External Validation of the Japanese Clinical Score for Mortality Prediction in Patients With Acute Heart Failure.

BACKGROUND: To predict mortality in patients with acute heart failure (AHF), we created and validated an internal clinical risk score, the KICKOFF score, which takes physical and social aspects, in addition to clinical aspects, into account. In this study, we validated the prediction model externally in a different geographic area.Methods and Results: There were 2 prospective multicenter cohorts (1,117 patients in Osaka Prefecture [KICKOFF registry]; 737 patients in Kochi Prefecture [Kochi YOSACOI study]) that had complete datasets for calculation of the KICKOFF score, which was developed by machine learning incorporating physical and social factors. The outcome measure was all-cause death over a 2-year period. Patients were separated into 3 groups: low risk (scores 0-6), moderate risk (scores 7-11), and high risk (scores 12-19). Kaplan-Meier curves clearly showed the score's propensity to predict all-cause death, which rose independently in higher-risk groups (P<0.001) in both cohorts. After 2 years, the cumulative incidence of all-cause death was similar in the KICKOFF registry and Kochi YOSACOI study for the low-risk (4.4% vs. 5.3%, respectively), moderate-risk (25.3% vs. 22.3%, respectively), and high-risk (68.1% vs. 58.5%, respectively) groups. CONCLUSIONS: The unique prediction score may be used in different geographic areas in Japan. The score may help doctors estimate the risk of AHF mortality, and provide information for decisions regarding heart failure treatment.

The clinical characteristics and outcomes of heart failure patient with chronic obstructive pulmonary disease from the Japanese community-based registry.

Both heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common diseases, but few studies have assessed the relationship between COPD and outcomes in patients with acute HF, especially in relation to age or ejection fraction (EF). The Kitakawachi Clinical Background and Outcome of Heart Failure Registry was a prospective, multicenter, community-based cohort and enrolled a total of 1,102 patients with acute HF between 2015 and 2017 in this study. The primary endpoint was defined as a composite endpoint that included all-cause mortality and hospitalization for HF. We stratified patients into two groups: those aged ≥ 80 years (elderly) and < 80 years (nonelderly). HF with preserved EF (HFpEF) was defined as EF ≥ 50%, whereas HF with reduced ejection fraction (HFrEF) was defined as EF < 50%. A total of 159 patients (14.4%) with COPD and 943 patients (83.6%) without COPD were included. COPD was found to be independently associated with a higher risk of the composite endpoint (adjusted hazard ratio: 1.42, 95% confidence interval: 1.14-1.77; p = 0.003). During a subgroup analysis, COPD was exposed as an independent risk factor of the composite endpoint in nonelderly patients; however, there was not such a finding observed among elderly patients. Separately, there was a significant association with COPD and the composite endpoint in patients with HFpEF. COPD showed a significantly higher risk of the composite endpoint after discharge in acute HF. However, this heightened risk was observable only in the subgroup of nonelderly patients and those of HFpEF.

Active Participation in Outpatient Cardiac Rehabilitation Is Associated With Better Prognosis After Coronary Artery Bypass Graft Surgery　- J-REHAB CABG Study.

BACKGROUND: There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.Methods and Results:We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03). CONCLUSIONS: This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.

Clinical Characteristics and Outcomes of Heart Failure Patients With Long-Term Care Insurance　- Insights From the Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: In Japan, the long-term care insurance (LTCI) system has an important role in helping elderly people, but there have been no clinical studies that have examined the relationship between the LTCI and prognosis for patients with acute heart failure (HF).Methods and Results:This registry was a prospective multicenter cohort, 1,253 patients were enrolled and 965 patients with acute HF aged ≥65 years were comprised the study group. The composite endpoint included all-cause death and hospitalization for HF after discharge. We divided the patients into 4 groups: (i) patients without LTCI, (ii) patients requiring support level 1 or 2, (iii) patients with care level 1 or 2, and (iv) patients with care levels 3-5. The Kaplan-Meier analysis identified a lower rate of the composite endpoint in group (i) than in the other groups. After adjusting for potentially confounding effects using a Cox proportional regression model, the hazard ratio (HR) of the composite endpoint increased significantly in groups (iii) and (iv) (adjusted HR, 1.62; 95% confidence interval [CI], 1.22-1.98 and adjusted HR, 1.62; 95% CI, 1.23-2.14, respectively) when compared with group (i). However, there was no significant difference between groups (i) and (ii). CONCLUSIONS: The level of LTCI was associated with a higher risk of the composite endpoint after discharge in acute HF patients.

