Association of Regression from Sustained to Paroxysmal Atrial Fibrillation With Clinical Outcomes: The Fushimi AF Registry.

In some cases, albeit infrequently, patients with atrial fibrillation (AF) may experience a regression from a sustained to a paroxysmal type. We sought to investigate how regression of AF is associated with outcomes. Among the patients with AF enrolled in the Fushimi AF Registry who were identified as having sustained AF at baseline, conversion of sustained to paroxysmal AF during follow-up was defined as AF regression. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiac death, myocardial infarction, ischemic stroke, systemic embolism, or hospitalization due to heart failure. Among 2,261 patients with sustained AF at baseline, AF regression was observed in 214 (9.5%) patients over a median follow-up period of 5.8 years (1.78% per patient-year). The annual incidence of MACE was significantly lower in patients with AF regression than in those without (3.47% vs 6.59% per patient-year, p <0.001, adjusted hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.38 to 0.72). Furthermore, AF regression was significantly associated with reduced risk of MACE during and after the regression period from sustained to paroxysmal forms (during the regression period: adjusted HR 0.45, 95% CI 0.22 to 0.90; after the regression period: adjusted HR 0.43, 95% CI 0.26 to 0.67). The incidence of MACE was comparable between spontaneous regression (35/178: 19.7%) and therapy-associated regression (either receiving catheter ablation or antiarrhythmic drugs before the regression) (7/36: 19.4%) (p = 0.98). Regression of AF was associated with lower incidence of adverse cardiovascular events. The risk of adverse events decreased significantly during the regression period, and this reduced risk persisted after regression. Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000005834.

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

Aims: 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). Methods and results: 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. Conclusion: 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.

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

AIMS: 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. METHODS AND RESULTS: 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 ± 10.5 years, 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 6.0 years, 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. CONCLUSIONS: 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.

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: Our community-based large prospective cohort suggests that proteinuria is independently associated with the incidence of HF events in Japanese patients with AF.

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

Background: 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. Objectives: This study aimed to construct and validate a machine learning (ML) prediction model for HF hospitalization in patients with AF. Methods: 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. Results: 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). Conclusions: 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 Concomitant Coronary Artery Disease With Cardiovascular Events in Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: 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. CONCLUSIONS: 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.

A case of successful radiofrequency catheter ablation for atrial tachycardia originating from the inferior vena cava using high-resolution mapping.

A 60-year-old man presented with sustained supraventricular tachycardia. Atrial tachycardia (AT), with the earliest atrial activation (EAA) occurring at the ostium of the coronary sinus, was reproducibly induced. Three-dimensional electroanatomical mapping (3DEAM) using a 3.5-mm distal electrode tip linear catheter (Thermocool) and radiofrequency energy (RF) was performed at the fractionated atrial electrogram site. It preceded at 30 ms to the EAA but did not terminate AT. Further 3DEAM using a multielectrode mapping catheter (Pentaray) demonstrated a centrifugal propagation pattern at the boundary zone between the right atrium and inferior vena cava. RF application here terminated AT, which then became non-inducible.

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

Background: The risk for thromboembolism depending on the different age subgroups in patients with atrial fibrillation (AF) has not been fully elucidated. Methods: The 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). Results: A 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. Conclusion: The risk and the impact of baseline characteristics on thromboembolism in patients with AF varied depending on the age subgroups.

10-Year Trends of Antithrombotic Therapy Status and Outcomes in Japanese Atrial Fibrillation Patients　- The Fushimi AF Registry.

BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke and death. Oral anticoagulants (OAC) are highly effective in reducing the risk of stroke, and direct oral anticoagulants (DOAC) became available worldwide in 2011.Methods and Results:The Fushimi AF Registry is an on-going prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The study cohort consisted of 4,489 patients (mean age 73.6 years, 59.6% male, mean CHADS2score 2.03), enrolled in 2011-2017. From 2011 to 2021, antithrombotic therapy has undergone a major transition; the proportion of patients receiving OAC has increased from 53% to 70%, with a steady uptake of DOAC (from 2% to 52%), whereas the proportion of patients receiving antiplatelet agents has decreased from 32% to 14%. Over a median follow-up of 5.1 years, the incidence of stroke/systemic embolism (SE), major bleeding, and all-cause death was 2.2%, 1.9%, and 4.9% per patient-year, respectively. The incidence of stroke/SE (1.6% vs. 2.3%; P<0.01), major bleeding (1.6% vs. 2.0%; P=0.07), and death (4.2% vs. 5.0%; P<0.01) was lower among patients enrolled in 2014-2017 than in 2011-2013, despite comparable baseline characteristics (age 73.2 vs. 73.7 years, CHADS2score 2.03 vs. 2.04, and HAS-BLED score 1.67 vs. 1.77, respectively). CONCLUSIONS: Over the past 10 years, there has been a major transition in antithrombotic therapy and a decline in the incidence of adverse events in AF patients.

Clinical Characteristics and Outcomes of Very Elderly Patients With Atrial Fibrillation at High Bleeding Risk　- The Fushimi AF Registry.

Background: The ELDERCARE-AF trial demonstrated that low-dose edoxaban prevented stroke or systemic embolism (SE) in very elderly Japanese patients with non-valvular atrial fibrillation (NVAF) in whom standard oral anticoagulant therapy was inappropriate because of high bleeding risk. The aim of this study was to elucidate the characteristics and outcomes of such patients in routine clinical practice. Methods and Results: Data were extracted from the Fushimi AF Registry for ELDERCARE-eligible NVAF patients aged ≥80 years, with a CHADS2 score ≥2 and ≥1 bleeding risk factors, as shown in the ELDERCARE-AF trial. ELDERCARE-eligible patients (n=549; 12.8% of the entire cohort, 52.9% of those aged ≥80 years and with CHADS2 score ≥2) were less often male, were older, had more comorbidity and higher risk scores than non-eligible patients from the entire cohort (n=3,734). The crude incidence (% per patient-year) of adverse events was significantly higher in ELDERCARE-eligible than non-eligible patients (stroke/SE, 4.8% vs. 2.0%; major bleeding, 3.6% vs. 1.9%; all-cause mortality, 15.5% vs. 3.9%; cardiovascular death, 2.7% vs. 0.6%; all log-rank P<0.001). Compared with non-eligible patients aged ≥80 years and with a CHADS2 score ≥2 (n=488), the incidence of stroke/SE, all-cause mortality, and cardiovascular death remained significantly higher in ELDERCARE-eligible patients. Conclusions: Patients with NVAF who met the inclusion criteria of the ELDERCARE-AF trial were common in routine clinical practice, and had poor clinical outcomes.

Characteristics and clinical outcomes in atrial fibrillation patients classified using cluster analysis: the Fushimi AF Registry.

AIMS: The risk of adverse events in atrial fibrillation (AF) patients was commonly stratified by risk factors or clinical risk scores. Risk factors often do not occur in isolation and are often found in multimorbidity 'clusters' which may have prognostic implications. We aimed to perform cluster analysis in a cohort of AF patients and to assess the outcomes and prognostic implications of the identified comorbidity cluster phenotypes. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Hierarchical cluster analysis was performed on 4304 patients (mean age: 73.6 years, female; 40.3%, mean CHA2DS2-VASc score 3.37 ± 1.69), using 42 baseline clinical characteristics. On hierarchical cluster analysis, AF patients could be categorized into six statistically driven comorbidity clusters: (i) younger ages (mean age: 48.3 years) with low prevalence of risk factors and comorbidities (n = 209); (ii) elderly (mean age: 74.0 years) with low prevalence of risk factors and comorbidities (n = 1301); (iii) those with high prevalence of atherosclerotic risk factors, but without atherosclerotic disease (n = 1411); (iv) those with atherosclerotic comorbidities (n = 440); (v) those with history of any-cause stroke (n = 681); and (vi) the very elderly (mean age: 83.4 years) (n = 262). Rates of all-cause mortality and major adverse cardiovascular or neurological events can be stratified by these six identified clusters (log-rank test; P < 0.001 and P < 0.001, respectively). CONCLUSIONS: We identified six clinically relevant phenotypes of AF patients on cluster analysis. These phenotypes can be associated with various types of comorbidities and associated with the incidence of clinical outcomes. CLINICAL TRIAL REGISTRATION INFORMATION: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.

