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Background: The lesion size index (LSI) predicts radiofrequency (RF) ablation lesion size and is an established parameter for pulmonary vein isolation. However, the effectiveness and safety of LSI for cavotricuspid isthmus (CTI) linear ablation remain unclear., Methods: This single-center retrospective study included 50 of patients (67 ± 10 years, 68% male) who underwent de novo CTI linear ablation between July 2020 and December 2020. The LSI target was set at 5.0 and 4.0 for the anterior 2/3 and posterior 1/3 segments, respectively. Acute procedural parameters of ablation were evaluated., Results: Acute bidirectional CTI block was achieved in all patients with an RF application time of 4.0 min (3.1-5.0 min), RF application number of 15 ± 7, and length of CTI of 36.9 ± 9.3 mm. First-pass bidirectional conduction block of the CTI was achieved in 39/50 (78%) patients. No major complications were observed. The contact force (CF) per application was significantly lower in the gap tag group than in the non-gap tag group (7 g [7-8 g] vs. 10 g [7-12 g], P = 0.0284)., Conclusions: LSI-guided CTI linear ablation is an effective and safe treatment approach. CF affects gap formation, even when the target LSI is the same., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Data 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 Analysis: We 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 Dissemination: The 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 Number: UMIN000047023., Competing Interests: Competing interests: The following authors have potential conflicts of interest: YO received research funding from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Pfizer and Boston Scientific Japan, and accepted remuneration from Bayer Healthcare, Daiichi-Sankyo and Bristol-Meyers Squibb. KNas accepted remuneration from Johnson & Johnson K.K. TK received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Bayer Healthcare, Boston Scientific and Medtronic Japan. HF accepted remuneration from Daiichi-Sankyo, Bayer Yakuhin, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Abbott Medical Japan, Medtronic Japan and Japan Lifeline. SN received speaker honoraria from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb and Medtronic Japan. WS received grants from Daiichi Sankyo Co., Ltd, and Nippon Boehringer Ingelheim; and remuneration for lectures, presentations, speakers bureaus, manuscript writing or educational events from Daiichi Sankyo, Nippon Boehringer Ingelheim, Bristol-Meyers Squibb, K.K., Bayer Yakuhin, Pfizer, Ono Pharmaceutical and Medtronic Japan. YM received lecture fees from Bayer Healthcare, Daiichi-Sankyo, Bristol-Meyers Squibb, Nippon Boehringer Ingelheim, Johnson & Johnson K.K., Japan Lifeline K.K, Medtronic Japan, Pfizer and Boston Scientific Japan. SSu received research funding from Daiichi Sankyo and remuneration from Bristol-Myers Squibb and Daiichi Sankyo. MHar received research funding from BIOTRONIK Japan, Medtronic Japan, Abbott Japan, Japan Lifeline, Nihon Kohden and Boston Scientific Japan, and accepted remuneration from Nippon Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Meyers Squibb, Medtronic Japan, Japan Life Line and Abbott Japan. TY received speaker honoraria from Medtronic Japan and Abbott Medical Japan. MTo received research funding from Japan Lifeline and consulting fee from Medtronic Japan. MTa belongs to the Section of Arrhythmia, Division of Cardiovascular Medicine, Department of Internal Medicine. This section supported by an endowment from Abbott Japan, Medtronic Japan and Boston Scientific Japan. MS is affiliated with an endowed division supported by BIOTRONIK Japan, Boston Scientific Japan K.K., Medtronic Japan and Abbott Medical Japan. AO taught courses endowed by BIOTRONIK, Abbott, Medtronic, Boston Scientific Japan and Japan Lifeline. KSa accepted remuneration from Abbott Japan, Medtronic Japan and Japan Lifeline. HKi accepted remuneration from Otsuka Pharmaceutical., AstraZeneca, Bristol-Meyers Squibb, Ono Pharmaceutical, Pfizer and Novo Nordisk. KMu received honoraria for Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, MSD, Kyowa Kirin, Yakult Pharmaceutical and Boehringer Ingelheim. KKus received speaker honoraria from Daiichi-Sankyo, Nippon Boehringer Ingelheim, Bayer Yakuhin, Pfizer and Medtronic Japan, and research grants from Medtronic Japan and JSR. KoM received speaker honoraria from Medtronic Japan and Abbott Japan, and research funding from Bristol-Meyers Squibb, Pfizer, Medtronic Japan, Japan Lifeline and Boston Scientific 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: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old., Methods: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed., Results: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase., Conclusions: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The local impedance (LI) is an emerging technology that monitors tissue-catheter coupling during radiofrequency (RF) ablation. The relationships between the LI, RF delivery time, and lesion formation remain unclear., Methods: Using an LI-enabled RF catheter in an ex vivo experimental model, RF lesions were created combined with various steps in the power (40 and 50 W), CF (10 g, 30 g, and 50 g), and time (10s, 20s, 30s, 40s, 50s, and 60s at 40 W and 5 s, 10s, 20s, 30s, 40s, 50s, and 60s at 50 W). The correlations between the LI drop, lesion size, and RF delivery time were evaluated. The rate of change in the time-dependent gain in the LI, depth, and diameter and the time to reach 90% decay of the peak dY/dT (time to 90% decay) were assessed., Results: The correlation between the LI drop and ablation time revealed non-linear changes. The time to a 90% decay in the LI drop differed depending on the RF ablation setting and was always shorter with the 50 W setting than 40 W setting. The LI drop always correlated with the lesion formation under all ablation power settings. Deeper or wider lesions were predominantly created within the time to 90% decay of the LI drop., Conclusion: The LI drop was useful for predicting lesion sizes. Deeper or wider lesions cannot be obtained with a longer ablation than the 90% decay time of the LI drop. A shorter ablation than the 90% decay time of the LI drop would be preferable for an effective ablation., Competing Interests: Authors declare no conflict of interests for this article., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background: Previous studies have identified noninvasive methods for predicting atrial fibrillation (AF) recurrence after catheter ablation (CA). We assessed the association between AF recurrence and atrial late potentials (ALPs), which were measured using P-wave signal-averaged electrocardiography (P-SAECG)., Methods: Consecutive patients with paroxysmal AF who underwent their first CA at our institution between August 2015 and August 2019 were enrolled. P-SAECG was performed before CA. Two ALP parameters were evaluated: the root-mean-square voltage during the terminal 20 ms (RMS 20 ) and the P-wave duration (PWD). Positive ALPs were defined as an RMS 20 <2.2 μV and/or a PWD >115 ms. Patients were allocated to either the recurrence or nonrecurrence group based on the presence of AF recurrence at the 1-year follow-up post-CA., Results: Of the 190 patients (age: 65 ± 11 years, 37% women) enrolled in this study, 21 (11%) had AF recurrence. The positive ALP rate was significantly higher in the recurrence group than in the nonrecurrence group (86% vs. 64%, p  = .04), despite the absence of differences in other baseline characteristics between the two groups. In the multivariate analysis, positive ALP was an independent predictor of AF recurrence (odds ratio: 3.83, 95% confidence interval: 1.05-14.1, p  = .04)., Conclusions: Positive ALP on pre-CA P-SAECG is associated with AF recurrence after CA., Competing Interests: The authors declare no conflict of interests for this article., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Competing Interests: Kazuhiro Satomi report lecture/consultant/advisory honoraria from Abbott and Medtronic. Wataru Shimizu, Junichi Nitta, Atsushi Kobori, Kengo Kusano report lecture/consultant/advisory honoraria from Medtronic. Satoshi Nagase belongs to a donation course of Medtronic. Takeshi Aiba belonged to a donation course of Medtronic.

