Atrial Fibrillation In Japan Research Articles

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non‐valvular atrial fibrillation in Japan

AbstractAimsThere are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non‐valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan.MethodsThis retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest‐neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE).ResultsAfter PS matching, 2955 DOAC‐ and 1603 warfarin‐treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β‐blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50–1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78–1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47–0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22–3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10–3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05–4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22–2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24–2.83).ConclusionsDOAC‐treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin‐treated patients. Prior stroke was shown to augment stroke risk by approximately three‐fold. This large real‐world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

Multicenter registry of the Watchman left atrial appendage closure device for patients with atrial fibrillation in Japan: The TERMINATOR registry

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific Japan Background Transcatheter left atrial appendage closure (LAAC) provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation (AF). A meta-analysis of previous two randomized trials reported improved rates of hemorrhagic stroke, cardiovascular/unexplained death, and nonprocedural bleeding compared to warfarin (1). Recently, the next-generation LAAC device, the Watchman FLX system, became available, and showed a low incidence of adverse events and a high incidence of anatomic closure (2). This transcatheter stroke prevention has already been approved in Asian countries. However, there is little data of LAAC in Asian population. Purpose This study sought to assess efficacy and safety of LAAC for patients with nonvalvular AF in Asia. Methods The TERMINATOR (Transcatheter Modification of Left Atrial Appendage by Obliteration with Device) registry is a multicenter nonrandomized study in Japan. This enrolled patients who underwent LAAC in 23 Japanese institutions. The LAAC was indicated for patients with nonvalvular atrial fibrillation in whom oral anticoagulation is required, but who have a risk of bleeding (history of BARC type 3 bleeding or HAS-BLED score ≥3 points). Baseline patient and procedural characteristics and clinical outcomes were evaluated. Results A total of 729 patients were enrolled between September 2019 and November 2021. The mean age was 74.9±8.8 years and the mean CHA2DS2-VASc score was 4.7±1.5. The Watchman generation 2.5 and FLX system were used in 469 (64.3%) and 260 patients (35.7%), respectively. Procedural success was achieved in 722 patients (99.0%). In-hospital adverse events were as follows; 6 tamponades (0.8%), 3 pericardial effusion (0.4%), 2 device embolization (0.3%), no stroke (0%), and no death (0%). During follow-up, device-related thrombus and all-cause death were reported in 16 (2.2%) and 23 patients (3.2%), respectively. Conclusions LAAC with the Watchman system provides compatible efficacy and safety outcomes in Asian population.

May 2022 Stroke Highlights

May 2022 <i>Stroke</i> Highlights

Additional Effects of Antiplatelet Therapy on Anticoagulant Agents in Patients With Bioprosthetic Valves and Atrial Fibrillation.

The additional effects of single-antiplatelet therapy (SAPT) on anticoagulant therapy are still unclear in patients with atrial fibrillation (AF) after bioprosthetic valve replacement.Methods and Results:We conducted a subanalysis of a multicenter, retrospective, observational registry of patients with bioprosthetic valves and AF in Japan. Patients administered anticoagulants alone comprised the ACA group (n=107), and patients given concomitant SAPT and anticoagulant therapy comprised the On SAPT group (n=82). The primary efficacy endpoint was the incidence of stroke/systemic embolism, and the primary safety endpoint was the incidence of major bleeding. The observation period was 46.3±24.6 months. The primary efficacy endpoint occurred in 12 patients, and the cumulative incidence of primary efficacy events was significantly higher in the ACA group compared with the On SAPT group (P=0.039). The primary safety endpoint occurred in 22 patients, and the cumulative incidence of primary safety events was similar between groups (P=0.66). No differences between the groups were observed for cardiac events. Additional SAPT on anticoagulant therapy in patients with bioprosthetic valves and AF was associated with a reduction in stroke/systemic embolic events, although the cumulative incidence of bleeding was similar, regardless of additional SAPT. These findings suggest that additional SAPT on anticoagulant therapy may be safe and effective in real-world clinical settings.

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

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

Echocardiographic Structure and Function in Elderly Patients With Atrial Fibrillation in Japan - The ANAFIE Echocardiographic Substudy.

