Fushimi Atrial Fibrillation Registry Research Articles

Association of left atrial enlargement with heart failure events in non-valvular atrial fibrillation patients with preserved left ventricular ejection fraction.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little is known regarding the risk stratification for incident HF in AF patients, especially with preserved left ventricular ejection fraction (LVEF). The Fushimi AF Registry is a community-based prospective survey of AF patients. From the registry, 3002 non-valvular AF patients with preserved LVEF and with the data of antero-posterior left atrial diameter (LAD) at enrolment were investigated. Patients were stratified by LAD (<40, 40-44, 45-49, and ≥50 mm) with backgrounds and HF hospitalization incidences compared between groups. Of 3002 patients [mean age, 73.5 ± 10.7 years; women, 1226 (41%); paroxysmal AF, 1579 (53%); and mean CHA2DS2-VASc score, 3.3 ± 1.7], the mean LAD was 43 ± 8 mm. Patients with larger LAD were older and less often paroxysmal AF, with a higher CHA2DS2-VASc score (all P < 0.001). Heart failure hospitalization occurred in 412 patients during the median follow-up period of 6.0 years. Larger LAD was independently associated with a higher HF hospitalization risk [LAD ≥ 50 mm: hazard ratio (HR), 2.36; 95% confidence interval (CI), 1.75-3.18; LAD 45-49 mm: HR, 1.84; 95% CI, 1.37-2.46; and LAD 40-44 mm: HR, 1.34; 95% CI, 1.01-1.78, compared with LAD < 40 mm) after adjustment by age, sex, AF type, and CHA2DS2-VASc score. These results were also consistent across major subgroups, showing no significant interaction. Left atrial diameter is significantly associated with the risk of incident HF in AF patients with preserved LVEF, suggesting the utility of LAD regarding HF risk stratification for these patients.

The gender difference in risk factor and incidence rate of hospitalization for heart failure in Japanese atrial fibrillation patients: The Fushimi AF Registry

Abstract Background Gender-specific medicine is of concern in cardiovascular medicine. However, the gender difference in risk factor and incidence rate of hospitalization for heart failure (HF) in Japanese atrial fibrillation (AF) patients is little known. The aim of this study is to compare the risk factor and incidence rate of HF hospitalization in male and female. Method In the Fushimi AF Registry, we started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and risk factor and incidence rate of HF hospitalization between the two groups. Result Male patients were younger (male vs, female; 71.5 years vs. 76.7 years, p&amp;lt;0.001), greater in body weight (65.0 kg vs. 51.2 kg, p&amp;lt;0.001), had lower pulse rate (77.5 bpm vs. 79.4 bpm, p=0.008), more often persistent/permanent type (52.0% vs. 48.2%, p=0.044), more likely to have previous stroke/systemic embolism (21.1% vs. 18.6%, p=0.039), diabetes mellitus (DM) (26.2% vs. 19.9%, p&amp;lt;0.001), coronary artery disease (CAD) (16.0% vs. 12.3%, p&amp;lt;0.001) and less likely to have prior HF (24.0% vs. 32.3%, p&amp;lt;0.001), chronic kidney disease (CKD) (33.7% vs. 39.3%, p&amp;lt;0.001) and had lower CHADS2 score (1.96 vs. 2.15, p&amp;lt;0.001). In prescription data, male patients more often received oral anticoagulant (58.2% vs. 52.1%, p&amp;lt;0.001) and less in diuretics. Systolic blood pressure, hypertension, prescription of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta blocker were comparable between the two groups. During the median follow-up of 1,824 days, the incidence rate of HF hospitalization was lower in male than female group (male vs. female: 1.74 vs. 2.09 per 100 person-years, log rank p=0.005). On multivariate Cox regression analysis, age, sustained type of AF, prior HF, DM, CAD and CKD were significantly associated with an increased risk of HF hospitalization in male group. On the other hand, age, prior HF, DM, CKD were significantly associated with an increased risk of HF hospitalization but neither sustained type of AF nor CAD was in female group. Conclusion The incidence rate of HF hospitalization was lower in male patients than female patients. The risk factor associated with HF hospitalization were different between male and female in Japanese AF patients.

