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Since music listening with headphones or earphones disturbs auditory information necessary for safety, pedestrians, for example, have a high risk of causing a severe accident. When listening to music and walking on the road with earphones or headphones, a person may fail to notice approaching vehicles from behind. It is because of the masking by the music played through headphones, which makes it difficult to perceive the sound of approaching vehicles. To improve such situations, the authors aim to actualize a listening environment where pedestrians enjoy listening to music with headphones with perceiving their ambient sounds. As a process, this report deals with a possible methodology to preserve auditory information for safety using sound localization of music. Authors investigate the effect of the music localization played through headphones on the perceptibility of the vehicle's approaching sound. The approaching sound of several types of cars are presented to listeners, who are asked to answer when the cars arrive at their places. The timing when the car reach is measured. The author will demonstrate the result of the investigation at the conference.

The motor sound on electric powered vehicle is quiet at low speeds. Thus, pedestrians have difficulty detecting the vehicles approaching them under urban noise. Although the vehicles were designed to play an alert sound to solve this problem, it has not been solved yet. Our previous studies found that characteristics of amplitude fluctuation, fluctuation frequency, non-periodic fluctuation and amplitude envelope, are effective to make them detect approaching vehicles. However, those studies were investigated under only a specific actual environment, weren't examined validity of detectability in those studies. Here, this paper investigates under another actual environment, examine the validity. Investigations were carried out by using synthesized complex sounds which were designed to have periodic and non-periodic amplitude fluctuations. Those complex sounds have characteristics of amplitude fluctuations in gasoline powered vehicle. Amplitude envelopes such as modulation wave in amplitude-modulated sound were set for deviations for time and amplitude, and amplitude-modulated complex sounds were synthesized using sine wave, sawtooth wave, and rectangle wave. Then, their effects on detectability by pedestrians were assessed in another actual environment. The results found that amplitude fluctuation enhances the ability with which people detect approaching electric powered vehicles in case of some complex sound.

We herein report a case of sudden death in a 20s male who presented with fever 1 week before and with abdominal pain and vomiting 2 days before death. Laboratory findings at the time of death were suspected the onset of fulminant type 1 diabetes accompanied by diabetic ketoacidosis and acute renal failure. A postmortem blood examination at several sites showed elevated levels of glucose and β-hydroxybutyrate, lower levels of C-peptide, insulin, 1,5-anhydroglucitol, and HbA1c of less than 8.7% based on the diagnostic criteria of FT1DM. Furthermore, glucose levels in vitreous humor and cerebrospinal fluid were very high. These results showed reflecting antemortem hyperglycemia. Postmortem serum pancreatic enzyme levels of lipase and elastase 1 were high. Antibodies to insulin, insulinoma-associated antigen-2 (IA-2), and zinc transporter 8 (ZnT8) were negative, while antibodies to glutamic acid decarboxylase (GAD) slightly exceeded the reference range (

AIMS We aimed to examine temporal changes in left ventricular (LV) structures and their prognostic impacts in patients with heart failure (HF) and preserved ejection fraction (HFpEF). METHODS AND RESULTS In the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) study (n = 10 219), we divided 2698 consecutive HFpEF patients (68.9 ± 12.2 years, 32.1% female) into three groups by LV hypertrophy (LVH) and enlargement (LVE) at baseline: (-)LVH/(-)LVE (n = 989), (+)LVH/(-)LVE (n = 1448), and (+)LVH/(+)LVE (n = 261). We examined temporal changes in LV structures and their prognostic impacts during a median 8.7-year follow-up. From (-)LVH/(-)LVE, (+)LVH/(-)LVE to (+)LVH/(+)LVE at baseline, the incidence of the primary outcome, a composite of cardiovascular death or HF admission, significantly increased. Among 1808 patients who underwent echocardiography at both baseline and 1 year, we noted substantial group transitions from baseline to 1 year; the transition rates from (-)LVH/(-)LVE to (+)LVH/(-)LVE, from (+)LVH/(-)LVE to (-)LVH/(-)LVE, from (+)LVH/(-)LVE to (+)LVH/(+)LVE, and from (+)LVH/(+)LVE to (+)LVH/(-)LVE were 27% (182/671), 22% (213/967), 6% (59/967), and 26% (44/170), respectively. In the univariable Cox proportional hazard model, patients who transitioned from (+)LVH/(-)LVE to (+)LVH/(+)LVE or remained in (+)LVH/(+)LVE had the worst subsequent prognosis [hazard ratio (HR) 4.65, 95% confidence interval (CI) 3.09-6.99, P

