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The effects of smoking on the prognosis of non-valvular atrial fibrillation (NVAF) patients are unclear.The Shinken Database 2004-11 (n = 17,517) includes all new patients visiting the Cardiovascular Institute between June 2004 and March 2012. Among these cases, 2,102 NVAF patients were identified. The effects of smoking on ischemic stroke (IS), intracranial hemorrhage (ICH), and coronary artery events including percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) were analyzed. Smokers were younger and had lower risk profiles compared with non-smokers. A similar tendency was observed between current and former smokers. In contrast, patients with high tobacco consumption were older and had higher risk profiles, including uncontrolled hypertension, compared with those with low tobacco consumption. In 8,159 patient-years, IS, ICH, PCI, and ACS occurred at rates of 7.7, 2.7, 12.4, and 3.0 per 1000 patient-years. In multivariate Cox regression analysis, smoking was not significantly associated with any adverse event. However, different effects of smoking were observed when stratified by age. In patients ≥ 65 years old, current smokers were independently associated with PCI. Moreover, current smokers and smokers with a total tobacco amount ≥ 800 were marginally and independently associated with IS. In patients < 65 years, current smokers were independently associated with ICH.Age appears to be one of the contributors to differentiation of the effects of smoking on cardiovascular events in our NVAF patients. In elderly patients who still smoke, smoking was associated with the promotion of atherosclerosis or thromboembolism, whereas in young patients it was associated with bleeding.

Background Trends of oral anticoagulant (OAC) prescription and incidence of thromboembolism (TE) and/or major bleeding (MB) in patients with non-valvular atrial fibrillation (NVAF) in Japan are still unclear. Methods and results We used data from Shinken Database 2004-2012, which included all new patients attending the Cardiovascular Institute between June 2004 and March 2013. Of them, 2,434 patients were diagnosed with NVAF. Patients were divided into 3 time periods according to the year of initial visit: 2004-2006 (n=681), 2007-2009 (n=833), and 2010-2012 (n=920). OAC prescription rate steadily increased from 2004-2006 to 2010-2012. Between 2004-2006 and 2007-2009, irrespective of increased warfarin usage, MB tended to decrease, presumably due to low-intensity therapy and avoidance of concomitant use of dual antiplatelets, but TE did not improve. In 2010-2012, direct OACs (DOAC), preferred in low-risk patients, may have contributed to not only decrease TE, but also increase MB, especially extracranial bleeds. In high-risk patients in that time period, mostly treated with warfarin, incidence of TE and MB did not improve. Conclusions The 9-year trend of stroke prevention indicated a steady increase of OAC prescription and a partial improvement of TE and MB. Even in the era of DOAC, TE prevention was insufficient in high-risk patients, and DOAC were associated with increased extracranial bleeding. (Circ J 2016; 80: 639-649).

BackgroundWe 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 resultsWe 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

Background The association between ABO blood type and the activated partial thromboplastin time (aPTT) under dabigatran therapy in nonvalvular atrial fibrillation (NVAF) patients is unclear. Methods and results Between 2011 March and 2015 May, data on ABO blood type and aPTT under dabigatran were obtained for 396 NVAF patients (baseline aPTT, 166). The prevalence of blood type O tended to increase or significantly increase according to baseline aPTT, aPTT under dabigatran, and their difference (∆aPTT) (P=0.054, 0.001, and 0.012, respectively). Conclusions In these NVAF patients, a high aPTT value under dabigatran therapy was associated with blood type O.

The effects of smoking on the prognosis of non-valvular atrial fibrillation (NVAF) patients are unclear.The Shinken Database 2004-11 (n = 17,517) includes all new patients visiting the Cardiovascular Institute between June 2004 and March 2012. Among these cases, 2,102 NVAF patients were identified. The effects of smoking on ischemic stroke (IS), intracranial hemorrhage (ICH), and coronary artery events including percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) were analyzed. Smokers were younger and had lower risk profiles compared with non-smokers. A similar tendency was observed between current and former smokers. In contrast, patients with high tobacco consumption were older and had higher risk profiles, including uncontrolled hypertension, compared with those with low tobacco consumption. In 8,159 patient-years, IS, ICH, PCI, and ACS occurred at rates of 7.7, 2.7, 12.4, and 3.0 per 1000 patient-years. In multivariate Cox regression analysis, smoking was not significantly associated with any adverse event. However, different effects of smoking were observed when stratified by age. In patients ≥ 65 years old, current smokers were independently associated with PCI. Moreover, current smokers and smokers with a total tobacco amount ≥ 800 were marginally and independently associated with IS. In patients65 years, current smokers were independently associated with ICH.Age appears to be one of the contributors to differentiation of the effects of smoking on cardiovascular events in our NVAF patients. In elderly patients who still smoke, smoking was associated with the promotion of atherosclerosis or thromboembolism, whereas in young patients it was associated with bleeding.

