IntroductionImplantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death caused by ventricular tachycardia or ventricular fibrillation in patients with ischemic and non-ischemic cardiomyopathy. However, the cost-effectiveness of ICD implantation in Japanese patients with heart failure and reduced left ventricular ejection fraction remains unclear. This study aimed to evaluate the cost-effectiveness of ICD implantation in a Japanese setting.MethodsA Markov model with 1-month cycles was developed to assess the cost-effectiveness of ICD implantation compared with conventional medical therapy. The analysis was conducted from the perspective of a public healthcare payer over a 30-year time horizon. Scenario analyses accounting for waning treatment effects were performed, as along with deterministic and probabilistic sensitivity analyses (PSA).ResultsIn the base-case analysis, the incremental cost-effectiveness ratio (ICER) was US $29,838 per quality-adjusted life year (QALY). In the scenario analyses, the ICER increased to US $40,205 and $36,199 per QALY when the treatment effect began to wane after 5 and 10 years, respectively. ICD efficacy and battery longevity had the greatest influence on the ICER. PSA showed that the ICER per QALY ranged from US $19,472 at the 2.5th percentile to US $83,365 at the 97.5th percentile.ConclusionsIn the Japanese healthcare context, ICD implantation for primary prevention was found to be more cost-effective than the reference value. However, depending on several assumptions, the ICER may exceed the reference value. Sensitivity analyses highlighted the significant impact of the hazard ratio and battery longevity on cost-effectiveness. Further research is needed to identify subpopulations with significantly different cost-effectiveness outcomes.

BACKGROUND:Atrial fibrillation (AF) is a common comorbidity in patients receiving implantable cardioverter-defibrillators (ICD) or cardiac resynchronization therapy (CRT) and is associated with increased mortality. However, most evidence comes from Western cohorts dominated by ischemic cardiomyopathy (ICM), limiting applicability to populations in which non-ICM (NICM) is more prevalent. Because NICM and ICM fundamentally differ in myocardial pathology and remodeling, the prognostic impact of AF may not be uniform across etiologies. OBJECTIVE:This study aimed to determine whether the prognostic impact of AF differs between NICM and ICM in ICD/CRT patients. METHODS:We analyzed data from 4,623 patients in a nationwide cardiac device registry. Outcomes were all-cause death, cardiac death, heart failure hospitalization, and ICD therapies. Multivariable Cox and Fine-Gray competing risk models were constructed using literature-based, MAGGIC-derived, and stepwise covariate selection strategies. Propensity score matching was performed within ICM and NICM subgroups. RESULTS:AF was associated with higher risks of mortality, cardiac death, and heart failure hospitalization in NICM across all models. In contrast, the association between AF and mortality in ICM was attenuated and no longer statistically significant after multivariable adjustment. After propensity score matching, AF remained associated with increased mortality in NICM but not in ICM. AF impact on rates of ICD therapies did not differ between etiologies. CONCLUSION:The prognostic impact of AF among ICD/CRT recipients differs markedly by cardiomyopathy etiology. AF identifies a high-risk subgroup within NICM, whereas its effect is attenuated in ICM. Etiology-specific risk assessment should be incorporated into clinical management.

Remote monitoring (RM) has been established as a standard tool for the management of patients with cardiac implantable electronic devices (CIEDs), offering advantages such as early event detection, fewer routine outpatient visits, and reduced mortality. As RM becomes more common, its appropriate implementation and the need for safe, efficient management have become increasingly important. This statement of the Japanese Heart Rhythm Society (JHRS) provides comprehensive guidance for medical professionals and device manufacturers involved in RM. Specifically, it outlines recommendations on personnel placement, workflow optimization, patient and caregiver education, alert notification settings, physiological parameter monitoring, and insurance claims. It also addresses the responsibilities of device manufacturers, the use of third-party resources, and strategies for reducing workload based on alert notifications. Recommendation classes and evidence levels were determined by the consensus of the writing team, and the proposed recommendations were reviewed and peer-reviewed by the JHRS' Committee on Implantable Devices.