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure (HF), stroke, and death. Although fibrillation cycle length (FCL) is used as a surrogate for atrial refractoriness, its impact on outcomes remains unclear. This study aimed to identify predictors of cardiovascular events, including FCL, in patients with long-standing persistent AF., Methods: The study included 190 consecutive patients with long-standing persistent AF (mean age 74 years, 74% male). Patients with valvular AF or hemodialysis-dependent end-stage renal disease and those on anti-arrhythmic drugs were excluded. The primary composite outcome was occurrence of cardiovascular events (myocardial infarction, HF), cerebrovascular events (stroke, transient ischemic attack), and all-cause death. FCL was calculated by fast Fourier transformation analysis of fibrillation waves in the surface electrocardiogram., Results: Over a median follow-up of 2.6 years, the primary outcome occurred in 31 patients (cardiovascular events, n = 18; cerebrovascular events, n = 8; all-cause death, n = 5). In multivariate analysis, longer FCL and history of HF were independent predictors of these outcomes. In a Cox proportional hazards model adjusted for age, sex, and history of HF, patients with an FCL > 160 ms (cut-off determined by receiver-operating characteristic curve analysis) were at increased risk of the outcome (hazard ratio 12.9; 95% confidence interval 4.99-44.10; p < 0.001)., Conclusions: FCL was independently associated with cardiovascular outcomes in patients with long-standing persistent AF., (© 2021. Springer Japan KK, part of Springer Nature.)