Aims Asymptomatic patients with structural heart diseases are classified as a population at high risk for heart failure (HF) in Stage B. However, limited data are available regarding incidence and related factors of de-novo HF (DNHF) considering competing risk in this population. Methods and results In 3362 Stage B patients (mean age 68 yrs, male 76%) from the CHART-2 Study (N = 10,219), we examined incidence of death and DNHF, defined as the first episode of either HF hospitalization or HF death, and factors related to DNHF. Results During the median 6.0-year follow-up, 627 deaths (31/1000 person-years) and 293 DNHF (15/1000 person-years) occurred. Among the 627 deaths, 212 (34%) and 325 (52%) were specified as cardiovascular and non-cardiovascular deaths, respectively. During the follow-up of 271 DNHF hospitalizations, we observed 124 deaths, including 65 (52%) cardiovascular and 47 (40%) non-cardiovascular deaths. The competing risk model showed that age, diabetes mellitus, stroke, atrial fibrillation, diastolic blood pressure, hemoglobin levels, estimated glomerular filtration ratio and left ventricular ejection fraction was significantly associated with DNHF. Bayesian structural equation modeling showed that many of these cardiac and non-cardiac variables contribute to DNHF by affecting each other, while diabetes mellitus was independently associated with DNHF. Conclusions Stage B patients had a high incidence of DNHF as well as that of death due to both cardiovascular and non-cardiovascular causes. Thus, management of Stage B patients should include multidisciplinary approaches considering both cardiac and non-cardiac factors, in order to prevent DNHF as well as non-HF death as a competing risk. Trial registration: clinicaltrials.gov identifier: NCT00418041 .

Background We have recently demonstrated that left ventricular ejection fraction (LVEF) dynamically changes over time with prognostic impacts in Stage C/D patients, namely, those who have a current or past history of heart failure (HF). However, it is unknown whether this is also the case in asymptomatic Stage B patients, namely, those who have a risk of HF, but do not have a history of HF. Methods In our CHART-2 Study (N = 10,219), we enrolled 4005 Stage B patients and divided them into 3 groups by LVEF; preserved EF (pEF, LVEF ≥50%, N = 3526), mid-range EF (mrEF, LVEF 41–49%, N = 302), and reduced EF (rEF, LVEF ≤40%, N = 177). We examined the prognostic impacts of LVEF transitions among the 3 groups in comparison with 4477 patients with Stage C/D HF. Results Stage B were characterized by less severe clinical status and better prognosis compared with Stage C/D. Stage B in mrEF and rEF at baseline dynamically transitioned to other groups at 1-year, whereas those in pEF unchanged; at 1-year, mrEF transitioned to pEF/rEF by 50/16%, and rEF transitioned to pEF/mrEF by 25/31%, respectively, whereas pEF transitioned to mrEF/rEF by only 3.6/0.7%, respectively, which were consistent with findings in findings with Stage C/D. Although LVEF decrease was directly associated with all-cause mortality in both the Stage B and Stage C/D with pEF, factors related to LVEF changes were different between the 2 groups. Conclusions In Stage B, LVEF dynamically changes with prognostic impacts as in Stage C/D, whereas different determination factors may be involved in the 2 stages. Clinical trial registration: Chronic Heart Failure Analysis and Registry in the Tohoku District (CHART)-2 (NCT00418041).

Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed.In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia.CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p0.05). In contrast, BNP decreased only in patients with higher BNP (p0.05). Also, CyPA decreased both in patients with lower (25 kg/mCyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.