BACKGROUND:Risk stratification for ventricular fibrillation (VF) in Brugada syndrome (BrS) remains a major clinical challenge. Atrial fibrillation is relatively common in BrS, suggesting that atrial conduction abnormalities may be related to arrhythmogenesis. A notched P wave on the surface electrocardiogram (ECG) reflects atrial conduction delay, but its prognostic significance for VF in BrS has not been fully established. OBJECTIVE:This study aimed to evaluate the association between notched P waves and life-threatening arrhythmic events in patients with BrS. METHODS:We analyzed 510 patients with BrS (mean age 51 ± 14 years; 95% men) enrolled in a prospective multicenter registry across 61 hospitals in Japan. Clinical and ECG parameters at enrollment were assessed, and patients were followed for cardiac events (VF, sustained ventricular tachycardia, or sudden cardiac death). RESULTS:During a mean follow-up of 107 ± 62 months, 58 patients (11%) experienced cardiac events. Notched P waves were present in 52 patients (10%). Patients with notched P waves had a significantly higher incidence of cardiac events than those without (27% vs 10%; P < .001). Kaplan-Meier analysis demonstrated lower event-free survival in patients with notched P waves (P < .001). In multivariable Cox regression, a notched P wave remained an independent predictor of cardiac events (hazard ratio 2.63; 95% confidence interval 1.35-4.78; P = .006), along with a history of VF. CONCLUSION:A notched P wave on a standard 12-lead ECG independently predicts life-threatening arrhythmias in BrS and may improve risk stratification by complementing conventional predictors.

Background:The Asia-Pacific Heart Rhythm Society Atrial Fibrillation (APHRS-AF) Registry is a prospective study in Asian metropolitan cities, which provides important information on the baseline characteristics, therapeutic patterns, and 1-year clinical outcomes in patients with atrial fibrillation (AF). This report describes data from Japanese patients recruited in this registry. Methods and Results:A total of 4666 patients with AF were enrolled. Of these, 794 patients were recruited from 28 large cardiovascular centers in Japan between 2015 and 2017. We analyzed 1-year follow-up outcome of these patients. Mean age at recruitment was 65.7 years and 69.0% were males. Major comorbidities were hypertension (37.5%), lipid disorder (29.0%), heart failure (15.9%), and diabetes mellitus (15.0%). Mean CHADS2 score, CHA2DS2-VASc score, and HAS-BLED score were 1.0, 2.0, and 1.1, respectively. At baseline, use of oral anticoagulants was 81%, including 7% prescribed a vitamin K antagonist (VKA) and 74% a direct oral anticoagulant (DOAC). Majority of the patients (N = 459, 57.8%) were planned to undergo catheter ablation. One-year follow-up was conducted in 743 patients. One-year all-cause mortality was 0.1% (n = 1) and the incidence of stroke/thromboembolic events was also 0.1% (n = 1). Major bleeding events were observed in 5 patients (0.7%), including 3 intracranial hemorrhages. Conclusion:In this 1-year analysis, a high prevalence of oral anticoagulant use was recorded. A low mortality rate and a low incidence of stroke/thromboembolic events were observed in Japanese patients of the APHRS-AF Registry.

