Yugo Yamashita

Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation The Fushimi Atrial Fibrillation Registry

Background and Purpose— There is controversy on the relationship of the type of atrial fibrillation (AF) to stroke. Although several studies show that patients with paroxysmal AF (PAF) have a stroke risk similar to those with persistent or permanent AF, recent studies suggest that PAF is associated with a lower rate of stroke. Limited data on stroke risk associated with PAF are evident in Asian populations. Methods— The Registry Study of Atrial Fibrillation Patients in Fushimi-ku (Fushimi AF Registry) is a community-based survey of patients with AF in Fushimi-ku, Kyoto, Japan. Patients were categorized into 2 types of AF: PAF or sustained (persistent or permanent) AF. We compared clinical events between PAF (n=1588) and sustained AF (n=1716). Results— Patients with PAF were younger, had less comorbidities, and received oral anticoagulants (OAC) less commonly. A lower risk of stroke/systemic embolism during follow-up period in the patients with PAF was consistently observed (non-OAC users: hazard ratio, 0.45; 95% confidence intervals, 0.27–0.75; P<0.01 and OAC users: hazard ratio, 0.59; 95% confidence interval, 0.35–0.93; P=0.03). The composite end point of stroke/systemic embolism/all-cause mortality was also lower in PAF, whether among OAC users (hazard ratio, 0.77; 95% confidence interval, 0.59–0.99; P=0.046) or non-OAC users (hazard ratio, 0.59; 95% confidence interval, 0.46–0.75; P<0.01). On multivariate analysis, PAF was an independent predictor of lower stroke/systemic embolism risk. Conclusions— In this large cohort of Japanese patients with AF, PAF was independently associated with lower incidence of stroke/systemic embolism than sustained AF. This may aid decision making for anticoagulation, especially in those patients with AF with few stroke risk factors. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.

Low Body Weight Is Associated With the Incidence of Stroke in Atrial Fibrillation Patients – Insight From the Fushimi AF Registry –

BACKGROUND Japanese patients with atrial fibrillation (AF) are generally small and lean, but knowledge of the clinical characteristics of those with low body weight (LBW: ≤50 kg) is limited. METHODS AND RESULTS The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions in Fushmi-ku, Japan. The BW and follow-up data were available for 2,945 patients. We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group. Patients in the LBW group accounted for 26.8% (788 patients) of the total. The LBW group was more often female, older, and had higher CHADS2score. The incidence of stroke/systemic embolism (SE) during follow-up was higher in the LBW group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.57-3.04; P<0.01), whereas that of major bleeding was comparable (HR: 1.05, 95% CI: 0.64-1.68; P=0.84). This trend was consistently observed in the subgroups stratified by age, sex, and oral anticoagulant prescription at baseline. Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE. CONCLUSIONS Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE, but the incidence of major bleeding was not particularly high.

Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry.

Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients.

Current Status and Outcomes of Direct Oral Anticoagulant Use in Real-World Atrial Fibrillation Patients - Fushimi AF Registry.

BACKGROUND The current status and outcomes of direct oral anticoagulant (DOAC) use have not been widely evaluated in unselected patients with atrial fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up data with oral anticoagulant (OAC) status were available for 3,731 patients by the end of November 2015. We evaluated OAC status and clinical outcomes according to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and major bleeding events during the median follow-up of 3.0 years was 224 (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the prevalence of DOAC use increased gradually and steadily, and that of warfarin, DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional hazards modeling incorporating change in OAC status as a time-dependent covariate for stroke/SE and major bleeding events, use of DOAC compared with warfarin was not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45). CONCLUSIONS In real-world clinical practice, there were no significant differences in stroke/SE events or major bleeding events for DOAC compared with warfarin in patients with AF.

Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation

Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameter > 45 mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (n = 1,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40–2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18–3.25; p < 0.01; with OAC; HR: 1.83, 95% CI: 1.21–2.82; p < 0.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25–2.42; p < 0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients.

Cardiac and Noncardiac Causes of Long-Term Mortality in ST-Segment–Elevation Acute Myocardial Infarction Patients Who Underwent Primary Percutaneous Coronary Intervention

Background— In patients with ST-segment–elevation acute myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention, long-term risks for cardiac and noncardiac death beyond acute phase of STEMI have not been thoroughly evaluated yet. Methods and Results— We identified 3942 STEMI patients who had primary percutaneous coronary intervention within 24 hours after onset between January 2005 and December 2007 in the CREDO-Kyoto AMI registry (Coronary Revascularization Demonstrating Outcome study in Kyoto Acute Myocardial Infarction) and evaluated their short-term (within 6-month) and long-term (beyond 6-month) incidences and causes of deaths. The cumulative 5-year incidence of all-cause death in the current study population was 20.4% (cardiac death, 12.2% and noncardiac death, 9.4%, respectively). The vast majority of deaths were cardiac in origin within 6-month (cardiac death, 8.0% and noncardiac death, 0.9%), whereas noncardiac death accounted for nearly two thirds of all-cause death beyond 6-month (cardiac death, 4.6% and noncardiac death, 8.5%). In the stratified analysis according to age, the proportion of noncardiac death was similar regardless of age although the absolute mortality rate was higher with increasing age. By the multivariable Cox regression models, the independent risk factors of all-cause death were advanced age, cardiogenic shock, renal dysfunction, large infarct size, and anterior wall infarction within 6 months after STEMI, and advanced age, previous heart failure, renal dysfunction, and liver cirrhosis beyond 6 months after STEMI, respectively. Conclusions— In STEMI patients who underwent primary percutaneous coronary intervention, the long-term risk for cardiac death was relatively low compared with that for noncardiac death, which accounted for nearly two thirds of all-cause death beyond 6 months.

