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Physical activity (PA) in the daily life is strongly related to prognosis in patients with or at high risk of heart failure (HF). However, factors limiting habitual exercise and their prognostic impacts remain unknown in HF patients. We sent questionnaires asking factors limiting habitual exercise in the daily life to 8370 patients with Stage A/B/C/D HF in our nationwide registry and received valid responses from 4935 patients (mean age 71.8 years, 71.0% male). Among the 5 components consisting of “busyness”, “weak will”, “dislike, “socioeconomic reasons” and “diseases” in the questionnaires, “busyness” (34.5%) and “diseases” (34.7%) were the most frequently reported factors limiting habitual exercise, while “socioeconomic reasons” were the least (15.3%). Multiple Cox proportional hazard models indicated that “busyness”and “diseases” were associated with better (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.39–0.72, P

BACKGROUND It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. METHODS AND RESULTS From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission. On multivariate inverse probability of treatment weighted (IPTW) Cox modeling, loop diuretics use was associated with worse prognosis with hazard ratio (HR) 1.28 (P

Background The prognostic impact of new-onset atrial fibrillation (AF) is not fully elucidated. Methods and results We examined 4,818 consecutive stage C/D chronic heart failure (CHF) patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). At enrollment, 1,859 (38.6%) of them had AF. Compared with the 2,953 patients without AF, AF patients were characterized by higher age (71 vs. 68 years), lower estimated glomerular filtration rate (58.9 vs. 61.9 ml/min/1.73 m(2)), higher brain natriuretic peptide (152 vs. 74.5 pg/ml), similar left ventricular ejection fraction (56.8 vs. 56.5%), and a similar prescription rate of β-blockers (48.1 vs. 50.6%) and renin-angiotensin system (RAS) inhibitors (72.9 vs. 71.6%). Among the patients without AF at enrollment, 106 (3.6%) developed new AF during the median 3.2-year follow-up, which was associated with increased mortality (adjusted hazard ratio, 1.72; P=0.013). In contrast, neither paroxysmal nor chronic AF at enrollment was associated with increased mortality. The mortality rate was significantly high in the first year after the onset of new AF. On inverse probability of treatment weighting analysis using propensity score, RAS inhibitors and statins were associated with reduced incidence of new AF, and diuretics were associated with increase of new AF. Conclusions Onset of new AF, but not a history of AF, is associated with increased mortality in CHF patients, especially in the first year.

Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure (HF) remain to be elucidated in Japan.From the Chronic Heart Failure Analysis and Registry in the Tohoku District-1 (CHART-1; 2000-2005, n=1,278) and CHART-2 (2006-present, n=10,219) Studies, we enrolled 1,006 and 3,676 consecutive symptomatic stage C/D HF patients, respectively. As compared with the patients in the CHART-1 Study, those in the CHART-2 Study had similar age and sex prevalence, and were characterized by lower brain natriuretic peptide, higher prevalence of preserved left ventricular ejection fraction (LVEF) and higher prevalence of hypertension, diabetes mellitus and ischemic heart disease (IHD), particularly IHD with LVEF ≥50%. From CHART-1 to CHART-2, use of renin-angiotensin system inhibitors, β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was decreased. Three-year incidences of all-cause death (24 vs. 15%; adjusted hazard ratio [adjHR], 0.73; P0.001), cardiovascular death (17 vs. 7%; adjHR, 0.38; P0.001) and hospitalization for HF (30 vs. 17%; adjHR, 0.51; P0.001) were all significantly decreased from CHART-1 to CHART-2. In the CHART-2 Study, use of β-blockers was associated with improved prognosis in patients with LVEF50%, while that of statins was associated with improved prognosis in those with LVEF ≥50%.Along with implementation of evidence-based medications, the prognosis of HF patients has been improved in Japan. (clinicaltrials.gov identifier: NCT00418041)