Abstract 16129: The Gender Difference in Risk Factors and Incidence Rate of Ischemic Stroke in Japanese Atrial Fibrillation Patients: The Fushimi AF Registry

Background: Gender-specific medicine is of concern in cardiovascular medicine. We previously reported that there was not gender difference in the incidence of ischemic stroke from the Fushimi AF Registry. However, the gender difference in risk factors of ischemic stroke in Japanese atrial fibrillation (AF) patients is little known. The aim of this study is to compare the risk factors and incidence rate of ischemic stroke in male and female using the latest data with longer follow-up. Method: In the Fushimi AF Registry, follow-up data were available for 4,496 patients. In the entire cohort, 2,677 were male and 1,819 were female. We compared clinical characteristics and risk factors and incidence rate of ischemic stroke between the two groups. Result: Male patients were younger (male vs. female; 71.5 years vs. 76.7 years, p&amp;lt;0.01), greater in body weight (65.0 kg vs. 51.2 kg, p&amp;lt;0.01), were more often sustained type (52.0% vs. 48.2%, p=0.04), more likely to have diabetes mellitus (26.2% vs. 19.9%, p&amp;lt;0.01), coronary artery disease (16.0% vs. 12.3%, p&amp;lt;0.01) and less likely to have prior heart failure (24.0% vs. 32.3%, p&amp;lt;0.01), chronic kidney disease (CKD) (33.7% vs. 39.3%, p&amp;lt;0.01) and had lower CHADS 2 score (1.96 vs. 2.15, p&amp;lt;0.01). In prescription data, male patients more often received oral anticoagulant (58.2% vs. 52.1%, p&amp;lt;0.01) and antiplatelet drug (APD) (29.0% vs. 23.8%, p&amp;lt;0.01). Hypertension, left atrium enlargement (LAE), previous stroke and major bleeding were comparable between the two groups. During the median follow-up of 1,824 days (longest 10 years), the incidence rate of ischemic stroke was not significantly different between two groups (0.86 vs. 0.89% per person-year, log rank p=0.32). On multivariate Cox regression analysis, age, previous stroke and LAE were significantly associated with an increased risk of ischemic stroke in both groups. CKD and prescription of APD were significantly associated with an increased risk of ischemic stroke in male, while body weight was in female. Conclusion: The incidence rate of ischemic stroke was not significantly different between male and female. The risk factors associated with ischemic stroke were different between male and female in Japanese AF patients.

Abstract 13820: Association of Cardiothoracic Ratio With Heart Failure Events in Atrial Fibrillation Without Heart Failure: The Fushimi AF Registry

Background: The cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess cardiac volume status. We previously reported that N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with higher incidence of clinical events in patients with atrial fibrillation (AF) without pre-existing heart failure (HF). However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF events in AF patients without HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we divided 1,049 patients into four groups according to their CTR and NT-proBNP level (median value: 495 ng/L) at baseline, and compared the incidence of HF events (composite of cardiac death or HF hospitalization) among the groups; G1 (Lower CTR&lt;50% and Lower NT-proBNP&lt;495, n=256), G2 (Higher CTR≥50% and Lower NT-proBNP&lt;495, n=268), G3 (Lower CTR&lt;50% and Higher NT-proBNP≥495, n=117) and G4 (Higher CTR≥50% and Higher NT-proBNP≥495, n=408). Results: During the median follow-up of 5.4 years, the incidence rates of HF events in the groups either having higher NT-pro BNP group or higher CTR group were higher, as compared with patients with lower CTR and lower NT-proBNP (G1: 0.5% per person-year, G2: 1.3%, G3: 1.6% and G4: 2.5%; p&lt;0.01) (Figure). Multivariate Cox regression analysis revealed that higher CTR (≥50%) was independently associated with the incidence of HF events in AF patients without prior HF hospitalization (hazard ratio: 1.47, 95% confidence interval: 1.09-2.00). Conclusion: In Japanese AF patients without pre-existing HF, higher CTR was associated with higher incidence of HF events irrespective of NT-proBNP level.

Abstract 17006: Clinical Characteristics and All-Cause Mortality After Non-Major Bleeding in Patients With Atrial Fibrillation Taking or Not Oral-Anticoagulant: The Fushimi AF Registry

