF patients were free from AF recurrence or had clinical/partial success status. Shorter procedure time and elimination of AF inducibility were independent predictors of mid-term success of AF ablation.

Activation pattern within Koch's triangle during sinus rhythm in patients with and without atrioventricular nodal reentrant tachycardia.

BACKGROUND: Several studies have visualized the slow pathway during sinus rhythm using high-density mapping of Koch's triangle (KT) in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, it is unclear whether the slow pathway can be visualized in all people. Therefore, we evaluated the activation pattern within KT during sinus rhythm in patients with and without AVNRT. METHODS: High-density mapping using the Advisor HD Grid mapping catheter (Abbott) within KT during sinus rhythm was created in 10 patients with slow-fast AVNRT and 30 patients without AVNRT. RESULTS: In 8 (80%) patients with AVNRT, the activation pattern pivoting around a block line (BL) within KT was observed. In 12 (40%) patients without AVNRT, similar activation pattern pivoting around BL was observed, but jump was observed in 11 (92%) of these patients. In all patients, the activation pattern pivoting around BL was observed in 17 (85%) of 20 patients with jump, but only 3 (15%) of 20 patients without jump (p < 0.0001). During jump, there was a long period of no potential from the last atrial potential within KT to the His bundle potential, suggesting the slow pathway conduction through the rightward inferior extension that cannot be visualized. A linear ablation between the pivot point and the septal tricuspid annulus was successful for slow-fast AVNRT. CONCLUSION: Although the slow pathway could not be visualized using high-density mapping during sinus rhythm, the activation pattern pivoting around BL within KT was observed in most patients with the dual pathway physiology, with or without AVNRT.

Impact of frailty in patients with non-valvular atrial fibrillation undergoing catheter ablation.

Background: The relationships between frailty and clinical outcomes in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) after catheter ablation (CA) have not been established. We evaluated the frailty rate of patients undergoing CA for NVAF, examined whether CA for NVAF improves frailty, and analyzed the CA outcomes of patients with and without frailty. Methods: Elderly Japanese patients (≥65 years; mean age: 72.8 years) who participated in the real-world ablation therapy with anti-coagulants in management of atrial fibrillation registry and who responded to the frailty screening index survey were included (n = 213). Frailty and AF recurrence were assessed preoperatively and at 3 and 6 months after CA. Results: Twenty-six patients (12.8%) were frail, 109 (53.7%) were pre-frail, and 68 (33.5%) were robust. Cardiovascular (frailty: 0.5%/person-year; pre-frailty: 0.1%/person-year; robust: 0.1%/person-year) and cardiac (frailty: 0.5%/person-year; pre-frailty: 0.1%/person-year; robust: 0.1%/person-year) events, as well as major bleeding (frailty: 0.3%/person-year; pre-frailty: 0.1%/person-year; robust: 0.1%/person-year), were numerically more frequent in the frailty group. No deaths from cardiovascular or stroke/systemic thromboembolic events occurred. A large proportion of patients did not experience 3-month (frailty: 96.2%; pre-frailty: 96.3%; robust: 88.2%) or 6-month (frailty: 88.5%; pre-frailty: 91.7%; robust: 86.8%) AF recurrence after CA. Weight loss, walking speed, and fatigue improved in the frailty and pre-frailty groups after CA. Conclusion: Japanese patients aged ≥65 years with frailty or pre-frailty had improved frailty screening index components, such as weight loss, walking speed and fatigue, after CA. Therefore, elderly patients with frailty or pre-frailty may benefit from CA for NVAF.

Decreased oral function in Japanese inpatients with schizophrenia.

AIM: Oral function in patients with schizophrenia has not been well-characterized. To address this, we performed a cross-sectional study of oral function in Japanese inpatients with schizophrenia. METHODS: We measured oral function, including occlusal force, tongue-lip motor function, tongue pressure, and masticatory function in 130 Japanese inpatients with schizophrenia. We then compared the frequency of clinical signs of oral hypofunction among 63 non-elderly and 67 elderly inpatients with schizophrenia, as well as data from 98 elderly control participants from a previous Japanese study. RESULTS: The frequency of reduced occlusal force was significantly higher in the elderly inpatients (76.2%) than in the non-elderly inpatients (43.9%) and elderly controls (43.9%). The frequency of decreased tongue-lip motor function in non-elderly inpatients (96.8%) and elderly inpatients (97.0%) was significantly higher than that in elderly controls (56.1%). The frequency of decreased tongue pressure in non-elderly inpatients (66.1%) and elderly inpatients (80.7%) was significantly higher than that in elderly controls (43.9%). Finally, the frequency of decreased masticatory function was highest in elderly inpatients (76.5%), followed by non-elderly inpatients (54.8%) and elderly controls (15.3%). CONCLUSION: Oral function was decreased in both non-elderly and elderly Japanese inpatients with schizophrenia compared with elderly controls.