Recent trends in the clinical characteristics, management and prognosis of dilated cardiomyopathy (DCM) remain to be examined in Japan.We compared 306 and 710 DCM patients in the Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-1 (2000-2005, n=1,278) and the CHART-2 (2006-present, n=10,219) Studies, respectively. Between the 2 groups of DCM patients, there were no significant differences in baseline characteristics. The prevalence of hypertension, dyslipidemia and diabetes mellitus were all significantly increased from the CHART-1 to the CHART-2 Study. The use of β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was significantly decreased in the CHART-2 Study. The 3-year mortality rate was significantly improved from 14% in the CHART-1 to 9% in the CHART-2 Study (adjusted HR, 0.60; 95% CI: 0.49-0.81; P=0.001). In particular, 3-year incidence of cardiovascular death was significantly decreased (adjusted HR, 0.26; 95% CI: 0.14-0.50, P0.001), while that of HF admission was not (adjusted HR, 0.90; 95% CI: 0.59-1.37, P=0.632). The prognostic improvement was noted in patients with BNP220 pg/ml, LVEF40%, β-blocker use and aldosterone antagonist use.Long-term prognosis of DCM patients has been improved, along with the implementation of evidence-based medication in Japan.

BACKGROUND: We examined the prevalence, predictors and prognostic impact of post-traumatic stress disorder (PTSD) after the Great East Japan Earthquake in patients with cardiovascular disease (CVD) in the CHART-2 study.METHODS and Results:The prevalence of PTSD was 14.7% at 6 months after the Earthquake. Female sex, experiencing the Tsunami, property loss, poverty, and insomnia medication use were associated with PTSD. The patients with PTSD more frequently experienced a composite of death, acute myocardial infarction, stroke and heart failure (18.5% vs. 15.0%, P=0.035). CONCLUSIONS: PTSD was frequent in CVD patients after the Earthquake and had an adverse prognostic impact. (Circ J 2015; 79: 664-667). Language: en

Background It is unclear whether the prognostic impact of diabetes mellitus (DM) in chronic heart failure (CHF) is influenced by ischemic heart disease (IHD) and/or nephropathy. Methods and results We enrolled 4,065 consecutive patients with stage C/D CHF (mean age, 69.0 years; 68.7% male) in the CHART-2 Study (n=10,219). We defined DM as current history of DM treatment or HbA1c ≥6.5% (National Glycohemoglobin Standardization Program [NGSP]), and nephropathy as urine albumin:creatinine ratio ≥30 mg/g or urine dipstick test ≥(±) at enrollment. Impacts of DM and nephropathy on the composite of death, myocardial infarction, stroke, and HF admission were examined. Among the 4,065 patients, 1,448 (35.6%) had DM, while IHD and nephropathy were also noted in 1,644 (40.4%) and in 1,549 (38.1%), respectively. During the median follow-up of 2.88 years, 1,025 (25.2%) reached the composite endpoint. On multivariate Cox regression, DM was significantly associated with the composite endpoint in all patients (HR, 1.17; P=0.02), and in those with IHD (HR, 1.38; P=0.004), but not in those without IHD (HR, 1.12; P=0.22; P for interaction=0.12). Furthermore, when the patients were stratified by nephropathy, DM was associated with worse prognosis only in the IHD patients with nephropathy. Conclusions The prognostic impact of DM was more evident in patients with IHD than in those without IHD, particularly when complicated with nephropathy.

Background:Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF).Methods and Results:In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and 60 ml·min–1·1.73 m–2, n=1,129) or mildly reduced eGFR (30–59.9 ml·min–1·1.73 m–2, n=789), respectively. In patients with severely reduced GFR (eGFR 80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Conclusions:Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function. (Circ J 2014; 78: 2890–2898)

Background:Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking.Methods and Results:In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P