BACKGROUND Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR

Background Seasonal variations in cardiovascular disease is well recognized. However, little is known about the presentations and outcomes of Japanese heart failure (HF) patients in the winter season. Methods and results We used a single hospital-based cohort from the Shinken Database 2004–2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 375 patients who were admitted owing to acute decompensated HF were included in the analysis. Of these patients, 136 (36%) were admitted in winter. Winter was defined as the period between December and February. The HF patients admitted in winter were older, and had a higher prevalence of hypertension and diabetes mellitus than the patients admitted in other seasons. Patients with conditions categorized as clinical scenario 1 tended to be admitted more commonly in winter. HF with preserved left ventricular ejection fraction (LVEF) was more common in HF patients admitted in winter than in those admitted in other seasons. Beta-blocker use at hospital discharge was more common in the patients admitted in other seasons. Kaplan–Meier curves and log-rank test results indicated that the incidences of all-cause death, cardiovascular death, and HF admission were comparable between the patients admitted in winter and those admitted in other seasons. Conclusions HF admission was frequently observed in the winter season and HF patients admitted in the winter season were older, and had higher prevalence of hypertension and diabetes mellitus, and preserved LVEF suggesting that we might need to pay more attention for elderly patients with hypertension, diabetes mellitus, and HF with preserved LVEF to decrease HF admissions in the winter season.

Background A novel risk scoring system (H2ARDD) for estimating the incidence of heart failure (HF) events in atrial fibrillation (AF) has been developed, which represents points assigned for organic heart disease (2 points), anemia (1 point), renal dysfunction (1 point), diabetes (1 point), and diuretic use (1 point). We aimed to clarify whether H2ARDD score is related to cardiopulmonary exercise testing (CPX) parameters in patients with AF. Methods The study population included 344 consecutive patients with AF who underwent CPX as initial screening between June 2004 and March 2012. The association between 4 CPX parameters and the incidence of HF events was analyzed by using multiple linear regression models. Results The peak O 2 uptake (peak V O 2 ), anaerobic (gas exchange) threshold (AT), and ratio of the increase in V O 2 to the increase in work rate (Δ V O 2 /ΔWR) were lower and the slope of the increase in ventilation to the increase in CO 2 output ( V E– V CO 2 slope) was higher in patients with than in those without each H2ARDD score component. Accordingly, the parameters significantly increased or decreased according to H2ARDD score. With the multiple linear regression models, H2ARDD score was independently associated with each CPX parameter even after adjustment for various cofactors. Conclusions H2ARDD score was independently associated with the well-established CPX parameters in patients with AF, suggesting a potential pathophysiological basis for a risk stratification system for predicting HF events in patients with AF.

Background: Prothrombin time (PT) distribution in Japanese nonvalvular atrial fibrillation (NVAF) patients under rivaroxaban therapy remains to be clarified. Methods and Results: Between May 2012 and July 2013, 115 NVAF patients received rivaroxaban (PT was measured in 94; reagent: recombiplastin). In these patients, (1) PT values were distributed widely from patient to patient and from peak to trough, (2) the time-dependence was obscure with sampling at any time in the outpatient clinic, and (3) the incidence of adverse events was too low for analyzing the relation with PT. Conclusions: We report the distribution of PT for Japanese NVAF patients under rivaroxaban therapy in real-world clinical practice. (Circ J 2014; 78: 763–766)

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.

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 (

BACKGROUND Tobacco smoking is a well-known risk factor for cardiovascular disease, but controversial results have been reported regarding its relationship with atrial fibrillation (AF). Moreover, no study on the relationship between smoking and AF has yet been undertaken in a Japanese context. METHODS AND RESULTS We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6,803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. AF was diagnosed in 1,698 and 598 men and women, respectively. In men, smokers were more prevalent in the AF than in the non-AF group (54.5% vs. 44.7%), whereas in women the prevalence of smokers was similar between AF and non-AF groups (14.4% vs. 15.4%). This discrepancy between the sexes seems to derive from a characteristic distribution pattern of smoking habit in women. After adjustment for various cofactors, smoking was independently associated with AF (odds ratio 1.54; 95% confidence interval 1.35-1.75; P

The mortality and morbidity of patients with stable angina pectoris (SAP) after percutaneous coronary intervention (PCI) in Japan differ from those in Western countries, although Japanese data are limited. We selected from the Shinken Database a single-hospital-based cohort of Japanese patients (n = 15,227) who visited The Cardiovascular Institute between 2004 and 2010 to undergo PCI. We followed-up the patients after PCI. A major adverse cardiac event (MACE) was defined as composite endpoints including all-cause death, acute myocardial infarction (AMI), and target-lesion revascularization (TLR). This study included 747 SAP patients (median follow-up period, 1,000 ± 703 days). The all cause mortality rate in SAP was 1.3% at 1 year, 2.7% at 3 years, and 6.1% at 5 years. The AMI rate was 0.5% at 1 year, 1.1% at 3 years, and 3.0% at 5 years, and the MACE rate was 14.0% at 1 year, 17.6% at 3 years, and 25.6% at 5 years. Moreover, new lesion PCI and heart failure admission continued to occur beyond 1 year after PCI without attenuation of their annual incidences up to 5 years. Multivariate analysis showed that poor left ventricular ejection fraction, chronic kidney disease (CKD), and absence of statin treatment were independent predictors of all-cause death of SAP patients after PCI. The results of the present study revealed the characteristics and long-term outcomes of Japanese SAP patients after PCI. The results of the present study suggest cardiorenal interaction and statin treatment play important roles in the long-term outcomes of Japanese CAD patients treated by PCI.