Background:Cardiac resynchronization therapy with defibrillator (CRT-D) improves survival, reduces hospitalization, and enhances quality of life in patients with heart failure and reduced ejection fraction (HFrEF). As heart failure prevalence increases in aging societies such as Japan, the associated clinical and economic burden continues to rise. Previous cost-effectiveness analyses conducted in multiple countries indicate that CRT-D may be cost-effective in selected patients with HFrEF. However, its cost-effectiveness within the Japanese health care system remains uncertain. Objective:This study aimed to evaluate the cost-effectiveness of CRT-D in patients with HFrEF within the Japanese health care setting. Methods:A partitioned survival model was developed with 3 health states: after treatment (follow-up), hospitalization, and death. Survival for CRT-D was estimated by reconstructing individual patient-level data from the Kaplan-Meier curve of the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study using the method proposed by Guyot et al followed by fitting multiple parametric models; the gamma distribution was selected for the base case analysis. Survival for optimal medical therapy (OMT), the comparator, was estimated by applying a hazard ratio from a published meta-analysis. Hospitalization rates and device longevity were derived from prior studies. Cost estimates were obtained from the JROAD-DPC (Japanese Registry Of All cardiac and vascular Disease-Diagnostic Procedure Combination) database and the Japanese medical fee schedule. Utility values were assigned according to New York Heart Association class assuming treatment-specific distributions. The analysis was conducted from the public health care payer perspective using a monthly cycle over a 20-year time horizon. Deterministic and probabilistic sensitivity analyses were performed. Additionally, scenario analyses were conducted by varying the duration of treatment effect. Results:In the base case analysis, per capita costs were ¥12,258,410 (¥1=US $0.006 as of July 7, 2026) for CRT-D and ¥640,056.90 for OMT, resulting in an incremental cost of ¥11,618,353. CRT-D generated 7.07 quality-adjusted life years (QALYs) compared with 4.75 QALYs for OMT, yielding an incremental gain of 2.32 QALYs. The incremental cost-effectiveness ratio (ICER) was ¥5,009,880 per QALY. Scenario analyses showed that, when treatment effect waned after 7.5 years, the ICER increased to ¥5,423,235 per QALY. When the time horizon was shortened to 10 years or extended to 30 years, the ICERs were ¥8,523,072 and ¥4,386,803 per QALY, respectively. Deterministic sensitivity analysis identified CRT-D efficacy (hazard ratio), discount rate, and initial treatment cost as primary ICER drivers. Probabilistic sensitivity analysis produced a median ICER of ¥5,022,618 (IQR ¥4,448,306-¥5,760,425) per QALY, with a 95% credible interval of ¥3,804,418 to ¥7,178,795. At a willingness-to-pay value of ¥5,000,000 per QALY, CRT-D had a 49.2% probability of being cost-effective. Conclusions:CRT-D demonstrated acceptable cost-effectiveness in patients with HFrEF in Japan. Treatment efficacy and initial cost were the primary determinants of economic value, emphasizing the importance of appropriate patient selection and strategies to reduce device costs.

Background Data on the spontaneous onset of ventricular tachyarrhythmias (VTAs) in Brugada syndrome (BrS), including polymorphic ventricular tachycardia (PVT) and monomorphic ventricular tachycardia (MVT), remain limited. Objectives The goal of this study was to compare the clinical profile and mode of initiation of PVT and MVT in BrS. Methods This retrospective multicenter registry included 154 patients with BrS from 29 centers with documented VTA initiation captured by implantable cardioverter-defibrillator (94.9%) or electrocardiogram (5.1%). A total of 234 VTAs were analyzed, and initiation patterns were classified by using predefined electrocardiographic criteria. Results PVT was observed in 80.5% of patients, MVT in 16.9%, and both in 2.6%. Patients with MVT tended to be older, exhibit drug-induced Brugada electrocardiogram, and were more frequently White. Pause-dependent initiation occurred in approximately 25% of PVT and approximately 33% of MVT episodes. Coupling intervals initiating PVT were nonsignificantly shorter than for MVT (median 368 milliseconds vs 395 milliseconds), with a significantly lower prematurity index and faster early arrhythmia cycle length. Antecedent premature ventricular complexes were present in approximately 43% of both VTA types, commonly sharing morphology with the initiating premature ventricular complex. The prevalence of pathogenic/likely pathogenic SCN5A mutation did not differ between groups. Conclusions In this largest analysis to date of spontaneous VTA onset in BrS, MVT occurred in a substantial minority and was associated with older age, White ethnicity, drug-induced electrocardiogram pattern, and a preceding tachycardia. Initiation patterns were broadly similar across arrhythmia types, although PVT exhibited a significantly lower prematurity index and faster early cycle length despite only nonsignificant shorter coupling intervals. These findings refine the clinical and electrophysiological characterization of BrS-related arrhythmias and delineate distinct features of PVT and MVT initiation.