Echocardiographic data on the cardiac structure and function in elderly patients with atrial fibrillation (AF) and heart failure (HF) are limited. This subcohort study of the ANAFIE Registry analyzed echocardiographic parameters to identify cardiac structural and functional characteristics. Of 32,726 subjects in the ANAFIE population, 1,494 (4.6%) were entered as the echocardiography subcohort. Half of the patients, including those with persistent and permanent AF, older age (≥80 years), and CHADS2score ≥2, had left atrial (LA) volume index ≥48 mL/m2, indicating severe LA enlargement. LA enlargement significantly correlated with impaired LA reservoir function, regardless of age and CHADS2score. Types of AF and rhythm were strongly related to LA volume and reservoir function (P<0.0001). Moderate-to-severe mitral and tricuspid regurgitation were significantly more common, and the early diastolic mitral inflow velocity to mitral annulus velocity ratio was significantly higher among patients with than without HF history (all, P<0.0001). In this subcohort, LA enlargement correlated with impaired LA reservoir function. Elderly patients with non-valvular AF and a history of HF had LA enlargement and dysfunction, increased LV mass index, low LV ejection fraction, and high heart rate.

Abstract 9099: Echocardiographic Score versus Conventional Clinical Risk Score to Predict Thromboembolic Events at Younger Ages or First Thromboembolic Events in Patients with Non-valvular Atrial Fibrillation in Japan: The Fushimi AF Registry

Introduction: In patients with atrial fibrillation (AF), age and history of stroke are the strongest risk factors of thromboembolism events (TE). However, in patients with AF, especially in those with younger age or without previous TEs, preventing TEs is of clinical importance. We reported that echocardiographic (Echo) parameters such as enlarged left atrial diameter (LAD) or increased relative wall thickness (RWT) of left ventricle (LV) or smaller LV end-diastolic diameter (LVDd) were associated with incidence of TEs. We assessed whether the score based on Echo parameters (Echo score) can discriminate TEs, and compared its performance with a conventional clinical risk score. Methods: In the Fushimi AF Registry, follow-up data were available for 4,472 patients. Of them, Echo data at enrollment were available for 3,246 patients with non-valvular AF (NVAF). We investigated the relationship between Echo score [RWT ≥0.409, LVDd &lt;50 mm, LAD &gt;45 mm, each 1 point] and incidence of ischemic stroke (IS)/systemic embolism (SE) during 3 year follow-up in all patients, and patients with younger age and without previous stroke/SE, respectively. Results: During the median follow-up period of 1,095 days, 149 IS/SE events occurred. The incidence of IS/SE according to the groups stratified by Echo score is shown (Figure). Even in those with younger age or without previous stroke/SE, Echo score nicely discriminated the risk of TEs and the c-statistic was higher than that of CHA 2 DS 2 -VASc score (Table). Conclusions: Echo score better discriminated TEs in NVAF patients even with younger age or without previous TEs, than CHA 2 DS 2 -VASc score. Further research is needed to generalize the result.

Current Status of Catheter Ablation for Atrial Fibrillation in Japan.

Catheter ablation for atrial fibrillation (AF) has been an established and frequently utilized approach in a variety of clinical settings. Nevertheless, real-world data about the clinical course of AF patients after initial catheter ablation remain limited, and these are mainly derived from particular registries or selected high-volume centers.In this study, we used health check-ups and insurance claims database from a Japanese insurance organization. The study population was comprised of 1777 patients who underwent catheter ablation for AF before June 2016. During the 3-year follow-up period, 396 (22.3%) patients underwent at least one repeated AF ablation, while 74 (4.2%) underwent two or more repeated ablations. In multivariate Cox regression analysis, longer time after AF diagnosis (7-11 months and ≥12 months versus 1-6 months) (HR, 1.05; 95% CI, 1.01-1.08 and HR, 1.04; 95% CI 1.02-1.07) was independently associated with repeated ablation. The discontinuation rates of OACs and AADs after the first ablation were 26.7% and 63.0% at 3 months and 75.2% and 89.1% at 1 year after the initial ablation, respectively. The former was independently associated with shorter time after AF diagnosis and lower diastolic blood pressure, whereas the latter was independently associated with older age, smaller CHADS2 score, and shorter time after AF diagnosis.We presented real-world data regarding the clinical course of young Japanese AF patients after initial catheter ablation based on a claims database in Japan.