Background The gender differences in patients with chronic heart failure (CHF) remain to be fully elucidated in the Japanese population. Methods and results We examined gender differences in clinical characteristics, treatment and long-term outcome in 4,736 consecutive CHF patients in stage C/D (mean age, 69 years) out of 10,219 patients registered in the CHF Registry, named CHART-2 Study (NCT 00418041). Compared with male patients (68%, n=3,234), female patients (32%, n=1,502) were 3.8 years older and had lower prevalence of ischemic heart disease, diabetes, smoking, myocardial infarction and cancer. At baseline, women had higher prevalence of preserved left ventricular function but had higher NYHA functional class and increased brain natriuretic peptide level. In women, aspirin, β-blockers and statins were less frequently used and diuretics were more frequently used. Crude mortality rate was similar between the genders during the median 3.1-year follow-up (52.4/1,000 and 47.3/1,000 person-years for women and men, respectively, P=0.225). On multivariate Cox regression analysis, women had a reduced risk of mortality (adjusted HR, 0.791; 95% CI: 0.640-0.979, P=0.031). Conclusions Substantial gender differences exist in stage C/D CHF patients in real-world practice in Japan. Although female CHF patients had better survival than male patients after adjustment for baseline differences, crude mortality rate was similar between the genders, possibly reflecting relatively severer clinical manifestations in women.

Aims It is still controversial whether elevated baseline heart rate (HR) is associated with higher mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF). We compared the impacts of baseline HR on mortality in patients with HFpEF and those with HF with reduced ejection fraction (HFrEF). Methods and results We enrolled consecutive 2688 patients in Stage C or D HF with sinus rhythm from our Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) Study (n = 10 219). The prognostic impact of HR increase was compared between the two groups, defined as left ventricular ejection fraction of 50% (HFpEF). Cox regression analysis revealed that elevated baseline HR was associated with increased all-cause mortality in both groups [hazard ratio for the highest tertile (HH) 1.77 in HFrEF, P = 0.008; HH1.82 in HFpEF, P = 0.001]. However, as for mode of death, elevated HR was associated with cardiovascular (CV) death in HFpEF (HH 2.17, P = 0.012), but the association was modest in HFrEF (HH1.49, P = 0.14): in particular, impact on HF death was different between HFpEF (HH 3.79, P = 0.020) and HFrEF (HH 1.07, P = 0.864). In contrast, the prognostic impact of baseline HR on non-CV death was noted only in patients with HFrEF. β-Blocker therapy was associated with reduced HF mortality in HFrEF (hazard ratio 0.49, P = 0.038) but not in HFpEF (hazard ratio 0.64, P = 0.321). Conclusions Elevated HR was associated with increased CV death in HFpEF compared with HFrEF, although its impact on all-cause mortality was comparable between the two groups.

The appropriate target ranges of heart rate (HR) and systolic blood pressure (SBP) for the management of chronic heart failure (CHF) patients remain to be elucidated in a large-scale cohort study.We examined 3,029 consecutive CHF patients with sinus rhythm (SR) (mean age, 67.9 years) registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study (CHART-2; NCT00418041). There were 357 deaths (11.8%) during the median follow-up of 3.1 years. We first performed the classification and regression tree analysis for mortality, identifying SBP89 mmHg, HR70 beats/min and SBP115 mmHg as the primary, secondary and tertiary discriminators, respectively. According to these, we divided the patients into low- (n=1,131), middle- (n=1,624) and high-risk (n=274) groups with mortality risk10%, 10-20% and20%, respectively. The low-risk group was characterized by SBP115 mmHg and HR70 beats/min and the high-risk group by SBP89 mmHg regardless of HR values or SBP 89-115 mmHg and HR76 beats/min. Multivariate Cox regression analysis revealed that the hazard ratio of all-cause death for low-, middle- and high-risk groups was 1.00 (reference), 1.48 (95% confidence interval (CI): 1.10-1.99, P=0.009) and 2.44 (95% CI 1.66-3.58, P0.001), respectively. Subgroup analysis revealed that age ≥70 years, diabetes, or reduced left ventricular function had higher hazard ratios in the high-risk group.The results demonstrate the usefulness of combined risk stratification of HR and SBP in CHF patients with SR.

