Takayuki Otsuka

Usefulness of Frequent Supraventricular Extrasystoles and a High CHADS2 Score to Predict First-Time Appearance of Atrial Fibrillation

Frequent supraventricular extrasystoles (SVEs) are associated with the subsequent first-time appearance of atrial fibrillation (AF) and ischemic stroke. The aim of this study was to investigate the combined role of SVEs and an AF-related risk score for ischemic stroke, the CHADS2 score, on the occurrence of new AF in patients in sinus rhythm. The Shinken Database 2004-2010 lists 3,263 patients who underwent 24-hour Holter monitoring. A total of 2,589 patients were analyzed, after excluding 674 patients previously diagnosed with AF. Frequent SVEs were defined as ≥102 beats/day (the top quartile) and the presence of a clinical background for a CHADS2 score ≥2 points as a high CHADS2 score. During the mean follow-up period of 571.4 ± 606.4 days, new AF occurred in 38 patients (9.4 per 1,000 patient-years). The incidence of new AF was 2.7 and 37.7 per 1,000 patient-years for patients with nonfrequent SVEs (<102 beats/day) and low CHADS2 scores and those with frequent SVEs and high CHADS2 scores, respectively. Multivariate Cox regression analysis showed that the hazard ratio for frequent SVEs and a high CHADS2 score compared with nonfrequent SVEs and a low CHADS2 score was 9.49 (95% confidence interval 3.20 to 28.15, p <0.001), even after adjustment for gender, age, medications, and echocardiographic parameters. In conclusion, frequent SVEs and a high CHADS2 score independently and synergistically predict the first-time appearance of AF in patients in sinus rhythm, indicating an approximately 10-fold higher risk. Patients meeting these criteria should have more aggressive early intervention for preventing AF.

Obesity paradox in Japanese patients after percutaneous coronary intervention: An observation cohort study

BACKGROUND The impact of obesity on Japanese patients who undergo primary percutaneous coronary intervention (PCI) remains unclear. METHODS AND RESULTS Within a single hospital-based cohort in the Shinken Database 2004-2010, which comprised all new patients (n=15227) who visited the Cardiovascular Institute, we followed patients who underwent PCI. Major adverse cardiac events (MACE)-death, myocardial infarction, or target lesion revascularization (TLR)-were defined as the composite endpoint. A total of 1205 patients were included in this study (median follow-up of 1037±703 days): 92 lean [body-mass-index (BMI)<20]; 640 normal-weight (BMI=20-24.9); 417 overweight (BMI=25-29.9); and 56 obese (BMI≥30). Mean age decreased and male gender increased with increasing BMI. Classic coronary risk factors were more common in overweight and obese patients than in normal-weight and lean patients. Chronic kidney disease (CKD) was more common in lean patients than in overweight and obese patients. Patients taking dual antiplatelet therapy, statins, beta-blockers, and renin-angiotensin-system inhibitors increased in a BMI-dependent manner. Obese patients had a significantly lower frequency of MACE, all-cause death, cardiac death, and hospital admission for heart failure than lean patients. Multivariate analysis showed that BMI category was independently associated with all-cause death after PCI. CONCLUSION Over-weight and obese patients were independently associated with favorable long-term clinical outcomes after PCI, suggesting that obesity paradox was applicable to Japanese patients after PCI in real-world clinical setting.

Recent mortality of Japanese patients with atrial fibrillation in an urban city of Tokyo.

BACKGROUND In Japan, the recent status of the mortality of atrial fibrillation (AF) patients is still unclear. METHODS AND RESULTS We used a single-hospital based cohort database in an urban city (Tokyo) in Japan, including all the new visitors from 2004 to 2009 (n=13,228). The non-adjusted death rates of AF patients for all-cause, stroke, and cardiovascular death were 1091, 97, and 727 per 100,000 patient-years, and the age-adjusted ones were 317 (95% CI, 316-318), 16 (95% CI, 16-16), and 238 (95% CI, 237-239), respectively. The age-adjusted relative risk of AF on all-cause mortality was 1.7 in the particular population. CONCLUSIONS The present study provides the most recent data about the characteristics and the mortality of AF patients in Tokyo, thus serving as the basic information for finding problems to solve regarding Japanese AF patients.

