Hiroto Kano

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.

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.

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.

Prevalence and the long-term prognosis of functional mitral regurgitation in Japanese patients with symptomatic heart failure

Functional mitral regurgitation (FMR) is a common and critical condition in patients with heart failure (HF); however, the prevalence and clinical outcome of FMR in Japanese real-world clinical practice remain unclear. Within a single hospital-based cohort in the Shinken Database 2004–2011, which comprised all new patients (n = 17,517) who visited the Cardiovascular Institute, we followed symptomatic HF patients. A total of 1,701 patients were included: 104 FMR patients (who had moderate to severe FMR) and 1,597 non-FMR patients (who had none or mild FMR). FMR patients had lower rates of hypertension and dyslipidemia, but higher rates of dilated cardiomyopathy, atrial fibrillation, and New York Heart Association functional class III/IV. FMR patients had higher levels of brain natriuretic peptide and lower left ventricular function. Use of cardiovascular drugs was more common among FMR patients. Kaplan–Meier curves revealed that the incidences of all-cause death, cardiovascular death, and admission for HF were significantly higher in FMR patients. The adjusted Cox regression analysis showed that significant FMR was associated with higher incidences of all-cause death [hazard ratio (HR) 2.179, 95 % confidence interval (CI) 1.266–3.751; P = 0.005], cardiovascular death (HR 2.371, 95 % CI 1.157–4.858; P = 0.018), and admission for HF (HR 1.819, 95 % CI 1.133–2.920; P = 0.013). FMR was common in Japanese symptomatic HF patients and was associated with adverse long-term outcomes. Establishing optimal therapeutic strategies for FMR is warranted.

Incidence and Predictors of Rehospitalization of Acute Heart Failure Patients

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.

Nine-Year Trend of Anticoagulation Use, Thromboembolic Events, and Major Bleeding in Patients With Non-Valvular Atrial Fibrillation – Shinken Database Analysis –

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. METHODSANDRESULTS 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).

The prognostic impact of worsening renal function in Japanese patients undergoing percutaneous coronary intervention with acute coronary syndrome

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 ≥0.3mg/dl above admission value. Persistent WRF was defined as an increase in creatinine during hospitalization of ≥0.3mg/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.