Background: The use of oral anticoagulants (OAC) in atrial fibrillation (AF) patients increases the risk of bleeding. However, the relationship between OAC use before and after non-major bleeding and all-cause mortality remains unknown. Purpose: We aimed to investigate the association between OAC prescription before and after non-major bleeding and all-cause mortality in AF patients. Method: In the Fushimi AF Registry, follow-up data were available in 4,496 patients by the end of February 2022. Patients were divided into four groups based on OAC prescription before and after non-major bleeding: G1 (OAC prescribed both before and after), G2 (OAC prescribed before but not after), G3 (OAC not prescribed before but prescribed after), and G4 (OAC neither prescribed before nor after). Non-major bleeding was defined as all bleeding except for major bleeding according to the criteria of the International Society on Thrombosis and Haemostasis. Result: During the median follow-up of 1,448 days, 733 patients experienced non-major bleeding. G1 had 452 patients, G2 had 54, G3 had 63, and G4 had 164. G1 and G2 were more often non-paroxysmal AF and had significantly higher prevalence of previous stroke or systemic embolism, heart failure and dyslipidemia and had higher CHADS2 scores than G3 and G4. All-cause mortality after non-major bleeding occurred in 91 patients in G1, 54 in G2, 63 in G3, and 164 in G4. (G1: 5.1%, G2: 13.0%, G3: 7.1%, and G4: 6.8% per patient-year, p=0.0004). Multivariate analysis showed that the G2 group had a higher incidence of all-cause mortality as compared with G1 (HR 2.49, 95%CI 1.58-3.93; p&lt;0.0001), G3 (HR 2.44, 95%CI 1.23-4.84; p=0.011), and G4 (HR 1.71, 95%CI 1.00-2.93; p=0.0502) [Figure]. Conclusion: Discontinuation of OAC therapy after non-major bleeding in Japanese AF patients was associated with increased all-cause mortality.

Abstract 13834: Prognosis of Patients With Atrial Fibrillation and Weight Loss: The Fushimi AF Registry

Background: Atrial fibrillation (AF) is a common cardiac arrythmia in the elderly, in whom frailty is often a clinical issue. Weight loss is one of the key factors of frailty, and we previously reported that low body wight (≤50 kg) was associated with higher mortality and morbidity in patients with AF. However, the association of weight loss with prognosis of AF patients is unclear. Methods: The Fushimi AF registry is a community based prospective survey of AF patients in Japan. We collected data on body weight annually, and changes in body weight were obtained in 2,922 patients (mean age, 73 years; female 39.3%; mean body weight 59.8 kg). We defined weight loss as decrease in body weight ≥ 4.5 kg or 5% in the past year based on the frailty-defining criteria in the Cardiovascular Health Study. Results: During the follow-up, 1319 patients had weight loss (7.9% per person-year). Patients with weight loss were older, and had more hypertension, diabetes, coronary artery disease, chronic kidney disease, and heart failure at baseline than those without. Prevalence of prior stroke/systemic embolisms (SE) and major bleeding were similar between patients with and without weight loss. In the logistic regression analysis, hypertension, diabetes, chronic kidney disease, and heart failure were positively associated with development of weight loss, and incidence of stroke/SE was inversely associated with weight loss. Landmark analysis after the onset of weight loss revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death. Incidence of heart failure hospitalization, stroke/SE, and major bleeding were comparable between patients with and without weight loss. After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.54-2.09) and cardiac death (hazard ratio, 1.67; 95% confidence interval, 1.15-2.43). Subgroup analyses revealed that weight loss was also significantly associated with higher all-cause and cardiac mortality regardless of age, sex, and body weight at baseline. Conclusion: In AF patients, weight loss was significantly associated with higher all-cause and cardiac mortality.

Abstract 12840: Left Atrial Enlargement is a Useful Predictor for Incident Heart Failure in Atrial Fibrillation Patients Without Pre-Existing Heart Failure

Background: Atrial fibrillation (AF) increases the risk of heart failure (HF). However, little focus has been placed on the risk stratification for HF in AF patients. Hypothesis: Left atrial diameter (LAD) is a simple prognostic parameter in patients with HF. We hypothesized that LAD is a useful predictor for incident HF in AF patients even without pre-existing HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we investigated 2,464 patients with the data of LAD at enrollment. We divided the patients into 4 groups stratified by LAD (&lt;40 mm, 40-44 mm, 45-49 mm, and ≥50 mm), and compared the backgrounds and incidence of HF hospitalization between the groups. Results: Of 2,464 patients (mean age: 72±11 years, female: 919 [37%], paroxysmal AF: 1,405 [57%], and mean CHA2DS2-VASc score: 3.0±1.6), the mean LAD was 42±8 mm (&lt;40 mm: 1007 [41%], 40-44 mm: 650 [26%], 45-49 mm: 467 [19%] and ≥50 mm: 340 [14%], respectively). Patients with larger LAD had a higher prevalence of elderly and non-paroxysmal AF, and had a higher CHA2DS2-VASc score (all P&lt;0.001). During the median follow-up of 6.0 years, 260 patients (11%) were hospitalized for HF (annual incidence: 1.8% per person-year). Kaplan-Meier curves revealed that LAD was able to stratify the incidence of HF hospitalization in AF patients without HF (Figure). Multivariable Cox regression analysis demonstrated that larger LAD were independently associated with the risk of HF after adjustment by age, sex, AF type, and CHA2DS2-VASc score (Figure). Conclusion: Larger LAD was significantly associated with the higher incidence of HF hospitalization in AF without pre-existing HF, suggesting the utility of LAD regarding the risk stratification for HF in these patients.

