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Background: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited., Methods: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events., Results: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years., Conclusions: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Subclinical leaflet thrombosis (SLT) can be one of the causes of transcatheter heart valve (THV) failure after transcatheter aortic valve implantation (TAVI). We sought to clarify the formation process of SLT and thrombogenicity during the perioperative period of TAVI. This multicenter, prospective, single-arm interventional study enrolled 26 patients treated with edoxaban for atrial fibrillation and who underwent TAVI for severe aortic stenosis between September 2018 and September 2022. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI in 18 patients and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD) (n = 11). SLT was observed in 16.7% (3/18) at 1 week, but decreased to 5.9% (1/17) at 3 months after TAVI. Patients with SLT at 1 week had a significantly decreased maximal leaflet thickness compared to those without SLT. Thrombogenicity assessed by T-TAS decreased markedly at 1 week and tended to increase at 3 months. The stagnation volume assessed by CFD was positively associated with a higher maximum leaflet thickness. This study showed the course of leaflet thrombus formation and visualization of stagnation in neo-sinus of THV in the acute phase after TAVI., (© 2024. The Author(s).)

Aims: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA., Methods and Results: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA., Conclusion: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF., Competing Interests: Conflict of interest: H.K. has received grants from Medtronic Japan, Nihon Kohden, Abbott Medical Japan, Fukuda Denshi, Boston Scientific Japan, Japan Lifeline, Nipro, and Biotronik Japan. K.T. has received honoraria from Bayer Yakuhin, Daiichi Sankyo, Kowa, MSD, Sanofi, and Takeda Pharmaceutical and grants from Astellas Pharma, Abbott Vascular Japan, Bayer Yakuhin, Boehringer Ingelheim Japan, Boston Scientific Japan, Bristol-Myers, Chugai Pharmaceutical, Daiichi Sankyo, Goodman, Japan Lifeline, Medtronic Japan, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Sanofi, Takeda Pharmaceutical, and Terumo. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Antithrombotic therapy is essential for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) because of the high risk of thrombosis, whereas a combination of antiplatelets and anticoagulants is associated with a high risk of bleeding. We sought to develop and validate a machine-learning-based model to predict future adverse events., Methods: Data from 2215 patients with AF and stable CAD enrolled in the Atrial Fibrillation and Ischaemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease trial were randomly assigned to the development and validation cohorts. Using the random survival forest (RSF) and Cox regression models, risk scores were developed for net adverse clinical events (NACE) defined as all-cause death, myocardial infarction, stroke or major bleeding., Results: Using variables selected by the Boruta algorithm, RSF and Cox models demonstrated acceptable discrimination and calibration in the validation cohort. Using the variables weighted by HR (age, sex, body mass index, systolic blood pressure, alcohol consumption, creatinine clearance, heart failure, diabetes, antiplatelet use and AF type), an integer-based risk score for NACE was developed and classified patients into three risk groups: low (0-4 points), intermediate (5-8) and high (≥9). In both cohorts, the integer-based risk score performed well, with acceptable discrimination (area under the curve 0.70 and 0.66, respectively) and calibration (p>0.40 for both). Decision curve analysis showed the superior net benefits of the risk score., Conclusions: This risk score can predict the risk of NACE in patients with AF and stable CAD., Trial Registration Numbers: UMIN000016612, NCT02642419., Competing Interests: Competing interests: KoK reports remuneration for lectures from Bayer Yakuhin, Daiichi-Sankyo, Novartis Pharma AG and Otsuka Pharmaceutical; has received trust