Background: Risk stratification in patients with Brugada syndrome (BrS) is challenging, especially in those at intermediate risk. The Predicting Arrhythmic evenT (PAT) score has recently been demonstrated to be excellent for predicting future arrhythmic events in patients without prior ventricular fibrillation (VF). However, validation studies are lacking. Objective: This study aimed to assess the performance of a novel risk stratification model in predicting future VF events in patients with BrS in a Japanese multicenter cohort. Methods: The PAT score was calculated for 413 patients with BrS (mean age, 50.9 +/- 13.6 years; 395 men) from 59 hospitals in Japan, including 314 patients without prior VF. The incidence of developing VF during the follow-up period was investigated. Results: During the 106.8-month follow-up period, 54 patients (13.1%) experienced VF events. Of the 314 patients without prior VF at enrollment, 14 (4.5%) experienced VF events. The incidence of VF events during the follow-up period was significantly higher in patients with PAT scores >= 10 than in those with scores < 10 (41/173 [23.7%] vs 13/240 [5.4%]; P < .0001) in the total cohort. No difference was observed in the incidence of VF events between patients with PAT scores >= 10 and < 10 among the 314 patients without prior VF (6/86 [7.0%] vs 8/228 [3.5%]; P = .22). PAT scores >= 10 predicted future VF events with a sensitivity and specificity of 42.9% and 73.3%, respectively. Conclusion: This Japanese multicenter registry demonstrated that the novel risk stratification model could not accurately predict future VF events in patients with BrS but without prior VF.

BACKGROUND AND AIMS:There are limited prospective data on the efficacy, safety, and impact on reverse remodelling of cryoballoon ablation as compared to radiofrequency ablation for persistent atrial fibrillation. METHODS:A prospective, multicentre, randomized, non-inferiority clinical trial was conducted to compare the efficacy and safety of cryoballoon vs radiofrequency ablation for persistent atrial fibrillation. A total of 500 patients with persistent atrial fibrillation were randomized across 12 centres. The primary endpoint was the occurrence of atrial tachyarrhythmias at 1 year with a 90-day blanking period after ablation. RESULTS:The final analysis included 499 patients, with a median age of 69 years (interquartile range, 61-74); 249 patients were allocated to the cryoballoon group, and 250 to the radiofrequency group. In the intention-to-treat analysis, the primary endpoint was observed in 56 patients (22.5%) in the cryoballoon group and 58 (23.2%) in the radiofrequency group, and the cryoballoon group demonstrated non-inferiority compared to the radiofrequency group for the primary endpoint (hazard ratio .99; 95% confidence interval, .69-1.43; P = .96). The radiofrequency group showed a greater reduction in left atrial size (left atrial volume index) at 1 year than the cryoballoon group [-11 mL/m2 (interquartile range, -19 to -4) vs -4 mL/m2 (interquartile range, -13 to 3), P < .001]. CONCLUSIONS:In this randomized trial, cryoballoon ablation was non-inferior to radiofrequency ablation for the occurrence of atrial tachyarrhythmias at 1 year in patients with persistent atrial fibrillation.

AbstractBackgroundAccurate prediction for survival in individualized patients with cardiac resynchronization therapy with a defibrillator (CRT‐D) is difficult.MethodsWe analyzed the New Japan cardiac device treatment registry (JCDTR) database to develop a survival prediction model for CRT‐D recipients.ResultsFour hundred and eighty‐two CRT‐D recipients, at the implantation year 2018–2021, with a QRS width ≥120 ms and left ventricular ejection fraction (LVEF) ≤35% at baseline, were analyzed. During an average follow‐up of 21 ± 10 months, death occurred in 66 of 482 CRT‐D patients (14%). A prediction model estimating annual survival probability was developed using Cox regression with internal validation. With seven explanation predictors (age >75 years, serum creatinine >1.4 mg/dL, blood hemoglobin <12 g/dL, heart rate ≥90/min, LVEF, prior NSVT, and QRS width <150 ms), the model distinguished patients with and without all‐cause death, with an optimism‐corrected C‐statistics of 0.766, 0.764, and 0.768, and calibration slope of 1.01, 1.00, and 1.00 at 1 year, 2 years, and 3 years. Additionally, we have devised the calculator of survival probability for individual CRT‐D recipients.ConclusionsUsing routine available variables, we have developed a survival prediction model for individual CRT‐D recipients.