Utility of left ventricular ejection fraction in atrial fibrillation patients without pre-existing heart failure.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus has been placed on the prevention of HF in patients with AF. Left ventricular ejection fraction (LVEF) is an established echocardiographic parameter in HF patients. We sought to investigate the association of LVEF with HF events in AF patients without pre-existing HF. The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. In this analysis, we excluded patients with pre-existing HF (defined as having one of the following: prior HF hospitalization, New York Heart Association class≥2 in association with heart disease, or LVEF<40%). Among 3233 AF patients without pre-existing HF, we investigated 2459 patients with the data of LVEF at enrolment. We divided the patients into three groups stratified by LVEF [mildly reduced LVEF (40-49%), below normal LVEF (50-59%), and normal LVEF (≥60%)] and compared the backgrounds and incidence of HF hospitalization between the groups. Of 2459 patients [mean age: 72.4±10.5years, female: 917 (37%), paroxysmal AF: 1405 (57%), and mean CHA2 DS2 -VASc score: 3.0±1.6], the mean LVEF was 66±8% [mildly reduced LVEF: 114 patients (5%), below normal LVEF: 300 patients (12%), and normal LVEF: 2045 patients (83%)]. Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P<0.01), but age and CHA2 DS2 -VASc score were comparable between the three groups (both P>0.05). During the median follow-up period of 6.0years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF [mildly reduced LVEF (40-49%): hazard ratio=2.98, 95% confidence interval=1.99-4.45 and below normal LVEF (50-59%): hazard ratio=2.01, 95% confidence interval=1.44-2.82, compared with normal LVEF (≥60%)] after adjustment by age, sex, type of AF, and CHA2 DS2 -VASc score. LVEF<60% was significantly associated with the higher risk of HF hospitalization across all major subgroups without significant interaction (P for interaction; all P>0.05). LVEF had an independent and incremental prognostic value for HF hospitalization in addition to natriuretic peptide levels in AF patients without pre-existing HF. Lower LVEF was significantly associated with the higher incidence of HF hospitalization in AF patients without pre-existing HF, leading to the future risk stratification for and prevention of incident HF in AF patients.

Proteinuria is independently associated with heart failure events in patients with atrial fibrillation: the Fushimi AF registry.

Previous studies have shown that proteinuria is independently associated with the incidence of atrial fibrillation (AF), and is also associated with the incidence of cardiovascular events such as stroke and thromboembolism in patients with AF. However, the association of proteinuria with heart failure (HF) events in patients with AF remains unclear. The Fushimi AF Registry is a community-based prospective study of patients with AF. Of the entire cohort of 4489 patients, 2164 patients had available data of proteinuria. We compared the clinical background and outcomes between patients with proteinuria (n=606, 28.0%) and those without (n=1558, 72.0%). Patients with proteinuria were older and had a higher prevalence of major co-morbidities. During the median follow-up of 5.0 years, the incidence rates of HF events (composite of cardiac death or HF hospitalization) were higher in patients with proteinuria than those without (4.1% vs. 2.1% person-year, P<0.01). Multivariate analyses revealed that proteinuria was an independent risk factor of the incidence of HF events [adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.13-1.74]. This association was consistent among the various subgroups, except for the age subgroup in which there was a significant interaction (P<0.01) between younger (<75 years) (unadjusted HR: 3.03, 95% CI: 2.12-4.34) and older (≥75 years) patients (unadjusted HR: 1.59, 95% CI: 1.23-2.05). Our community-based large prospective cohort suggests that proteinuria is independently associated with the incidence of HF events in Japanese patients with AF.

Impact of baseline blood pressure on adverse outcomes in Japanese patients with non-valvular atrial fibrillation: the J-RISK AF.

This study aimed to investigate the impact of baseline blood pressure (BP) on adverse outcomes in patients with atrial fibrillation (AF), using a pooled analysis performed on data from J-RISK AF, a large-scale cohort of Japanese patients with AF. Of the 16 918 patients from five major AF registries including the J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry, 15 019 non-valvular AF (NVAF) patients with baseline BP values (age, 70.0 ± 11.0 years; men, 69.1%) were analysed. Incidence rates of adverse events were evaluated between patients divided into baseline systolic BP quartiles or at 150 mmHg. During the follow-up period of 730 days, ischaemic stroke, major bleeding, all-cause death, and cardiovascular death occurred in 277, 319, 718, and 275 patients, respectively. Hazard ratios (HRs) for ischaemic stroke and major bleeding were comparable among the quartiles, whereas HRs for all-cause and cardiovascular deaths in the lowest quartile with systolic BP <114 mmHg were significantly higher [HR 1.43, 95% confidence interval (CI) 1.13-1.81; and HR 1.47, 95% CI 1.01-2.12, respectively] than in the third quartile, even after adjusting for known confounding factors. In patients with a systolic BP of ≥150 mmHg, adjusted HR for major bleeding was significantly higher than that of <150 mmHg (HR 1.64, 95% CI 1.12-2.40). In Japanese patients with NVAF, a baseline systolic BP <114 mmHg was significantly associated with higher all-cause and cardiovascular mortality. In contrast, a systolic BP ≥150 mmHg was an independent risk factor for major bleeding.