research/joint research funds from Bayer Yakuhin, and Daiichi-Sankyo; and has received scholarship funds from Abbott Medical. SY reports grants from Takeda Pharmaceutical, Abbott and Boston Scientific, and personal fees from Daiichi-Sankyo and Bristol Myers Squibb. MA reports grants from the Japan Agency for Medical Research and Development; personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim; and grants and personal fees from Bayer Yakuhin and Daiichi-Sankyo. JA reports personal fees from Bayer Yakuhin and Sanofi and grants and personal fees from Daiichi-Sankyo. TM reports grants from the Japan Cardiovascular Research Foundation, and personal fees from Nippon Boehringer Ingelheim, Daiichi-Sankyo, AstraZeneca and Bayer Yakuhin. MN reports grants and personal fees from Bayer Yakuhin, Daiichi-Sankyo and Sanofi and personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim. KaM reports personal fees from Amgen Astellas BioPharma, Astellas Pharma, MSD, Bayer Yakuhin, Sanofi, Takeda Pharmaceutical, Daiichi-Sankyo, Nippon Boehringer Ingelheim and Bristol Myers Squibb. NH reports grants and personal fees from Bayer Yakuhin, Nippon Boehringer Ingelheim and personal fees from Bristol Myers Squibb. KaK reports grants from the Japan Cardiovascular Research Foundation grants and personal fees from Bayer Yakuhin, Daiichi-Sankyo, Sanofi, MSD and AstraZeneca, and personal fees from Bristol Myers Squibb and Nippon Boehringer Ingelheim. AH reports grants and personal fees from Boston Scientific Japan, Otsuka Pharmaceutical, Sanofi, Astellas Pharma, Bristol Myers Squibb, Daiichi-Sankyo, Bayer Yakuhin, Fukuda Denshi, Abbott Japan, Japan Lifeline, Takeda Pharmaceutical and Sumitomo Dainippon Pharma, and personal fees from Toa Eiyo, Nippon Boehringer Ingelheim, Amgen Astellas BioPharma, and AstraZeneca. HO reports personal fees from Towa Pharmaceutical, Bristol Meyers Squibb, Pfizer, Toa Eiyo, Bayer Yakuhin, and Novartis Pharma. KT received significant research grant from AMI, Bayer Yakuhin, Bristol-Myers K.K., EA Pharma, Mochida Pharmaceutical, and scholarship fund from AMI, Bayer Yakuhin, Boehringer Ingelheim Japan, Chugai Pharmaceutical, Daiichi-Sankyo, Edwards Lifesciences Corporation, Johnson & Johnson K.K., Ono Pharmaceutical, Otsuka Pharmaceutical, Takeda Pharmaceutical, and honoraria from Amgen K.K., Bayer Yakuhin, Daiichi-Sankyo, Kowa Pharmaceutical, Novartis Pharma K.K., Otsuka Pharmaceutical, Pfizer Japan, and belongs to the endowed departments donated by Abbott Japan, Boston Scientific Japan K.K., Fides-one, GM Medical, ITI, Kaneka Medix, Nipro, Terumo, Abbott Medical, Cardinal Heaith Japan, Fukuda Denshi, Japan Lifeline, Medical Appliance, Medtoronic Japan., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Current guidelines equally recommend direct oral anticoagulants (DOACs) and warfarin for atrial fibrillation (AF) patients with a bioprosthetic valve (BPV); however, there are limited data comparing DOACs and warfarin in AF patients with an aortic BPV., Methods and results: This post-hoc subgroup analysis of a multicenter, prospective, observational registry (BPV-AF Registry) aimed to compare DOACs and warfarin in AF patients with an aortic BPV. The primary outcome was a composite of stroke, systemic embolism, major bleeding, heart failure requiring hospitalization, all-cause death, or BPV reoperation. The analysis included 479 patients (warfarin group, n=258; DOAC group, n=221). Surgical aortic valve replacement was performed in 74.4% and 36.7% of patients in the warfarin and DOAC groups, respectively. During a mean follow up of 15.5 months, the primary outcome occurred in 45 (17.4%) and 32 (14.5%) patients in the warfarin and DOAC groups, respectively. No significant difference was found in the primary outcome between the 2 groups (adjusted hazard ratio: 0.88, 95% confidence interval: 0.51-1.50). No significant multiplicative interaction was observed between the anticoagulant effects and type of aortic valve procedure (P=0.577)., Conclusions: Among AF patients with an aortic BPV, no significant difference was observed in the composite outcome of adverse clinical events between patients treated with warfarin and those treated with DOACs, suggesting that DOACs can be used as alternatives to warfarin in these patients.

Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records (1,800,255 patients) at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9% (32,686 records) had cerebrovascular disease as a comorbidity and 2.1% (11,362 records) included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06-1.14], 2.02 [1.91-2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7% (63,647 records) had cardiovascular disease listed as comorbidity and 3.3% (11,834 records) as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality (adjusted OR [95% confidence interval]: 1.29 [1.22-1.37]). In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial., Competing Interests: Dr. Iihara reports personal fees and other funding from Megwell, personal fees from Daiichi Sankyo. Co. Ltd., personal fees from Otsuka Pharmaceutical, and grants from Idorsia Pharmaceuticals Japan outside of the submitted work. Dr. Komuro reports grants and personal fees from Daiichi Sankyo Company, Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from Takeda Pharmaceutical Company Ltd., grants from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma Ltd., grants from Idorsia Pharmaceuticals Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Toa Eiyo Ltd., and personal fees from AstraZeneca, and personal fees from Pfizer Japan Inc. outside of the submitted work. Dr. Matoba reports grants and personal fees from Bayer Yakuhin, Ltd., grants from Amgen, personal fees from Merck & Co., Inc., and personal fees from Abbott Vascular outside of the submitted work. Dr. Nishimura reports personal fees from Philips Japan, Ltd., personal fees from Tokyo Electric Power Company, personal fees from Terumo Company, and personal fees from H.U. group holdings outside of the submitted work. Dr. Nakayama reports personal fees from Pfizer Japan Inc, AstraZeneca K.K., Astellas Pharma Inc., Toppan Forms Co., InterSystems Corporation, Fujitsu Research Institute, Nikkei Business Publications, Inc., NIHON KOHDEN Co., FUKUDA DENSHI, Deloitte Tohmatsu Consulting LLC, and PwC Consulting LLC, outside of the submitted work. Dr. Toyoda reports personal fees from Daiichi-Sankyo, personal fees from Bayer Yakuhin, personal fees from Bristol-Myers-Squibb, personal fees from Outsuka Pharmaceutical Company Ltd., personal fees from Novartis Pharma Japan., and personal fees from Abbott Medical Japan Co., Ltd.,outside of the submitted work. Dr. Tsujita reports personal fees from Amgen K.K., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Pfizer Japan Inc., grants from AMI Co., Ltd., grants from Bristol-Myers K.K., grants from EA Pharma Co. Ltd., grants from Mochida Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim, grants from Chugai Pharmaceutical Co., Ltd., grants from Edwards Lifesciences Corporation., grants from Johnson & Johnson K.K., grants from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., other funding from Abbott Japan Co., Ltd., other funding from Boston Scientific Japan K.K., other funding from Fides-one, Inc., other funding from ITI Co., Ltd., other funding from Kaneka Medix Co., Ltd., other funding from Nipro Corporation, other funding from Terumo Co., Ltd., other funding from Abbott Medical Co., Ltd., other funding from Cardinal Health Japan, other funding from Fides-one, Inc., other funding from Fukuda Denshi Co., Ltd., other funding from Japan Lifeline Co., Ltd., other funding from Medical Appliance Co., Ltd., and other funding from Medtronic Japan Co., Ltd. outside of the submitted work. Dr. Yasuda reports personal fees from Bristol-Meyers, grants and personal fees from Bayer, personal fees from Daiichi-Sankyo, grants and other funding from Takeda Pharmaceutical Company Ltd., grants from NEC, grants from Daiichi-Sankyo, grants and other funding from Abbott, other funding from Terumo Co., Ltd., other funding from Nihon Kohden, other funding from Medtronic, other funding from Japan Lifeline, other funding from Otsuka, other funding from Ono, other funding from Nippon Boehringer Ingelheim, other funding from Kowa, other funding from Zeon, other funding from Shionogi, other funding from Nippon-Shinyaku, other funding from Mochida, and other funding from Tesco outside of the submitted work. Dr. Miyamoto reports personal fees from Tokyo Marine, personal fees from Nichido Fire Insurance Co., Ltd., personal fees from Fujitsu Co., Ltd., personal fees from Softbank Co., Ltd., personal fees from Meiji Yasuda Life Insurance Company., and personal fees from Saraya Co., Ltd. outside of the submitted work. Dr. Ogawa reports personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., and personal fees from Novartis Pharma Co., Ltd., personal fees from Takeda Pharmaceutical Co., LTD, personal fees from Daiichisankyo Co., Ltd., personal fees from Eisai Co., Ltd., personal fees from Teijin Co., Ltd. personal fees from Behringer Ingelheim Co., Ltd., Abbott Medical Japan Co., Ltd. outside of the submitted work. No other potential conflict of interest relevant to this article was reported. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated., Methods and results: This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding., Conclusions: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia-peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia-peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P =0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P =0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log-rank test, P <0.001). Conclusions The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia-peripheral arterial tonometry. Long-term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.