Thyroid Function in 3000 Cases of Patients With Atrial Fibrillation Treated With Catheter Ablation

Objective: Thyroid hormones have various effects on cardiac and circulatory systems, leading to arrhythmias and heart failure. In Europe and the United States, it has been reported that elevated thyroid hormones within the normal range have been reported to be associated with a risk of atrial fibrillation, however, there was no report on Japanese cases, a country that differs in iodine intake and ethnicity from the West. Therefore, we evaluated the abnormality of thyroid function in a large number of cases of atrial fibrillation (AF) who received catheter ablation (RFCA) in Japan. Methods: We evaluated 2,937 cases of atrial fibrillation (2,084 males, mean age 64.1±10.7 years and 853 females, 69.0±8.5 years) who underwent RFCA at the Gunma Prefectural Cardiovascular Center between 2012 and 2018. As a control we used a total of 15,660 participants for health check-up (9,176 males, mean age 49.7±9.8 years and 6,484 females, 48.9±10.3 years) from 2006 to 2013, and we evaluated thyroid function after adjusting for gender-specific age. Results: The prevalence of overt hyperthyroidism was significantly higher in the RFCA-treated male group (0.43%) than in the control group (0.07%), even after adjusting for age (p<0.01). Similarly, the prevalence of subclinical hyperthyroidism was also significantly higher in the RFCA-treated male group (3.12%) than in the control group (0.94%) after adjusting for age (p<0.01). On the other hand, subclinical hypothyroidism was significantly lower in the RFCA-treated group after adjusting for age (2.97% in the RFCA-treated group and 3.93% in the control group, p<0.01). Females showed the same results as males. Conclusions: In an iodine rich country Japan, not only overt hyperthyroidism but also subclinical hyperthyroidism is an obvious risk factor for severe atrial fibrillation in Japan. Intriguingly, subclinical hypothyroidism might contribute to the prevention of atrial fibrillation, suggesting that slightly higher serum TSH levels might be better for elderlies.

Clinical outcomes of ablation versus non-ablation therapy for atrial fibrillation in Japan: analysis of pooled data from the AF Frontier Ablation Registry and SAKURA AF Registry.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA2DS2-VASc score < 3 (HR 0.66 [vs. CHA2DS2-VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA2DS2-VASc score < 3.

Abstract 16184: Lamin A Deficiency Leads to Electrophysiological and Nuclear Abnormalities Reminiscent of Atrial Cardiomyopathy in Zebrafish

Introduction: Mutations in the lamin A/C ( LMNA ) gene have been causally linked to atrial arrhythmias and cardiac conduction disease (CCD) in young adults. However, the mechanism by which the laminopathy leads to perturbed cardiac electrophysiology has not been fully elucidated. Hypothesis: We hypothesize that protein-truncating variants in LMNA will impair the mechano-protection force in the nuclear envelope and will lead to early-onset cardiomyocyte degeneration and CCD. Methods: In a multi-regional registry of early-onset CCD and atrial fibrillation in Japan, we performed whole-exome DNA sequencing of 23 probands. Using CRISPR/Cas9, we generated indels of candidate gene homologues in zebrafish and characterized cardiac physiology using optical mapping technology and immunohistochemistry. Results: Among all probands, our study revealed four rare nonsense variants in the nuclear protein-coding genes. We focused on a LMNA protein-truncating variant, c.339dupT (p.K114X fsX1), and created a variant in the zebrafish lmna that produced a similar truncation. Lmna -/- zebrafish larvae showed shortened atrial action potential duration (APD) (msec.) compared to wild-type controls (162 ± 19 vs 227 ± 79, p&lt;0.05), while conduction velocities (CV) did not vary between the genotypes. In contrast, the atrioventricular canal of lmna -/- embryos exhibited prolonged APD (399 ± 51 vs 322 ± 47, p&lt;0.05) and slower CV (mm/sec.) (0.37 ± 0.12 vs 0.57 ± 0.12, p&lt;0.05) than controls. Immunohistochemistry demonstrated that atrial cardiomyocytes of embryonic lmna -/- zebrafish displayed significantly decreased cell numbers and smaller cell size compared to those of controls, which in turn developed into abnormal nuclear structures in adult. Conclusions: These findings suggest that lamin A is a prerequisite for proper atrial cardiomyocyte morphology in embryonic zebrafish, and is indispensable for correct cardiac electrophysiology and -conduction.