Abstract 10755: Association Between Weight Loss and Prognosis in Patients With Atrial Fibrillation: The Fushimi AF Registry

Background: Weight loss is one of the key factors of frailty, and we previously reported that low body weight (≤50 kg) was associated with higher mortality and morbidity in patients with atrial fibrillation (AF). However, the association of weight loss with prognosis in AF patients is unclear. Methods: From the Fushimi AF registry, 2,523 patients with data on changes in body weight at 1 year after enrollment and follow-up data after 1 year were included in the analysis. We defined weight loss as changes in body weight ≤-4.5 kg based on the frailty-defining criteria in the Cardiovascular Health Study. Results: At 1 year after enrollment, 273 (10.8%) patients had weight loss. Mean body weight (changes) at 1 year in patients with and without weight loss were 58.8±14.1 (-8.7±5.8) and 60.7±13.1 (0.7±3.4) kg, respectively (P=0.03). Patients with weight loss were more likely to be male, and had more heart failure, diabetes and chronic kidney disease at baseline. Age and prevalence of prior stroke/systemic embolisms (SE) were similar between the groups, but patients with weight loss had higher incidence of heart failure hospitalization (12.5% and 4.7%) and stroke/SE (4.8% and 2.2%) before 1-year follow-up. Landmark analysis after 1 year revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death (Figure A), but not stroke/SE or major bleeding. Incidence of heart failure hospitalization tended to be higher in patients with weight loss, but not statistically significant. Patients with weight loss also showed higher all-cause and cardiac mortality even in those without low body weight (Figure B). After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.43-2.21). Conclusion: In AF patients, weight loss was significantly and independently associated with higher all-cause mortality.

Abstract 12315: Prognostic Value of Proteinuria on Cardiac Events in Japanese Patients With Atrial Fibrillation: The Fushimi AF Registry

Background: Previous studies have suggested that proteinuria is independently associated with incidence of atrial fibrillation (AF). However, data regarding the impact of proteinuria on clinical outcomes in patients with AF are limited. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available in 4,489 patients, and 2,164 patients with available data of proteinuria as the results of the urine test by dipstick were examined. We divided these patients into three groups according to the level of proteinuria; positive group (n=339), trace group (n=267) and negative group (n=1,558). Results: Patients in positive group and trace group were older (positive vs. trace vs. negative; 75.9±9.7 vs. 75.7±10.8 vs. 73.4±10.5; p&lt;0.01), had higher prevalence of heart failure (HF), hypertension, diabetes mellitus and renal dysfunction (estimated glomerular filtration rate &lt;60 ml/min/1.73 m 2 ), and had higher CHADS 2 score (2.6±1.4 vs. 2.5±1.3 vs. 2.0±1.3; p&lt;0.01) and HAS-BLED score (2.2±1.2 vs. 1.9±1.0 vs. 1.7±1.0; p&lt;0.01). During the median follow-up of 2,978 days, the incidence rates of cardiac events (composite of cardiac death or HF hospitalization during follow-up) were higher in patients in both of positive group and trace group than patients in negative group (3.8% vs. 4.0% vs. 1.9% per person-year; p&lt;0.01) (Figure). Multivariate Cox proportional hazards regression analysis revealed that proteinuria was an independent determinant of cardiac events (positive vs. negative; adjusted hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.12-1.85, trace vs. negative; adjusted HR: 1.60, 95% CI: 1.23-2.09). Conclusion: In Japanese patients with AF, the presence of proteinuria, even if it was trace level, was associated with higher incidence of cardiac events.

