Validation of a Supportive and Palliative Care Indicator Tool Among Patients Hospitalized Due to Heart Failure.

BACKGROUND: Palliative care, including symptom alleviation and advance-care planning, is relevant for patients with heart failure (HF). The Supportive and Palliative Care Indicator Tool (SPICT) is a tool for identifying patients who may benefit from palliative-care assistance but has not been validated in patients hospitalized due to HF. METHODS AND RESULTS: Clinical backgrounds, symptom burdens and outcomes were evaluated using the SPICT as assessed on admission in consecutive hospitalized patients with HF. SPICT-positive was defined when 2 or more general indicators and a New York Heart Association class ≥ III were present. Of 601 patients hospitalized due to HF (mean age: 79 ± 12 years; male, 314 [52%]; and mean left ventricular ejection fraction: 44 ± 18%), 100 (17%) patients were SPICT-positive. SPICT-positive patients were older (85 ± 9 vs 78 ± 12 years; P < 0.001) and had higher clinical frailty scales (6 ± 1 vs 4 ± 1 points; P < 0.001), whereas symptom burdens assessed by the Integrated Palliative care Outcome Scale were not different (17 [13, 28] vs 20 [11, 26] points; P = 0.97) when compared with patients who were SPICT-negative. During the median follow-up period of 518 days, 178 patients (30%) died. Being SPICT-positive was independently associated with higher all-cause mortality (hazard ratio: 3.49, 95% confidence interval: 2.41-5.05; P < 0.001) after adjusting for age, sex, New York Heart Association class IV, Get-With-The-Guideline risk score, N-terminal pro B-type natriuretic peptide levels, and left ventricular ejection fractions. CONCLUSIONS: In patients admitted for HF, being SPICT-positive was significantly associated with higher all-cause mortality rates, suggesting the utility of the SPICT as an indicator to initiate advance-care planning for end-of-life care among patients hospitalized due to HF.

Differential Prognostic Impact of Clinical Congestion between Preserved versus Reduced Ejection Fraction in Patients Hospitalized for Acute Decompensated Heart Failure: Findings from the Japanese Kyoto Congestive Heart Failure Registry.

BACKGROUND: Most patients hospitalized for heart failure (HF) present with signs of congestion. Prognostic significance of clinical congestion may vary depending on left ventricular ejection fraction (LVEF). This study aims to investigate the prognostic impact of congestion across different LVEF categories. METHODS AND RESULTS: Composite congestion scores (CCSs; 0-9) derived from the severity of edema, jugular venous pressure, and orthopnea, were analyzed on admission and at discharge in 3787 patients hospitalized for HF (LVEF ≥ 40%: n = 2347, LVEF < 40%: n = 1440). The median admission CCS was 4 in both LVEF strata (P = .64). Adjusted hazard ratios (HRs; 95% confidence interval [CI]) of the moderate (CCS 4-6) and severe congestion [7-9] groups relative to the mild congestion [0-3] group on admission for a composite of all-cause death or HF rehospitalization were 1.20 (1.04-1.39, P = .01) and 1.54 (1.27-1.86, P < .001) in the LVEF ≥ 40% stratum, and 1.20 (1.01-1.44, P = .04) and 0.82 (0.61-1.07, P = .14) in the LVEF < 40% stratum, respectively (Pinteraction< .001). A total of 16% of the patients with LVEF ≥40% and 14% with LVEF <40% had residual congestion (CCS ≥ 1) at discharge, which was associated with a respective adjusted HR of 1.40 (1.18-1.65, P < .001) and 1.25 (0.98-1.58, P = .07) for postdischarge death or HF rehospitalization (Pinteraction = 0.63). CONCLUSION: The severity of clinical congestion on admission was associated with adverse clinical outcomes in patients with LVEF ≥ 40%, but not in those with LVEF < 40%. These findings warrant further studies to better understand the detailed profile of congestion across the LVEF spectrum.