The recurrence of atrial fibrillation (AF) after catheter ablation (CA) is still an unsolved issue. Although structural remodeling is relatively well defined, the method to assess electrical remodeling of the atrium is not well established. In this study, we evaluated the relationship between atrial conduction properties and recurrence after CA for AF. One hundred six consecutive patients (66 ± 11 years old, male: 68%) who underwent CA for AF with a CARTO system from July 2016 to July 2019 were enrolled in this study. An activation map of both atria was constructed to precisely evaluate the total conduction time, distance, and conduction velocity between the earliest and latest activation sites during sinus rhythm. All parameters were compared between the patients with or without AF recurrence. Of the patients, 27 had an AF recurrence (Rec group). The left atrial (LA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (101.2 ± 17.9 vs. 116.9 ± 18.0 cm/s, P < 0.01). Likewise, the right atrial (RA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (81.1 ± 17.5 vs. 103.6 ± 25.4 cm/s, P < 0.01). A multivariate logistic analysis demonstrated that the LA and RA conduction velocities were independent predictors of AF recurrence, with adjusted odds ratios of 0.95 (95% confidential interval: 0.91-0.98, P < 0.01) and 0.94 (0.89-0.98, P < 0.01), respectively. In conclusion, slower conduction velocity of the atrium was associated with AF recurrence after pulmonary vein isolation., (© 2021. Springer Japan KK, part of Springer Nature.)

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., (© 2021. Springer Japan KK, part of Springer Nature.)