Background: It has been shown that most paroxysmal atrial fibrillation (AF) can be terminated by pulmonary vein (PV) isolation alone, suggesting that rapid discharges from PV drive AF. To define the driving mechanism of AF, we compared the activation sequence in the body of left atrium (LA) to that within PV., Methods: Endocardial noncontact mapping of LA body (LA group; n = 16) and selective endocardial mapping of left superior PV (LSPV) (PV group; n = 13) were performed in 29 paroxysmal AF patients. The frequency of pivoting activation, wave breakup, and wave fusion observed in LA were compared to those in LSPV to define the driving mechanism of AF. Circumferential ablation lesion around left PV was performed after right PV isolation to examine the effect of linear lesion around PV on AF termination both in LA and PV groups., Results: The frequency of pivoting activation, wave breakup, and wave fusion in PV group were significantly higher than those in LA group (36.5 ± 17.7 vs 5.0 ± 2.2 times/seconds, p < 0.001, 10.1 ± 4.3 vs 5.0 ± 2.2 times/seconds, p = 0.004, 18.1 ± 5.7 vs 11.0 ± 5.2, p = 0.002). Especially in the PV group, the frequency of pivoting activation was significantly higher than that of wave breakup and wave fusion (36.5 ± 17.7 vs 10.1 ± 4.3 times/seconds, p < 0.001, 36.5 ± 17.7 vs 18.1 ± 5.7 times/seconds, p < 0.001). These disorganized activations in LSPV were eliminated by the circumferential ablation lesion around left PV (pivoting activation; 36.5 ± 17.7 vs 9.3 ± 2.3 times/seconds, p < 0.001, wave breakup; 10.1±1.3 times/seconds, p = 0.003, wave fusion; 18.1 ± 5.7 vs 5.7 ± 1.8, p < 0.001), resulted in AF termination in all patients in both LA and PV groups., Conclusions: Activation sequence within PV was more disorganized than that in LA body. Frequent episodes of pivoting activation rather than wave breakup and fusion observed within PV acted as the driving sources of paroxysmal AF., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of intra-atrial conduction delay on the recurrence of atrial tachyarrhythmia after radio frequency catheter ablation (RFCA) has not been fully elucidated., Methods: We retrospectively analyzed 155 AF patients who were sinus rhythm at the start of RFCA. The conduction time from the onset of the earliest atrial electrogram at the high right atrium (HRA) to the end of the latest electrogram at the coronary sinus (CS) during sinus rhythm was defined as HRA-CS conduction time. Pulmonary vein isolation (PVI) was performed followed by linear roof lesion and complex fractionated atrial electrogram (CFAE) ablation until AF termination. We evaluated atrial tachyarrhythmia recurrence 12 months after RFCA., Results: The follow-up data were available for 148 patients. The recurrence of atrial tachyarrhythmia was noted in 28 (18.9%) patients. Atrial tachyarrhythmia recurrence patients had longer HRA-CS conduction times (151.3 ± 22.1 ms vs 160.1 ± 32.6 ms, p = .017). The patients were divided into the long or short HRA-CS conduction time group. The Kaplan-Meier analysis revealed that the long HRA-CS conduction time group held a higher risk of atrial tachyarrhythmia recurrence (log-rank test, p = .019). The multivariable Cox hazard analysis revealed that a long HRA-CS conduction time was a significant risk factor for the recurrence of atrial tachyarrhythmia, despite a long AF duration, persistent AF, and larger left atrial diameter (LAD) were not statistically significant., Conclusions: The HRA-CS conduction time was the primary influencing factor that predicted the recurrence of atrial tachyarrhythmia after catheter ablation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

It remains unclear whether AF is maintained by rotor. We evaluated the significance of rotor during atrial fibrillation (AF). Prevalence, location, and stability of rotational reentry (RR) in the left atrium were clarified by endocardial non-contact mapping in 66 AF patients. RR was classified into three categories: RR continued at stable site (Stable-RR), RR observed intermittently at the same site (Intermittent-RR), and RR observed at different locations (Different-RR). Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation following pulmonary vein isolation) until AF termination and elucidated the consequence of radiofrequency lesion delivered within RR site on AF termination and recurrence. One hundred and nineteen RRs were observed. There were 54 patients with RR (RR Group) and 22 patients without RR (Non-RR Group). Prevalence of Different-RR (n = 81) was significantly higher than Stable-RR (n = 16, p < 0.001) and Intermittent-RR (n = 22, p < 0.001). The intervals involved in RR occupied only 22.4% of total activation time. There was no significant difference in the prevalence of AF termination nor AF/atrial tachycardia recurrence between RR and non-RR Groups (46 vs. 9 patients, p = 0.317, and 13 vs. 1 patients, p = 0.271) and between patients in whom radiofrequency lesion was involved in RR and those was not (24 vs. 22 patients, p = 0.210, and 6 vs. 7 patients, p = 0.506). In conclusion, most RRs were observed transiently and often shifted its locations. Radiofrequency lesion delivered within RR site did not correlate with AF termination nor recurrence, suggesting that RR is not a driving source during AF.