Atrial fibrillation (AF) is associated with an increased risk of stroke and other thromboembolic events. Left atrial (LA) thrombus formation is closely related to LA dysfunction, particularly to decreased LA appendage flow velocity (LAA-FV) in patients with AF. We estimated LAA-FV using parameters noninvasively obtained by transthoracic echocardiography (TTE) in patients with paroxysmal AF.Echocardiographic and clinical parameters were assessed in 190 patients with nonvalvular paroxysmal AF showing sinus heart rhythm during transesophageal echocardiography (TEE) and TTE.LAA-FV (60 ± 22 cm/s) significantly correlated with the time interval between the initiation of the P-wave on ECG and that of the A-wave of transmitral flow on TTE (PA-TMF, correlation coefficient, -0.32; P < 0.001), LA dimension (LAD, -0.31; P < 0.001), septal a' velocity of tissue Doppler imaging (TDI, 0.35; P < 0.001), E/e' ratio (-0.28, P < 0.001), E velocity of transmitral flow (-0.20, P = 0.008), E/A ratio of transmitral flow (-0.18, P = 0.02), CHA2DS2-VASc score (-0.15, P = 0.04), and BNP plasma level (-0.32, P = 0.002). Multivariate analysis revealed that PA-TMF (standardized partial regression coefficient, -0.17; P = 0.03), a' velocity (0.24, P = 0.004), and LAD (-0.20, P = 0.01) were independent predictors of LAA-FV (multiple correlation coefficient R, 0.44; P < 0.001).Parameters of atrial remodeling, ie, decreased a' velocity, increased LAD, and PA-TMF during sinus rhythm may be useful predictors of LA blood stasis in patients with nonvalvular PAF. LAA-FV can be estimated using these TTE parameters instead of TEE.

SummaryBackgroundThe presence of heart failure (HF) with preserved ejection fraction (HFPEF) is increasingly recognized. However, prognostic factors for HFPEF remain unclear.Methods and resultsThe 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 CO2 output (VE-VCO2 slope) was higher (40.6±8.5 vs. 34.6±7.9, p

SummaryBackgroundThe effect of early statin initiation on secondary prevention remains uncertain in unselected Japanese populations with coronary artery disease (CAD).MethodsWe investigated the mortality and morbidity in CAD patients according to presence or absence of statins within 3 months after the diagnosis of CAD in the Shinken Database cohort study. The primary endpoint was all-cause mortality.ResultsData were available on 789 Japanese patients with CAD (male 78.8%). Among those, 351 patients (44.5%) received a statin. The mean (SD) baseline low-density lipoprotein (LDL)-cholesterol levels were 113.6 (35.7) mg/dL in the statin group and 113.6 (26.4) mg/dL in the non-statin group (p=0.992). Unadjusted 2-year survival in patients with or without statins was 98.4% and 92.1%, respectively (p

Patients with coronary artery disease (CAD) frequently have impaired renal function, but the prevalence and influence of renal dysfunction on their prognosis in Japan remain uncertain. With a prospective study comprising all the new patients who had visited our hospital between 2004 and 2007 (n=6562), we investigated the prevalence of renal dysfunction and its influence on the prognosis of CAD patients. The glomerular filtration rate (GFR) was calculated by using the GFR equation used for the Japanese population. Of those, 797 patients with CAD and blood tests available were analyzed (median follow-up periods of 693 days). Patients were further classified into four subgroups according to estimated GFR value (eGFR): normal (90or =eGFR, 12.2%), mildly impaired (60or =eGFR90, 58.3%), moderately impaired (30or =eGFR60, 23.6%) and severely impaired renal function (eGFR30, 5.9%). The 2-year survival and cardiovascular event (cardiac death, nonfatal myocardial infarction or readmission for heart failure)-free rates were significantly different among the four subgroups: 98.9, 97.7, 89.3 vs. 67.8%, respectively (P0.001 for trend), and 100, 98.8, 89.0 vs. 70.0%, respectively (P0.001 for trend). The age- and gender-adjusted mortality increased significantly in moderately impaired (hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.383-7.017) and in severely impaired subgroups (HR 10.1, 95% CI 4.244-24.178) compared with those with eGFR of 60 or more. After adjustment for baseline differences, eGFR was independently associated with death and cardiovascular events (HR 0.983 and 0.981, 95% CI 0.968-0.998 and 0.965-0.998, respectively). In conclusion, our study identified the prevalence and association of eGFR with prognosis in Japanese patients with CAD, suggesting that strict care for not only CAD but also renal dysfunction is needed for further prevention of cardiovascular events.

Repeated hospitalization due to acute decompensated heart failure (HF) is a pandemic health problem in Japan. However, it is difficult to predict rehospitalization after discharge for acute decompensated HF. We used a single hospital-based cohort from the Shinken Database 2004-2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 282 patients discharged after their first acute HF admission were included in the analysis. The median follow-up period was 908 ± 865 days. Of these patients, rehospitalization due to worsening HF occurred in 55 patients. The cumulative rate of rehospitalization was 17.5% at 1 year, 21.4% at 2 years, and 25.5% at 3 years. Patients with rehospitalization were older than those without rehospitalization. Prevalence of diabetes mellitus (DM) was more common in patients with rehospitalization. Average heart rate (HR) tended to be higher in patients with rehospitalization. Loop diuretics were more commonly used at hospital discharge in patients with rehospitalization. Multivariate Cox regression analysis revealed that age ≥ 75 years, DM, HR ≥ 75 bpm at discharge, and use of loop diuretics at discharge were independent predictors for rehospitalization. The number of these independent risk factors could be used to clearly discriminate between the HF rehospitalization low-, middle- and high-risk patients. HF rehospitalization commonly occurred in patients who were discharged after their first acute HF admission. Older age, DM, increased HR, and loop diuretics use at discharge were independently associated with HF rehospitalization. By simply counting these risk factors, we might be able to predict the risk of HF rehospitalization after discharge.