Clinical characteristics and long-term clinical outcomes of Japanese heart failure patients with preserved versus reduced left ventricular ejection fraction: A prospective cohort of Shinken Database 2004–2011

BACKGROUND Clinical data on the mortality and morbidity of unselected Japanese patients with heart failure (HF) are limited. In this study, we aimed to determine the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with preserved or reduced left ventricular ejection fraction (LVEF). METHODS AND RESULTS We used a single hospital-based cohort from the Shinken Database 2004-2011 that comprised all new patients (n=17,517) visiting the Cardiovascular Institute Hospital. A total of 1,525 patients diagnosed with symptomatic HF at the initial visit were included in the analysis. Of these, 1121 patients (74%) exhibited a preserved LVEF (>50%) and 404 patients (26%) had a reduced LVEF (≤ 50%). HF patients with preserved LVEF (HFpEF) were older and more often female than patients with reduced LVEF (HFrEF). Kaplan-Meier curves and log-rank test results showed that HFpEF patients had a better prognosis than HFrEF patients. However, there were no significant differences in clinical outcomes between HFpEF and HFrEF patients when the analysis was limited to inpatients. Cox regression analysis showed that HFpEF patients had a significantly lower risk of all-cause death (p=0.027; hazard ratio, 0.547, 95% confidence interval, 0.321-0.933). Multivariate analyses performed separately showed that the independent predictors of all-cause death in HFrEF were advanced age, lower body mass index, diabetes mellitus, and the absence of statin treatment, whereas those for HFpEF were advanced age, absence of dyslipidemia, anemia, and left ventricular hypertrophy. CONCLUSIONS This prospective cohort study identified the clinical characteristics, long-term outcomes, and prognostic factors of Japanese HF patients with reduced and preserved ejection fractions in a real-world clinical setting.

Effects of statin treatment in patients with coronary artery disease and chronic kidney disease.

Statins reduce cardiovascular morbidity and mortality from coronary artery disease (CAD). However, the effects of statin therapy in patients with CAD and chronic kidney disease (CKD) remain unclear. Within a single hospital-based cohort in the Shinken Database 2004–2010 comprising all patients (n = 15,227) who visited the Cardiovascular Institute, we followed patients with CKD and CAD after percutaneous coronary intervention (PCI). A major adverse cardiovascular and cerebrovascular event (MACCE) was defined by composite end points, including death, myocardial infarction, cerebral infarction, cerebral hemorrhage, and target lesion revascularization. A total of 391 patients were included in this study (median follow-up time 905 ± 679 days). Of these, 209 patients used statins. Patients with statin therapy were younger than those without. Obesity and dyslipidemia were more common, and the glomerular filtration rate (GFR) was significantly higher, in patients undergoing statin treatment. MACCE and cardiac death tended to be less common, and all-cause death was significantly less common, in patients taking statins. Multivariate analysis showed that low estimated GFR, poor left ventricular ejection fraction, and the absence of statin therapy were independent predictors for all-cause death of CKD patients after PCI. Statin therapy was associated with reduced all-cause mortality in patients with CKD and CAD after PCI.

Impact of aging on the clinical outcomes of Japanese patients with coronary artery disease after percutaneous coronary intervention

Japan has become an aging society, resulting in an increased prevalence of coronary artery disease. However, clinical outcomes of elderly Japanese patients after percutaneous coronary intervention (PCI) remain unclear. Of the 15,227 patients in the Shinken Database, a single-hospital-based cohort of new patients, 1,214 patients who underwent PCI, was evaluated to determine the differences in clinical outcomes between the elderly (≥75 years) (n = 260) and the non-elderly (<75 years) (n = 954) patients. A major adverse cardiac event (MACE) was defined as a composite end point, including all-cause death, myocardial infarction (MI), and target lesion revascularization. Male gender and obesity were less common, and the estimated glomerular filtration rate (eGFR) was significantly lower in the elderly than in the non-elderly. Left ventricular ejection fraction (LVEF) was comparable between these groups. Left main trunk disease and multivessel disease were more common in the elderly than in the non-elderly group. Occurrence of MACE was frequent, and the incidences of all-cause death, cardiac death, and the admission rate for heart failure were significantly higher in the elderly patients. Multivariate analysis showed that prior MI, low eGFR, and poor LVEF were independent predictors for all-cause death in the elderly patients. Elderly patients had worse clinical outcomes than the non-elderly patients. Low eGFR and LVEF were independent predictors of all-cause death after PCI, suggesting that left ventricular dysfunction and renal dysfunction might synergistically contribute to the adverse clinical outcomes of the elderly patients undergoing PCI.

A New Scoring System for Evaluating the Risk of Heart Failure Events in Japanese Patients With Atrial Fibrillation

Risk stratification for heart failure (HF) in patients with atrial fibrillation (AF) has not been well established. The aim of this study was to identify the predictors of HF events in patients with AF, consequently developing a new risk-scoring system that stratifies the risk for HF events. In this prospective, single hospital-based cohort, all patients who presented from July 2004 to March 2010 were registered (Shinken Database 2004-2009). Follow-up was maintained by being linked to the medical records or by sending study documents of prognosis. Of the 13,228 patients in the Shinken Database 2004-2009, 1,942 patients with AF were identified. Of the patients with AF, HF events (hospitalization or death from HF) occurred in 147 patients (7.6%) during a mean follow-up period of 776 ± 623 days. After identifying the parameters that were independently associated with the incidence of HF events (coexistence of organic heart diseases, anemia [hemoglobin level <11 g/dl], renal dysfunction [estimated glomerular filtration rate <60 ml/min/m(2)], diabetes mellitus, and the use of diuretics), a new scoring system was developed, the H(2)ARDD score (heart diseases = 2 points, anemia = 1 point, renal dysfunction = 1 point, diabetes = 1 point, and diuretic use = 1 point; range 0 to 6 points). This scoring system discriminated the low- and high-risk populations well (incidence in patients scoring 0 and 6 points of 0.2% and 40.8% per patient-year, respectively) and showed high predictive ability (area under the curve 0.840, 95% confidence interval 0.803 to 0.876). In conclusion, the new H(2)ARDD score may help identify the population of patients with AF at high risk for HF events.