Background The benefits of antithrombotic therapy (ATT) for atrial fibrillation (AF) are occasionally offset by major bleeding complications. However, the clinical benefits and risks of ATT in AF patients, with special references to comorbidities, such as heart failure (HF), coronary artery disease (CAD), and the patterns of AF, remain to be fully elucidated. Methods A total of 3221 consecutive AF patients from our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N = 10,219) were divided into 4 groups based on ATT at enrollment; no-ATT, anticoagulant alone, antiplatelet alone, and both of them (AC&AP). Then, efficacy and safety outcomes including thromboembolic events, major bleeding, and mortality were evaluated among the 4 groups. Results Anticoagulant monotherapy was associated with reduced risk of ischemic stroke in patients with but not in those without HF, CAD, or non-paroxysmal AF. Although there was no significant difference in major bleeding among the 4 groups, a composite of thromboembolism and major bleeding occurred more frequently in the AC&AP group, even in combination with anticoagulants and single antiplatelet therapy, indicating that the combination therapy is more harmful than anticoagulant monotherapy for AF patients, especially for those with HF or CAD. Lastly, no-ATT group was associated with worse prognosis compared with other 3 groups. Conclusions These results indicate that ATT is beneficial for AF patients particularly for those with HF, CAD, or non-paroxysmal AF and that among ATT, anticoagulant monotherapy may be most profitable for both clinical benefits and risks for AF patients.

Aims The study aims to evaluate the prognostic significance of impaired glucose tolerance (IGT) with reference to albuminuria in patients with chronic heart failure (CHF). Methods and results We examined 535 CHF patients (mean 66 years, women 25%) in the control arm of our SUPPORT trial, in which we examined additive impact of olmesartan in hypertensive patients with symptomatic CHF treated with β‐blockers and/or angiotensin‐converting enzyme inhibitors. We examined the association between glycaemic abnormality (assessed by 75 g of oral glucose tolerance test) and albuminuria for a composite outcome of all‐cause death, myocardial infarction, stroke, and HF hospitalization. IGT patients (N = 113, mean 67.2 years) were older and more frequently treated with β‐blockers compared with those with normal glucose regulation (N = 142, mean 64.0 years) and those with diabetes mellitus (N = 280, mean 65.7 years). Multivariable Cox proportional hazard models revealed that, as compared with normal glucose regulation (NGR), IGT was associated with increased risk of the outcome when complicated by albuminuria [hazard ratio (HR) 2.25; 95% confidence interval (CI) 1.14–4.42; P = 0.019] but not when uncomplicated by albuminuria (HR 0.76; 95% CI 0.35–1.60, P = 0.47) (P for interaction = 0.041). This was also the case for diabetes mellitus and albuminuria (HR 2.06; 95% CI 1.17–3.61; P = 0.012). Among IGT patients without albuminuria, 21 (29%) developed albuminuria at 1‐year visit, which was again associated with poor prognosis (HR 7.36; 95% CI 1.39–38.98, P = 0.019). Conclusions These results indicate that IGT is associated with poor prognosis when complicated by albuminuria in CHF patients, demonstrating the importance of combined early stages of glucose intolerance and renal dysfunction in the management of CHF.