In a patient referred for the evaluation of non-sustained monomorphic ventricular tachycardia on Holter recordings, ventricular fibrillation was electrically induced during electrophysiologic study. Despite the absence of structural heart diseases, his ECG revealed J wave and ST segment elevation in the inferior leads, which showed circadian variation and were augmented by the sodium channel blocker, pilsicainide. This case might lead us to notice a new concept, a 'latent' type of variant Brugada syndrome, and these ECG findings and changes might serve as its diagnostic sign.

Background The prognostic impact of worsening renal function (WRF) in acute coronary syndrome (ACS) patients is not fully understood in Japanese clinical practice, and clinical implication of persistent versus transient WRF in ACS patients is also unclear. Methods With a single hospital-based cohort in the Shinken database 2004–2012 ( n = 19,994), we followed 604 ACS patients who underwent percutaneous coronary intervention (PCI). WRF was defined as an increase in creatinine during hospitalization of ≥0.3 mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3 mg/dl above admission value and maintained until discharge, whereas transient WRF was defined as that WRF resolved at hospital discharge. Results WRF occurred in 78 patients (13%), persistent WRF 35 patients (6%) and transient WRF 43 patients (7%). WRF patients were older and had a higher prevalence of chronic kidney disease, history of myocardial infarction (MI), and ST elevation MI. WRF was associated with elevated inflammatory markers and reduced left ventricular (LV) ejection fraction in acute, chronic phase. Incidence of all-cause death and major adverse cardiac events (MACE: all-cause death, MI, and target lesion revascularization) was significantly higher in patients with WRF. Moreover, in the WRF group, incidences of all-cause death and MACE were higher in patients with persistent WRF than those with transient WRF. A multivariate analysis showed that as well as older age, female gender, and intubation, WRF was an independent determinant of the all-cause death in ACS patients who underwent PCI. Conclusions In conclusion, WRF might have a prognostic impact among Japanese ACS patients who underwent PCI in association with enhanced inflammatory response and LV remodeling. Persistent WRF might portend increased events, while transient WRF might have association with favorable outcomes compared with persistent WRF.

Background: This study investigated the progression of paroxysmal atrial fibrillation (AF) to the persistent form in Japanese asymptomatic AF patients. Methods and Results: Data were derived from a single hospital-based cohort in the Shinken Database 2004–2012 (n=19,994), in which 1,176 patients were diagnosed as having paroxysmal AF. AF progression occurred in 115 patients (6.0%/year) during the mean follow-up period (1,213±905 days). Although patients who were asymptomatic at the initial visit (n=468) had a low-risk profile compared with symptomatic patients, they had greater AF progression at follow-up (unadjusted hazard ratio, 1.611; 95% CI: 1.087–2.389; P=0.018). Absence of symptoms, male sex, and cardiomyopathy were independent predictors for AF progression in the multivariate model. It was noted that asymptomatic patients were less likely to undergo pulmonary vein isolation (PVI). In addition, the interaction term between asymptomatic AF and absence of PVI could be another independent predictor for AF progression. Prognosis was similar between asymptomatic and symptomatic patients with AF. Conclusions: Irrespective of low-risk profile, patients with asymptomatic paroxysmal AF had greater progression of AF compared with symptomatic patients. This paradoxical result appeared to be the result of less intensive clinical management, including invasive rhythm control. (Circ J 2014; 78: 1121–1126)

A 65-year-old man with Brugada-type electrocardiogram (ECG) was admitted to our hospital for chest pain, palpitation and faintness. In the cardiac electrophysiological study, no ventricular tachyarrthymia was induced either at baseline or after pilsicainide (50 mg) infusion. Intravenous administration of pilsicainide exaggerated ST-segment elevation in V(1-4) and converted it to the coved type in V(1), accompanied by severe chest pain. Coronary angiography revealed the vasospasm of the right coronary artery was induced by pilsicainide, not by ergonovine. This is the first case report of coronary vasospasm induced by a pure sodium channel blocker in a patient with Brugada-type ECG.

Tobacco smoking is a well-known risk factor for cardiovascular disease, but controversial results have been reported regarding its relationship with atrial fibrillation (AF). Moreover, no study on the relationship between smoking and AF has yet been undertaken in a Japanese context.We used data from the Shinken Database 2004-2011 (men/women, n=10,714/6,803, respectively), which included all new patients attending the Cardiovascular Institute between June 2004 and March 2012. AF was diagnosed in 1,698 and 598 men and women, respectively. In men, smokers were more prevalent in the AF than in the non-AF group (54.5% vs. 44.7%), whereas in women the prevalence of smokers was similar between AF and non-AF groups (14.4% vs. 15.4%). This discrepancy between the sexes seems to derive from a characteristic distribution pattern of smoking habit in women. After adjustment for various cofactors, smoking was independently associated with AF (odds ratio 1.54; 95% confidence interval 1.35-1.75; P0.001) without a significant interaction between sex categories (P=0.195).Smoking was independently associated with AF without a significant interaction between sex categories among Japanese patients visiting a cardiovascular hospital. Further studies using a prospective cohort design are required to confirm a causal link between smoking and AF in Japanese patients.

