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.

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.

Multisystem inflammatory syndrome and lymphohistiocytic myocarditis after Covid-19 vaccine in a middle-aged woman.

We describe a 51-year-old otherwise healthy woman hospitalized for hypotension, fever, and weakness 4 days after the second-dose Covid-19 mRNA vaccine. Elevated inflammatory markers, natriuretic peptide levels and troponin levels, and slightly reduced left ventricular ejection fraction of 50% were noted. We also found the multiple organ damage, including mucocutaneous, gastrointestinal, and neurologic systems. In addition, we revealed the positive results for anti-nucleocapsid SARS-CoV-2 IgG, albeit negative for SARS-CoV-2 polymerase chain reaction testing, suggesting the prior asymptomatic Covid-19 infection. We finally diagnosed her as multisystem inflammatory syndrome after vaccination. Of note, we obtained myocardial specimen from the patients and demonstrated the lymphohistiocytic myocarditis, which is a rare form of myocarditis.

Caseous calcification of mitral annulus evaluated by multi-modality imaging including cardiac magnetic resonance parametric mapping.

We report an 85-year-old woman with caseous calcification of mitral annulus (CCMA), a rare variant of mitral annular calcification with caseous degeneration, in which imaging findings were useful for elucidating the pathogenesis and diagnosis. Since the CCMA is considered to be benign, it is important for clinicians to differentiate CCMA from other cardiac masses using multi-modality imaging in order to avoid unnecessary surgery. To the best of our knowledge, there is a paucity of literature regarding cardiac magnetic resonance (CMR) parametric mapping, an emerging technique, for evaluating CCMA. In the present case, by using multi-modality imaging including CMR parametric mapping, we were able to characterize the abnormal structure at mitral annulus non-invasively, and diagnosed the structure as CCMA. CMR with parametric mapping may have a role in the identification and definition of cardiac masses including CCMA. Learning objective: Caseous calcification of mitral annulus (CCMA) is a rare variant of mitral annular calcification, but is not infrequently encountered in daily practice. Multi-modality imaging including cardiac magnetic resonance is useful for the diagnosis of CCMA. Differential diagnosis of cardiac masses at the mitral annulus including CCMA is important, and clinicians need to know the multi-modality imaging findings related to CCMA.

A case of infective endocarditis mimicking antineutrophil cytoplasmic antibody-associated vasculitis.

Infective endocarditis (IE) is not a common disease, but it remains a serious condition. Antineutrophil cytoplasmic antibodies (ANCA) are often positive in IE, and discrimination between IE and ANCA-associated vasculitis is important because misdirected selection of therapy can lead to catastrophic consequences. We report a case of IE mimicking ANCA-associated vasculitis in which we were able to make a correct diagnosis and perform treatment. This case suggests that it is important to consider IE as a differential diagnosis in ANCA-positive patients. Learning objective: Antineutrophil cytoplasmic antibodies (ANCA) are associated with primary systemic vasculitis. However, ANCA have also been described in other conditions and infective endocarditis (IE) was considered an important cause of ANCA.Discrimination between IE and ANCA-associated vasculitis is important, although it is sometimes difficult. We report a case of IE mimicking ANCA-associated vasculitis. ANCA-positive patients with nonspecific symptoms should be suspected of having IE, checked for heart murmurs, and tested by echocardiography and blood cultures.

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.

Isometric Handgrip Stress Test during Right Heart Catheterization in Patients with Mitral Regurgitation -A Case Series Study.