[Upstream therapy for atrial fibrillation].

Upstream therapy to prevent atrial remodeling associated with hypertension, heart failure, or inflammation may deter the development of new AF or rate of recurrence or progression to permanent AF. Treatments with ACEI, ARB, and statins are usually referred to as upstream therapies for AF. There is a sustained reduction in new-onset AF in patients with significant underlying heart disease treated with ACEI or ARB, but evidence is less robust in patients with moderate structural heart disease and recurrent AF. Evidence in support of the use of statins for prevention of AF, except for post-operative AF, is insufficient to produce any robust recommendation. There is as yet no consensus regarding the intensity and duration of treatment and type of statins.

Initial multicenter clinical experience with the first-generation endoscopic guided laser balloon in Japan.

BACKGROUND: Isolation of the pulmonary veins (PVs) is the golden standard for atrial fibrillation (AF) ablation. To achieve a permanent PV isolation, the endoscopic guided HeartLight laser balloon system was invented. We analyzed the safety and efficacy of this laser balloon system. METHODS AND RESULTS: Three hundred four patients from 21 investigational sites inside Japan were enrolled in this study. One thousand sixty-two out of 1175 PVs (90.4%) were isolated using the HeartLight laser balloon. The isolation rate of the left superior, left inferior, right superior, and right inferior PVs was 87.8%, 91.3%, 91.6%, and 92.1%, respectively. The procedure time, defined as the time from the venous access to taking out the balloon, was 155 ± 39 min. The fluoroscopic time was 44 ± 25 min. The mean follow-up period was 309 ± 125 days. The freedom from AF recurrence at 3 months was 89.0% and at 12 months 82.1%. Adverse events occurred in 22 patients (7.2%) including phrenic nerve injury lasting more than 3 months in 1.6% and strokes in 1.0% of the patients. CONCLUSIONS: This initial experience demonstrated that the laser balloon ablation was feasible for PV isolation in Japanese AF patients.

Association Between the Number of Remaining Teeth and Body Mass Index in Japanese Inpatients with Schizophrenia.

Purpose: There is little evidence regarding the effects of dental status on body mass index (BMI) in inpatients with schizophrenia. Thus, we performed a cross-sectional study to explore the associations between the number of remaining teeth and BMI in Japanese inpatients with schizophrenia. Patients and Methods: We performed multiple regression analysis to assess the effects of potential predictors (age, sex, number of remaining teeth, number of antipsychotics prescribed, chlorpromazine equivalent dose, and antipsychotic type) on BMI in 212 inpatients with schizophrenia. We then compared the number of remaining teeth between inpatients with schizophrenia and the Japanese general population (3283 individuals) from the Japan Dental Diseases Survey 2016, using an analysis of covariance with age and sex as covariates. Results: Multiple regression analysis showed that the number of remaining teeth and the number of antipsychotics prescribed were significantly correlated with BMI (standardized regression coefficient = 0.201 and 0.235, respectively). In the analysis of covariance, inpatients with schizophrenia had significantly fewer remaining teeth compared with the Japanese general population (mean 14.8 [standard deviation: 10.9] vs mean 23.0 [standard deviation: 8.1]). Conclusion: These results suggested that tooth loss and antipsychotic polypharmacy affect BMI in inpatients with schizophrenia, and that inpatients with schizophrenia lose more teeth compared with the general population.

Cryoballoon ablation for paroxysmal atrial fibrillation in Japan: 2-year safety and efficacy results from the Cryo AF Global Registry.