Prognostic Value of the Severity of Clinical Congestion in Patients Hospitalized for Decompensated Heart Failure: Findings From the Japanese KCHF Registry.

BACKGROUND: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF. METHODS AND RESULTS: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316). CONCLUSIONS: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Prevalence, Temporal Change, and Determinants of Anxiety and Depression in Hospitalized Patients With Heart Failure.

BACKGROUND: Anxiety and depression may be under-recognized in patients with heart failure (HF). We therefore investigated the prevalence and temporal change of these symptoms in hospitalized patients with HF. METHODS AND RESULTS: We prospectively evaluated consecutive hospitalized patients with HF using the Hospital Anxiety and Depression Scale (HADS) on admission and at discharge. The HADS-A (anxiety) and HADS-D (depression) scores were categorized as follows; 0-7, no symptoms; 8-10, mild; and 11-21, significant anxiety or depression. Symptom worsening was defined as the HADS category at discharge being poorer than that on admission. Of 224 patients (mean age 77.5 years), 35 (16%) and 62 (28%) had significant symptoms of anxiety and depression, respectively. During hospitalization, the HADS-A significantly decreased (on admission; median 6 [interquartile range (IQR) 3-9] vs at discharge; median 4 [IQR 2-7], P < .01), whereas the HADS-D did not improve (on admission; median 8 [IQR 5-11] vs at discharge; median 8 [IQR 4-11], P =.82). Anxiety and depression worsened during hospitalization in 19 (10%) and 40 (21%) patients, respectively. Advanced age, higher natriuretic peptide levels, and acute-on-chronic HF were associated with worsening anxiety, and longer hospitalization length was associated with worsening depression. CONCLUSIONS: Anxiety and depression were common and depression persisted during HF hospitalization.

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.

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.

Starting Neurohormonal Antagonists in Patients With Acute Heart Failure With Mid-Range and Preserved Ejection Fraction.

BACKGROUND: The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain.Methods and Results: This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or ß-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and ß-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), ß-blocker only (n=189, 22.0%), and both ACE-I/ARB and ß-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the ß-blocker only group, and 16.4% in the both ACE-I/ARB and ß-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and ß-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002). CONCLUSIONS: In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a ß-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or ß-blocker.

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.

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.

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.

Progression From Paroxysmal to Sustained Atrial Fibrillation Is Associated With Increased Adverse Events.

Background and Purpose- Atrial fibrillation (AF) is a common arrhythmic disorder among the elderly and sometimes progresses from paroxysmal to sustained (persistent or permanent) types. Clinical outcomes of patients with progression of AF were unknown. This study assessed the characteristics of patients with AF progression and the impact of AF progression on various clinical events. Methods- The Fushimi AF Registry is a community-based prospective survey of the patients with AF in Fushimi-ku, Kyoto. Analyses were performed on 4045 patients, which included 1974 paroxysmal AF (PAF; 48.8%) and 2071 sustained (persistent or permanent) AF (SAF; 51.2%) at baseline. Results- During the median follow-up period of 1105 days, progression of AF occurred in 252 patients with PAF (4.22 per 100 person-years). Multivariate Cox regression analysis demonstrated that progression of AF was significantly associated with an increased risk of ischemic stroke or systemic embolism (adjusted hazard ratio [HR], 4.10; 95% CI, 1.95-8.24; P<0.001 [versus PAF without progression]; adjusted HR, 2.20; 95% CI, 1.11-4.00; P=0.025 [versus SAF]) during progression period from paroxysmal to sustained forms. The risk after the progression was equivalent to SAF (adjusted HR, 1.54; 95% CI, 0.78-2.75; P=0.201 [versus SAF]). AF progression was significantly associated with a higher risk of hospitalization for heart failure (adjusted HR, 2.70; 95% CI, 1.55-4.52; P<0.001 [versus PAF without progression]; adjusted HR, 1.81; 95% CI, 1.08-2.88; P=0.026 [versus SAF]). Conclusions- Progression of AF was associated with increased risk of clinical adverse events during arrhythmia progression period from PAF to SAF among Japanese patients with AF. The risk of adverse events was transiently elevated during progression period from PAF to SAF and declined to the level equivalent to SAF after the progression. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000005834.