The Japanese Heart Rhythm Society established a nationwide, mandatory, multi-center, prospective, observational registry of transvenous lead extraction (TLE) named the Japanese lead extraction registry (J-LEX) in 2018. As of the end of 2024, a cumulative total of approximately 5400 cases has been registered across 140 participating centers since 2018. The registry includes all consecutive transvenous extractions, excluding surgical-only cases. The indication of TLE was an infection in 54.5%, and the guideline classification was class I in 59.8% and class IIa in 21.8%. As for non-infectious indications, TLE is performed for abandoned leads in case of lead failure or device upgrade, and for lead-related trouble such as pain, vessel stenosis or occlusion, too many leads, tricuspid valve regurgitation, and difficulty with radiation therapy. In 2024, the TLE procedure was attempted on patients with a median age of 71.3 years, female in 32.7%, in the hybrid operating room in 73.3%, and in a standard OR with a C-arm fluoroscope in 11.5%. The average implantation duration of the target leads was 8.5 years. Complete removal was achieved in 96.7% of the target leads, and clinical success in 97.3% of the patients. Perioperative complications were observed in 4.8% of the patients. Three patients died during a TLE operation, and 11 patients died in-hospital (cardiac death in three patients and non-cardiac death in eight patients).

Background:Brugada syndrome (BrS) is an inherited cardiac channelopathy associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). Although implantable cardioverter-defibrillators (ICDs) are the primary therapy for SCD prevention, the risk stratification of elderly patients with BrS remains unclear. This study aimed to evaluate the incidence and risk factors of life-threatening arrhythmias in elderly patients with BrS. Methods:We analyzed 523 patients with BrS (mean age 51 ± 13 years, 497 men) enrolled in the multicenter prospective Japan Idiopathic Ventricular Fibrillation Study. Patients were categorized into the elderly (>60 years, n = 150) and nonelderly (≤60 years, n = 373) groups. Clinical characteristics, programmed electrical stimulation (PES) results, and outcomes, including cardiac events (CEs: VF, fast ventricular tachycardia, or SCD), were compared. Statistical analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. Results:During a mean follow-up of 106 ± 62 months, 59 patients (11%) experienced CE. The annual CE incidence was lower in the elderly group than in the nonelderly group (0.7% vs. 1.5%, p = 0.016). History of VF independently predicted CE occurrence in elderly patients (hazard ratio: 23.5, p < 0.001). Asymptomatic elderly patients exhibited a negligible risk of CE. PES did not predict CE occurrence in the elderly group. Conclusions:Elderly patients with BrS have a better prognosis than nonelderly patients, particularly if they are asymptomatic. A history of VF is a key risk factor for life-threatening arrhythmias in elderly patients with BrS.

Background:The widespread use of cardiac implantable electronic devices (CIEDs), combined with increasing global cremation rates, has raised concerns regarding potential explosion risks during cremation. Lithium batteries within these devices may rupture due to heat-induced internal pressure, potentially threatening crematorium infrastructure and staff safety. Despite these concerns, real-world data on explosion behavior and its consequences remain limited. This study aimed to assess the explosion characteristics of CIEDs during cremation and evaluate their impact on facility safety, with the goal of informing evidence-based guidelines. Methods:Combustion experiments were performed using full-scale cremation furnaces set at 1100°C and 800°C. A total of 13 CIEDs (7 pacemakers and 6 implantable cardioverter-defibrillators) were tested, with synchronized audio-video monitoring. Additionally, nationwide survey data were collected from 2044 crematoria across Japan, focusing on cremation practices, reported damage, and staff injuries. Results:All tested devices exploded, with mean ignition-to-explosion times of 4.3 ± 1.1 min at 1100°C and 5.4 ± 2.0 min at 800°C (p = 0.19). Seventeen explosion events were observed, yet no structural damage to the chambers occurred. Survey data revealed a decline in cremation refusal due to CIEDs-from 11.0% in 2012 to 4.6% in 2013 and 3.0% in 2014 (p < 0.001). According to respondents, this trend likely reflects an increased collaboration with medical associations, modernization of crematorium facilities, and dissemination of practical safety information. Conclusions:Cremation of CIEDs without removal appears safe under modern, regulated facilities. However, region-specific guidelines remain necessary due to international variability in infrastructure and practices.