Background: Esophageal injury (EI) is a serious complication that occurs after catheter ablation of atrial fibrillation (AF), however predictable factor of EI is unclear., Methods: Among 308 patients who underwent AF ablation, upper gastrointestinal tract endoscopy was performed the next day after ablation to examine for EI. To define the primary factor that predicts EI, patients' characteristics, number and amount of radiofrequency energy applied to the posterior wall, ablation procedure, and the shortest distance between esophagus and posterior left atrium measured on contrast computed tomography (SD-CT) were analyzed., Results: EI was found in 27 patients (8.8%). There were no significant differences in the patient characteristics, number and amount of radiofrequency energy applied to posterior wall or ablation procedure between patients with (Injury Group) and without EI (Non-Injury Group). However, SD-CT in the Injury Group was significantly shorter than that in Non-Injury Group (2.3±0.6mm vs 4.1±0.9mm, p<0.001). The area under a receiver operating characteristic curve using SD-CT as a predictive marker in EI patients was 0.988 (p<0.001). When the cut-off value of SD-CT was set at 2.9mm, the sensitivity and specificity for EI diagnosis were 92.3% and 96.8%, and the positive predictive value and negative predictive value were 0.75 and 0.99, respectively., Conclusions: EI observed after catheter ablation of AF was closely associated with the SD-CT. Patients with SD-CT below 2.9mm have a potential risk of EI and thus must be strictly followed., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

We detected symptomatic atrial fibrillation in a 64-year-old man who had undergone mitral valvuloplasty. While performing transesophageal echocardiography (TEE) in the left lateral decubitus position, we detected an isoechoic mass lesion at the bottom of the left atrial appendage (LAA). After changing the patient's position from left to right, the mass lesion dropped down from the bottom of the LAA, spread out into the left atrium, and appeared as a spontaneous echocardiographic contrast with mobility. We therefore diagnosed the mass lesion as not a thrombus but sludge. Changing the patient's position during TEE is useful for distinguishing sludge from thrombi., (© 2018 The Authors. Echocardiography Published by Wiley Periodicals, Inc.)

Background: Experimental studies suggest that angiotensin II-receptor blockers can influence atrial remodeling and may prevent atrial fibrillation (AF). Therefore, we hypothesized that irbesartan may prevent the recurrence of AF following either catheter ablation or electrical cardioversion of AF., Methods: Study on the Effect of Irbesartan on Atrial Fibrillation Recurrence in Kumamoto (SILK study) is a prospective, multicenter, randomized, and open-label comparative evaluation of the effects of irbesartan and amlodipine on AF recurrence in hypertensive patients with AF who are scheduled to undergo catheter ablation or electrical cardioversion of AF. The primary end point was either AF or atrial tachycardia (AT) recurrence. AF/AT recurrence was evaluated for 6 months using 24-h Holter electrocardiogram and portable electrocardiogram. The secondary endpoints included the change in blood pressure, the interval from the procedure to the first AF/AT recurrence, cardiovascular events, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), and changes in the biomarkers [brain natriuretic polypeptide (BNP), high-sensitivity C-reactive protein (hs-CRP), urinary albumin/creatinine]., Results: The study enrolled 98 patients (irbesartan; n=47, amlodipine; n=51). The recurrence of AF/AT was observed in 8 patients (17.0%) in the irbesartan group and in 10 patients (19.6%) in the amlodipine group. There was no significant difference in the AF/AT recurrence between the irbesartan and amlodipine groups. Blood pressure decreased similarly in both groups. There were no significant differences between the two groups as regards to the interval from the procedure to the first AF/AT recurrence, occurrence of cardiovascular events, changes in LAD and LVEF. BNP and urinary albumin/creatinine significantly decreased similarly in both groups, but no significant difference was found in hs-CRP between the two groups., Conclusions: In hypertensive patients with AF, treatment with irbesartan did not have any advantage over amlodipine in the reduction of AF/AT recurrence after catheter ablation or electrical cardioversion., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR 10 -AUC 30 ) in the AR chip, and to measure plasma concentrations of DOACs at On-anticoagulant. In addition, the two-dimensional area covered by thrombi (%) in the capillary was analyzed every 3 minutes after sample applications. The AR 10 -AUC 30 correlated weakly and negatively with plasma concentrations of DOACs, and the levels at On-anticoagulant were lower in all groups than at Off-anticoagulant. AR 10 -AUC 30 levels at Off- and On-anticoagulant were identical among the groups. The thrombi areas in early phase were significantly larger in rivaroxaban and apixaban than warfarin and dabigatran groups. The findings suggested that visual analysis of the AR-chip can identify the differential inhibitory patterns of warfarin and DOACs on thrombus formation under flow condition.