Current Status, Time Trends and Outcomes of Combination Therapy With Oral Anticoagulant and Antiplatelet Drug in Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: The combination of oral anticoagulant (OAC) and antiplatelet drug (APD) increases the bleeding risk in atrial fibrillation (AF). Non-vitamin K antagonist OAC (NOAC) have been increasingly used since 2011. We investigated current status, time trends and outcomes of AF patients using combination therapy in 2011-2017. Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Of 2,378 patients with OAC at enrollment, 521 (22%) received combination therapy, while 1,857 (78%) received OAC alone. When compared with OAC alone, combination therapy patients had more comorbidities, but approximately 30% had no atherosclerotic disease. From 2011 to 2017, the prevalence of combination therapy decreased from 26% to 14%. The prevalence of NOAC increased in those on combination therapy. Off-label under-dosing of NOAC increased year by year, especially in combination therapy. During follow-up, the incidence of major bleeding (hazard ratio [HR], 1.42; 95% CI: 1.03-1.95) and stroke/systemic embolism (HR, 1.48; 95% CI: 1.09-2.00) was higher in the combination therapy than in the OAC alone group. CONCLUSIONS: In Japanese AF patients receiving OAC, the prevalence of combination therapy decreased, with the proportion of NOAC use increasing in 2011-2017. Many patients, however, received off-label NOAC under-dosing, especially in the combination therapy group. Patients with combination therapy had higher incidences of major bleeding as well as stroke/systemic embolism, compared with OAC monotherapy.

Incidence and Risk Factors of Stroke or Systemic Embolism in Patients With Atrial Fibrillation and Heart Failure　- The Fushimi AF Registry.

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome, but the effect of the type and severity of HF on the incidence of stroke or systemic embolism (SE) in atrial fibrillation (AF) patients is unclear.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 3,749 patients. We defined pre-existing HF as having one of the following: prior hospitalization for HF, presence of HF symptoms (NYHA ≥2), or reduced ejection fraction (<40%). At baseline, 1,008 (26.9%) patients had pre-existing HF. On multivariate analysis, the incidence of stroke/SE was not associated with pre-existing HF (hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.92-1.64) or each criterion for the definition of pre-existing HF, but was associated with high B-type natriuretic peptide (BNP) or N-terminal proBNP levels (above the median of the pre-existing HF group) at baseline (HR, 1.65; 95% CI, 1.06-2.53). Stroke/SE was markedly increased in the initial 30-day period following hospital admission for HF (HR, 12.0; 95% CI, 4.59-31.98). CONCLUSIONS: The effect of HF on the incidence of stroke/SE may depend on the stage or severity of HF in patients with AF. The incidence of stroke/SE was markedly increased in the 30 days after admission for HF, but compensated 'stable' HF did not appear to confer an independent risk.

Demographics, Management, and In-Hospital Outcome of Hospitalized Acute Heart Failure Syndrome Patients in Contemporary Real Clinical Practice in Japan　- Observations From the Prospective, Multicenter Kyoto Congestive Heart Failure (KCHF) Registry.

BACKGROUND: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF). Methods and Results: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40-49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72-86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001). CONCLUSIONS: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.

A study on indices of apixaban anticoagulation: A single-center prospective study.