BACKGROUND Metabolic syndrome (MetS) is involved in the increased risk of atherosclerotic cardiovascular diseases. We have previously reported that the prevalence of MetS is more than 2-fold greater in patients with chronic heart failure (CHF) than in the general population in Japan. However, the prognostic impact of MetS in CHF patients remains to be elucidated. METHODS AND RESULTS In the present nationwide, large-scale clinical study in Japan, we enrolled 4,762 patients with Stage C/D CHF. The prevalence of MetS by the definition of the Japanese Committee for the Diagnostic Criteria in 2005 was 41.3% (50.6% in males, 21.5% in females). MetS was characterized by higher prevalence of males, obesity and lifestyle-related comorbidities, including glucose intolerance, dyslipidemia and hypertension. Multivariate Cox hazard analysis showed that MetS was associated with increased incidence of the composite of all-cause death and atherosclerotic events in males (hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.06-1.54, P=0.011) but not in females (HR 1.23, 95% CI 0.87-1.75, P=0.241). Among the components of MetS, over waist circumference and glucose intolerance were significantly associated with increased incidence of the composite endpoint (HR 1.23, P=0.038, and HR 1.29, P

Background: The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated. Methods and Results: We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P Conclusions: As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.

Background: Metabolic syndrome (MetS) is a pathological condition with a clustering of metabolic components and is substantially associated with increased risk of atherosclerotic cardiovascular diseases. However, prognostic impacts of MetS in patients with chronic heart failure (CHF) remain to be fully elucidated. Methods and Results: From the database of our nationwide, multicenter observational study with 10,464 CHF patients in stage A/B/C/D in Japan, 4,764 patients with Stage C/D CHF were enrolled. The prevalence of MetS, according to the Japanese standard diagnostic criteria, was 39.6% (48.7% in males and 20.5% in females), which was almost twice higher as compared with the general population in Japan. CHF patients with MetS were characterized by higher prevalence of male, obesity and lifestyle-related diseases, including diabetes mellitus, hypertension and hyperlipidemia. Although univariate Cox proportional hazard analysis revealed that MetS was not associated with increased incidence of composite of all-cause death and atherosclerotic cardiovascular events (unadjusted HR 0.92; 95% CI 0.81-1.04, P=0.177), multivariate analysis adjusted with body mass index (BMI) alone or fully adjusted with clinical backgrounds showed that MetS was associated with increased incidence of the composite endpoint (BMI-adjusted HR 1.33; 95% CI 1.15-1.55, P2 , but not in those with BMI≥25.0kg/m 2 ( Table ). Conclusions: These results indicate that MetS is associated with worse prognosis in patients with Stage C/D CHF, particularly in male patients without obesity.

BACKGROUND We aimed to elucidate the prognostic impact of anemia with special reference to the clinical background of patients with chronic heart failure (CHF). METHODS AND RESULTS We examined 4,646 consecutive patients with Stage C/D CHF registered in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (n=10,219). Among them, 1,627 (35%) had anemia and were characterized by higher age (74 vs. 66 years), lower estimated glomerular filtration rate (52.8 vs. 66.1 ml/min/1.73 m(2)) and higher B-type natriuretic peptide levels (154.5 vs. 81.8 pg/ml) (all P

BACKGROUND The risk of patients with aortic stenosis (AS) should be stratified not only by AS severity but also by comorbidities. METHODS AND RESULTS We aimed to develop a risk score for mortality in 412 patients with AS (pressure gradient ≥30 mmHg, mean age 74.9 years, male 52.4%) in the CHART-2 Study (n=10,219). During a 3-year follow-up, 73 (17.7%) patients died. Crude 3-year mortality of patients in New York Heart Association (NYHA) classes I, II, and III/IV was 9.5%, 16.5%, and 49.7%, respectively (P

We examined the prevalence, predictors and prognostic impact of post-traumatic stress disorder (PTSD) after the Great East Japan Earthquake in patients with cardiovascular disease (CVD) in the CHART-2 study. METHODS AND RESULTS: The prevalence of PTSD was 14.7% at 6 months after the Earthquake. Female sex, experiencing the Tsunami, property loss, poverty, and insomnia medication use were associated with PTSD. The patients with PTSD more frequently experienced a composite of death, acute myocardial infarction, stroke and heart failure (18.5% vs. 15.0%, P=0.035).PTSD was frequent in CVD patients after the Earthquake and had an adverse prognostic impact.

