The Japanese Catheter Ablation Registry (J-AB): Annual report in 2022.

The Japanese Catheter Ablation (J-AB) registry, started in August 2017, is a voluntary, nationwide, multicenter, prospective, observational registry, performed by the Japanese Heart Rhythm Society (JHRS) in collaboration with the National Cerebral and Cardiovascular Center. From January 2022, the data registration system was changed from Research Electronic Data Capture (REDCap) system to Fountayn system. The purpose of this registry was to collect the details of target arrhythmias, the ablation procedures, including the type of target arrhythmias, outcomes, and acute complications in the real-world settings. During the year of 2022, we have collected a total of 90,042 procedures (mean age of 66.7 years and 65.9% male) from 614 participant hospitals. Detailed data were shown in Figures and Tables.

Element accumulation in the tracheal and bronchial cartilages of monkeys.

Compositional changes in the tracheal and bronchial cartilages can affect respiratory ventilation and lung function. We aimed to elucidate element accumulation in the tracheal and bronchial cartilages of monkeys and divided it into four sites: the tracheal, tracheal bifurcation, left bronchial, and right bronchial cartilages. The elemental content was analyzed using inductively coupled plasma atomic emission spectrometry. The average calcium content was two to three times higher in the tracheal cartilage than in the other three cartilages. The trends of phosphorus and zinc were similar to those of calcium. The average calcium, phosphorus, and zinc cartilage contents were the highest in the tracheal cartilage and decreased in the following order: the left bronchial, right bronchial, and tracheal bifurcation cartilages. These findings revealed that differences existed in element accumulation between different sites within the same airway cartilage and that calcium, phosphorus, and zinc accumulation mainly occurred in the tracheal cartilage. A substantial direct correlation was observed between age and calcium content in the tracheal and bronchial cartilages and all such monkeys with high calcium content were > four years of age. These results suggest that calcium accumulation occurs in the tracheal and bronchial cartilages after reaching a certain age. An extremely substantial direct correlation was observed between calcium and phosphorus contents in the tracheal and bronchial cartilages. This finding is similar to the previously published calcium and phosphorus correlations in several other cartilages, suggesting that the calcium and phosphorus contents of cartilage exist in a certain ratio.

Assessment of the safety and efficacy of catheter ablation for atrial fibrillation in very elderly patients: insight from the national prospective registry study.

BACKGROUND AND AIMS: This study evaluated the safety and efficacy of catheter ablation in treating atrial fibrillation (AF) among the elderly population. METHODS: A total of 170 017 AF ablation procedures prospectively enrolled from 482 facilities between 2017 and 2020 were analysed. They were stratified into six age groups, ranging from < 65 to ≥ 85 years, in 5-year increments. A cut-off of 80 years was set for dividing participants into two groups. The primary endpoints included procedure-related complications and 1-year arrhythmia recurrence after a 3-month blanking period. RESULTS: Patients ≥ 80 years constituted 7.2% of procedures in 2017, which significantly increased to 9.6% by 2020 (p < 0.001). This older group predominantly comprised women, with smaller stature and body mass index, a higher prevalence of paroxysmal AF, and a higher rate of initial ablation procedures. The overall complication rate was 2.8%, showing a positive correlation with age (p < 0.001), peaking at 4.3% for patients ≥ 85 years. Older age remained a significant independent risk factor for complications (odds ratio: 1.36 [1.24, 1.49], p < 0.001). Cardiac tamponade, ischemic stroke, and sick sinus syndrome were more common in the elderly. The recurrence rate in the total population was 16.0% and did not differ significantly between age groups (log-rank p = 0.473), remaining consistent even after adjusting for multiple variables. CONCLUSIONS: Although age increases complication risk, recurrence rates remained steady across age groups, suggesting that AF ablation is a reasonable option for elderly individuals, contingent on careful patient selection for safety. (ClinicalTrials.gov: NCT03729232).