Background: Non-vitamin K antagonist oral anticoagulants are used to prevent thromboembolism in patients with atrial fibrillation. The T-TAS "Total Thrombus-formation Analysis System" (Fujimori Kogyo Co Ltd) was developed for quantitative analysis of thrombus formation using microchips with thrombogenic surfaces (collagen, platelet chip [PL] ; collagen plus tissue factor, atheroma chip [AR]). We evaluated the utility of T-TAS in predicting periprocedural bleeding in atrial fibrillation patients undergoing catheter ablation (CA)., Methods and Results: After exclusion of 20 from 148 consecutive patients undergoing CA, the remaining 128 patients were divided into 2 treatment groups: the warfarin group (n=30) and the non-vitamin K antagonist oral anticoagulants group (n=98). Blood samples obtained on the day of CA (anticoagulant-free point) and at 3 and 30 days after CA were used in T-TAS to compute the thrombus formation area under the curve (AUC; AUC for the first 10 minutes for PL tested at flow rate of 24 μL/min [PL24-AUC10]; AUC for the first 30 minutes for AR tested at flow rate of 10 μL/min [AR10-AUC30]). AR10-AUC30 and PL24-AUC10 levels were similar in the 2 groups on the day of CA. Levels of AR10-AUC30, but not PL24-AUC10, were significantly lower in the 2 groups at days 3 and 30 after CA. Multiple logistic regression analyses identified the AR10-AUC30 level on the day of CA as a significant predictor of periprocedural bleeding events (odds ratio 5.7; 95% CI 1.54-21.1; P=0.009). Receiver operating characteristic analysis showed that the AR10-AUC30 level on the day of CA significantly predicted periprocedural bleeding events (AUC 0.859, 95% CI 0.766-0.951; P<0.001). The cutoff AR10-AUC30 level was 1648 for identification of periprocedural bleeding events., Conclusions: These results suggested that the AR10-AUC30 level determined by T-TAS is a potentially useful marker for prediction of bleeding events in atrial fibrillation patients undergoing CA., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Because diastolic late mitral annular velocity (a') obtained by transthoracic-echocardiography (TTE) represents left atrial (LA) function, we investigated the clinical significance of a' in heart failure (HF) with a preserved left ventricular (LV) ejection fraction (HFpEF). We enrolled 448 consecutive HFpEF patients (sinus rhythm: 66.3%, atrial fibrillation [AF] rhythm: 33.7%) and performed TTE under stable conditions after optimal therapy. In patients with sinus rhythm, a' values were measured at septal mitral annuli. A' had weak but significant negative correlations with the natural-logarithm-B-type natriuretic peptide (Ln-BNP), LA diameter, LV mass index and tricuspid regurgitation pressure gradient. Receiver operating characteristic (ROC) curve analysis showed that the best cut-off value of a' and systolic mitral annular velocity (s') for the prediction of HF-related events were 7.45 cm/s and 6.5 cm/s with areas under the curve (AUC) of 0.841 and 0.682, respectively. The AUC of ROC analysis for the logistic regression model of a' plus s' was improved to 0.97. In Kaplan-Meier analysis, HFpEF patients with low-a' (<7.45 cm/s) had a significantly higher risk of total cardiovascular and HF-related events (both p <.01 by log-rank test) than those with high-a' (≥ 7.45 cm/s) and were prognostically equivalent to those with AF. Multivariate Cox proportional hazard analysis identified low-a' as an independent predictor of both total cardiovascular (hazard ratio [HR]: 0.823, 95% confidence interval [CI]: 0.714–0.949, p =.007) and HF-related events (HR: 0.551, 95% CI: 0.422–0.720, p <.001). A' value measurement is a non-invasive and useful method for risk stratification in HFpEF. • a' is easily measured by transthoracic echocardiography. • a' can be a robust marker of left atrial function. • The risk stratification of HFpEF patients is important. • a' can be a useful marker of the risk stratification. [ABSTRACT FROM AUTHOR]

Anticoagulants are widely used for prevention of cerebral infarction in patients with atrial fibrillation (AF) while it is possible that anticoagulants increase bleeding events in daily medical practices. Recently, we reported that the total thrombus-formation analysis system (T-TAS)was useful for evaluating thrombogenicity. In this study, we examined whether T–TAS was practical for predicting bleeding risk in coronary artery disease (CAD) patients with AF.This study was the retrospective analysis of the 580 patients with CADwho underwent coronary angiography (CAG). Blood samples obtained on the day of CAG were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip; PL24-AUC10, AUC for PL chip). We divided the total study patients into two groups according to the presence of AF; 49 CAD patients with AF (AF-CAD) and 531 without (non-AF-CAD). We compared clinical characteristics and prognosis between two groups. Primary outcome was 1-year bleeding events that were defined by ISTH bleeding criteria.Compared to the non-AF-CAD, AF-CAD were more likely to have stroke, chronic kidney disease, and peripheral arterial disease. PL24-AUC10levels were similar between groups, whereas AR10-AUC30levels in