Left atrial appendage size in patients with atrial fibrillation in Japan and the United States.

Left atrial appendage (LAA) evaluation is important to select the optimal LAA closure device for patients with atrial fibrillation (AF). The LAA characteristics of Japanese patients remain uninvestigated. We compared the LAA size and morphology between 212 Japanese AF patients before catheter ablation and 119 AF patients undergoing LAA closure in the United States (US). We measured the LAA ostial dimension and depth by transesophageal echocardiography in all patients and determined the LAA morphology types of Japanese patients by multidetector cardiac computed tomography and those of US patients by LAA angiography. The maximum LAA ostial dimension was significantly larger in Japanese patients than in US patients (22.6 ± 4.1mm vs. 21.5 ± 3.5mm, P = 0.02). Also, Japanese patients had larger maximum dimension and depth corrected by body surface area than US patients in both paroxysmal and nonparoxysmal AF groups. The angle showing the maximum dimension was 0° or 135° in approximately 75% of patients in both groups. The common LAA morphology types were "cauliflower" and "chicken wing" in Japanese patients and "cactus" and "windsock" in US patients. In this study, Japanese patients had a larger LAA size than US patients. Because the maximum LAA dimension was obtained at the same angles, the LAA measurement method for US patients can be applicable to Japanese patients.

A Pooled Analysis of the Prognostic Significance of Brugada Syndrome with Atrial Fibrillation.

Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF. We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events. BrS patients with AF in all studies (OR 1.92, 95% CI:0.91to 4.04, P =0.09; Heterogeneity: P = 0.03, I2=61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P=0.91; Heterogeneity: P = 0.006, I2=80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P=0.002; Heterogeneity: P = 0.40, I2=0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001). On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.

Age-Related Differences in the Clinical Characteristics and Treatment of Elderly Patients With Atrial Fibrillation in Japan - Insight From the ANAFIE (All Nippon AF In Elderly) Registry.

Atrial fibrillation (AF) is increasing as the global population ages. Elderly AF patients (≥75 years) have a worse prognosis than younger patients, and effective management is often difficult due to multiple comorbidities. This analysis examined the age-related differences in clinical characteristics and treatment in real-world elderly Japanese AF patients.Methods and Results:The ANAFIE Registry is a multicenter, prospective, observational registry of 32,726 non-valvular AF patients aged ≥75 years. The present study assessed the age-related differences in baseline clinical status and anticoagulant therapy between age groups 75-<80, 80-<85, 85-<90, and ≥90 years. The prevalence of persistent or permanent AF increased, and that of paroxysmal AF decreased, with increasing age (trend P<0.0001). The risk of stroke, based on CHADS2and CHA2DS2-VASc scores, and bleeding, based on HAS-BLED score, increased with age. Both warfarin and apixaban were used more often as age increased (trend P<0.0001, for each), while other anticoagulants were used less. Anticoagulant doses were significantly lower in older patients. Permanent/persistent AF, comorbidities, and cardiovascular and bleeding risk all increased significantly with age. Furthermore, use of warfarin and apixaban increased with age, accompanied by a decrease in other oral anticoagulant usage.

Current Status and Clinical Outcomes of Oral Anticoagulant Discontinuation After Ablation for Atrial Fibrillation in Japan ― Findings From the AF Frontier Ablation Registry ―

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 CHA2DS2-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 CHA2DS2-VASc scores but not with OAC status. 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.

P1865Incidence and predictors of invasively-treated pericardial effusion during catheter ablation of atrial fibrillation in Japan