Extensive ablation for elderly patients with persistent atrial fibrillation: insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: In patients with persistent atrial fibrillation (AF), extensive ablation for substrate modification, such as linear ablation or complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation (PVI) remains controversial. Previous studies investigating extensive ablation have demonstrated its varying efficacy, suggesting the possible heterogeneity of its efficacy. Aging is a major risk factor for AF and is associated with atrial remodeling. We aimed to compare the efficacy and safety of the extensive ablation strategy compared with PVI alone strategy between young and elderly patients. METHODS: This study is a post-hoc analysis of the multicenter, randomized controlled, noninferiority trial investigating the efficacy and safety of PVI-only (PVI-alone arm) compared with extensive ablation (PVI-plus arm) in patients with persistent AF (EARNEST-PVI trial). We divided the overall population into 2 groups based on age and assessed treatment effects. RESULTS: In the young group (age <65 years, N = 206), there was no significant difference in the recurrence rate between the PVI-alone group and PVI-plus group [hazard ratio (HR): 1.00, 95 % CI: 0.57-1.73, p = 0.987], whereas the recurrence rate was significantly lower in the PVI-plus group compared to the PVI-alone group in the elderly group (age ≥65 years, N = 291) (HR: 0.47, 95 % CI: 0.29-0.76, p = 0.0021) (p for interaction = 0.0446). There were no fatal procedural complications. CONCLUSION: In patients with persistent AF, the extensive ablation strategy was more effective than the PVI-alone strategy in elderly patients, while the effectiveness of both approaches was comparable in young patients. TRIAL REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03514693. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022454 Unique ID issued by UMIN: UMIN000019449.

Development and validation of a sensitive and simultaneous liquid chromatography tandem mass spectrometry method for the determination of eight phytocannabinoids in various CBD products.

In this study, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of eight phytocannabinoids in various cannabidiol (CBD) products from Japanese market. This method was combined with electrospray ionization in positive mode and sample preparation with QuEChERS. Three types of commercial products such as honey, chocolate, and gummies were used to perform accurate quantification with unified protocol of LC-MS/MS and QuEChERS. The limit of detection and quantification were 5-20 µg g-1 and 10-40 µg g-1, respectively. Reproducibility was ensured using matrices free of target foods, resulting in an accuracy within ±10 % and a precision with a relative standard deviation of less than 5 % for all targets. Finally, this analytical method was applied to 8 series of commercial samples from the Japanese market. This unified protocol will serve as a reference as an official method in Japan.

Extensive ablation for persistent atrial fibrillation patients with mitral regurgitation: Insights from the EARNEST-PVI prospective randomized trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients. METHODS: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications. RESULTS: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms. CONCLUSIONS: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers. METHODS AND RESULTS: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

[Implementation and Evaluation of Risk Communication Regarding Residual Pesticides].

In this study, a public seminar on risk communication methods was conducted to raise awareness and disseminate accurate knowledge about residual pesticides to consumers. Additionally, surveys on consumer awareness were conducted on the attendees before and after the seminar to evaluate its effectiveness. Responses were obtained from 84 participants. The paired t-test was used to analyze the changes in awareness before and after the seminar. The results showed significant improvements in "trust in the government" and "understanding of residual pesticides." Furthermore, step-wise multiple regression analysis was performed to explore the factors influencing satisfaction with the risk communication seminar, and the item "understanding of the safety of residual pesticides in food" was extracted. Understanding food safety is a crucial concern in daily life for consumers. To enable consumers to have an accurate understanding of food risks and make appropriate judgments, it is essential to continue implementing risk communication and conveying information about food safety and security in the future.

Duration of atrial fibrillation persistence: Implications for recurrence risk after catheter ablation and efficacy of additional substrate ablation.