PURPOSE: Catheter ablation is a recommended rhythm control therapy after failed or intolerant antiarrhythmic drug (AAD) treatment for patients with atrial fibrillation (AF). This study evaluates clinical performance and safety of pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front Advance) in Japan. METHODS: Cryo AF Global Registry is a prospective, multi-center registry. Patients with paroxysmal AF (PAF) were treated at 10 Japanese hospitals. Efficacy was evaluated by freedom from a ≥ 30-s recurrence of AF/atrial flutter (AFL)/atrial tachycardia (AT), AF-related symptoms, and quality of life using the EQ-5D-3L questionnaire. The safety endpoint was serious device- and procedure-related adverse events. RESULTS: The study included 352 patients with PAF (65 ± 10 years of age, 36% female, 36% without prior failure of AAD). Mean duration since first diagnosis of AF was 3.0 ± 5.5 years. Serious device- and procedure-related adverse event rate was 2.6% (95% CI: 1.2-4.8%). Freedom from AF/AFL/AT was 88.5% (95% CI: 84.7-91.4%) at 12 months and 86.7% (95% CI: 81.1-90.8%) at 24 months. The number of patients with ≥ 1 AF symptom was significantly decreased from 88% at enrollment to 22% (p < 0.01) at 12-month follow-up. General quality of life using EQ-5D did not improve significantly after 12 months in the summary score. However, in the visual analog scale score, there was improvement (5.8 ± 18.4; p < 0.01). CONCLUSIONS: This study demonstrates that cryoablation used for PVI is a safe and effective treatment in real-world use for patients with PAF in Japan.

Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II study).

AIMS: Atrial fibrillation (AF) is a common arrhythmia frequently associated with hypertension. This study was designed to test the hypothesis that lowering blood pressure by angiotensin II-receptor blockers (ARB) has more beneficial effects than by conventional calcium channel blockers (CCB) on the frequency of paroxysmal AF with hypertension. METHODS AND RESULTS: The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is an open-label randomized comparison between an ARB (candesartan) and a CCB (amlodipine) in the treatment of paroxysmal AF associated with hypertension. Using daily transtelephonic monitoring, we examined asymptomatic and symptomatic paroxysmal AF episodes during a maximum 1 year treatment. The primary endpoint was the difference in AF frequency between the pre-treatment period and the final month of the follow-up. The secondary endpoints included cardiovascular events, development of persistent AF, left atrial dimension, and quality-of-life (QOL). The study enrolled 318 patients (66 years, male/female 219/99, 158 in the ARB group and 160 in the CCB group) treated at 48 sites throughout Japan. At baseline, the frequency of AF episodes (days/month) was 3.8 ± 5.0 in the ARB group vs. 4.8 ± 6.3 in the CCB group (not significant). During the follow-up, blood pressure was significantly lower in the CCB group than in the ARB group (P < 0.001). The AF frequency decreased similarly in both groups, and there was no significant difference in the primary endpoint between the two groups. There were no significant differences between the two groups in the development of persistent AF, changes in left atrial dimension, occurrence of cardiovascular events, or changes in QOL. CONCLUSIONS: In patients with paroxysmal AF and hypertension, treatment of hypertension by candesartan did not have an advantage over amlodipine in the reduction in the frequency of paroxysmal AF (umin CTR C000000427).

Catheter ablation of atrial fibrillation. -State of the Art-.

Atrial fibrillation (AF) is an arrhythmia associated with increased morbidity and mortality. Since the first report of catheter ablation curing AF, numerous techniques have evolved, from linear ablation to segmental pulmonary vein (PV) isolation, to extensive encircling PV isolation, to left atrial (LA) linear ablation, to ablation of complex fragmented atrial electrograms (CFAEs) and ablation of ganglionated plexi. A new approach for complete isolation of the posterior LA, including all PVs, is box isolation. PV isolation is associated with a high clinical success rate in paroxysmal AF. However, in persistent AF or longstanding persistent AF, PV isolation only may not be sufficient, so additional ablation at sites with CFAEs is needed to improve the clinical outcome. A hybrid approach of combining PV isolation plus CFAE ablation is highly effective in the majority of patients with persistent AF or longstanding persistent AF. Thus, AF ablation is an effective and established treatment for AF that offers an excellent chance of a lasting cure. It is about time that AF ablation became a first-line therapy for selected patients with AF.

Antithrombotic therapy in atrial fibrillation: evaluation and positioning of new oral anticoagulant agents.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for stroke. For more than 60 years, warfarin has been the only approved anticoagulant for prevention of stroke in patients with AF. Although highly effective, it has many limitations that make its use difficult. Therefore, several novel anticoagulants are under development to overcome the limitations of warfarin, and some of these have entered phase III clinical trials. Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. It has also been approved in the United States and Japan for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In this review, the mechanism of action and pharmacological properties of new anticoagulants are described in detail, and the correct use of dabigatran in clinical practice is discussed.