BackgroundBoth the prevalence of atrial fibrillation and coronary artery disease (CAD) is increasing in aged societies. However, limited data are available regarding the prevalence of CAD and the incidence of coronary events in Japanese patients with nonvalvular atrial fibrillation (NVAF).Methods and resultsThe data in this study were derived from Shinken Database 2004–2010, which includes 15,227 new patient visitors to the Cardiovascular Institute between June 2004 and March 2011. In the database, 1835 patients were diagnosed with NVAF (mean age 63 years, mean CHADS2 score 1.1±1.1, and 75% were men). The prevalence of CAD at the initial visit was 118 patients (6.4%). They were older age and had a greater prevalence of men, more history of congestive heart failure and more history of cardiovascular risk factors rather than those without. During the follow-up period of 532±599 days, coronary events (myocardial infarction, unstable angina, and stable angina) occurred in 51 patients (1.9%/year). Multivariate analysis showed that a history of CAD (p

Resting heart rate (HR) is a surrogate marker of exercise capacity, which has been observed in patients with sinus rhythm (SR). The aim of this study was to examine and compare the relationships between resting HR and peak VO2 in atrial fibrillation (AF) and SR. Two thousand one hundred sixty

Summary 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.

To examine the vasospastic activity of coronary arteries which have been subjected to previous balloon angioplasty, we conducted an acetylcholine provocative test at diagnostic catheterization in 147 consecutive patients. All patients underwent successful elective angioplasty and had follow-up angiography 1 to 6 months after the procedure. Sixty-two patients had a history of prior myocardial infarction and 43 patients had multivessel coronary artery disease. Angioplasty was performed on 176 vessels. Incremental doses of acetylcholine (25 micrograms, 50 micrograms, 100 micrograms) were injected into the right and left coronary arteries over a period of 1 min. The incidence of coronary spasm of arteries which had been subjected to angioplasty was 44%. Angiographic restenosis was observed in 59 patients (40%). There was no correlation between the occurrence of coronary spasm and the presence of restenosis. The maximal dose of injected acetylcholine was smaller in patients with positive evidence of spasm than in patients with negative evidence of spasm (55 +/- 27 micrograms vs 82 +/- 28 micrograms, p < 0.01). In patients with single vessel coronary artery disease, the incidence of spasm of the contralateral artery, i.e. the artery without angioplasty, was lower than that of the artery subjected to angioplasty (22% vs 46%, p < 0.01). Thus, the data suggest that coronary arteries which have been previously subjected to angioplasty have enhanced vasospastic activity in response to acetylcholine.

The incidence of diabetes is increasing, and the disease has become an important predictor of prognosis in patients with coronary artery disease (CAD), although adverse events often occur without warning. Thus, risk stratification of diabetic CAD patients is important for secondary prevention. This study tests the hypothesis that brachial-ankle pulse wave velocity (baPWV), a marker for arterial stiffness obtained by simple and noninvasive automated devices, can be a risk stratification index to predict prognosis in diabetic patients with CAD. The prognosis of CAD patients with diabetes in the Shinken Database cohort study was investigated by dividing patients into two groups based on baPWV measurements. The composite endpoint was death, nonfatal myocardial infarction, repeat revascularization or readmission for heart failure. Data were available on 564 CAD patients, with a median follow-up of 25.4 months. Of these patients, 191 had type 2 diabetes. The higher baPWV among diabetic patients was defined as a median baPWV of 1730 cm s(-1) or more. The 3-year Kaplan-Meier estimates of event-free survival were 72.8% in diabetic patients with lower baPWV and 51.3% in those with higher baPWV, respectively (P=0.031). Multivariate analysis revealed that a higher baPWV was independently associated with poorer short-term prognosis (hazard ratio, 1.97; 95% confidence interval, 1.01-3.84) in diabetic CAD patients. In conclusion, baPWV, a marker for arterial stiffness, can be a risk stratification index for short-term prognosis in clinical practice, suggesting the need for further aggressive treatment and strict follow-up in CAD patients with diabetes and higher baPWV.

Prognosis of patients with heart failure (HF) remains unclear in Japan and should be determined in a prospective fashion. A prospective cohort of The Shinken Database comprised details on all of the new patients, including both inpatients and outpatients, who visited The Cardiovascular Institute Hospital in 2004-2005. HF patients were defined as those with symptomatic HF coexisting with structural heart diseases. Among 4,255 patients who visited our hospital, 597 patients (male/female 414/183, age 65.1 +/- 12.9 years, LVEF 56.2 +/- 18.0%) were diagnosed as presenting symptomatic HF. Ischemic heart disease was present in 305 (51.1%), valvular heart disease in 212 (35.5%), dilated cardiomyopathy in 59 (9.9%), hypertrophic cardiomyopathy in 24 (4.0%), hypertensive heart disease in 14 (2.3%), and others in 67 (11.2%). Hypertension, atrial fibrillation, and diabetes were observed in 35.3%, 27.4%, and 23.7%, respectively. During the mean follow-up period of 539 +/- 257 days, 40 deaths (5.0% per year) occurred, including 34 cardiovascular deaths (4.5% per year, NYHA class II: 1.0%, III: 11.3%, IV: 36.6% per year, respectively). The present study showed that the prognosis of Japanese patients with HF among moderate to severe severity was found to be similar to that of Western countries. Multiple Cox hazard analysis identified the presence of chronic kidney disease and NYHA class as independent predictors for cardiovascular death. This prospective cohort study identified the prevalence, prognosis, and risk factors in HF patients to provide a basis for therapeutic management in Japan.