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

Several studies have reported that C-reactive protein (CRP), an inflammatory biomarker, predicts cardiovascular events independently of low-density lipoprotein cholesterol levels. However, no study examined whether temporal changes in CRP levels are associated with clinical events in patients with previous myocardial infarction (MI).We examined 2184 consecutive patients with previous MI and CRP data at baseline in the Chronic Heart Failure Registry and Analysis in the Tohoku district-2 (CHART-2) Study. During the median 6.4 years follow-up, 592 all-cause, 245 cardiovascular, and 273 non-cardiovascular deaths occurred. Patients with CRP ≥ 2.0 mg/L at baseline had significantly increased incidence of all-cause (hazard ratio (HR) 1.68, P 0.001) and non-cardiovascular death (HR 1.86, P 0.001), compared with those with CRP 2.0 mg/L. Temporal changes in CRP levels were associated with prognosis; among patients with CRP ≥ 2.0 mg/L at baseline, those with CRP ≥ 2.0 mg/L at 1-year had significantly increased incidence of all-cause (HR 2.12, P 0.001), cardiovascular (HR 2.31, P 0.001), and non-cardiovascular death (HR 2.29, P 0.001). Among patients with CRP 2.0 mg/L at baseline, those with CRP ≥ 2.0 mg/L at 1-year had significantly increased incidence of all-cause (HR 1.76, P 0.001) and cardiovascular death (HR 2.10, P = 0.001). These results remained significant after adjusted with the inverse probability of treatment weighted models using propensity sore. Furthermore, as compared with patients with CRP 2.0 mg/L at both baseline and 1-year, those with CRP ≥ 2.0 mg/L at both baseline and 1-year had increased incidence of all-cause, cardiovascular, and non-cardiovascular death.These results provide the evidence that temporal increases in CRP levels are associated with increased clinical events in patients with previous MI.

Although several factors, including heart failure (HF) and inflammation, are known to increase the incidence of cancer, it remains unknown whether HF may increase cancer mortality, especially with a reference to inflammation.We examined 8843 consecutive cardiovascular patients without a prior history of cancer in our CHART-2 Study (mean 68 yrs., female 30.9%). As compared with patients without HF (Stage A/B, N = 4622), those with HF (Stage C/D, N = 4221) were characterized by higher prevalence of diabetes, previous myocardial infarction, atrial fibrillation, and stroke. During the median 6.5-year follow-up (52,675 person-years), 282 cancer deaths occurred. HF patients had significantly higher cancer mortality than those without HF in both the overall (3.7 vs, 2.8%, hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.79, P = 0.004) and the propensity score-matched cohorts (HR 1.46, 95%CI 1.10-1.93, P = 0.008), which was confirmed in the competing risk models. The multivariable Cox proportional hazard model in the matched cohort showed that HF was associated with increased cancer mortality in patients with C-reactive protein (CRP) ≥ 2.0 mg/L (HR 1.87, 95%CI 1.18-2.96, P = 0.008) at baseline, but not in those with CRP 2.0 mg/L (HR 0.89, 95%CI 0.54-1.45, P = 0.64) (P for interaction = 0.03). Furthermore, temporal changes in CRP levels were associated with cancer death in the overall cohort; HF patients with CRP ≥ 2.0 mg/L at both baseline and 1-year had significantly increased cancer death, while those with CRP ≥ 2.0 mg/L at baseline and 2.0 mg/L at 1-year not.These results provide the first evidence that HF is associated with increased cancer death, especially when associated with prolonged inflammation.

To ensure that experiences and lessons learned from the unprecedented 2011 Great East Japan Earthquake are used to improve future disaster planning, the Japan Diabetes Society (JDS) launched the “Research and Survey Committee for Establishing Disaster Diabetes Care Systems Based on Relevant Findings from the Great East Japan Earthquake” under the supervision of the Chairman of the JDS. The Committee conducted a questionnaire survey among patients with diabetes, physicians, disaster medical assistance teams (DMATs), nurses, pharmacists, and nutritionists in disaster areas about the events they saw happening, the situations they found difficult to handle, and the needs that they felt required to be met during the 2011 Great East Japan Earthquake. A total of 3,481 completed questionnaires were received. Based on these and other experiences and lessons reported following the 2011 Great East Japan Earthquake and the 2004 Niigata‐Chuetsu Earthquakes, the current “Manual for Disaster Diabetes Care” has been developed by the members of the Committee and other invited authors from relevant specialties. To our knowledge, the current Manual is the world's first to focus on emergency diabetes care, with this digest English version translated from the Japanese original. It is sincerely hoped that patients with diabetes and healthcare providers around the world will find this manual helpful in promoting disaster preparedness and implementing disaster relief.

