Masahiro Esato

Current status of clinical background of patients with atrial fibrillation in a community-based survey:The Fushimi AF Registry

BACKGROUND Atrial fibrillation (AF) increases the risks of stroke and death, and the prevalence of AF is increasing significantly. Until recently, warfarin was the only oral anticoagulant for stroke prevention, but novel anticoagulants are now under development. METHODS AND RESULTS The Fushimi AF Registry is a community-based survey of AF patients. We aimed to enroll all of the AF patients in Fushimi-ku, which is located at the southern end of the city of Kyoto. Fushimi-ku is densely populated with a total population of 283,000, and is assumed to represent a typical urban community in Japan. On the basis of the general prevalence of AF in the Japanese (0.6%), we estimated the total number of AF patients as 1700. A total of 76 institutions, a large proportion of which were private clinics, participated in the study. At present, we have enrolled 3183 patients from March 2011 to June 2012 (approximately 1.12% of total population). The mean age was 74.2±11.0 years, and 59.3% of subjects were male. The mean body weight was 58.5±13.2 kg, and the proportions with a body weight of less than 50 kg and 60 kg were 25.7% and 55.0%, respectively. The type of AF was paroxysmal in 46.0%, persistent in 7.3%, and permanent in 46.7%. Major co-existing diseases were hypertension (60.6%), heart failure (27.9%), diabetes (23.2%), stroke (19.4%), coronary artery disease (15.0%), myocardial infarction (6.4%), dyslipidemia (42.4%), and chronic kidney disease (26.4%). The mean CHADS2 score was 2.09±1.35: 0 in 11.8% of patients, 1 in 27.1%, and 2 in 29.1%. Warfarin was prescribed in only 48.5% of patients, whereas anti-platelet drugs, mainly aspirin, were prescribed for more than 30% of the patients. CONCLUSIONS The Fushimi AF Registry provides a unique snapshot of current AF management in an urban community in Japan.

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.

Measuring luminal esophageal temperature during pulmonary vein isolation of atrial fibrillation

AIM To investigate the luminal esophageal temperature (LET) at the time of delivery of energy for pulmonary vein isolation (PVI). METHODS This study included a total of 110 patients with atrial fibrillation who underwent their first PVI procedure in our laboratory between March 2010 and February 2011. The LET was monitored in all patients. We measured the number of times that LET reached the cut-off temperature, the time when LET reached the cut-off temperature, the maximum temperature (T max) of the LET, and the time to return to the original pre-energy delivery temperature once the delivery of energy was stopped. RESULTS Seventy-eight patients reached the cut-off temperature. It took 6 s at the shortest time for the LET to reach the cut-off temperature, and 216.5 ± 102.9 s for the temperature to return to the level before the delivery of energy. Some patients experienced a transient drop in the LET (TDLET) just before energy delivery. Ablation at these sites always produced a rise to the LET cut-off temperature. TDLET was not observed at sites where the LET did not rise. Thus, the TDLET before the energy delivery was useful to distinguish a high risk of esophageal injury before delivery of energy. CONCLUSION Sites with a TDLET before energy delivery should be ablated with great caution or, perhaps, not at all.

Clinical Impact of Asymptomatic Presentation Status in Patients With Paroxysmal and Sustained Atrial Fibrillation: The Fushimi AF Registry

BACKGROUND: The clinical characteristics and outcomes of asymptomatic patients with paroxysmal or persistent/permanent atrial fibrillation (AF) are largely unknown. METHODS: The Fushimi AF Registry is a community‐based prospective survey of patients with AF who visited the participating medical institutions in Fushimi‐ku, Japan. We investigated the clinical characteristics and outcomes of asymptomatic vs symptomatic patients in the paroxysmal AF (PAF; n = 1,837) and persistent/permanent (sustained atrial fibrillation [SAF]; n = 1,912) subgroups. RESULTS: In the PAF group, asymptomatic patients were older (asymptomatic vs symptomatic group, 74.1 vs 71.1 years of age; P < .01), more often male (62.1% vs 55.6%; P < .01), and had a higher CHA2DS2‐VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, history of stroke, vascular disease, age 65–74 years, and female sex) score (mean, 3.37 ± 1.73 vs 2.99 ± 1.63; P < .01), whereas the prevalence of major co‐morbidities and CHA2DS2‐VASc scores were comparable in the SAF group. Multivariable analysis indicated that age (≥ 75 years), history of stroke/systemic embolism, male sex, and chronic kidney disease were independent determinants of asymptomatic status in the PAF group, whereas age was nonsignificant in the SAF group. During the follow‐up period, all‐cause mortality was significantly higher (hazard ratio, 1.71 [95% CI, 1.31–2.29]; P < .01) in asymptomatic patients compared with symptomatic patients in the PAF group, whereas it was comparable in the SAF group. CONCLUSIONS: Asymptomatic clinical status is associated with older age, male sex, more co‐morbidities with a higher stroke risk profile, and a higher incidence of all‐cause death in patients with PAF; these characteristics and outcomes were not seen in the SAF group. TRIAL REGISTRY: UMIN Clinical Trials Registry; No.: UMIN000005834; URL: www.umin.ac.jp/ctr/index.htm.