Major adverse cardiovascular events and mortality after catheter ablation in Japanese patients with atrial fibrillation: The Fushimi AF Registry.

BACKGROUND: The impact of catheter ablation (CA) on the long-term clinical outcomes in atrial fibrillation (AF) are unclear due to limited cohort investigations. METHODS: The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. Of 4465 patients enrolled between March 2011 and July 2019, analyses were performed on 2639 patients (492 patients who underwent CA and 2147 patients who received standard rhythm- and/or rate-control drug therapy at baseline). We compared the baseline characteristics and the incidence of major adverse cardiovascular events (MACE: the composite of cardiovascular death, heart failure hospitalization, myocardial infarction, ischemic stroke or systemic embolism), and all-cause mortality during the follow-up using propensity score matching. RESULTS: After entering 20 covariates in the current matching analysis, 342 patients who underwent CA and 342 matched patients who received drug therapy, with a median follow-up of 1865 days, were included. The patients who underwent CA were significantly associated with lower incidence of MACE (hazard ratio (HR) 0.56, 95% confidential interval (CI) 0.36-0.86; P = 0.0077), and all-cause mortality (HR 0.47, 95% CI 0.29-0.75; P = 0.0016). CONCLUSION: CA was associated with lower incidences of MACE and all-cause mortality for patients with AF as compared with those who received drug therapy. The most common event of MACE in patients who underwent CA was heart failure hospitalization. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000005834.

Prognostic significance of natriuretic peptide levels in atrial fibrillation without heart failure.

OBJECTIVES: Natriuretic peptides are an important prognostic marker in patients with heart failure (HF). However, little is known regarding their prognostic significance in patients with atrial fibrillation (AF) without HF and natriuretic peptides levels are underused in these patients in daily practice. METHODS: The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We investigated patients with AF without HF (defined as prior HF hospitalisation, New York Heart Association functional class≥2 or left ventricular ejection fraction<40%) using the data of B-type natriuretic peptide (BNP, n=388) or N-terminal pro-B-type natriuretic peptide (NT-proBNP, n=771) at enrolment. BNPs were converted to NT-proBNP using a conversion formula. We divided the patients according to quartiles of NT-proBNP levels and compared the backgrounds and outcomes. RESULTS: Of 1159 patients (mean age: 72.1±10.2 years, median CHA2DS2-VASc score: 3 and oral anticoagulant (OAC) prescription: 671 (56%)), the median NT-proBNP level was 488 (IQR 169-1015) ng/L. Patients with high NT-proBNP levels were older, had higher CHA2DS2-VASc scores and had more OAC prescription (all p<0.001). Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of stroke/systemic embolism, all-cause death and HF hospitalisation during a median follow-up period of 5.0 years (log rank, all p<0.001). Multivariable Cox regression analyses revealed that NT-proBNP levels were an independent predictor of adverse outcomes even after adjustment by various confounders. CONCLUSION: NT-proBNP levels are a significant prognostic marker for adverse outcomes in patients with AF without HF and may have clinical value. TRIAL REGISTRATION NUMBER: UMIN000005834.

Long-term clinical outcomes after major bleeding in patients with atrial fibrillation: the Fushimi AF registry.

AIMS: Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P < 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P < 0.01), history of major bleeding (7.7% vs. 4.0%; P < 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P < 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06-3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16-3.41; P < 0.01)]. CONCLUSION: In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. TRIAL REGISTRATION: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020).