The effectiveness of statins remains to be examined in patients with heart failure (HF) with preserved ejection fraction (EF). METHODS AND RESULTS: Among 4,544 consecutive HF patients registered in the Chronic Heart Failure Registry and Analysis in the Tohoku district-2 (CHART-2) between 2006 and 2010, 3,124 had EF ≥50% (HFpEF; mean age 69 years; male 65%) and 1,420 had EF50% (HF with reduced EF (HFrEF); mean age 67 years; male 75%). The median follow-up was 3.4 years. The 3-year mortality in HFpEF patients was lower in patients receiving statins [8.7% vs. 14.5%, adjusted hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.58-0.94; P0.001], which was confirmed in the propensity score-matched cohort (HR, 0.72; 95% CI, 0.49-0.99; P=0.044). The inverse probability of treatment weighted further confirmed that statin use was associated with reduced incidence of all-cause death (HR, 0.71; 95% CI, 0.62-0.82, P0.001) and noncardiovascular death (HR, 0.53; 95% CI, 0.43-0.66, P0.001), specifically reduction of sudden death (HR, 0.59; 95% CI, 0.36-0.98, P=0.041) and infection death (HR, 0.53; 95% CI, 0.35-0.77, P=0.001) in HFpEF. In the HFrEF cohort, statin use was not associated with mortality (HR, 0.87; 95% CI, 0.73-1.04, P=0.12), suggesting a lack of statin benefit in HFrEF patients.These results suggest that statin use is associated with improved mortality rates in HFpEF patients, mainly attributable to reductions in sudden death and noncardiovascular death.

Background: Several studies have reported that the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) was similar to that of patients with reduced ejection fraction. However, sex differences in clinical characteristics and mortality of HFpEF patients remains to be fully elucidated. Methods: Among the 10,219 patients registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study, we examined sex differences in clinical characteristics, treatment and long-term outcome of 3,124 patients with HFpEF in stage C/D (EF≥50%, mean age 69.4 years, 34.7% female). We constructed the Kaplan-Meier curves and Cox hazard models for all-cause death to evaluate sex difference in mortality. Results: Female patients, as compared with male patients, were characterized by higher age (71.6 vs. 68.3 years, P Conclusions: Although female HFpEF patients had comparable all-cause mortality with males, they had severer HF and higher cardiovascular mortality than males.

Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF). METHODS AND RESULTS: In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and27.4 mg/g. There were 506 composite endpoints (24.8%) during the median follow-up of 2.69 years. On Kaplan-Meier analysis and multivariate Cox modeling, subclinical microalbuminuria was significantly associated with increased composite endpoints with hazard ratios of 1.90 (P0.001) and 2.29 (P0.001) in patients with preserved (60 ml·min(-1)·1.73 m(-2), n=1,129) or mildly reduced eGFR (30-59.9 ml·min(-1)·1.73 m(-2), n=789), respectively. In patients with severely reduced GFR (eGFR30 ml·min(-1)·1.73 m(-2), n=121),80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function.

Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking. METHODS AND RESULTS: In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P0.001). Among the reasons for requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and C/D (29.0%). Compared with the non-NC group, the NC group was characterized by higher age, higher prevalence of female gender and cerebrovascular disease, and increased plasma brain natriuretic peptide regardless of HF stage. During a median follow-up of 12.7 months after the survey, the NC group had a significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%, P0.001). On multivariate logistic analysis depressive mental status (hazard ratio [HR], 3.61; P0.001) and dementia (HR, 2.70; P0.001) were significantly associated with NC need.In HF patients, NC need is considerably high and is associated with increased mortality regardless of HF stage in Japan.