Abstract Purpose and method Japanese Heart Rhythm Society requested electrophysiology centers to register the data of patients who underwent catheter ablation for atrial fibrillation (AF) in designated eight months from 2011 to 2017. We assessed the incidence and predictors of pericardial effusion (PE) as an early complication of AF ablation. Results More than two hundred EP centers reported the data of 13,233 AF ablation cases (age; 64.2±10.7 years, male; 72.6%, paroxysmal AF; 63.4%). Clinically significant complications occurred in 601 subjects (4.5%). Critical PE occurred in 116 patients (0.8%), while six of them required open-chest surgery. Overall complication rate did not show significant changes. In contrast, incidence of PE declined over time (2012:1.2%, 2017:0.5%, p=0.003). Multiple logistic regression analysis showed that seven factors were related with higher incidence of PE. Among these factors, primary extra-PV ablation and hypertrophic cardiomyopathy (HCM) were more remarkably associated with higher rate of PE (PVI[−] vs. PVI[+]= 9.0% vs. 0.8%, OR 12.3, p&lt;0.001; HCM: [+] vs. [−] = 2.6% vs. 0.8%, OR 3.26, p=0.001). Comorbidity of coronary artery disease (CAD) and use of CARTO system were related with lower PE rate (CAD: [+] vs [−] = 0.2% vs. 0.9%, OR 0.22 [p=0.034], CARTO: [+] vs [−] = 0.7% vs. 1.2%, OR 0.52 [p=0.001]). None of cryobaloon ablation, gender, type of AF, center volume, periprocedural oral anticoagulant, or left atrial diameter was significantly related with the occurrence of PE. Conclusions Incidence of critical PE decreased recently. HCM and primary extra-PV ablation were outstanding predictors of critical PE.

Abstract WP256: Administration of Cilostazol Clarifies the Burden Atrial Fibrillation in Non-Cardioembolic Stroke

Introduction: The survey of atrial fibrillation (AF) is routinely recommended in acute stroke case, even in patients without AF on admission, because the AF leads to a sever stroke. Cilostazol is often used for stroke patients without AF in Japan; however, it has the adverse events of palpitation due to the vessels dilatation by increased nitric oxide. We hypothesized that administration of cilostazol may clarify the burden AF in stroke patients without AF. Methods: From our prospective randomized control study, (randomized to dual antiplatelet therapy using cilostazol and aspirin or aspirin alone targeted patients for non-cardioembolic stroke [ADS]), patients assessed the presence of AF were retrospectively analyzed. Presence of AF was detected using ECG monitoring and Holter ECG. All patients were divided into the AF group and the non-AF group and imaging and laboratory findings were compared between the 2 groups. Multivariate regression analysis was conducted to evaluate the independent factors related to new AF. Results: 1194 patients (793 [66%] men; median age [IQR] of 69 [61-77] years, NIHSS score 2 [1-4], onset-to-admission 10.8 [4.7-20.5] hours) patients were included. AF was newly detected in 41 patients (3 by ECG, 21 by the ECG monitoring and 17 by the Holter ECG) during hospitalization. Patients randomized to the combined cilostazol and aspirin therapy frequently had the AF than those to aspirin alone (29/596 [5%] vs. 12/598 [2%], p=0.007). AF group was older than the non-AF group (76 [72-82] vs. 68 [60-77] years, p&lt;0.001). NIHSS score was similar between AF and non-AF group (5 [3-12] vs. 4 [2-6] p=0.062). Serum brain natriuretic peptide (BNP) level was higher in AF group (65.9 [31.7-145.5] vs. 25.6 [13.1-52.5] ng/ml. p&lt;0.001). Regarding imaging findings, cardio-thoracic ratio (CTR) was elevated (p&lt;0.001), multiple infarcts was frequent (p=0.003) and the infarcts size was larger (&gt;1.5cm) (p&lt;0.001) in AF group. By multivariate regression analysis, cilostazol administration was the independent factor for new AF detection (odds ratio 2.81, 95%CI: 1.30-6.09, p=0.009) adjusting for age, infarct size and number, CTR, BNP, and NIHSS score. Conclusion: Administration of cilostazol increases the detectability of AF in acute non-cardioembolic stroke.

Comparative effectiveness and safety of warfarin and dabigatran in patients with non-valvular atrial fibrillation in Japan: A claims database analysis