The long-term safety and efficacy of sirolimus-eluting stents (SES) remain uncertain in real practice in Japan.We used a hospital-based cohort (n = 6,562) comprising all the new patients who had visited our hospital between 2004 and 2007 to investigate the mortality and morbidity after SES or bare-metal stent (BMS) implantation.Of the total, coronary artery disease was observed in 822 patients (12.5%), and SES or BMS were implanted in 208 and 167 patients, respectively. Patients receiving SES more often had diabetes but less often presented with acute myocardial infarction (MI). Median follow-up periods were 815 and 894 days for SES and BMS, respectively (p = 0.305). Intravascular ultrasound (IVUS) was used at a high rate (90%) in both groups, and maximum pressure inflation for SES was high at approximately 18 atm. The unadjusted cumulative incidence of all-cause death and major adverse cardiac events (MACE) (cardiac death, MI or target vessel revascularization) at 2 years was 4.3% versus 7.2% (p = 0.233) and 16.3% versus 32.9% (p0.001), respectively. In multivariate analysis, all-cause mortality was similar between SES (hazard ratio [HR] 0.981, 95% confidence interval [CI] 0.366-2.632) and BMS, but SES significantly reduced MACE (HR 0.468, 95% CI 0.280-0.784). Definite stent thrombosis set by the Academic Research Consortium was not observed in either group, and the incidence of cerebral hemorrhage was 0.5% in SES and 1.2% in BMS, respectively (p = 0.588).SES used in real-world settings appeared to be safe and significantly associated with a lower risk of adverse events at long-term follow up in Japan, especially utilizing a careful stent deployment technique including high-pressure inflation and IVUS use.

Background Prognosis of Japanese patients with atrial fibrillation (AF) should be determined in a prospective cohort study. Methods and Results A prospective cohort of The Shinken Database 2004 comprised details on all the new patients who visited The Cardiovascular Institute Hospital in 2004 (n=2,412), which included 286 AF patients (11.8%, 205 males, 64.1±12.3 years, 165 paroxysmal). In this Japanese cohort of AF patients, the prevalence of congestive heart failure (CHF) was low compared with that in Westerners. Total mortality and cardiovascular morbidity of these patients were also quite low, 1.7% and 11.2% at 1 year, respectively. However, patients with CHF exhibited higher mortality (7.3%), and hospitalization for CHF increased the rate to 22.6%. There was no significant difference in mortality between paroxysmal and persistent AF. Multiple Cox-hazard regression analysis identified hospitalization at initial visit and lack of anticoagulation as independent predictors for mortality, and existence of CHF as the only independent predictor for cardiovascular morbidity. Conclusions The present study identified the mortality (1.7%) and morbidity (11.2%) of Japanese AF patients during 1 year after initial visit. Hospitalization for CHF and lack of anticoagulation were independent predictors for mortality, suggesting important roles of co-morbidities of Japanese AF patients. (Circ J 2008; 72: 914 - 920)

To investigate the effect of Amrinone (AMR) on left ventricular regional wall motion, we performed contrast ventriculography before and after administration of AMR in patients with myocardial infarction. Three patients had anterior myocardial infarction, one had inferior infarction, and one had posterior infarction. All patients had abnormal regional wall motions corresponding with the territory of electrocardiographic abnormal ities. In four of the five patients the regional wall motions of the infarct area were improved by administration of AMR (1mg/kg). The results suggest that the positive inotropic effect of AMR may influence not only normal myocardium but also stunned myocardium.

The purpose of this study is to evaluate the acute and chronic results of directional coronary atherectomy (DCA) using the Flexi-Cut atherectomy catheter to treat a left anterior descending artery (LAD) proximal lesion and the device's effect on the ostium of the left circumflex (LCx) immediately and during the postprocedure follow-up period.From June 2001 to October 2004, 74 lesions were treated by DCA alone for LAD proximal lesions. Quantitative coronary angiography was performed pre-, post-DCA and during the follow-up period for the treated site and the LCx ostium.The angiographic restenosis rate was 12.2%. The target lesion revascularization rate was 9.5%. After the procedure and during follow up, there was no evidence of LCx stenosis (% DS50%) caused by DCA.This study suggests that DCA for LAD proximal lesions is a feasible strategy and does not affect the LCx ostium.