Different Impact of Resting Heart Rate on Adverse Events in Paroxysmal and Sustained Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: Heart rate (HR) is an important factor in atrial fibrillation (AF); however, it remains unclear whether the impact of HR differs between paroxysmal AF and sustained (persistent and permanent) AF.Methods and Results:The association of resting HR during AF with adverse events (composite of all-cause death, hospitalization for heart failure, stroke/systemic embolisms, myocardial infarction, and arrhythmic events) in 1,064 paroxysmal and 1,610 sustained AF patients from the Fushimi AF Registry were investigated. These patients were divided into 4 groups based on their resting HR; ≥110 beats/min (bpm), 80-109 bpm, 60-79 bpm, and <60 bpm. The number of patients in each group was 486, 400, 172, and 22 for paroxysmal AF, and 205, 734, 645, and 71 for sustained AF, respectively. Among patients with sustained AF, a HR ≥110 bpm was associated with a higher incidence of adverse events at 1 year and during the entire follow up (median of 1,833 days) (hazard ratio [95% confidence interval] compared with a HR of 60-79 bpm: 1.90 [1.31-2.72] at 1 year, 1.38 [1.10-1.72] during the entire follow up). Patients with a HR <60 bpm showed higher incidence of adverse events at 1 year; however, the incidence of adverse events did not differ among all HR groups of paroxysmal AF. CONCLUSIONS: Baseline HR was associated with adverse events in sustained AF, but not in paroxysmal AF.

Cardiovascular Events and Mortality in Patients With Atrial Fibrillation and Anemia (from the Fushimi AF Registry).

Data regarding the associations of anemia (hemoglobin level <13.0 g/dl in men and <12.0 g/dl in women) with clinical outcomes in patients with atrial fibrillation (AF) remains scarce. This study sought to investigate the associations of anemia with the incidences of stroke or systemic embolism, major bleeding, heart failure (HF) hospitalization, and all-cause mortality including its causes, using the data from a Japanese community-based survey, the Fushimi AF Registry. A total of 4,169 AF patients were divided into the 3 groups, based on the baseline hemoglobin level: no (n = 2,622), mild (11.0 to <13.0 g/dl for men and <12.0 g/dl for women; n = 880), and moderate/severe anemia (<11.0 g/dl; n = 667). During a median follow-up of 1,464 days, the incidences of major bleeding, HF hospitalization, and mortality increased with higher rates of cardiac death, in accordance with anemic severity. On multivariate analyses, the higher risk of moderate/severe anemia, relative to no anemia, for major bleeding remained statistically significant (hazard ratio [HR]: 2.00, 95% confidential interval [CI]: 1.48 to 2.72). The risks of those with anemia, relative to no anemia, for HF hospitalization (mild; HR: 1.87, 95% CI: 1.51 to 2.31, and moderate/severe; HR: 2.02, 95% CI: 1.59 to 2.57) as well as for mortality (mild; HR: 1.80, 95% CI: 1.50 to 2.16, and moderate/severe; HR: 2.95, 95% CI: 2.45 to 3.55) were also higher, but not for stroke/systemic embolism. These relations were consistent, regardless of the use of oral anticoagulants. In conclusion, anemia was associated with higher risks of HF hospitalization, mortality, and major bleeding in AF patients.

Impact of Valvular Heart Disease on Mortality, Thromboembolic and Cardiac Events in Japanese Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: There is a growing burden of valvular heart disease (VHD) and atrial fibrillation (AF) due to population aging, but data regarding the characteristics and outcomes of patients with AF and concomitant VHD are lacking.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. Among 3,566 patients with available echocardiographic data, 20% had VHD, consisting of 131 valvular AF (VAF: 3.7%) and 583 nonvalvular AF with VHD (NVAF-VHD: 16.3%). Here, VAF was defined as AF with mitral stenosis or a prosthetic heart valve. AF patients with VHD were older, had more comorbidities with a higher CHADS2 score, and were prescribed oral anticoagulants more frequently than those without VHD. After adjusting for confounders, VHD was not associated with stroke or systemic embolism, all-cause mortality, or cardiac death. NVAF-VHD was significantly associated with an increased risk of hospitalization for heart failure (adjusted hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.16-1.78), whereas VAF was not (HR, 1.28; 95% CI, 0.86-1.92). Among all types of VHD, aortic valve diseases were associated with a higher risk of cardiac events, whereas mitral valve diseases were not. CONCLUSIONS: Although VHD did not significantly affect thromboembolism or mortality, it affected cardiac events depending on type, with aortic valve diseases having higher risk, in Japanese patients with AF.