It is still controversial whether elevated baseline heart rate (HR) is associated with higher mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF). We compared the impacts of baseline HR on mortality in patients with HFpEF and those with HF with reduced ejection fraction (HFrEF).We enrolled consecutive 2688 patients in Stage C or D HF with sinus rhythm from our Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) Study (n = 10 219). The prognostic impact of HR increase was compared between the two groups, defined as left ventricular ejection fraction of 50% (HFrEF) and 50% (HFpEF). Cox regression analysis revealed that elevated baseline HR was associated with increased all-cause mortality in both groups [hazard ratio for the highest tertile (HH) 1.77 in HFrEF, P = 0.008; HH1.82 in HFpEF, P = 0.001]. However, as for mode of death, elevated HR was associated with cardiovascular (CV) death in HFpEF (HH 2.17, P = 0.012), but the association was modest in HFrEF (HH1.49, P = 0.14): in particular, impact on HF death was different between HFpEF (HH 3.79, P = 0.020) and HFrEF (HH 1.07, P = 0.864). In contrast, the prognostic impact of baseline HR on non-CV death was noted only in patients with HFrEF. β-Blocker therapy was associated with reduced HF mortality in HFrEF (hazard ratio 0.49, P = 0.038) but not in HFpEF (hazard ratio 0.64, P = 0.321).Elevated HR was associated with increased CV death in HFpEF compared with HFrEF, although its impact on all-cause mortality was comparable between the two groups.

Background Although angiotensin receptor blockers (ARBs) are now one of the first-line drug classes for the management of hypertension, recommendations for the management of chronic heart failure (CHF) are limited. The supplemental benefit of angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial investigates whether an additive treatment with an ARB, olmesartan, reduces the mortality and morbidity in hypertensive patients with stable chronic heart failure. Methods and results The SUPPORT trial is a prospective randomized open-label blinded endpoint study. Between October 2006 and March 2010, 1147 stable CHF patients treated with evidence-based medications were successfully randomized to either olmesartan or control group. In the olmesartan group, the ARB was initiated at the dose of 5.0–10 mg, and was then increased up to 40 mg/day, when possible. No ARBs were allowed in the control group. Primary outcome measure in the SUPPORT trial is the composite of all-cause death, non-fatal acute myocardial infarction, non-fatal stroke and hospital admission due to worsening heart failure. The participants will be followed for at least 3 years until March 2013. Conclusions The SUPPORT trial will elucidate the supplemental benefits of an ARB, olmesartan, in hypertensive patients with CHF.

Prognostic Impacts and Temporal Changes of Post-Traumatic Stress Disorder after the Great East Japan Earthquake in Patients with Heart Failure A Report from the CHART-2 Study Takeo Onose, Yasuhiko Sakata, Masanobu Miura, Soichiro Tadaki, Ryoichi Ushigome, Takeshi Yamauchi, Kenjiro Sato, Kanako Tsuji, Ruri Abe, Kotaro Nochioka, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa; Tohoku University Graduate School of Medicine, Sendai, Japan

the lower group than higher group. Blood hemoglobin level was lower in the lower group than higher group (11.162.1 g/dl vs. 12.562.1 g/dl, p!0.0001). Red cell distribution width was greater in the lower group. There was no difference in the hospitalization length. Mortality due to heart failure during the hospital course was more common in the lower group than higher group (6.4% vs. 2.1%, p!0.05). There was no difference in the mortality after 30 days, 3 months and 6 months after discharge. Rehospitalization due to heart failure 3 months and 6 months after discharge was more common in the lower group than higher group (9.0 vs. 23.3%, p!0.005; 11.2% vs. 27.6%, p!0.001). Abnormal renal function, coupled with underlying reduced cardiac function and abnormal erythropoiesis, is associated with adverse clinical outcomes in patients with ADHF.