Abstract 11512: Association Between Use of Oral Anticoagulants After Minor Bleeding and Mortality Outcomes in Patients With Atrial Fibrillation: The Fushimi AF Registry

Introduction: Oral anticoagulants (OAC) reduce the risk of ischemic stroke, but may increase the risk of major or minor bleeding in atrial fibrillation (AF) patients. However, little is known about the management of anticoagulation in patients with AF after a minor bleeding event. This study assessed the association between use of OAC and outcomes in AF patients after minor bleeding. Methods: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. A total cohort of 4,489 AF patients were analyzed in the present study. We investigated patients in whom minor bleeding occurred during follow-up period, and compared between patients with OAC and those without OAC after minor bleeding. Results: During the median follow-up period of 1,844 days, minor bleeding occurred in 744 patients (5.7% per patient-year). After excluding patients with missing prescription data after minor bleeding, 494 patients were prescribed OAC and 234 were not prescribed after minor bleeding. Patients with OAC were more often non-paroxysmal type of AF (27.4% vs 48.0%, p&lt;0.01), and were more likely to have previous thromboembolism (23.3% vs 11.5%, p&lt;0.01) and heart failure (29.4% vs 19.2%, p&lt;0.01). They had significantly higher CHADS2 score (2.11 vs 1.79, p&lt;0.01). They were less likely to have history of major bleeding (2.6% vs 5.6%, p&lt;0.05). All-cause mortality after minor bleeding occurred in 91 patients with OAC (4.5% per patient-year) and 62 (7.5% per patient-year) patients without OAC with hazard ratio (HR) 0.62 (95% confidence interval [CI], 0.45-0.86; p&lt;0.01). After adjusted by age, sex, type of AF, and comorbidities, patients with OAC after minor bleeding were significantly associated with lower incidence of all-cause mortality (HR 0.52 [95% CI, 0.37-0.73; p&lt;0.01]). Conclusions: Conclusion: Use of OAC after minor bleeding was significantly associated with lower incidence of all-cause mortality in Japanese AF patients.

Abstract 13240: The Relationship Between History of Valve Surgery and Heart Failure Event in Japanese Atrial Fibrillation Patients: The Fushimi Af Registry

Background: We previously reported that valvular heart disease (VHD) was associated with an increased risk of hospitalization for heart failure (HF) in Japanese atrial fibrillation (AF) patients. However, the association of history of surgery for VHD with HF hospitalization remains unknown. Method: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, which is a typical urban district of Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,489 patients by the end of July 2021. In the entire cohort, 747 patients had VHD. We divided them to surgery group (n=182) and non-surgery group (n=565). We compared clinical characteristics and incidence rates of HF hospitalization between two groups. Result: Patients who received valve surgery were younger (72.0 years vs. 78.0 years, p&amp;lt;0.001), had lower systolic blood pressure (118 mmHg vs. 123 mmHg, p=0.02) and pulse rate (75.5 bpm vs. 79.1 bpm, p=0.003), more often paroxysmal type (46.7% vs. 31.0%, p&amp;lt;0.001), less likely to have hypertension (51.1% vs. 66.2%, p&amp;lt;0.001) and had lower CHADS2 score (2.09 vs. 2.55, p&amp;lt;0.001) than non-surgery group. Body weight, sex, prior HF, chronic kidney disease and prescription data were comparable between two groups. During the median follow-up of 1,679 days, the incidence rate of HF hospitalization was lower in surgery group than non-surgery group (2.58% vs. 4.43% per person-year, respectively, log rank p=0.001). On multivariate Cox regression analysis, history of surgery was not significantly associated with a lower risk of HF hospitalization (adjusted hazard ratio 0.76; 95% confidence interval 0.52-1.12, p=0.16). Conclusion: The incidence rate of HF hospitalization was lower in patients with valve surgery than non-surgery group. However, history of valve surgery was not independently associated with a lower risk of HF hospitalization in Japanese AF patients.

Abstract 10746: Association of Left Ventricular Relative Wall Thickness With Thromboembolism in Non-Valvular Atrial Fibrillation Patients With or Without Hypertension: The Fushimi Af Registry

Introduction: Hypertension (HT) is the main cause of atrial fibrillation (AF) and left ventricular (LV) hypertrophy. Meanwhile, LV hypertrophy can be also the manifestation of some cardiomyopathies. We reported that increased LV relative wall thickness (RWT) was associated with the incidence of thromboembolism events (TE) in patients with non-valvular AF (NVAF). We investigated the association of RWT with TEs in NVAF patients with or without HT. Methods: In the Fushimi AF Registry, follow-up data were available for 4,489 patients. Of them, RWT values at enrollment were available for 3,408 patients with NVAF (with HT: n=2,159, without HT: n=1,249). We investigated the relationship between each RWT quartile and the incidence of TEs. Results: During the median follow-up period of 1,838 days, 297 TEs occurred. Regardless of the coexistence of HT, higher RWT groups had higher CHA 2 DS 2 -VASc score and higher HELT-E 2 S 2 score and the prescription of oral anticoagulants were comparable among the four groups. The incidence of TEs according to the groups stratified by each RWT quartile with or without HT is shown (Figure). In the multivariate analysis, higher RWT was independent predictors of TEs in the patients with or without HT (Table). The incidence rate of TEs were comparable between RWT&gt;0.6 patients with HT and without HT (2.11 vs. 2.73% per patient-year, log-rank; p=0.67), whereas the patients with HT had higher CHA 2 DS 2 -VASc and HELT-E 2 S 2 scores. Conclusions: RWT was independently associated with the incidence of TEs among Japanese patients with NVAF regardless of the concomitance of HT.