Thyroid Storm with Heart Failure Treated with a Short-acting Beta-adrenoreceptor Blocker, Landiolol Hydrochloride.

Beta-adrenoreceptor blockers are essential in controlling the peripheral actions of thyroid hormones and a rapid heart rate in patients with thyroid storm, although they should be used with great caution when there is the potential for heart failure. A 67-year-old woman was diagnosed as having thyroid storm in addition to marked tachycardia with atrial fibrillation and heart failure associated with a reduced left ventricular function. The administration of an oral beta blocker, bisoprolol fumarate, induced hypotension and was not tolerable for the patient, whereas landiolol hydrochloride, a short-acting intravenous beta-adrenoreceptor blocker with high cardioselectivity and a short elimination half-life, was useful for controlling the patients tachycardia and heart failure without causing hemodynamic deterioration.

Asymptomatic Lower Extremity Deep Vein Thrombosis ― Clinical Characteristics, Management Strategies, and Long-Term Outcomes ―

BACKGROUND The prognosis of asymptomatic deep vein thrombosis (DVT) is uncertain and there is no consensus on the necessity of detection and treatment.Methods and Results:We retrospectively evaluated 300 patients with asymptomatic lower extremity DVT screened from 4,514 consecutive patients on ultrasound at Kyoto University Hospital between January 2010 and September 2015. The subjects had concomitant active cancer in 40%, unprovoked DVT in 59%, and distal DVT in 70%. The cumulative 5-year incidences of symptomatic recurrent venous thromboembolism (VTE); major bleeding; and all-cause death were 14.5%, 16.6%, and 34.1%, respectively. Among 232 patients (77%) with prolonged anticoagulant therapy, anticoagulants were discontinued in 48.4% at 1 year. Anticoagulant therapy was associated with a significantly higher incidence of major bleeding compared with the non-anticoagulant group (20.5% vs. 1.5%, P=0.01) with no significant effect on the incidence of VTE. In patients with active cancer, the favorable effect of anticoagulants relative to no anticoagulants for VTE was significant (HR, 0.22; 95% CI: 0.05-0.95). CONCLUSIONS Prolonged anticoagulants therapy was implemented in the majority of patients with asymptomatic DVT, but was associated with a significantly higher risk for major bleeding. On subgroup analysis in patients with active cancer, however, there appeared to be a benefit of prolonged anticoagulant therapy in decreasing the rate of symptomatic recurrent VTE.

COMPARISON OF SHORT- AND LONG-TERM MORTALITY BETWEEN ST-SEGMENT ELEVATION AND NON-ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION

The difference of mortality risk between ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) has not been thoroughly evaluated yet. Among 5420 patients enrolled in the Coronary REvascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) acute myocardial infarction (

Asian patients versus non-Asian patients in the efficacy and safety of direct oral anticoagulants relative to vitamin K antagonist for venous thromboembolism: A systemic review and meta-analysis

INTRODUCTION The standard for treatment and secondary prevention of venous thromboembolism (VTE) has been vitamin K antagonist (VKA), which might be associated with a higher risk of bleeding particularly in Asian patients. Direct oral anticoagulants (DOAC) have been shown to be safer alternatives for VTE. It remains unclear whether this is the case in Asian ethnicity. MATERIALS AND METHODS We performed a meta-analysis of randomized controlled trials to evaluate the efficacy and safety of DOACs in Asian and non-Asian patients with acute VTE. We searched MEDLINE, CENTRAL, and ClinicalTrials.gov. The efficacy endpoint was recurrent VTE or VTE-related death. The safety endpoint was major bleedings or clinically relevant non-major bleedings. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS We identified 6 studies that comprised 3542 Asian and 23,481 non-Asian patients. The efficacy of DOACs was comparable with VKA in both Asian and non-Asian patients (OR, 0.90; 95% CI, 0.55-1.49; P = 0.69 for Asian patients; OR, 0.92; 95% CI, 0.78-1.08; P = 0.32 for non-Asian patients; P interaction = 0.94). DOACs significantly reduced the safety endpoint compared with VKA in Asian patients (OR, 0.64; 95% CI, 0.51-0.80; P < 0.001), while DOACs were associated with non-significant reduction in non-Asian patients (OR, 0.73; 95% CI, 0.53-1.01; P = 0.06), indicating that the reduction seemed numerically more prominent in Asian patients, although there was no statistically significant interaction (P interaction = 0.49). CONCLUSIONS The efficacy of DOACs was comparable with VKA irrespective of ethnicity, and DOACs could be safer alternatives in Asian patients.