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. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences., Conclusions: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Background: Although the coexistence of heart failure (HF) with atrial fibrillation (AF) exhibits poor outcomes, the correlation between AF status and outcomes after exercise-based cardiac rehabilitation (CR) remains unclear in older individuals with HF., Objective: This retrospective study aimed to investigate the impact of AF on changes in physical function and prognosis after CR in older individuals with HF., Methods: We enrolled consecutive individuals with HF who were ≥ 60 years old who received 5-month CR. Exercise-based CR involved moderate-intensity aerobic exercises tailored to each participant. Isometric quadriceps strength (QS) and 6-min walk distance (6MWD) were measured as physical function, at baseline and 5 months thereafter. We compared QS and 6MWD changes from baseline to the 5-month observation period (QS and 6MWD) between sinus rhythm and AF. We examined composite incidence of all-cause death or unplanned readmission after 5-month CR and analysed the association of QS and 6MWD with clinical events, estimating adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs)., Results: Of the 764 participants, 476 (62%) had sinus rhythm, and 288 (38%) had AF. AF was associated with lower QS and 6MWD at baseline. The 2 groups did not differ in QS and 6MWD after adjusting for clinical confounders. With sinus rhythm, greater change in QS and 6MWD was significantly associated with reduced incidence of clinical events (QS tertile: aHR 0.75 [95% CI 0.60-0.92]; 6MWD tertile: aHR 0.59 [95% CI 0.46-0.76]); however, with AF, this association was observed for only 6MWD and not QS (QS: aHR 0.92 [95% CI 0.72-1.17]; 6MWD: aHR 0.73 [95% CI 0.54-0.98])., Conclusion: AF in older individuals with HF is associated with reduced physical function at baseline but not response to exercise-based CR. Furthermore, positive response of physical function after CR is associated with better prognosis regardless of AF, which suggests that exercise-based CR is potentially effective in older individuals with HF and AF., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: Patients with coronary artery disease (CAD) and atrial fibrillation (AF) can be treated with multiple antithrombotic therapies including antiplatelet and anticoagulant therapies; however, this has the potential to increase bleeding risk. Here, we aimed to evaluate the efficacy and safety of P2Y 12 inhibitors and aspirin in patients also receiving anticoagulant therapy., Methods: We evaluated patients from the Atrial Fibrillation and Ischaemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial who received rivaroxaban plus an antiplatelet agent; the choice of antiplatelet agent was left to the physician's discretion. The primary efficacy and safety end points, consistent with those of the AFIRE trial, were compared between P2Y 12 inhibitors and aspirin groups. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation or death from any cause. The primary safety end point was major bleeding according to the International Society on Thrombosis and Haemostasis criteria., Results: A total of 1075 patients were included (P2Y 12 inhibitor group, n=297; aspirin group, n=778). Approximately 60% of patients were administered proton pump inhibitors (PPIs) and there was no significant difference in PPI use in the groups. There were no significant differences in the primary end points between the groups (efficacy: HR 1.31; 95% CI 0.88 to 1.94; p=0.178; safety: HR 0.79; 95% CI 0.43 to 1.47; p=0.456)., Conclusions: There were no significant differences in cardiovascular and bleeding events in patients with AF and stable CAD taking rivaroxaban with P2Y 12 inhibitors or aspirin in the chronic phase., Trial Registration Number: UMIN000016612; NCT02642419., Competing Interests: Competing interests: HF reports personal fees from Nippon Boehringer Ingelheim and Daiichi Sankyo. JA reports personal fees from Bayer Yakuhin and Sanofi, and grants and personal fees from Daiichi Sankyo. SY reports grants from Takeda Pharmaceutical, Abbott and Boston Scientific, and personal fees from Daiichi Sankyo and Bristol-Meyers. KKa reports Grants-in-Aid for Scientific Research (20K08451) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and grants and personal fees from Bayer Yakuhin and Daiichi Sankyo. MA reports grants from the Japan Agency for Medical Research and Development (AMED), personal fees from Bristol-Myers Squibb and Nippon Boehringer Ingelheim, and grants and personal fees from Bayer Yakuhin and 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. KMi 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, grants from Nippon Boehringer Ingelheim and personal fees from Bristol-Myers Squibb. KKi 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 and Bayer Yakuhin; grants from 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. All other authors declare no financial relationships relevant to the contents of this paper., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Ablation index (AI) is a useful tool of the CARTO® system to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF). However, the optimal distance between neighboring ablation points (interlesion distance (ILD)) is still unclear. Here, we evaluated the optimal ILDs in the AI-guided PVI., Methods: Forty-nine AF patients who underwent AI-guided PVI in our institute from July 2018 to March 2019 were retrospectively enrolled in this study. Target AI was set at 500 and 400 for anterior and posterior walls, respectively, and we compared the ILDs with and without electrical gaps after a first encircling PVI., Results: In both PV, the ILDs with electrical gaps were longer than those without electrical gaps. The best cutoff values of ILD to detect the electrical gaps using the ROC curve were 5.4 mm for the RPV anterior wall (AUC, 0.67; sensitivity, 0.42; specificity, 0.84, P < 0.01) and 4.4 mm for the RPV posterior wall (AUC, 0.68; sensitivity, 0.91; specificity, 0.39, P < 0.01). Similarly, the best cutoff values of ILD were 5.5 mm for the LPV anterior wall (AUC, 0.74; sensitivity, 0.65; specificity, 0.82, P < 0.01) and 5.1 mm for the LPV posterior wall (AUC, 0.67; sensitivity, 0.79; specificity, 0.53, P =0.03)., Conclusion: The optimal interlesion distances for PVI were different in each PV segment. To achieve the first-pass isolation, less than 5.4/4.4 mm for the RPV anterior/posterior and 5.5/5.1 mm for the LPV anterior/posterior walls of interlesion distances were the best cutoff values in the patients with AF., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Lethal arrhythmias including ventricular tachycardia and fibrillation (VT/VF) are common complications of acute myocardial infarction (AMI). Predictors of in-hospital VT/VF after AMI, however, have not been thoroughly investigated. In this study, we sought to elucidate the predictors of in-hospital VT/VF events after AMI in the Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET). Methods and Results: In-hospital VT/VF was defined as a hemodynamically unstable VT or VF in the first week of hospitalization, on which the patients were classified as the VT/VF group. Of the patients in the J-MINUET study, 3,175 were finally enrolled in this study. A total of 114 patients had VT/VF. On multivariate logistic analysis, maximum creatine kinase >3,000 IU/L (adjusted OR, 1.67; 95% CI: 1.085-2.572; P=0.02), Killip class III or IV (adjusted OR, 8.93; 95% CI: 5.668-14.082; P<0.0001), initial Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 (adjusted OR, 1.67; 95% CI: 1.035-2.709; P=0.03), and concomitant chronic kidney disease (CKD; adjusted OR, 1.80; 95% CI: 1.105-2.938; P=0.02) were identified as independent predictors for in-hospital VT/VF. Conclusions: From the J-MINUET study, extensive myocardial damage, cardiogenic shock, lower grade initial TIMI flow on coronary angiography, and concomitant CKD were independent predictors of in-hospital VT/VF after AMI., Competing Interests: The authors declare no conflicts of interest. J.A., Y.O., T.I., and Y. Miyamoto are members of Circulation Reports’ Editorial Team., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