Background Few simple risk models, without echocardiography have been developed for patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) (HFpEF). Methods To develop a risk score to predict all-cause death for HFpEF patients, we examined 1277 HF patients with LVEF ≥50% and BNP ≥100 pg/ml in the CHART-2 Study, a large-scale prospective cohort study for HF in Japan. We selected the optimal subset of covariates for the score with Cox proportional hazard models and random survival forests (RSF). Results During the median 5.7-year follow-up, 576 deaths occurred. Cox models and RSF analyses consistently indicated age ≥75 years, albumin Conclusions We developed a simple risk score to predict long-term prognosis of HFpEF patients. The 3A3B score, comprising 6 commonly available parameters in daily practice, has potential utility in the risk stratification and management of HFpEF patients.

Objective— Secondary prevention for recurrent myocardial infarction (MI) is one of the most important therapeutic goals in patients with old MI (OMI). Although statins are widely used for this purpose, there remains considerable residual risk even after LDL (low-density lipoprotein cholesterol) is well controlled by statins. Approach and Results— We examined clinical impacts of nHDL (nonhigh-density lipoprotein cholesterol) and its major components triglyceride and LDL as residual risks for acute MI recurrence, using the database of our CHART (Chronic Heart Failure Analysis and Registry in the Tohoku District)-2 Study, the largest-scale cohort study of cardiovascular patients in Japan. We enrolled 1843 consecutive old MI patients treated with statins (mean age 67.3 years, male 19.2%) in the CHART-2 Study. The incidence of recurrent acute MI during the median 8.6-year follow-up was compared among the groups divided by the levels of nHDL ( Conclusions— These results indicate that management of residual risks for acute MI recurrence should include nHDL management considering both LDL and triglyceride in old MI patients under statin treatment. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00418041.

Background: Although balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated. Methods and Results: This study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP)

Complete revascularization with PCI is not always achieved in patients with ischemic HF. Therefore, this study aimed to elucidate the prognostic impact of residual coronary stenosis (RS) after percutaneous coronary intervention (PCI) in patients with ischemic heart failure (HF).We analyzed a total of 1307 patients with symptomatic HF and a history of PCI registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. RS that was defined as the presence of ≥70% luminal stenosis in major coronary arteries at the last coronary angiography.Among the study population, 851 patients (65.1%) had RS. During a median follow-up period of 3.2 years, patients with RS had higher all-cause mortality than those without it even after propensity score matching (21.9 vs. 11.6%, log-rank P = 0.027). Multivariable Cox hazard analysis also showed the negative impact of RS on all-cause death in ischemic HF patients [hazard ratio (HR):1.62, 95% confidence interval (CI): 1.07-2.46, P = 0.024]. Importantly, when divided all subjects into three subgroups by left ventricular ejection fraction (LVEF) [LVEF 40% (HFrEF), LVEF 40-49% (HFmrEF), and LVEF ≥ 50% (HFpEF)], inverse probability of treatment weighted method provided a similar result that RS after PCI was an independent risk factor for death in the HFpEF [HR(95%CI); 1.94(1.22-3.09), P 0.01] and HFmrEF [4.47(1.13-14.98), P 0.01] groups, but not in the HFrEF group [1.20(0.59-2.43), P = 0.62].These results indicate that RS after PCI could aggravate long-term prognosis of ischemic HF patients with moderate- to well-preserved EF, but not those with reduced EF.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH). The prognosis of PVOD patients remains poor, since no effective medical therapy is yet available. Imatinib is a tyrosine kinase inhibitor specific for platelet-derived growth factor receptor and is expected as a treatment option for pulmonary arterial hypertension (PAH). Recently, it has been reported that imatinib improved functional capacity of a patient with PVOD. We here report a patient with suspected PVOD who has been successfully treated with imatinib and is alive for 6 years after diagnosis. A 57-year-old woman was admitted to a hospital for severe dyspnea. Echocardiography suggested the presence of PH, because tricuspid regurgitation pressure gradient was elevated. The patient was then transferred to our hospital by an ambulance ahead of schedule due to fever and worsening dyspnea. Because the patient had no left heart disease, we diagnosed that she had PAH associated with severe right heart failure. We immediately started treatment with nitric oxide (NO) for her severe hypoxia; however, it caused pulmonary edema. We suspected PVOD from CT characteristics and pulmonary edema after PAH-targeted vasodilator therapy, and then started oral imatinib treatment. In response to imatinib, her pulmonary edema gradually improved. Since then, the patient has been alive for 6 years with imatinib and pulmonary vasodilators. At present, lung transplantation is the only effective therapy for PVOD with limited availability. We therefore propose that imatinib may be a treatment option for PVOD and a bridge to lung transplantation.