Long-term Effects of the 2011 Japan Earthquake and Tsunami on the Incidence of Heart Failure: A Community-based Study MOTOYUKI NAKAMURA, FUMITAKA TANAKA, HIROSHI ENDOF, MIKIO KAWAKAMI, TATSUYA MATSUMOTO, OSAMU NISHIYAMA, TOSHIYUKI ONODA Internal Medicine, Iwate Medical Univ, Cardiology, Iwate Ofunato Hospital, Internal Medicine, Iwate Kamaishi Hospital, Cardiology, Iwate Kuji Hospital, Cardiology, Iwate Ninohe Hospital, Preventive Medicine, Iwate Medical Univ

Purpose: It is still controversial whether elevated baseline heart rate (HR) is associated with higher mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF). We compared the prognostic impact of baseline HR between patients with HFpEF and those with HF with reduced ejection fraction (HFrEF). Methods and results: We enrolled consecutive 2,688 patients with symptomatic Stage C/D HF with sinus rhythm from our Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) Study (n=10,219). The prognostic impact of HR increase was compared between HFrEF (LVEF 50%, n=1,803). Cox regression analysis revealed that elevated baseline HR was significantly associated with increased all-cause mortality in both groups (hazard ratio for the highest tertile (HH) 1.77 in HFrEF, P=0.008; HH1.82 in HFpEF, P=0.001) (Figure 1). However, elevated HR was significantly associated with cardiovascular (CV) death in HFpEF (HH 2.17, P=0.012) but not in HFrEF (HH1.49, P=0.14). Furthermore, the impact of elevated HR on HF death was different between HFpEF (HH 3.79, P=0.020) and HFrEF (HH 1.07, P=0.864). This was also the case for CV death in patients without β-blocker therapy in both HFpEF (HH 2.89, P=0.013) and HFrEF (HH 2.07, P=0.131). Furthermore, β-blocker therapy was significantly associated with reduced HF mortality in HFrEF (hazard ratio 0.51, P=0.041) but not in HFpEF (hazard ratio 0.59, P=0.243). ![Figure][1] Figure 1 Conclusions: These results indicate that elevated HR is associated with increased CV death, particularly HF death, in HFpEF compared with HFrEF, whereas its impact on all-cause mortality is comparable between the 2 groups. They also suggest that β-blocker therapy is associated with improved HF mortality in HFrEF but not in HFpEF. [1]: pending:yes

Purpose: The aim of this study was to investigate the association among cardiovascular disease severity, the Disaster experiences and the development for post-traumatic stress disorder (PTSD) in patients with cardiovascular diseases (CVD). Methods: With questionnaires sent in September 2011, we examined the relationship among CVD severity, the experiences and the risk for PTSD in 4,490 CVD patients who suffered from the Disaster in the Chronic Heart Failure Analysis and Registry in the Tohoku Districrt-2 (CHART-2). Psychological disorder was evaluated by the Japanese version of the Impact of Event Scale-Revised (IESR-J, a score of ≥25 was defined as PTSD). Results: Among the 4,490 patients (mean age, 67.5±11.1 years; male, 70.3%), 592 had PTSD (13.2%), who were more likely to be female (37.8% vs. 28.5%, P

Background: Increasing prevalence of heart failure (HF) is an urgent public health issue worldwide. Although the ACC/AHA Guidelines emphasize the importance to prevent the development of HF in asymptomatic Stage-B patients, little is known about the etiology and predictors for transition to symptomatic HF in Stage-B patients. Method: Among the 10,219 subjects registered in our cohort, named as the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) study, we enrolled 4,463 Stage-B patients in the present study. We analyzed the predictors for de novo HF in asymptomatic Stage-B patients by Akaike's information criterion (AIC). Results: Mean age was 67.3±12.4 years old, and male patients accounted for 71%. Regarding etiologies for asymptomatic cardiac structure abnormalities, the prevalence of ischemic heart disease, valvular heart disease, and cardiomyopathy was 51, 19, and 10%, respectively. During the median follow-up period of 3.0 years, 280 deaths (6.0%), 103 cardiovascular deaths (2.2%) and 165 de novo HF requiring hospitalization (3.5%) were noted. A stepwise Cox regression analysis with AIC revealed that development of de novo HF in Stage-B patients could be predicted by age (Hazard ratio (HR) 1.02, P=0.013), diastolic blood pressure (DBP) (HR 0.97, P=0.001), paroxysmal atrial fibrillation (PAF) (HR 2.50, P70 yrs.), low DBP (