BACKGROUND: Depending on the characteristics of patients, the blood concentration of apixaban can unexpectedly increase, possibly leading to bleeding events. Anti-FXa activity reflects the apixaban blood concentration; however, measurement of this activity is both time-consuming and expensive. The current study aimed to evaluate the usefulness of routinely measured coagulation indices as future indicators of the efficacy and safety of apixaban. METHODS: Eighteen nonvalvular atrial fibrillation patients administered apixaban (average, 52.5 days) were prospectively enrolled in our hospital. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were measured by using the Coagpia® Reagent kits. RESULTS: The PT and the APTT increased significantly after the administration of apixaban (PT: p < 0.001, APTT: p < 0.001). While the apixaban plasma concentration by evaluating anti-FXa activity was not significantly correlated with the APTT after administration of apixaban, the concentration closely correlated with the PT (ß = 0.765, p < 0.001) and the percentage change in the PT from before and after the administration of apixaban (ß = 0.650, p = 0.005). CONCLUSION: The usefulness of routinely monitoring PT in patients administered apixaban during the ordinary clinical medicine should be investigated further by large clinical trials.

Clinical characteristics and cardiovascular outcomes in patients with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF Registry.

Management of atrial fibrillation (AF) with current rhythm-control therapy has an uncertain impact on outcomes. Among 3731 patients in the Fushimi AF Registry, a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, we investigated the characteristics and outcomes in 478 patients receiving rhythm-control therapy (anti-arrhythmic drug and/or catheter ablation) alone, with 1279 patients receiving rate-control therapy (beta-blockers, calcium channel blockers, and digoxin) alone serving as a reference. The Rhythm-control group, 26% of which had prior catheter ablation, was younger (70.5 ± 10.8 vs. 74.3 ± 10.4 years, P < 0.001) with lower CHA2DS2-VASc score (2.71 ± 1.63 vs. 3.64 ± 1.62, P < 0.001) and received oral anticoagulants less frequently than the Rate-control group. During the median follow-up of 1107 days, the incidence of the composite of cardiac death and heart failure (HF) hospitalization was lower with rhythm control (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.14-0.36; P < 0.001), whereas that of ischemic stroke/systemic embolism was not significantly different (HR 0.64, 95% CI 0.35-1.10; P = 0.12), when compared to rate control. Propensity score-matching analysis as well as multivariate analysis further supported the relation of Rhythm-control group to the lower incidence of the composite of cardiac death and HF hospitalization. Rhythm-control therapy by anti-arrhythmic drug and/or catheter ablation in the contemporary clinical practice was associated with the lower incidence of the composite of cardiac death and HF hospitalization, as compared with rate-control therapy in a Japanese AF cohort. However, given the fundamental differences in baseline clinical characteristics between the rhythm- and Rate-control groups, the results cannot be generalizable.

Correction to: Clinical characteristics and cardiovascular outcomes in patients with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF Registry.

In the original publication of the article, the data of Body mass index ≥ 25 (kg/m2)a is published incorrectly in Table 1. Since this is categorical variable, the data should have been expressed as a number (percentage), not as mean ± standard deviation. The corrected version of Table 1 is as below.

Sex-Related Differences in the Clinical Events of Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: Female sex is considered a risk factor for thromboembolism in patients with atrial fibrillation (AF), and is included in the risk stratification scheme, CHA2DS2-VASc score. The purpose of the present study was to investigate the clinical outcomes of female Japanese AF patients.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto. Follow-up data were available for 3,878 patients. Female AF patients (n=1,551, 40.0%) were older (77.0 vs. 71.4 years; P<0.001) than male patients (n=2,327, 60.0%). Female patients were more likely to have heart failure (31.1% vs. 23.7%; P<0.001). Previous stroke incidence (19.2% vs. 21.4%; P=0.083) was comparable between male and female patients. During the median follow-up period of 1,102 days, Cox regression analysis demonstrated that female sex was not independently associated with a risk of stroke or systemic embolism (adjusted hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.54-1.00, P=0.051). However, female sex showed an association with a lower risk of intracranial hemorrhage (adjusted HR 0.54; 95% CI: 0.30-0.95, P=0.032) and all-cause death (adjusted HR 0.56; 95% CI: 0.46-0.68, P<0.001). CONCLUSIONS: We demonstrated that female sex is not independently associated with an increased risk of thromboembolism, but is associated with a decreased risk of intracranial hemorrhage and all-cause death in Japanese AF patients enrolled in the Fushimi AF Registry.

Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.