It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction

Background: Data on sex differences in heart failure (HF) with reference to left ventricular ejection fraction (LVEF) are limited. Methods and Materials: We examined 4683 consecutive patients (mean 69 years) with HF in the CHART-2 study. Results: Compared to men (N = 3188), women with HF (N = 1495) were older and had a lower prevalence of ischemic heart disease and cancer, received less implementation of evidence-based treatment, and were characterized by more severe HF in terms of higher New York Heart Association (NYHA) functional class and increased brain natriuretic peptide (BNP) levels, despite greater preservation of LVEF. During the median 6.3-year follow-up, all-cause mortality was comparable between women and men (32.8% vs 33.2%, P = .816), while women had higher cardiovascular mortality, particularly among those with LVEF ≥50%. Although no sex differences existed in cause of death among patients with LVEF ≤ 40% and 41% to 49%, women had a higher proportion of cardiovascular death and lower proportion of noncardiovascular death than men among those with LVEF ≥ 50%. Multivariable Cox regression models showed that women with HF had reduced risk of both cardiovascular and noncardiovascular death, regardless of LVEF category. Beta-blockers were associated with improved mortality in women but not men with LVEF ≤ 40%, while renin–angiotensin system inhibitors were not associated with improved mortality in women with LVEF ≥ 50% but were in men. Conclusion: In addition to sex-specific differences in the age of onset, etiology and response to treatment, women with heart failure and preserved left ventricular ejection fraction (LVEF ≥ 50%) have higher cardiovascular mortality than men. Sex-related management of congestive heart failure should include a consideration of LVEF.

Aims Although balloon pulmonary angioplasty (BPA) improves haemodynamics and short-term prognosis in patients with inoperable chronic thrombo-embolic pulmonary hypertension (CTEPH), the long-term effects of BPA, and procedure-related complications remain to be fully elucidated. Methods and results From July 2009 to October 2016, we performed a total of 424 BPA sessions in 84 consecutive patients with inoperable CTEPH. We used 3D reconstructed computed tomography to determine target lesions of pulmonary arteries and optical computed tomography to select balloon size, if needed. In 77 patients (92%) who completed the BPA treatment [65 ± 14 (SD) years-old, male/female 14/63], haemodynamics and exercise capacity were examined at 6 months after last BPA and in the chronic phase [>12 months after first BPA, 31 (20, 41) months]. The BPA treatment significantly improved mean pulmonary arterial pressure (38 ± 10 to 25 ± 6 mmHg), pulmonary vascular resistance (7.3 ± 3.2 to 3.8 ± 1.0 Wood units), and 6-minute walk distance (380 ± 138 to 486 ± 112 m) (all P