the AF-CADwere lower than the non-AF-CAD(p<0.001). Logistic regression analysis revealed that high age (odds ratio 1.96; 95% CI 1.10-3.50; P=0.023), low hemoglobin (odds ratio 1.76; 95% CI 1.10-2.82; P=0.018), low platelet counts (odds ratio 5.21; 95% CI 3.26-8.32; P<0.001) and anticoagulant use (odds ratio 9.75; 95% CI 2.79-34.1; P<0.001) were associated with reduced thrombogenicity. Twenty-six patients (4.5%) had bleeding events during follow-up [8 cases (16.3%) in AF-CAD, 18 (3.4%) in non-AF-CAD]. Kaplan-Meiercurve analysis showed a worse 1-year bleeding event-free survival rate for AF-CADcompared to non-AF-CAD(p<0.001). In multivariate Cox hazards analysis, low AR10-AUC30 (hazard ratio 3.89; 95%CI 1.09-13.9; p=0.036) and anticoagulant use (hazard ratio 4.27; 95% CI 1.81-10.0; p=0.001) were significant predictors for 1-year bleeding events.The present findings suggested that AR10-AUC30level determined by T-TAS could be a useful marker for predicting high bleeding risk in AF-CADpatients. [ABSTRACT FROM AUTHOR]

Background: It has been reported that the recurrence of atrial fibrillation (AF) after the initial catheter ablation (CA) procedure was caused by the reconnection of pulmonary vein (PV), presence of non-PV foci and progression of left atrial remodeling. However, it has not been fully clarified if there was a difference in the mechanism of early and late recurrent AF after initial CA for AF. Objectives: The purpose of this study was to investigate whether or not there was a difference in the mechanism of recurrent AF between the early and late phase recurrent cases. Furthermore, we investigated if this difference is related to the subsequent clinical outcome after the repeated ablation procedure. Methods: The consecutive 143 patients (paroxysmal AF; n=90, persistent AF; n=53) who underwent CA for recurrent AF were included in this study. CA of AF was performed in a stepwise fashion using an AF termination as a procedural endpoint (PVI, roof line/complex fractionated atrial electrogram ablation and non-PV foci ablation) at the initial and repeated ablation sessions. During the repeated session, we investigated the mechanism of the recurrent AF and compared it between the early (recurrence within 1 year after previous session; Early-Group) and late phase (recurrence more than 1 year after previous session; Late-Group) recurrent cases. Also we compared the clinical outcome between the Early- and Late-Groups. Results: There were 103 patients in the Early-Group and 40 patients in the Late-Group. There was no significant difference in the clinical characteristics and variables, type of AF, and echocardiographic parameters between the Early- and Late-Groups. Prevalence of PV reconnection was significantly higher in the Early-Group than that in the Late-Group (89/103 patients; 86% vs 15/40 patients; 38%, p<0.001). However, prevalence of non-PV foci was significantly higher in the Late-Group than that in the Early-Group (26/40 patients; 65% vs 16/103 patients; 16%, p<0.001). Kaplan-Meier analysis revealed that the non-PV foci significantly associated with poor AF free survival ratio (log-rank test: p=0.008). Thus, recurrence of AF after repeated session in the Late-Group was significantly higher than that in the Early-Group (log-rank test: p=0.010). Conclusion: PV reconnection was frequent in the early recurrence cases, while the non-PV foci was often observed in the late recurrence cases. Presence of non-PV foci may derive from the progression of diseased atrium and thus resulted in the poor clinical outcome in late recurrence cases. [ABSTRACT FROM AUTHOR]

Introduction: Left atrial (LA) structure are altered in the majority of HF with preserved LVEF (HFpEF) patients. Because diastolic late mitral annular velocity (a') measured by transthoracic-echocardiography (TTE) is reported to represent the severity of LA remodeling, we investigated clinical significance of a' in HFpEF. Methods: We enrolled 422 consecutive HFpEF patients (sinus rhythm [SR]: 79.9%, and atrial fibrillation [AF] rhythm: 20.1%), and performed TTE at stable condition after optimal therapy for HF. In patients with SR at the time of TTE, a' values as an average of tissue Doppler velocities measured at septal and lateral mitral annuli. All HFpEF patients were followed until occurrence of cardiovascular events. Results: In HFpEF patients with SR, a' had a weak but significant negative correlations with B-type natriuretic peptide (BNP) (r=0.22, p<0.001), LA volume (r=0.28, p<0.001), the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e') (r=0.24, p<0.001) and LV mass index (LVMI) (r=0.35, p<0.001). In multivariate logistic-regression analysis, E/e' and LVMI were significantly and independently associated with decreased a' (both, p<0.05). HFpEF patients with low-a' (<8; median value of a') had significantly higher BNP (p=0.01) and prevalence of hypertension (p<0.01), and lower prevalence of coronary artery disease (p=0.01) than those with high-a' (≧8). In Kaplan-Meier analysis, HFpEF patients with paroxysmal-AF had a significant higher risk of all cardiovascular and HF-related events than those with SR (both, log-lank test, p<0.01), and was prognostically equivalent to those with chronic-AF. Furthermore, HFpEF patients with low-a' had a significant higher risk of cardiovascular events and HF-related events (both, log-lank test, p<0.01) than those with high-a', and was prognostically equivalent to those with AF. Multivariate-Cox-hazard analysis identified that low-a' as an independent predictor of both cardiovascular (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 1.22-3.78, p=0.01) and HF-related events (HR: 4.37, 95%CI: 1.64-11.6, p<0.01). Conclusions: Measurement of a' value by TTE is a non-invasive and useful method for risk stratification in HFpEF patients. [ABSTRACT FROM AUTHOR]