Aims Although various predictors of in-stent restenosis (ISR) have been reported, the subject of parameters relating to ISR on intravascular ultrasound (IVUS) still leaves room for discussion. The aim of this study was to clarify the strongest predictors of ISR using IVUS. Methods and results Ninety-two native coronary lesions undergoing single bare-metallic stent implantation were investigated retrospectively. We classified them into the ISR (n = 46) and non-ISR (n = 46) groups using quantitative coronary angiography. On serial IVUS studies, plaque morphology, and areas and volumes of each component in vessel were evaluated. Among all parameters, diabetes mellitus and soft plaque appearing hypoechoic on IVUS were associated with ISR. By multivariate analysis, soft plaque was the only independent predictor of ISR (p = 0.0057). Compared with non-soft plaque, soft plaque had a larger plaque reduction rate (-7.1% vs. -1.6%, p=0.0613) and smaller percent plaque volume (53.0% vs. 55.5%, p=0.0273) after stenting. Conversely, soft plaque had a larger neointimal area (4.39 vs. 3.33 mm 2 , p = 0.0437) and percent plaque area (80.5% vs. 75.1%, p = 0.0503) at follow-up. Conclusion Soft plaque detected on IVUS was the strongest predictor of ISR. Soft plaque was compressed more easily by stenting, however, causing more proliferation of neointima subsequently and resulted in a worse prognosis.

The aim of this retrospective study was to determine the predictors of diffuse in-stent restenosis (ISR) among the lesions causing the first ISR by intravascular ultrasound (IVUS) studies.Although some predictors of diffuse ISR have been reported, parameters on IVUS relating to diffuse ISR are not well characterized.We classified 52 ISR lesions that had undergone successful stent implantation and led to restenosis into two types--focal and diffuse ISR--using quantitative coronary angiography. Restenosis was defined asor =50% diameter stenosis, and diffuse ISR as lesion lengthor =10 mm at follow-up. The remodeling index (RI) was defined as the vessel area at the target lesion divided by that of averaged reference segments.There were no significant differences in patient, angiographic, and procedural characteristics between the focal (n = 25) and diffuse (n = 27) ISR groups. Baseline RI was significantly greater in the diffuse ISR group (1.03 +/- 0.18 vs. 0.88 +/- 0.24, p = 0.0159). Negative remodeling, defined as RI0.9, was detected in 60% of the focal ISR group and in only 26% of the diffuse ISR group. By logistic regression analysis, baseline RI was the only independent predictor of diffuse ISR (p = 0.0341). Moreover, volumetric analyses revealed that lesions developing into diffuse ISR had less capacity to compensate for further plaque growth.Among the first ISR lesions, baseline positive remodeling was the most powerful predictor of diffuse ISR. Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at higher risk.

In a patient referred for the evaluation of non-sustained monomorphic ventricular tachycardia on Holter recordings, ventricular fibrillation was electrically induced during electrophysiologic study. Despite the absence of structural heart diseases, his ECG revealed J wave and ST segment elevation in the inferior leads, which showed circadian variation and were augmented by the sodium channel blocker, pilsicainide. This case might lead us to notice a new concept, a 'latent' type of variant Brugada syndrome, and these ECG findings and changes might serve as its diagnostic sign.

Objective: To assess the heart rate turbulence (HRT) in patients with systolic dysfunction. Methods: From Shinken Database 2004-8 including all the new patients (n=11123), 68 patients (aged 58.9 years; 12 women) with low EF (EF 0% and TS

Clinicopharmacological study of bevantolol, a newly developed β1-selective β-blockingagent was carried out in Japanese healthy male volunteers. The pharmacokinetics, pharmacodynamics, and safety were investigated after single and once-daily repeated oraladministration of 100 mg and 200 mg of bevantolol. The following results were obtained.(1) The time to the maximum plasma concentration (tmax) on an empty stomach was about 0.7 hr and the elimination half-life in α-phase (t1/2α) and in β-phase (t1/2β) were about 1. 4 hr and 9 to 10 hr, respectively. The area under the plasma concentration curve (AUC) and the maximum plasma concentration (Cmax), which showed about a threefold interindividual variation, were about two times greater after the 200 mg dose than after the100 mg dose.(2) On a full stomach, tmax was prolonged to 2 hr. No sign of accumulation was noted after seven days of once-daily repeated doses.(3) The reduction in resting blood pressure after dosing of bevantolol was mild, while pulse rate decreased singnificantly. Fall in blood pressure after postural change from supine to standing position was not evident.(4) Exercise-induced tachycardia and increase in rate-pressure product were significantly attenuated by bevantolol. A high correlation existed between the percent reduction [%R] HR in exercise-induced tachycardia and the logarithm of the plasma concentration of bevantolol.(5) Resting fingertip blood flow measured by venous occlusion plethysmography did not decrease after repeated doses of 100 mg of bevantolol.(6) Regarding subjective symptoms, complaints of headache, dull headache, and gastrointestinal disturbance were noted in some subjects. No profound influence was recognized on the clinical laboratory data. After repeated doses of 100 mg of bevantolol, one subject developed transient loss of consciousness accompanied by a fall in blood pressure and pulse rate. Therefore, careful attention should be paid when the drug isused.

The exercise tolerance and plasma concentration of a long acting isosorbide dinitrate (ISDN) NRR were studied in 6 patients with stable effort angina after 6 hr of therapywith 20 mg of NRR using symptom-limited multistage ergometer exercise. The results weresummarized as follows.(1) The initiation time of chest pain was significatly prolonged (P

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.