Relationship of Hypertension and Systolic Blood Pressure With the Risk of Stroke or Bleeding in Patients With Atrial Fibrillation: The Fushimi AF Registry

BACKGROUND Hypertension is considered a major risk factor of stroke and systemic embolism (SE) as well as bleeding in patients with atrial fibrillation (AF). The purpose of this study was to investigate the relationship of hypertension and systolic blood pressure (SBP) with the risk of stroke/SE or bleeding in AF patients. METHODS The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000. Follow-up data were available for 3,713 patients (follow-up rate 90.0%) as of August 2015, and the median follow-up period was 1,035 days. RESULTS We compared the clinical backgrounds at baseline, and follow-up outcomes of AF patients between those with hypertension (HTN; n = 2,304, 62.1% of total) and those without (non-HTN; n = 1,409). History of hypertension was neither associated with the incidence of stroke/SE, ischemic stroke, hemorrhagic stroke nor major bleeding. However, when we divided the HTN group by baseline SBP ≥150 mm Hg (HTN-high blood pressure [HBP]: n = 305, 13.3% of HTN group) or <150 mm Hg (HTN-low blood pressure [LBP]: n = 1,983), HTN-HBP group was significantly associated with a higher incidence of both stroke/SE (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.08-2.72) and major bleeding (HR: 2.01, 95% CI: 1.21-3.23) compared with the non-HTN group. In contrast, HTN-LBP group was not associated with the risk of stroke/SE or major bleeding, compared with the non-HTN group. CONCLUSION The incidences of stroke/SE and bleeding were higher in AF and hypertension patients with elevated SBP. UMIN Clinical Trials Registry: UMIN000005834.

Benefit to Decrease Esophageal Damage using an Ablation Catheter with Increased Irrigation Channels for Pulmonary Vein Isolation

An ablation catheter has been developed with six additional irrigation channels at the proximal end of the ablating electrode. We investigated the potential improvement of esophageal damage when the number of irrigation channels of the ablation catheter was increased during pulmonary vein isolation (PVI).

Causes of death in Japanese patients with atrial fibrillation: The Fushimi Atrial Fibrillation Registry

Aims To investigate the causes of death and the associated clinical factors in patients with atrial fibrillation (AF) in the contemporary clinical practice. Methods and results The Fushimi AF Registry is a community-based prospective survey of AF patients since March 2011 in Fushimi-ku, Kyoto. We investigated causes of death and the clinical indicators of cardiovascular (CV) and non-CV death in 4045 patients with available follow-up data by the end of November 2016. The mean age was 73.6 ± 10.9 years and the mean CHA2DS2-VASc score was 3.38 ± 1.69. Oral anticoagulants were prescribed in 55% of patients. During a median follow-up of 1105 days, there were 705 all-cause deaths (5.5%/year); 180 CV (26% of total deaths), 381 non-CV (54%), and 144 undetermined causes (20%). The most common causes of CV and non-CV death were heart failure (14.5%), malignancy (23.1%), and infection/sepsis (17.3%), while mortality due to stroke was only 6.5%. Mortality due to infection/sepsis and undetermined causes increased with aging. On multivariate analysis, the strongest indicator of CV death was pre-existing heart failure [hazard ratio (HR) 2.42, 95% confidence interval (CI) 1.66-3.54; P < 0.001] and that of non-CV death was anaemia (HR 2.84, 95% CI 2.22-3.65; P < 0.001). Conclusion In a Japanese community-based AF cohort, CV death was not mainly related to stroke but to heart failure. Non-CV death, mainly malignancy and infection, comprised more than a half of all deaths, which increased substantially in accordance with aging. Clinical factors that were associated with CV and non-CV death were distinct.