Objective The severity of mitral regurgitation (MR) dynamically changes during a stress test. Isometric handgrip is a readily-available stress test in daily practice; however, little is known regarding the response to isometric handgrip in MR patients during right heart catheterization. We aimed to evaluate this issue from our case-series study. Methods We retrospectively investigated consecutive MR patients using the isometric handgrip stress test during right heart catheterization at our institution between October 2019 and April 2021. After resting measurements were obtained, sustained maximum-effort hand dynamometer grasping was maintained for about 2-3 minutes. We investigated the differences in right heart catheterization data between at rest and during handgrip, and evaluated the individual response to the isometric handgrip stress test. Results We investigated a total of 15 patients (mean age: 75±6 years, moderate/severe MR: 7/8, primary/secondary MR: 8/7, mean left ventricular ejection fraction: 56±16%, exertional dyspnea: 10). During the handgrip test, the pulmonary capillary wedge pressure (PCWP) significantly increased [9 (8, 13) mmHg at rest to 20 (15, 27) mmHg during handgrip; p<0.001]. PCWP changes varied among individuals (range 2-22 mmHg) and were not correlated with patients' backgrounds including age, the natriuretic peptide levels, left ventricular ejection fraction, left atrial diameter or E/e' (all p>0.05). Patients with PCWP ≥25 mmHg during handgrip had a higher prevalence of exertional dyspnea than those without [6 (100%) vs. 4 (44%); p=0.04]. Conclusion We observed dynamic and varied hemodynamic changes during isometric handgrip in MR patients, suggesting that further research is needed to evaluate the clinical value of this maneuver.

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.

Ischemic Stroke in Acute Decompensated Heart Failure: From the KCHF Registry.

Background Heart failure (HF) is a known risk factor for ischemic stroke, but data regarding ischemic stroke during hospitalization for acute decompensated HF (ADHF) are limited. Methods and Results We analyzed the data from a multicenter registry (Kyoto Congestive Heart Failure [KCHF] Registry) that enrolled 4056 consecutive patients with ADHF in Japan (mean age, 78 years; men, 2238 patients [55%]; acute coronary syndrome [ACS], 239 patients [5.9%]). We investigated the incidence and predictors of ischemic stroke during hospitalization for ADHF. During the hospitalization, 63 patients (1.6%) developed ischemic stroke. The median interval from admission to the onset of ischemic stroke was 7 [interquartile range: 2-14] days, and the most common underlying cause was cardioembolism (64%). Men (OR, 1.87; 95%CI, 1.11-3.24), ACS (OR, 2.31; 95%CI, 1.01-4.93), absence of prior HF hospitalization (OR, 2.21; 95%CI, 1.24-4.21), and high B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) levels (above the median) at admission (OR, 3.15; 95%CI, 1.84-5.60) were independently associated with ischemic stroke. In patients without ACS, the independent risk factors for ischemic stroke were fully consistent with those in the main analysis. Higher quartiles of BNP/NT-proBNP levels were significantly associated with higher incidence of ischemic stroke (P for trend, <0.001). Patients with ischemic stroke showed higher in-hospital mortality, longer length of hospital stay, and poorer functional status at discharge. Conclusions During hospitalization for ADHF, 1.6% of the patients developed ischemic stroke. Men, ACS, absence of prior HF hospitalization, and high BNP/NT-proBNP levels at admission were independently associated with ischemic stroke.

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.

Iatrogenic ventricular fibrillation caused by inappropriately synchronized cardioversion in a patient with pre-excited atrial fibrillation: A case report.

Direct-current (DC) cardioversion is effective at terminating arrhythmias in an emergency. During treatment, energy delivery synchronizing with the QRS complex is essential to avoid ventricular fibrillation (VF) caused by a shock on the T wave, which is the vulnerable period of ventricular repolarization. However, distinguishing the QRS from the T wave is difficult in some patients with abnormal, irregular, and varying QRS complexes. We report the case of a 45-year-old man who had iatrogenic VF caused by inappropriate synchronization with the T wave during cardioversion of pre-excited atrial fibrillation due to high ventricular rates and varying R wave amplitude affected by an accessory pathway. .

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).

Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study.

Background Whether circulating growth differentiation factor 15 (GDF-15) levels differ according to smoking status and whether smoking modifies the relationship between GDF-15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF-15 and the impact of smoking status on the association between GDF-15 and all-cause death. GDF-15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF-15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log-transformed GDF-15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF-15. The prognostic value of GDF-15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

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.

Distinct Characteristics of VEGF-D and VEGF-C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease.

Background VEGF-D (vascular endothelial growth factor D) and VEGF-C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF-C level is inversely and independently associated with all-cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF-D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF-D was measured. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3-year follow-up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-I, and high-sensitivity C-reactive protein), and VEGF-C, the VEGF-D level was significantly associated with all-cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF-D, either alone or in combination with VEGF-C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all-cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF-D value seems to independently predict all-cause mortality.

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.