BACKGROUND: The optimal duration of atrial fibrillation (AF) persistence for predicting poor outcomes after catheter ablation of long-standing AF (LsAF) and the best ablation strategy for these patients remain unclear. OBJECTIVE: We aimed to assess the impact of the duration of AF persistence on outcomes after catheter ablation of AF. METHODS: We analyzed the Efficacy of Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation (EARNEST-PVI) trial data comparing pulmonary vein isolation (PVI) alone (PVI-alone) with additional linear ablation or defragmentation (PVI-plus) in persistent AF (PerAF). Patients who received catheter ablation by contact force-sensing catheter were enrolled in the study. In patients with LsAF, the optimal cutoff duration of AF persistence was evaluated. With use of the threshold, patients with LsAF were divided into 2 groups and compared with PerAF <1 year for arrhythmia-free survival after a 3-month blanking period. RESULTS: The optimal cutoff duration was 2.4 years. Of 458 patients, arrhythmia-free survival rates for LsAF 1-2.4 years were comparable to those of PerAF (hazard ratio [HR], 1.01; 95% CI, 0.67-1.52). However, LsAF >2.4 years had a higher recurrence risk than PerAF (HR, 2.22; 95% CI, 1.42-3.47). In LsAF >2.4 years, the PVI-plus strategy showed advantages over the PVI-alone strategy (HR, 0.36; 95% CI, 0.14-0.89). However, the interaction effect between LsAF 1-2.4 years and LsAF >2.4 years did not reach statistical significance (P = .116). CONCLUSION: Whereas LsAF 1-2.4 years has similar outcomes to those of PerAF, LsAF >2.4 years was linked to higher arrhythmia recurrence risks. For LsAF >2.4 years, the PVI-plus strategy showed a potential to be superior to the PVI-alone strategy.

Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

Radiofrequency Catheter Ablation for Atrial Fibrillation Patients on Hemodialysis (From the Kansai Plus Atrial Fibrillation Registry)　- Clinical Impact of Early Recurrence.

BACKGROUND: Catheter ablation (CA) for atrial fibrillation (AF) in patients on hemodialysis (HD) is reported to have a high risk of late recurrence (LR). However, the relationship between early recurrence (ER) within a 90-day blanking period after CA in AF patients and LR in HD patients remains unclear. METHODS AND RESULTS: Of the 5,010 patients in the Kansai Plus Atrial Fibrillation Registry, 5,009 were included in the present study. Of these patients, 4,942 were not on HD (non-HD group) and 67 were on HD (HD group). HD was an independent risk factor for LR after the initial CA (adjusted hazard ratio 1.6; 95% confidence interval 1.1-2.2; P=0.01). In patients with ER, the rate of sinus rhythm maintenance at 3 years after the initial CA was significantly lower in the HD than non-HD group (11.4% vs. 35.4%, respectively; log-rank P=0.004). However, in patients without ER, there was no significant difference in the rate of sinus rhythm maintenance at 3 years between the HD and non-HD groups (67.7% vs. 74.5%, respectively; log-rank P=0.62). CONCLUSIONS: ER in HD patients was a strong risk factor for LR. However, even HD patients could expect a good outcome without ER after the initial CA.

The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration.

Adverse environmental stress causes depressive symptoms with the impairments of memory formation, cognition, and motivation, however, their underlying neural bases have not been well understood, especially based on the observation of living animals. In the present study, therefore, the mice model of restraint-induced stress was examined electrophysiologically to investigate the alterations of hippocampal sharp wave ripples (SWRs) and theta rhythms. In addition, the therapeutic effects of physical exercise on the amelioration of those hippocampal impairments were examined in combination with a series of behavioral tests. The data demonstrated that chronic restraint stress caused the reductions of occurrence and amplitude of hippocampal SWRs and the decreases of occurrence, duration, and power of theta rhythms, while physical exercise significantly reverted them to the levels of healthy control. Furthermore, hippocampal adult neurogenesis and microglial activation, previously reported to be involved in the etiology of depression, were histologically examined in the mice. The results showed that the impairment of neurogenesis and alleviation of microglial activation were induced in the depressed mice. On the other hand, physical exercise considerably ameliorated those pathological conditions in the affected brain. Consistently, the data of behavioral tests in mice suggested that physical exercise ameliorated the symptomatic defects of motivation, memory formation, and cognition in the depressed mice. The impairments of hippocampal SWRs and theta rhythms in the affected hippocampus are linked with the symptomatic impairments of cognition and motivation, and the defect of memory formation, respectively, in depression. Taken together, this study demonstrated the implications of impairment of the hippocampal SWRs and theta rhythms in the etiology of depression and their usefulness as diagnostic markers of depression.

Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization.

BACKGROUND: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization.Methods and Results: Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07). CONCLUSIONS: A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.

Comparison of 3-nitrophenylhydrazine, O-benzyl hydroxylamine, and 2-picolylamine derivatizations for analysis of short-chain fatty acids through liquid chromatography coupled with tandem mass spectrometry.

Short-chain fatty acids (SCFAs) are metabolites derived from gut microbiota and implicated in host homeostasis. Hence, the profiling SCFAs from biological samples plays an important role in revealing the interaction between gut microbiota and pathogens. Previous studies, liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with various derivatization strategies have been performed to obtain the SCFA profiles from biological samples. However, it is poor evidence to compare these derivatization regents and conditions. Thus, we present the evaluation of three major derivatization reagents, namely 3-nitrophenylhydrazine (3-NPH), O-benzylhydroxylamine (O-BHA), and 2-picolylamine (2-PA), for the analysis of eight SCFAs classified as C2-C5 isomers using LC-MS/MS. First, in a reversed-phase LC separation, 3-NPH showed good retention capacity. Although O-BHA derivatization showed higher sensitivity and good retention capacity than 2-PA, only 2-PA derivatization could successfully separate eight SCFAs. The matrix effects in human serum ranged 77.1-99.0% (RSD ≤ 3.4%, n = 6) for 3-NPH derivatives, 91.0-94.6% (RSD ≤ 5.4%, n = 6) for O-BHA derivatives, 81.6-99.5% (RSD ≤ 8.0%, n = 6) for 2-PA derivatives. These compared results showed each characteristic of 3-NPH, O-BHA, and 2-PA for SCFA derivatization based on LC-MS/MS approaches.

The Japanese Catheter Ablation Registry (J-AB): Annual report in 2021.

The Japanese Catheter Ablation (J-AB) registry, started in August 2017, is a voluntary, nationwide, multicenter, prospective, observational registry, performed by the Japanese Heart Rhythm Society (JHRS) in collaboration with the National Cerebral and Cardiovascular Center using a Research Electronic Data Capture system. The purpose of this registry is to collect the details of target arrhythmias, the ablation procedures, including the type of target arrhythmias, outcomes, and acute complications in the real-world settings. During the year of 2021, we have collected a total of 89 609 procedures (mean age of 66.1 years and 65.9% male) from 506 participant hospitals. Detailed data are shown in Figures and Tables.

The observation of below-the-knee artery by optical frequency domain image and angioscopy: a case series.

Background: Endovascular treatment (EVT) is a well-established treatment for patients with chronic limb-threatening ischaemia, and below-the-knee (BTK) artery is its main target, although the re-intervention rate is still high. Understanding of the characteristics of BTK artery atherosclerosis would be required to overcome this issue. In this case series, we elucidated the characteristics of non-stenotic BTK artery atherosclerosis in the patients who received EVT of the superficial femoral artery (SFA) using optical frequency domain imaging (OFDI) and angioscopy. Case summary: We presented five patients who underwent EVT of SFA and subsequent observation of ipsilateral BTK artery using OFDI and angioscopy. Patients one and two had advanced atherosclerosis; however, patients three, four, and five had only mild atherosclerosis. Discussion: All patients had multiple risk factors for atherosclerosis and stenosis/occlusion of the SFA and ipsilateral BTK arteries. Furthermore, some patients had several other atherosclerotic vascular diseases suggesting the presence of advanced systemic atherosclerosis. On the other hand, some patients with multiple BTK artery stenosis/occlusion did not have advanced atherosclerosis in the examined BTK artery. The absence of significant atherosclerosis in a BTK artery in patients with multiple stenoses or occlusion in other ipsilateral BTK arteries may suggest some mechanism of vessel occlusion other than atherosclerosis. Further investigations are needed to clarify the mechanism.

Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.