Treatment strategy and clinical outcome in Japanese patients with atrial fibrillation

Many large-scale randomized control trials (RCTs) have been performed regarding treatment strategy in atrial fibrillation (AF) in Western countries and also in Japan. However, limited data are available concerning real-world relationships between the treatment strategy and prognosis of AF patients. Out of a prospective cohort of The Shinken Database 2004 (n = 2 412), 286 AF patients (male 205, 64.1 ± 12.3 years, paroxysmal form 165) were retrospectively investigated. The percentage of AF patients under the rhythm control strategy was evaluated using the Kaplan-Meier method, which showed the cumulative proportion of rhythm control strategy was ∼30% at the 90th day after the initial visit and 40.0% at 1 year. The average time to the first rhythm control strategy was 68.3 ± 106.7 days. Those under rhythm control strategy were associated with fewer coexisting organic cardiac diseases, a younger age, and smaller left atrial dimension. Consequently, they showed very good prognosis (cumulative incidence rate of cardiovascular events at 1 year was 0.0%). Careful induction of rhythm control strategy, which was adopted in ∼40% of the patients in the real world, was associated with fewer comorbidities and therefore might lead to better prognosis, although this does not mean the direct effects of rhythm control strategy.

Role of cardiopulmonary dysfunction and left atrial remodeling in development of acute decompensated heart failure in chronic heart failure with preserved left ventricular ejection fraction

BACKGROUND The presence of heart failure (HF) with preserved ejection fraction (HFPEF) is increasingly recognized. However, prognostic factors for HFPEF remain unclear. METHODS AND RESULTS The data were derived from Shinken Database 2004-2010, a prospective cohort study (n=15,227). We examined 301 consecutive HFPEF patients (New York Heart Association Class II or greater) and tracked them for an average 3.5 years. Cardiopulmonary exercise testing (CPX), blood exams, and ultrasound cardiogram (UCG) were performed at the first medical examination. Acute decompensated HF (ADHF) admission was observed in 19 patients (6.3%). CPX showed that the anaerobic threshold was lower (7.3±4.8mL/min/kg vs. 9.7±4.3mL/min/kg, p=0.02) and slope of the increase in ventilation to the increase in CO(2) output (VE-VCO(2) slope) was higher (40.6±8.5 vs. 34.6±7.9, p<0.01) in patients with ADHF admission than those without. Serum brain natriuretic peptide (BNP) tended to be higher and left atrial (LA) dimension was significantly greater (47.0±15.8mm vs. 41.0±9.9mm, p=0.01) in patients with ADHF admission than those without. Multivariate analysis showed that higher VE-VCO(2) slope and greater LA dimension were independent determinants of ADHF admission. CONCLUSION An aggravated CPX parameter and LA dilatation were associated with ADHF admission in patients with symptomatic HFPEF, suggesting the prognostic role of cardiopulmonary dysfunction during exercise and LA remodeling in the pathogenesis of decompensated HF development in HFPEF.

Association between smoking habits and the first-time appearance of atrial fibrillation in Japanese patients: Evidence from the Shinken Database

BACKGROUND We previously reported a cross-sectional analysis regarding the relationship between smoking and atrial fibrillation (AF) in a single hospital-based cohort with Japanese patients, but the effect of cessation of smoking and/or total tobacco consumption were unclear. METHODS AND RESULTS We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. After excluding those previously diagnosed with AF (n=2296), 15,221 patients (men/women, n=9016/6205) were analyzed. During the follow-up period of 2.0±2.1 years (range 0.0-8.1), the incidence rates of new AF in smokers and non-smokers were 9.0 and 5.0 per 1000 patient-years, respectively. In adjusted models with Cox regression analysis, smokers were independently associated with new AF [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.09-2.00]. Also, current smokers (HR 1.81, 95% CI 1.17-2.79) and smokers with Brinkman index ≥800 (HR 1.69, 95% CI 1.05-2.70) were independently associated with new AF. However, in current smokers, the HRs were not different by Brinkman index (Brinkman index <800/≥800; HR 1.81/1.82, 95% CI 1.07-3.05/0.94-3.51, respectively). CONCLUSIONS Smoking was independently associated with the first-appearance of AF in patients in sinus rhythm, especially when the patients continued their smoking habit. However, in patients who continued smoking, difference by total tobacco consumption was not observed, suggesting the significance of cessation of smoking for preventing AF. Our data are limited because of a single hospital-based nature and a relatively short observation period.