Abstract 10446: Prognostic Significance of Left Ventricular Ejection Fraction in Atrial Fibrillation Patients Without Pre-Existing Heart Failure

Introduction: Atrial fibrillation (AF) increases the risk of heart failure (HF). However, little focus has been placed on the prevention of HF in patients with AF. Hypothesis: Left ventricular ejection fraction (LVEF) is an established echocardiographic parameters in patients with HF. We hypothesized that LVEF is a useful predictor for incident HF in AF patients even without HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients without pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or LVEF &lt;40%), we investigated 2,459 patients with the data of LVEF at enrollment. We divided the patients into 3 groups stratified by LVEF (mildly reduced LVEF [40-49%], below normal LVEF [50-59%], and normal LVEF [≥60%]), and compared the backgrounds and incidence of HF hospitalization between the groups. Results: Of 2,459 patients (mean age: 72.4±10.5 years, female: 917 [37%], paroxysmal AF: 1,405 [57%], and mean CHA 2 DS 2 -VASc score: 3.0±1.6), the mean LVEF was 66±8% (mildly reduced LVEF: 114 [5%], below normal LVEF: 300 [12%] and normal LVEF: 2,045 [83%], respectively). Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P&lt;0.01). During the median follow-up period of 6.0 years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Kaplan-Meier curves revealed that LVEF at enrollment could stratify the incidence of HF hospitalization in AF patients without pre-existing HF ( Figure ). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF after adjustment by age, sex, AF type and CHA 2 DS 2 -VASc score ( Figure ). Conclusion: LVEF at enrollment could stratify the incidence of HF hospitalization in patients with AF, suggesting the importance of measuring LVEF in all AF patients even without HF.

Machine Learning Risk Prediction for Incident HeartFailure in Patients With Atrial Fibrillation.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus is placed on the risk stratification for, and prevention of, incident HF in patients with AF. This study aimed to construct and validate a machine learning (ML) prediction model for HF hospitalization in patients with AF. The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We divided the data set of the registry into derivation (n=2,383) and validation (n=2,011) cohorts. An ML model was built to predict the incidence of HF hospitalization using the derivation cohort, and predictive ability was examined using the validation cohort. HF hospitalization occurred in 606 patients (14%) during a median follow-up period of 4.4 years in the entire registry. Data of transthoracic echocardiography and biomarkers were frequently nominated as important predictive variables across all 6 ML models. The ML model based on a random forest algorithm using 7 variables (age, history of HF, creatinine clearance, cardiothoracic ratio on x-ray, left ventricular [LV] ejection fraction, LV end-systolic diameter, and LV asynergy) had high prediction performance (area under the receiver operating characteristics curve [AUC]: 0.75) and was significantly superior to the Framingham HF risk model (AUC: 0.67; P< 0.001). Based on Kaplan-Meier curves, the ML model could stratify the risk of HF hospitalization during the follow-up period (log-rank; P< 0.001). The ML model revealed important predictors and helped us to stratify the risk of HF, providing opportunities for the prevention of HF in patients with AF.

Association of beta blocker use with new-onset heart failure and mortality in atrial fibrillation without pre-existing heart failure: the Fushimi AF registry