Living Alone and Gender Differences in Rehospitalization for Heart Failure After Discharge Among Acute Heart Failure Patients.

Home treatment for heart failure (HF) is one of the most important problems in patients after discharge as a secondary preventive measure for rehospitalization for HF. However, there are no detailed studies on gender differences in sociopsychological factors such as living alone for HF rehospitalization among patients with acute HF (AHF).This prospective multicenter cohort study enrolled patients with AHF between April 2015 and August 2017. Patients of each gender with first AHF were divided into those living alone and those not living alone. The primary endpoint was defined as rehospitalization for HF after discharge. Cox proportional hazard analysis was performed to determine the association between living alone and the endpoint.Overall, 581 patients were included in this study during the 3-year follow-up. The proportion of rehospitalization for HF was significantly higher in patients living alone than in those not living alone among male patients. However, female patients showed no difference in endpoints between the two groups. The difference was independently maintained even after adjusting for differences in social backgrounds in male patients (adjusted hazard ratio (HR) 2.02; 95% confidence interval (CI), 1.07-3.70). In female patients, the HR for rehospitalization for HF showed no difference between the two groups (adjusted HR, 0.99; 95% CI, 0.56-1.69).In this study population, male patients living alone after first AHF discharge had a higher risk of rehospitalization for HF than those not living alone, but these differences were not observed in female patients.

Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of cardiovascular disease: a 12-month follow-up.

BACKGROUND: Gliptins should have beneficial effects beyond glycemic control, potentially on the pathophysiology of cardiovascular (CV) diseases, with some basic studies demonstrating this possibility. However, we are yet to answer whether there are any direct CV effects in the clinical setting. We aimed to examine the beneficial effects of sitagliptin in Japanese patients with diabetes and high CV risk for 12 months. METHODS: This was a prospective, multicenter, observational study of 205 patients with type 2 diabetes. All participants had more than one major CV risk factor and were treated with sitagliptin for 12 months. At 3 or 12 months, we examined the effects of treatment on glycemic control, CV function (by electrocardiography, echocardiography, and reactive hyperemia-peripheral arterial tonometry), and CV biomarkers. RESULTS: Patients were predominantly elderly (68.8 ± 9.9 years) and male (71.5 %) and typically had more than three CV risk factors (79.2 %). Treatment with sitagliptin significantly reduced the hemoglobin A1c (HbA1c) level from 7.09 % ± 0.81 % at baseline to 6.67 % ± 0.69 % at 3 months and 6.68 % ± 0.73 % at 12 months (both P < 0.001). The reduction in HbA1c was also in tandem with the decrease in the level of high-sensitive C-reactive protein throughout the study. Independent of the change in HbA1c, sitagliptin reduced systolic (-7.0 ± 18.9 mmHg) and diastolic blood pressure (-5.1 ± 11.7 mmHg) at 12 months, and this was associated with a decrease in urinary albumin. In contrast, there were no beneficial effects on cardiac and endothelial function or on the levels of serum B-type natriuretic peptide, high-sensitive troponin T, and urinary 8-hydroxy-2'-deoxyguanosine. CONCLUSIONS: In Japanese patients with diabetes and multiple CV risk factors, sitagliptin showed a decrease in blood pressure associated with an improvement in albuminuria in addition to glycemic control. TRIAL REGISTRATION: UMIN000005663.

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure　- The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015. We compared the clinical characteristics and social background of the super-elderly group (≥85 years old) and the non-super-elderly group (<85 years old). This study included 647 patients; 11.8% of the super-elderly patients were living alone, 15.6% were living with only a partner, and of these, only 66.7% had the support of other family members. The super-elderly group had less control over their diet and drug therapies than the non-super-elderly group. Most patients in the super-elderly group were registered for long-term care insurance (77.4%); 73.5% of the super-elderly patients could walk independently before admission, but only 55.5% could walk independently at discharge, whereas 94% of the non-super-elderly patients could walk independently before admission and 89.4% could walk independently at discharge. CONCLUSIONS: The KICKOFF Registry provides unique detailed social background information of Japanese patients with HF. Super-elderly patients are at serious risk of social frailty; they need the support of other people and their ability to perform activities of daily living decline when hospitalized.