Association of relative wall thickness of left ventricle with incidence of thromboembolism in patients with non-valvular atrial fibrillation: The Fushimi AF Registry.

AIMS: Atrial fibrillation (AF) increases the risk of thromboembolism, such as ischaemic stroke or systemic embolism (SE). The aim of this study was to investigate the relationship between left ventricular relative wall thickness (RWT) and the risk of thromboembolism in patients with non-valvular AF. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the patients with AF in Japan. Analyses were performed on 3067 non-valvular AF patients, in which RWT values determined by transthoracic echocardiography were available at the baseline. The high-RWT group (RWT above the median) was more often female, older, and had higher systolic blood pressure, CHADS2 and CHA2DS2-VASc scores, as compared with low-RWT group. During the median follow-up period of 1309 days, there was a higher incidence of ischaemic stroke/SE in the high-RWT group [unadjusted hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.42-2.59]. On multivariate Cox regression analysis, including the components of CHA2DS2-VASc score, left atrial diameter, oral anticoagulant prescription at baseline, and type of AF, high RWT was independently associated with ischaemic stroke/SE (adjusted HR, 1.81; 95% CI, 1.34-2.47). Stratified analysis demonstrated no significant interaction for any subgroups. In Kaplan-Meier analysis, ordinal RWT quartiles stratified the incidence of ischaemic stroke/SE. Finally, addition of RWT to CHA2DS2-VASc score increased the performance of risk stratification for the incidence of stroke/SE. CONCLUSION: Relative wall thickness was independently associated with ischaemic stroke/SE among Japanese patients with non-valvular AF, suggesting the importance of left ventricular morphology in contributing to adverse outcomes, particularly thromboembolism.

Current status of percutaneous coronary intervention in patients with atrial fibrillation: The Fushimi AF Registry.

BACKGROUND: Antithrombotic therapies that are optimal for atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) have been studied but remain uncertain. We often encounter difficulties in choosing an appropriate antithrombotic therapy with antiplatelet agents after PCI in AF patients treated with oral anticoagulant due to a high CHADS2 score. Since there are no data on the incidences of PCI procedures in AF patients, we evaluated those incidences as well as the association between PCI and the CHADS2 score using data from the Fushimi AF Registry. METHODS: The Fushimi AF Registry is a community-based prospective cohort study of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 4325 patients, and the median follow-up was 3.6 (interquartile range: 1.9-5.9) years. RESULTS: There were 143 PCI procedures performed in 122 patients during follow-up, and 28 (20%) were emergent ones. The crude incidence of PCI procedures was 9.36 per 1000 person-years. At 1 and 3 years, the cumulative incidences of PCI were 46 (1.1%) and 85 (2.4%), respectively. As for 4 age groups: <65 (n = 765), 65-75 (n = 1359), 75-85 (n = 1586), and 85≤ years (n = 615), the rates of PCI were 0.4%, 1.4%, 1.4%, and 0.6% at 1 year, and were 1.4%, 2.7%, 2.8%, and 1.6% at 3 years, respectively. The incidence of PCI procedures in patients with a CHADS2 score ≥2 (n = 2651, 61.3%) was higher than that in patients with a CHADS2 score ≤1 (n = 1674, 38.7%). Among the factors making up the CHADS2 score, only diabetes mellitus was associated with PCI procedures in patients with AF (hazard ratio, 1.95; 95% confidence interval, 1.34-2.83; p = 0.0005). CONCLUSIONS: About 1 in 100 AF patients underwent PCI annually, and patients with a CHADS2 score ≥2 were associated with higher incidences of PCI procedures.