Abstract Background Heart failure (HF) is one of the major complications in atrial fibrillation (AF). We previously reported that not a few AF patients without pre-existing HF (defined as prior HF hospitalization, New York Heart Association functional class≥2, or left ventricular ejection fraction (LVEF)&amp;lt;40%) subsequently developed new-onset HF. Beta blockers are the established therapy for HF, but it remains unclear whether beta blockers prevent new-onset HF and improve outcomes in AF patients without preexisting HF. Methods In the Fushimi AF registry, 778 of 3,262 patients without pre-existing HF were receiving beta blockers at baseline. We investigated the incidence of new-onset HF defined as cardiac death or HF hospitalization, and all-cause death in a propensity-matched cohort (N=1,198; mean age, 71 years; 39% female; mean LVEF, 66%). Additionally, annual follow-up prescription data before the onset of events were collected in 294 of patients with beta blockers and 395 of those without beta blockers. We also investigated the association of starting or stopping beta blockers with the incidence of new-onset HF and all-cause death. Results During the median follow-up of 5.8 years, new-onset HF and all-cause death occurred in 77 (12.9%) and 118 (19.7%) of patients with beta blockers, and 70 (11.7%) and 131 (21.9%) of those without beta blockers, respectively. Incidence of new-onset HF was comparable between patients with and without beta blockers (Figure 1), and incidence of all-cause death was also comparable between the two groups (Figure 2). In exploratory subgroup analyses, there was no interaction in the association of beta blockers with the incidence of events, except for pulse rate for new-onset HF and left atrial size for all-cause death. Hazard ratio of beta blockers for new-onset HF tended to be lower in patients with higher pulse rates (&amp;gt;84 bpm) (Figure 1), and that for all-cause death was lower in those without left atrial enlargement (Figure 2). Of patients with follow-up prescription data, beta blockers were stopped in 55 (18.7%) and started in 97 (24.6%) patients, respectively. Patients with starting beta blockers had higher pulse rate (78.5±17.3 vs 74.9±13.9 bpm; p=0.03) and more symptomatic AF (58.8% vs 46.0%; p=0.03) compared to those without starting beta blockers, while there was no difference in baseline characteristics between those with and without stopping beta blockers. During the follow-up, the incidences of new-onset HF and all-cause death were also comparable between the patients with and without stopping beta blockers and those with and without starting beta blockers. Conclusion Beta blockers were not associated with the incidence of new-onset HF and all-cause death in AF patients without pre-existing HF. However, the exploratory subgroup analyses suggested the existence of subjects who may benefit from beta blockers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.

Association of Concomitant Coronary Artery Disease With Cardiovascular Events in Patients With Atrial Fibrillation - The Fushimi AF Registry.

Atrial fibrillation (AF) patients often have concomitant coronary artery disease (CAD); however, there are little data on clinical characteristics and outcomes of such patients in daily clinical practice in Japan.Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 4,464 patients, and the median follow up was 5.1 (interquartile range: 2.3-8.0) years. History of CAD was present in 647 patients (14%); of those patients, 267 (41%) had history of myocardial infarction (MI). Patients with CAD were older and had more comorbidities than those without CAD. The crude incidences (% per patient-year) of cardiovascular events were significantly higher in patients with CAD than those without CAD (cardiac death: 1.8 vs. 0.7, stroke or systemic embolism [SE]: 2.9 vs. 2.1, MI: 0.6 vs. 0.1, composite of those events: 5.1 vs. 2.8, respectively, all log-rank P<0.01). After multivariate adjustment, concomitant CAD was associated with incidence of cardiac events, and history of MI was associated with incidence of MI; however, neither history of CAD nor MI was associated with the incidence of stroke/SE. In Japanese AF patients, concomitant CAD was associated with higher prevalences of major co-morbidities and higher incidences of cardiovascular events; however, history of CAD was not associated with the incidence of stroke/SE.

Age-dependent risk for thromboembolism in atrial fibrillation: The Fushimi AF registry.

BackgroundThe risk for thromboembolism depending on the different age subgroups in patients with atrial fibrillation (AF) has not been fully elucidated.MethodsThe Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto. Follow-up data were available for 4,466 patients by the end of 2019. Clinical determinants and the description of variables which interact and lead to the incidence of thromboembolism (the composite of ischemic stroke and systemic embolism [SE]) were identified in overall population and in age subgroups (≤64, 65–74, and ≥ 75 years).ResultsA total of 314 patients developed thromboembolism during the median follow-up of 1,610 days (1.56 per 100 person-years). The independent determinants were age advance (per 10 years, hazard ratio [HR]: 1.51, 95% confidence interval [CI]: 1.22–1.86, P < 0.001), low body weight (HR: 1.91, 95% CI: 1.35–2.70, P < 0.001), history of stroke or SE (HR: 2.06, 95% CI: 1.54–2.76, P < 0.001), chronic kidney disease (HR: 1.34, 95% CI: 1.01–1.78, P = 0.043), and left atrial enlargement (HR: 1.57, 95% CI: 1.18–2.10, P = 0.0021). With regard to the age subgroup analysis, diabetes mellitus (P = 0.043), vascular disease (P = 0.005), male sex (P = 0.022), and sustained AF (P = 0.014) indicated significantly relevant interactions between the age subgroups and thromboembolism.ConclusionThe risk and the impact of baseline characteristics on thromboembolism in patients with AF varied depending on the age subgroups.