Change in carotid intima-media thickness in a high-risk group of patients by intensive lipid-lowering therapy with rosuvastatin: subanalysis of the JART study.

Carotid intima-media thickness (IMT), a measure of atherosclerosis, is modulated by multiple risk factors. Accordingly, comprehensive control of risk factors is indispensable for management of atherosclerosis. In this study, as a posthoc analysis of the JART Study we planned two analyses. In the main analysis, we evaluated the effect of intensive lipid-lowering therapy with rosuvastatin on carotid IMT in high-risk patients. We also evaluated efficacy in the presence or absence of each risk factor using the full analysis population in the JART Study. Patients with low-density lipoprotein cholesterol (LDL-C) ≥ 140 mg/dL and max-IMT ≥ 1.1 mm were randomized to rosuvastatin or pravastatin therapy for 12 months. Dosages were allowed to increase to 10 mg/day and 20 mg/day to achieve LDL-goals (aggressive goals for rosuvastatin group and guideline goals for pravastatin group). For the main analysis, we assessed 200 high-risk patients (105 in the rosuvastatin group), as category III or secondary prevention according to the Japan Atherosclerosis Society guideline 2007, whereas we assessed 289 patients in the other analysis. Rosuvastatin significantly slowed the percentage change in mean-IMT at 12 months compared with pravastatin (1.40 ± 10.03% versus 6.43 ± 13.77%, P = 0.005). LDL-C was reduced by 48.1% in the rosuvastatin group and 27.9% in the pravastatin group. The rate of achieving the LDL-C goal was significantly greater in the rosuvastatin group compared with the pravastatin group (P < 0.001). Rosuvastatin slowed the change in mean-IMT in the presence of every risk factor. Thus, intensive lipid-lowering therapy reduced progression of carotid IMT in high-risk patients.

Effect of long-term intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness--Justification for Atherosclerosis Regression Treatment (JART) extension study.

BACKGROUND: Recently, it was reported from the Justification for Atherosclerosis Regression Treatment (JART) Study that intensive therapy with rosuvastatin significantly slowed progression of carotid intima-media thickness (IMT) compared with conventional therapy with pravastatin at 12 months. To assess the long-term efficacy of intensive therapy, the present extension study was conducted. METHODS AND RESULTS: Subjects in the intensive therapy group of the JART Study were asked to participate in the extension study and to continue rosuvastatin treatment. A total of 113 subjects were enrolled into the extension study and were included in the analysis. At 24 months, the mean daily dose of rosuvastatin (±SD) was 7.9±2.9 mg. Mean change in mean IMT was -0.005 mm (range, -0.024 to 0.015 mm) at 24 months (P=0.633, compared with baseline). Rosuvastatin lowered low-density lipoprotein cholesterol (mean±SD) by 46.4±13.8% and elevated high-density lipoprotein cholesterol (mean±SD) by 8.9±24.0% at 24 months compared with baseline. Gray scale median was measured in 25 subjects. It increased by 16.93±33.12 (mean±SD) % at 12 months and by 22.50±52.83% at 24 months from baseline (P=0.017, P=0.044, respectively). CONCLUSIONS: Two-year treatment with rosuvastatin inhibited progression of carotid IMT. Rosuvastatin also improved the plaque composition, and this qualitative change occurred relatively early after starting therapy.

Two cases of reversible left ventricular hypertrophy during recovery from takotsubo cardiomyopathy.

We report 2 cases of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy (stress-induced cardiomyopathy) during recovery of cardiac function. The first case involved a 72-year-old woman who presented with cerebral infarction. On admission, an elevated troponin I and decreased apical wall motion were observed with normal myocardial perfusion imaging. The second case involved a 79-year-old woman who presented with angina, anxiety resulting from emotional stress, slightly decreased apical wall motion, and normal epicardial arteries. In both cases, apical hypertrophy of the left ventricle was observed at approximately 3 weeks after onset, when the wall motion had improved. The ventricular wall gradually became thinner over time. To our knowledge, this is the first report of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy. We hypothesize the hypertrophic signaling in the myocardium was stimulated by catecholamines, which are the suggested etiology of takotsubo cardiomyopathy, and the hypertrophied myocardium gradually returned to normal as the syndrome receded.