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 CHA 2 DS 2 -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 CHA 2 DS 2 -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.

We have shown that a dipeptidyl peptidase 4 (DPP-4) inhibitor suppresses atrial remodeling in a canine atrial fibrillation (AF) model. Glucagon-like peptide-1 (GLP-1) is increased by DPP-4 inhibitors. However, it is not clear whether GLP-1 is involved in the suppression of atrial remodeling. In this study, we evaluated the effect of liraglutide (a GLP-1 analog) on atrial electrophysiological changes using the same canine AF model. We established a canine AF model using continuous 3-week rapid atrial stimulation in seven beagle dogs divided into two groups: a liraglutide group with four dogs (3-week atrial pacing with liraglutide (150 µg/kg/day) administration) and a pacing control group with three dogs (3-week pacing without any medicine). We evaluated the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility every week during the protocol using implanted epicardial wires against the surfaces of both atria. In the pacing control group, the AERP was gradually shortened and the CV was decreased along the time course. In the liraglutide group, the AERP was similarly shortened as in the pacing control group (94 ± 4% versus 85 ± 2%, respectively; p = 0.5926), but the CV became significantly higher than that in the pacing control group after 2 and 3 weeks (95 ± 4 versus 83 ± 5%, respectively; p = 0.0339). The AF inducibility was gradually increased in the pacing control group, but it was suppressed in the liraglutide group (5 ± 9% versus 73 ± 5%; p = 0.0262). Liraglutide suppressed electrophysiological changes such as AF inducibility and CV decrease in our canine AF model.