Background We and others have previously reported that the Great East Japan Earthquake (GEJE) caused a significant but transient increase in cardiovascular diseases and deaths in the disaster area. However, it remains to be examined whether the GEJE had a long-term prognostic influence in large-scale cohort studies. This point is important when analyzing the data before and after the GEJE in the cohort studies in the disaster area. Methods We examined 8676 patients registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study ( N = 10,219) between 2006 and 2010 and were alive after March 10, 2011. Results There were 48 GEJE-related deaths, causing a sharp and transient increase in all-cause death within a month after the GEJE. However, after excluding the GEJE-related deaths, the cubic polynomial spline smoothing showed no significant increase in all-cause death, heart failure admission, non-fetal acute myocardial infarction, or non-fetal stroke during the median 3-year follow-up after the GEJE. The extrapolation curves beyond the GEJE, which were obtained by the parametric survival models based on the survival data censored on the GEJE, were not significantly different from the Kaplan–Meier curves estimating the survival functions of deaths and cardiac events during the total follow-up period without considering the impacts of the GEJE. Furthermore, the multivariate Cox proportional hazard model applied to the matched cohort of the baseline data and the data after the GEJE showed no significant differences in the impacts of prognostic factors on all-cause mortality before and after the GEJE. Conclusions These results indicate that the GEJE had no significant long-term prognostic impact after the earthquake in cardiovascular patients in the disaster area.

The aim of this study was to evaluate the association of functional mitral regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or nonischemic origin with outcomes in patients discharged alive after hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 3,357 patients were evaluated to assess the association of FMR, preserved or reduced EF, and ischemic or nonischemic origin with the primary end point (all-cause death and readmission for HF after discharge). At the time of discharge, FMR was assessed semiquantitatively (classified as none, mild, or moderate to severe) by color Doppler analysis of the regurgitant jet area. According to multivariable analysis, in the ischemic group, either mild or moderate to severe FMR in patients with a preserved EF had a significantly higher risk of the primary end point than patients without FMR (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to 3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic origin, only moderate to severe FMR was associated with a significantly higher risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the nonischemic group, there was no significant association between FMR and the primary end point in patients with either a preserved or reduced EF. In conclusion, among patients with acute decompensated HF with a preserved or reduced EF, the association of FMR with adverse outcomes may differ between patients who had an ischemic or nonischemic origin of HF.

To evaluate whether the extent of perfusion defects assessed by examining lung perfused blood volume (PBV) images is a stronger estimator of the clinical severity of chronic thromboembolic pulmonary hypertension (CTEPH) compared with other computed tomography (CT) findings and noninvasive parameters.We analyzed 46 consecutive patients (10 men, 36 women) with CTEPH who underwent both dual-energy CT and right-heart catheter (RHC) examinations. Lung PBV images were acquired using a second-generation dual-source CT scanner. Two radiologists independently scored the extent of perfusion defects in each lung segment employing the following criteria: 0, no defect, 1, defect in50% of a segment, 2, defect in ≥50% of a segment. Each lung PBV score was defined as the sum of the scores of 18 segments. In addition, all of the following were recorded: 6-min walk distance (6MWD), brain natriuretic peptide (BNP) level, and RHC hemodynamic parameters including pulmonary artery pressure (PAP), right ventricular pressure (RVP), cardiac output (CO), the cardiac index (CI), and pulmonary vascular resistance (PVR). Bootstrapped weighted kappa values with 95% confidence intervals (CIs) were calculated to evaluate the level of interobserver agreement. Correlations between lung PBV scores and other parameters were evaluated by calculating Spearman's rho correlation coefficients. Multivariable linear regression analyses (using a stepwise method) were employed to identify useful estimators of mean PAP and PVR among CT, BNP, and 6MWD parameters. A p value0.05 was considered to reflect statistical significance.Interobserver agreement in terms of the scoring of perfusion defects was excellent (κ=0.88, 95% CIs: 0.85, 0.91). The lung PBV score was significantly correlated with the PAP (mean, rho=0.48; systolic, rho=0.47; diastolic, rho=0.39), PVR (rho=0.47), and RVP (rho=0.48) (all p values0.01). Multivariable linear regression analyses showed that only the lung PBV score was significantly associated with both the mean PAP (coefficient, 0.84, p0.01) and the PVR (coefficient, 28.83, p0.01).The lung PBV score is a useful and noninvasive estimator of clinical CTEPH severity, especially in comparison with the mean PAP and PVR, which currently serve as the gold standards for the management of CTEPH .

