Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

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.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- A Report From the CURRENT AS Registry.

BACKGROUND: The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). CONCLUSIONS: Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Relation of renal function to mid-term prognosis of stable angina patients with high- or low-dose pitavastatin treatment: REAL-CAD substudy.

BACKGROUND: It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction. METHODS: The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m2 (n = 1,164), who were randomized to pitavastatin 4mg or 1mg therapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina, and was assessed by the log-rank test and Cox proportional hazards model. RESULTS: The baseline characteristics and medications were largely well-balanced between two groups. The magnitude of low-density lipoprotein cholesterol (LDL-C) reduction at 6 months in high- and low-dose pitavastatin groups was comparable among all eGFR categories. During a median follow-up of 3.9 years, high- compared with low-dose pitavastatin significantly reduced cardiovascular events in patients with eGFR ≥60 (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58-0.91; P = .006), and reduced but not significant for patients with eGFR ≥45 and <60 (HR 0.85; 95% CI, 0.63-1.14; P = .27) or eGFR <45 mL/Min/1.73 m2 (HR 0.90; 95% CI 0.62-1.33; P = .61). An interaction test of treatment by eGFR category was not significant (P value for interaction = .30). CONCLUSION: Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

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.

Long-Term Impact of Diabetes Mellitus on Initially Conservatively Managed Patients With Severe Aortic Stenosis.

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

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.

Age-Related Differences in the Effects of Initial Aortic Valve Replacement vs. Conservative Strategy on Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis.

BACKGROUND: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016). CONCLUSIONS: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.

Transcatheter Aortic Valve Implantation vs. Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Real-World Clinical Practice.

BACKGROUND: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan. METHODS AND RESULTS: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69). CONCLUSIONS: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.

Reasons for Choosing Conservative Management in Symptomatic Patients With Severe Aortic Stenosis　- Observations From the CURRENT AS Registry.

BACKGROUND: There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians' recommendations.Methods and Results:Among 3,815 consecutive patients with severe aortic stenosis (AS) enrolled in the CURRENT AS registry, the study population comprised 2,005 symptomatic patients, who were subdivided into 3 groups by their treatment strategy and the reasons for conservative strategy (Initial AVR group: n=905; Patient rejection group: n=256; Physician judgment group, n=844). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalization. Patients in the patient rejection group as compared with those in the physician judgment group were younger, and had less comorbidities, and lower surgical risk scores. The cumulative 5-year incidence of the primary outcome measure in the patient rejection group was markedly higher than that in the initial AVR group, and was similar to that in the physician judgment group (60.7%, 19.0%, and 66.4%, respectively). CONCLUSIONS: Patient rejection was the reason for non-referral to AVR in nearly one-quarter of the symptomatic patients with severe AS who were managed conservatively. The dismal outcome in patients who refused AVR was similar to that in patients who were not referred to AVR based on physician judgment despite less comorbidities and lower surgical risk scores in the former than in the latter.

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.

Acute Heart Failure in Patients With Severe Aortic Stenosis　- Insights From the CURRENT AS Registry.

BACKGROUND: Clinical profiles of acute heart failure (AHF) complicating severe aortic stenosis (AS) remain unclear.Methods and Results:From a Japanese multicenter registry enrolling consecutive patients with severe AS, 3,813 patients were categorized into the 3 groups according to the symptom of heart failure (HF); No HF (n=2,210), chronic HF (CHF) (n=813) and AHF defined as hospitalized HF at enrolment (n=790). Median follow-up was 1,123 days with 93% follow-up rate at 2 years. Risk factors for developing AHF included age, female sex, lower body mass index, untreated coronary artery stenosis, anemia, history of HF, left ventricular ejection fraction <50%, presence of any combined valvular disease, peak aortic jet velocity ≥5 m/s and tricuspid regurgitation pressure gradient ≥40 mmHg, and negative risk factors included dyslipidemia, history of percutaneous coronary intervention and hemodialysis. Respective cumulative 5-year incidences of all-cause death and HF hospitalization in No HF, CHF and AHF groups were 37.1%, 41.8% and 61.8% (P<0.001) and 20.7%, 33.8% and 52.3% (P<0.001). Even in the initial aortic valve replacement (AVR) stratum, AHF was associated with excess 5-year mortality risk relative to No HF and CHF (adjusted hazard ratio [HR] 1.64; 95% confidence interval [CI]: 1.14-2.36, P=0.008; adjusted HR 1.47; 95% CI: 1.03-2.11, P=0.03, respectively). CONCLUSIONS: AHF complicating severe AS was associated with an extremely dismal prognosis, which could not be fully resolved by AVR. Careful management to avoid the development of AHF is crucial.

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.

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.