Background:Evidence supporting the benefit from primary prevention implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy with a defibrillator (CRT-D) for heart failure with reduced ejection fraction (HFrEF) is scarce in real-world settings. Methods:We analyzed propensity score matched cohorts of patients eligible for Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) from Japan cardiac device treatment registry (JCDTR) and Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). The former served as the defibrillator therapy group and the latter as the conventional therapy group. Results:During an average follow-up of 24 months, death occurred in 35 of 285 patients (12%) with defibrillator therapy and 65 of 285 patients (23%) with conventional therapy. Adjusted hazard ratios of all-cause death, sudden death, heart failure death, and noncardiac death in defibrillator versus conventional therapy were 0.616 (95% confidence interval [CI]: 0.402-0.943, p = 0.026), 0.274 (95% CI: 0.103-0.731, p = 0.0097), 0.362 (95% CI: 0.172-0.764, p = 0.0077) and 1.45 (95% CI: 0.711-2.949, p = 0.31). After accounting for death without appropriate defibrillator therapy as a competing risk, the cumulative incidence of first appropriate defibrillator therapy in the defibrillator therapy group was nearly identical to that of all-cause death in the conventional therapy group. Subgroup analyses indicated a lack of defibrillator benefit in patients with hypertension (p = 0.01 for interaction). Conclusions:Primary prevention ICD/CRT-D reduced the risk of all-cause mortality of patients with HFrEF eligible for SCD-HeFT compared to conventional therapy in the real-world cohort.

BACKGROUND:In Japan, the implantation of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) is not covered by insurance reimbursement, and the underuse of ICDs has been noted. Therefore, this study analyzed the medical costs incurred due to a lack of primary prevention ICD therapy for SCD. METHODS AND RESULTS:This retrospective cohort study analyzed data from 4 advanced critical care centers between January 2020 and December 2024. From a database of 3,606 cases of cardiac arrest, there were 348 patients with a documented rhythm at the time of arrest that could have been treated with an ICD. Of these patients, 43 (12.4%) had documented evidence of heart failure treatment and were eligible for ICD implantation before experiencing a cardiac arrest. The total mean (±SD) medical cost for these patients was US $11,679±14,666 (¥1,775,150±2,229,272). CONCLUSIONS:In this multicenter retrospective analysis, we identified a subset of patients who were eligible for primary prevention ICD therapy but did not receive it prior to experiencing sudden cardiac arrest. These cases were associated with substantial post-arrest medical costs. Our findings highlight the potential clinical and economic impact of the underutilization of ICDs in Japan and suggest that broader implementation of guideline-directed ICD therapy for primary prevention may reduce both mortality and healthcare expenditure.

INTRODUCTION:Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS.METHODS:Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined.RESULTS:During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively.CONCLUSION:Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

BACKGROUND:Although catheter ablation (CA) has become a standard therapeutic approach to atrial fibrillation (AF), it imposes a low but relevant risk of thromboembolic complications of around 0.5%-1%, including ischemic strokes, and has an additional risk of clinically silent cerebral embolisms (SCEs) of 10%-40%. Both cryoballoon (CB) and radiofrequency (RF) ablation are routinely used clinically worldwide, yet there are few prospective data comparing the incidence of cerebral embolism after CA of AF between CB and RF ablation. METHODS:The aim of the Embo-Abl study will be to compare the incidence of cerebral embolisms on 3 T diffusion-weighted image magnetic resonance imaging (MRI) after CA of AF between CB and RF ablation in patients with AF in a prospective, multicenter, open-label, controlled, randomized fashion. The primary endpoint of the Embo-Abl study will be the occurrence of MRI-detected SCE 1-3 days after CA. The patients will be registered and randomly assigned to either the CB or RF ablation group in a 1:1 ratio. The study cohort will include 230 patients with AF from a multicenter in Japan. RESULTS:The results of this study are currently under investigation. CONCLUSION:The Embo-Abl study will be the first to compare the incidence of periprocedural cerebral embolisms caused by CA of AF between CB and RF ablation in a prospective, multicenter, randomized, controlled fashion.

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.