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

Background: Cardiac alternans is promoted by heart failure (HF)-induced calcium (Ca 2+ ) cycling abnormalities. Late sodium current (I Na,L ) is enhanced in HF and promotes Ca 2+ overload; however, mechanisms underlying an antiarrhythmic effect of I Na,L blockade in HF remain unclear., Objective: The purpose of this study was to determine whether ranolazine suppresses cardiac alternans in HF by normalizing Ca 2+ cycling., Methods: Transmural dual optical mapping of Ca 2+ transients and action potentials was performed in wedge preparations from 8 HF and 8 control (normal) dogs. Susceptibility to action potential duration alternans (APD-ALT) and Ca 2+ transient alternans (Ca-ALT) was compared at baseline and with ranolazine (5-10 μM)., Results: HF increased APD- and Ca-ALT compared to normal (both P <.05), and ranolazine suppressed APD- and Ca-ALT in both groups (P <.05). The incidence of spatially discordant alternans (DIS-ALT) was increased by HF (8/8) compared to normal (4/8; P <.05), and ranolazine decreased DIS-ALT in HF (4/8; P <.05).Not only did ranolazine mitigate HF-induced Ca 2+ overload, it also attenuated APD-ALT to Ca-ALT gain (amount of APD-ALT produced by Ca-ALT). In HF, APD-ALT to Ca-ALT gain was significantly increased (0.55 ± 0.02) compared to normal (0.44 ± 0.02; P <.05) and was normalized by ranolazine (0.36 ± 0.05; P <.05), representing a complementary mechanism by which I Na,L blockade suppressed cardiac alternans., Conclusion: Ranolazine attenuated arrhythmogenic cardiac alternans in HF, both by suppressing Ca-ALT and decreasing the coupling gain of APD-ALT to Ca-ALT. Blockade of I Na,L may reverse impaired Ca 2+ cycling to mitigate cardiac alternans, representing a mechanism underlying the antiarrhythmic benefit of I Na,L blockade in HF., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study. In the dogs with rapid pacing, the atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated and blood was sampled every week. After the entire protocol, atrial tissue was sampled for histological examinations using HE, Azan, and dihydroethidium (DHE) staining to evaluate any tissue damage or oxidative stress. The pacing control group exhibited a gradual AERP shortening and CV decrease along the time course as previously reported. In the linagliptin group, the AERP shortening was not affected, but the CV decrease was suppressed in comparison to the control group (p < 0.05). The AF inducibility was increased in the control group and suppressed in the linagliptin group (p < 0.05). The control group exhibited tissue fibrosis, the degree of which was suppressed in the linagliptin group. DHE staining exhibited suppression of the reactive oxygen species expression in the linagliptin group in comparison to the pacing control group. Linagliptin, a DPP-4-inhibitor, suppressed the AF inducibility, CV decrease, and overexpression of oxidative stress in the canine AF model. Such suppressive effects of linagliptin on AF in the canine model may possibly be related to the anti-oxidative effect.

Background: Severe hypothermia (SH) is known to be arrhythmogenic, but the effect of therapeutic hypothermia (TH) on arrhythmias is unclear. It is hypothesized that susceptibility to Ca-mediated arrhythmia triggers would be increased only by SH.Methods and Results:Spontaneous Ca release (SCR) and resultant delayed afterdepolarizations (DADs) were evaluated by optical mapping in canine wedge preparations during normothermia (N, 36℃), TH (32℃) or SH (28℃; n=8 each). The slope (amplitude/rise time) of multicellular SCR (mSCR) events, a determinant of triggered activity, was suppressed in TH (24.4±3.4%/s vs. N: 41.5±6.0%/s), but significantly higher in SH (96.3±8.1%/s) producing higher amplitude DADs in SH (35.7±1.6%) and smaller in TH (5.3±1.0% vs. N: 10.0±1.1%, all P<0.05). Triggered activity was only observed in SH. In isolated myocytes, sarcoplasmic reticulum (SR) Ca release kinetics slowed in a temperature-dependent manner, prolonging Ca transient rise time [33±3 (N) vs. 50±6 (TH) vs. 88±12 ms (SH), P<0.05], which can explain the decreased mSCR slope and DAD amplitude in TH. Although the SR Ca content was similar in TH and SH, Ca spark frequency was markedly increased only in SH, suggesting that increased ryanodine receptor open probability could explain the increased triggered activity during SH., Conclusions: Temperature dependence of Ca release can explain susceptibility to Ca-mediated arrhythmia triggers in SH. This may therefore explain the increased risk of lethal arrhythmia in SH, but not during TH.

Aliskiren, a direct renin inhibitor is expected to achieve sufficient suppression of renin-angiotensin system. We evaluated the effect of aliskiren on the electrical and structural remodeling in a canine atrial fibrillation (AF) model. Twenty-eight dogs were divided into three groups: (1) pacing control group (n = 12), with continuous atrial rapid pacing for 3 or 6 weeks, (2) pacing + aliskiren group (n = 12), with oral aliskiren (30 mg/kg/day), and (3) sham group (n = 4), no pacing nor drug administration. Electrophysiological properties and AF inducibility were evaluated every week. After the protocol, the left atrial tissue was sampled for the further histological and mRNA analysis. The electrical remodeling, AF inducibility, the left atrial enlargement and interstitial fibrosis were observed in pacing control group and were more prominent in the 6-week protocol (vs. 3 week, p < 0.05). The mRNA expressions of matricellular proteins exhibited upregulation in 3-week pacing control, but these upregulations became insignificant in 6 weeks. In contrast, collagen type 3 exhibited significant upregulation in 6 week but not in 3-week protocol. These changes were suppressed in the pacing + aliskiren group. Aliskiren suppressed the atrial remodeling in a canine AF model. This effect was accompanied by the suppression of tissue fibrosis.