BackgroundSeveral reports have identified that decline in renal function and presence of proteinuria are closely associated with incidence of atrial fibrillation (AF). However, it is still unclear whether these kidney-related markers are associated with the progression of AF from paroxysmal to persistent form.Methods and resultsAmong the new patients who visited the Cardiovascular Institute Hospital between 2004 and 2010 (Shinken Database 2004–2010, n=15,227), both estimated glomerular filtration rate (eGFR) and proteinuria were measured in 1074 AF patients (paroxysmal/persistent 579/495, respectively), who were divided into tertiles of eGFR (the borderlines were 60.07 and 73.67ml[min−1]1.73[m−2], respectively), and then further divided into the two categories with/without proteinuria. The average value of eGFR was lower (63.1ml[min−1]1.73[m−2] vs. 68.8ml[min−1]1.73[m−2], p

Summary Background Several hospital-based investigations have reported that a high proportion of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF). The purpose of this study was to determine the prevalence, prognosis, and predictors for mortality of Japanese HF patients with preserved versus reduced LVEF in a prospective cohort fashion. Methods and results Our hospital-based database including inpatients and also outpatients was used for analysis. Out of 4255 new patients, 597 patients (male/female 414/183, age 65.1 ± 12.9 years) were diagnosed as having symptomatic HF at the initial visit. Among 589 HF patients undergoing echocardiography, 398 (67.6%) showed a preserved LVEF (>50%) and 191 (32.4%) had a reduced LVEF (≤50%). Patients with preserved LVEF were older ( p = 0.004) and more likely to be female ( p = 0.002). During follow-up of an average 539 days, 34 cardiovascular deaths occurred, and patients with preserved LVEF showed a better prognosis than those with reduced LVEF (3.2% vs. 7.4% per year, p = 0.0097). Multivariate Cox hazards analysis identified LVEF as an independent predictor in all HF patients. Also, separated group analysis showed that presence of chronic kidney disease was independently associated with poor prognosis irrespective of HF types. Conclusions This prospective cohort study identified prevalence and prognosis of HF in Japanese in- and outpatients, where patients with preserved LVEF showed a better prognosis than those with reduced LVEF.

Background A blue letter (safety advisory) for dabigatran was issued by the Japanese Ministry of Health, Labour and Welfare in August 2011. Changes in physicians’ attitudes toward dabigatran use before and after the blue letter have not been previously reported. Methods and results Between March 2011 and July 2012, dabigatran was prescribed to 404 Japanese patients with nonvalvular atrial fibrillation at The Cardiovascular Institute (Tokyo, Japan). Patients were divided into three groups according to the first prescription date: phase I (before the blue letter, n = 135); phase II (after the blue letter and before permission for longer-term prescriptions, n = 112); and phase III (after permission for longer-term prescriptions, n = 157). In phase II, dabigatran use tended to be avoided for patients with older age, renal dysfunction, receiving antiplatelet medication, or p-glycoprotein inhibitors. Measurement of activated partial thromboplastin time significantly increased from phase I to III. In phase III, the tendencies seen in phase II were reversed: dabigatran use in patients with older age and renal dysfunction tended to increase, but decreased or remained the same in patients receiving antiplatelet medications or p-glycoprotein inhibitors. Conclusions We described the changes in the attitudes of attending physicians toward dabigatran prescription after the blue letter in a specialized hospital for cardiovascular care in Japan, which, we believe, involve useful information for safe use of dabigatran in a real-world clinical setting. However, a true impact or effect of the blue letter should be ascertained in a nationwide, multicenter study.

Summary Background Mortality and morbidity after acute coronary syndrome (ACS) in Japan appear to be different from those in Western countries due to different social healthcare systems, races, geographical locations, and interventional procedures, although data are limited in Japan. Methods With a hospital-based cohort study comprising all the new patients who had visited our hospital between 2004 and 2007 (n = 6562), we identified all-cause mortality, the composite endpoint of cardiac death, non-fatal myocardial infarction (MI), or target vessel revascularization and the predictors. Results Of the total, 293 patients were included with a discharge diagnosis of ACS (median follow-up of 24.5 months). Non-ST elevation-ACS (NSTE-ACS) (unstable angina and non-ST elevation MI) and ST elevation MI (STEMI) were observed in 165 (56.3%) and 128 (43.7%) patients, respectively. Percutaneous coronary intervention or coronary artery bypass graft surgery was performed in 72.7% and 14.5% of NSTE-ACS patients, respectively and in 82.8% and 10.2% of STEMI patients. The use of aspirin, ticlopidine, and beta-blockers for NSTE-ACS patients were 93.3%, 66.9%, and 38.0%, respectively, with corresponding rates of 96.0%, 75.4%, and 57.1% for STEMI patients. All-cause mortality rates in NSTE-ACS and STEMI were 1.8% and 5.5% at 30 days, respectively, and 6.3% and 12.9% at 2 years, with corresponding rates of 3.7% and 8.7% at 30 days, respectively, and 23.4% and 35.6% at 2 years for the composite endpoint. Multivariate analysis showed that predictors for mortality were older age (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.018–1.244) and estimated glomerular filtration rate value (HR 0.96, 95% CI 0.929–0.988) in NSTE-ACS, and older age (HR 1.10, 95% CI 1.011–1.119) and congestive heart failure on admission (HR 20.0, 95% CI 2.439–164.4) in STEMI. Conclusions The present study identified long-term mortality, morbidity, and predictors of adverse events for Japanese patients with ACS.