Objective— The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) remains to be elucidated. Thrombin-activatable fibrinolysis inhibitor (TAFI) inhibits fibrinolysis. It remains to be elucidated whether TAFI is directly involved in the pathogenesis of CTEPH. We examined potential involvement of TAFI in the pathogenesis of CTEPH in humans. Approach and Results— We enrolled 68 consecutive patients undergoing right heart catheterization in our hospital, including those with CTEPH (n=27), those with pulmonary arterial hypertension (n=22), and controls (non–pulmonary hypertension, n=19). Whole blood clot lysis assay showed that the extent of clot remaining after 4 hours was significantly higher in CTEPH compared with pulmonary arterial hypertension or controls (41.9 versus 26.5 and 24.6%, both P P 1 (an inhibitor of activation of platelets). Importantly, plasma levels of TAFI were significantly correlated with the extent of clot remaining after 4 hours. In addition, the extent of clot remaining after 4 hours was improved with an activated TAFI inhibitor. Conclusions— These results indicate that plasma levels of TAFI are elevated in patients with CTEPH and are correlated with resistance to clot lysis in those patients.

Background Although B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are released in equimolar proportions, their values differ depending on clinical conditions. A useful conversion formula between BNP and NT-proBNP remains to be developed for the clinical use. Aim To develop a conversion formula from BNP to NT-proBNP. Methods In the derivation cohort, 923 patients with chronic heart failure, in whom both BNP and NT-proBNP values were available, were enrolled from our SUPPORT (Supplemental Benefit of ARB in Hypertensive Patients with Stable Heart Failure using Olmesartan) trial. The validation cohort included 1154 consecutive patients with or at risk of cardiovascular diseases, in whom both BNP and NT-proBNP values were measured simultaneously at Tohoku University Hospital. We regressed log10 NT-proBNP onto log10 BNP and factors influencing BNP and NT-proBNP values. Results We adopted the model with the smallest Akaike information criterion consisting of log10 BNP, age, sex, BMI, creatinine clearance (CCr), hemoglobin, and atrial fibrillation (AF). As compared with the previously reported conversion formulas, the present conversion formula utilized non-linear transformation by spline function, and exhibited the strongest correlation between actual and calculated values of NT-proBNP (r = 0.928). The root mean squared error (RMSE) of the present conversion formula was smallest compared with the previously reported conversion formulas, indicating that this formula most effectively converts BNP values to NT-proBNP values. Conclusions We have developed a useful conversion formula from BNP to NT-proBNP values, using age, sex, BMI, CCr, hemoglobin, and AF, which could be widely used in daily clinical practice.

Self-care behaviors (ScB) are associated with symptoms and outcomes in patients with heart failure (HF). However, little is known about gender differences in the prognostic relevance of ScB in HF patients.We examined gender differences in ScB of HF patients regarding its prognostic associations with mortality and HF hospitalization with a reference to ScB dimensions. The European Heart Failure Self-Care Behavior Scale (EHFScBS) was used to evaluate ScB in 2233 patients with Stage C/D HF in the CHART-2 Study.Male patients (n=1583) were younger (71 vs. 73 yrs) and had lower ScB (median 33 vs. 31) (all p0.001) than females (n=650). During the median follow-up of 2.57 years, patients with high ScB (score 12-32, n=1090), as compared with low ScB patients (score 33-60, n=1143), had significantly increased all-cause mortality in males [adjusted hazard ratio (aHR) 1.44, p=0.02] but not in females (aHR 0.80, p=0.40) (p for interaction 0.02), while ScB was not significantly associated with incidence of HF hospitalization in both genders. Among the 3 dimensions in EHFScBS, complying with regimen was associated with decreased mortality in females, but not in males (p for interaction 0.003), while asking for help was related with increased incidence of HF hospitalization in males (aHR 1.34, p=0.072) but not in females (aHR 0.98, p=0.931) (p for interaction 0.048).There were gender differences in the prognostic relevance of self-care with mortality and incidence of HF hospitalization, suggesting that self-care should be implemented considering gender differences to improve prognosis.

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.