Purpose: Recent reports have documented the appearance of Brugada-type ST elevation in cases of overdose of antiepileptic drugs (AEDs). However, little is known about changes on electrocardiographs (ECGs) during AED use at therapeutic doses. AEDs may cause Brugada-type ST elevation or J-wave-like intraventricular conduction delays through an ion channel-blocking effect. In the present study, we sought to elucidate ECG abnormalities in patients on AED therapy., Methods: The study population consisted of 120 consecutive patients with epilepsy who continued to take AEDs and had ECGs recorded during these therapies. Their clinical background and ECGs were retrospectively analyzed. Brugada-type ST elevation was classified according to the consensus report on Brugada syndrome. A J-wave-like ECG abnormality was defined as the appearance of notching or slurring of the QRS complex (>0.1mV) in the inferior/lateral leads., Results: Of the 120 patients, 15 (12.5%) exhibited Brugada-type ST elevation and 35 (29.2%) showed a J-wave-like ECG abnormality. Polytherapy with sodium channel-blocking AEDs (e.g., carbamazepine, phenytoin, lamotrigine) was more frequently observed in patients with Brugada-type ST elevation (p=0.048). However, the serum concentrations of these medicines did not differ between patients with and without ECG abnormalities (carbamazepine: 7.9±4.1 vs. 7.2±5.9μg/dL; phenytoin: 12.7±4.1 vs. 15.5±9.5μg/dL, NS)., Conclusion: ST-T abnormalities were frequently seen in patients using AEDs. The presence of Brugada-type ST elevation was associated with polytherapy with sodium channel-blocking AEDs., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Aims: We evaluated the effect of carvedilol, a beta-blocker with anti-oxidative action, against the atrial fibrillation (AF) inducibility, the development of atrial remodeling and the oxidative stress markers in a canine AF model., Methods and Results: AF model was produced by performing 6-week rapid atrial stimulation in 15 dogs. The animals were divided into the following three groups: (I) pacing + carvedilol group (n=5); (II) pacing control group (n=5); and (III) non-pacing group (n=5). AF inducibility was gradually increased along the time course in the pacing control group. In the pacing + carvedilol group, the AF inducibility was suppressed especially in the latter phase of protocol in comparison with the pacing control group. Although carvedilol has beta-blocking effect, pacing control and pacing + carvedilol groups did not exhibit difference in the heart rate (177±13 vs. 155±13 bpm, P=0.08). On 8-hydroxy-2'-deoxyguanosine (8-OHdG), dihydroethidium and dichlorodihydrofluorescein diacetate staining, enhanced oxidative stress was observed in the atrial tissue in the pacing control, but not in the pacing + carvedilol group., Conclusions: Carvedilol suppressed AF inducibility and oxidative stress in the canine AF model.

Chronic heart failure (CHF) is a clinical complex showing end -stage of several cardiovascular disorders. Patients with CHF are disclosed to both of high mortality and high morbidity. Most of them repeat frequently the hospitalization. In CHF patients, neurohumoral factors such as renin -angiotensin -aldosterone systems (RAAS) are enhanced, and they result in high level of angiotensin, aldosterone and catecholamine in the cardiovascular tissue. Most of the hormones are known as cardiotoxic agent. The activated RAAS is closely linked with progression of cardiac remodeling. Thus, ACE inhibitor can block this linkage. Recently, several randomized controlled trials in large scale reveal that the ACE inhibitor is a beneficial tool for not only CHF therapy but also CHF prevention. The blocking effects by ACE inhibitor are playing a crucial role in releasing the CHF patients from several burdens.

A 74-year-old female developed aortocoronary dissection during percutaneous coronary intervention. The forceful manipulation of the guide catheter and contrast medium injection seemed to be the cause of the aortocoronary dissection involving the coronary sinus of Valsalva. The entry of the dissection was closed with subsequent obliteration of the false lumen by coronary stenting under the guidance of intracoronary ultrasonography and angiography.