Introduction: Previous clinical studies demonstrated the high prevalence of AF among patients with HF, and that the prevalence of both AF and HF worsen their prognosis. However, little is known about the impact of AF on prognosis of HF with preserved LVEF (HFpEF) patients. Methods: We enrolled 512 consecutive HFpEF patients, admitted from 2006 to 2013, and followed them until occurrence of cardiovascular events. AF patients were classified into paroxysmal AF (p-AF) and chronic AF (c-AF) groups. p-AF was defined as an episode of AF that terminates spontaneously in less than seven days irrespective of heart rhythm on admission. Results: Of the 512 HFpEF patients, 149 (29.1%) patients presented in AF, of which 76 (14.8%) were p-AF and 73 (14.3%) were c-AF. NYHA-functional class (p<0.05 and p<0.001) and B-type natriuretic peptide (p=0.003 and p<0.001) in c-AF group were significantly higher than those in p-AF and sinus rhythm (SR), accompanied by significant reduction of LVEF (p<0.05 and p<0.01) and LV stroke-volume index (p=0.003 and p<0.001) in c-AF. Furthermore, left atrial diameter and tricuspid-regurgitation pressure-gradient assessed by echocardiography in p-AF were significantly higher than those in SR (p<0.001 and p<0.05) as expected, and those in c-AF were further higher than those in p-AF (both, p<0.001). During a median follow-up of 1145 days, occurrences of fatal or nonfatal stroke were relatively low-frequent and comparable among three groups (SR: 1.7%, p-af: 5.3% and c-af: 2.7%). In Kaplan-Meier analysis, by contrast, HFpEF patients with p-AF had a significant higher risk of cardiovascular and HF-related events (both, log-lank test, p<0.05) than those with SR, and was prognostically equivalent to those with c-AF. Multivariate-Cox-hazard analysis identified that presence of both p-AF and c-AF as independent predictors of both cardiovascular (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 1.22-3.78, p=0.01, and HR: 4.37, 95% CI: 1.64-11.6, p<0.01) and HF-related events (HR: 4.37, 95% CI: 1.64-11.6, p<0.01, and HR: 4.37, 95% CI: 1.64-11.6, p<0.01). Conclusions: Coexisting AF, regardless whether c-AF or p-AF, was common and closely associated with increased risk of both cardiovascular and HF-related events in HFpEF. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that the short distance between the esophagus and the posterior left atrium (LA) is closely associated with the occurrence of esophageal injury (EI) after catheter ablation of atrial fibrillation (AF). Meanwhile, it has not been fully elucidated whether esophageal temperature monitoring sufficiently prevent the EI. Objectives: The purpose of this study was to examine the usefulness of esophageal temperature monitoring for avoiding the EI. Further we analyzed the relation between the incidence of EI and the distance between the esophagus and the posterior LA measured on the contrast computed tomography (CT). Methods: Among 400 patients (paroxysmal AF; 295 patients and persistent AF; 105 patients) who underwent catheter ablation of AF, upper gastrointestinal tract endoscopy was performed the next day after ablation to examine for EI. The incidence of EI was compared between 92 patients who used esophageal temperature probe (ETP) (ETP Group) and 308 patients who did not used ETP (Non-ETP Group) during ablation. The shortest distance between esophagus and posterior LA measured on contrast CT (SD-CT) was also compared between the ETP and Non-ETP Groups. Results: EI was found in 29 patients (7.3%). The SD-CT in patients with EI was significantly lower than that in patients without EI (2.3±0.6 vs 4.1±0.8 mm, p<0.001). The prevalence of EI in ETP Group was significantly lower than that in the Non-ETP group (2/92 patients; 2.2 % vs 27/308 patients; 8.8 %, p=0.032). There was no significant difference in the SD-CT between the ETP Group and Non-ETP group (3.96±0.98 vs 4.19±1.01 mm, p=0.54). However, the SD-CT in patients with EI was significantly shorter than the SD-CT in patients without EI, both in the ETP Group (2.3±0.6 vs 4.1±0.9 mm, p<0.001) and in the Non-ETP Group (2.5±0.2 vs 4.2±0.9 mm, p=0.017), respectively. Conclusions: The incidence of EI was significantly correlated with SD-CT. However, the use of esophageal temperature monitoring during AF catheter ablation procedure prevented the occurrence of EI even when the SD-CT was short. These indicate that esophageal temperature monitoring is useful for the prevention of EI, especially in patients with short SD-CT. [ABSTRACT FROM AUTHOR]