BackgroundAntithrombotic therapy, including direct oral anticoagulants, is recommended in patients with non-valvular atrial fibrillation (NVAF) who are at intermediate-to-high risk of stroke. The aims of this study were to assess the patterns of oral anticoagulant (OAC) prescription in Japanese patients with NVAF and compare the effectiveness and safety of dabigatran and warfarin. MethodsThis was a retrospective observational study of adults with NVAF who initiated dabigatran or warfarin between March 14, 2011 and June 30, 2016, using electronic claims data of approximately 12.94 million patients from 230 hospitals. Propensity score matching was used to derive equal patient cohorts. Outcomes included the combined incidence of stroke, systemic embolism, and intracranial bleeding (primary endpoint) and the incidence of major bleeding (secondary endpoint). ResultsOverall, 400,884 patients were included. Among those prescribed an OAC, warfarin was the most common (34.3%). For the comparison of dabigatran and warfarin, 4606 patients were propensity-score matched in each cohort. Dabigatran recipients had lower incidences of stroke, systemic embolism, and intracranial bleeding [29.0 vs. 35.6 per 1000 patient-years; hazard ratio (HR), 0.72; 95% confidence interval (CI): 0.53–0.97; p=0.031] and major bleeding (6.4 vs. 11.3 per 1000 patient-years; HR, 0.55; 95% CI: 0.30–0.99; p=0.048). The most common type of bleeding in both groups was gastrointestinal and the incidence was lower in dabigatran recipients (1.6 vs. 6.4 per 1000 patient-years; HR, 0.24; 95% CI: 0.08–0.69; p=0.009). ConclusionsIn Japan, dabigatran was associated with a lower risk of stroke, systemic embolism, and intracranial bleeding and major bleeding compared with warfarin in patients with NVAF.

PMD15 - Economic Burden of Atrial Fibrillation in Japan

The burden of AF including stroke related costs is considered to remain substantial. The objective of this study is to assess the annual health care cost of AF in Japan. A systematic literature review was conducted through searching MEDLINE and Ichushi-Web to identify evidence used in the analysis. We estimated the total number of patients with AF in Japan based on the prevalence rate of AF and the size of Japanese population. Total costs included treatment costs of major events associated with AF (stroke and bleedings), AF treatment costs and post-event long-term care costs. AF patients are assumed to be treated with warfarin, DOACs, or no treatment. Annual drug costs and outpatient costs were included and dosage of each drugs were correlated to relevant observational studies. The incidence rates of ischemic stroke (IS), hemorrhagic stroke (HS), intracranial hemorrhage (ICH) and gastrointestinal bleeding and average cost of each event were retrieved from the literature. Treatment costs of stroke and ICH were estimated by severity of disability. Annual number of IS, HS, ICH and gastrointestinal bleeding was estimated to be approximately 23,000, 8,500, 9,400 and 14,000, respectively. The annual medical cost and long-term care cost per patient was estimated to be JPY 104,000 - 145,000. The number of AF patients in Japan was 1.32 million in 2017, therefore, the nation-wide annual medical cost and long-term care cost of AF was estimated to be approximately JPY 137.5 billion - 191.4 billion over this period. The annual medical cost and long-term care cost of AF in Japan was high. As the prevalence of AF tends to be higher in the elderly population, the incidence of AF will further increase making the impact of the burden more enormous in Japan due to a large proportion of the population entering old age.

Prevalence and clinical characteristics of obstructive- and central-dominant sleep apnea in candidates of catheter ablation for atrial fibrillation in Japan

IntroductionWe aimed to study the prevalence and types of sleep apnea (SA) as well as their clinical characteristics in atrial fibrillation (AF) ablation candidates in Japan. MethodsBefore catheter ablation, 197 consecutive AF patients (age: 60 ± 9 years, body mass index; 25.0 ± 3.0) were evaluated with portable polygraphy. We compared the clinical characteristics, according to the severity of SA as well as its types, as defined by the presence of obstruction and the mixed vs. central apnea indices. ResultsThe mean apnea–hypopnea index (AHI) was 17.7 ± 11.9, with 135 AF patients having an AHI ≥10 (68.5%). Patients with an AHI ≥10 had a significantly higher body mass index, plasma brain natriuretic peptide (BNP) level, prevalence of hypertension, and larger left atrial size. Among patients with an AHI ≥10, the incidence of obstructive-dominant SA was 60.9% and that of central-dominant SA was 7.6%. The prevalence of hypertension was significantly higher in obstructive-dominant SA patients (obstructive vs. central: 48.3% vs. 20.0%, P = 0.038). The obstructive apnea index correlated with plasma BNP level and age, but the central and mixed apnea indices did not. ConclusionsThe prevalence of SA was common in AF ablation candidates, even without an obesity epidemic, and the SA type was predominantly obstructive. Portable polygraphy was useful for detecting undiagnosed SA patients in AF ablation candidates.