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BACKGROUND A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.

Cases of coronary artery occlusion due to the exclusion of pulmonary artery aneurysm are extremely rare, and there are few reports of surgical treatment. A 60-year-old woman with pulmonary hypertension due to an atrial septal defect and obstruction of the left main coronary trunk due to the exclusion of a giant pulmonary artery aneurysm underwent surgery. The surgery included atrial septal defect closure, tricuspid annulus plasty, pulmonary artery aneurysmorrhaphy, and coronary artery bypass grafting. One and a half years after the surgery, no re-expansion of the pulmonary artery was observed, and the symptoms of heart failure had improved. There are no reports of improvement in pulmonary valve regurgitation by aneurysmorrhaphy in pulmonary artery aneurysm. Surgery for pulmonary artery aneurysm with the exclusion of other organs was effective, and aneurysmorrhaphy for pulmonary artery aneurysm was acceptable.

The use of left ventricular mechanical dyssynchrony (LVMD), which has been reported to be responsible for unfavorable outcomes, might improve conventional risk-stratification by clinical indices including QRS duration (QRSd) and systolic dysfunction in patients with heart failure (HF). Following measurements of 12-lead QRSd and left ventricular ejection fraction (LVEF), three-dimensional (3-D) LVMD was evaluated as a standard deviation (phase SD) of regional mechanical systolic phase angles by gated myocardial perfusion imaging in 829 HF patients. Patients were followed up for a mean period of 37 months with a primary endpoint of lethal cardiac events (CEs). In an overall multivariate Cox proportional hazards model, phase SDs were identified as significant prognostic determinants independently. The patients were divided into 4 groups by combining with the cut-off values of LVEF (35% and 50%) and QRSd (130 ms and 150 ms). The groups with lower LVEF and prolonged QRSd more frequently had CEs than did the other groups. Patient groups with LVEF

Background: The evaluation of stable coronary artery disease (SCAD) has evolved, and contemporary clinical practice guidelines emphasize the importance of in-depth consideration of procedure indications, risk stratification, and results of non-invasive imaging tests. However, little is known about the appropriate selection of imaging modalities for ischemia evaluation and the comparative cost-effectiveness in real-world clinical practice. Methods and Results: The Japanese Comprehensive Health-Economic Assessment for Appropriate Cardiac Imaging Strategy including Outcome and cost-effectiveness in Stable Coronary Artery Disease Study (J-CONCIOUS), a multicenter observational study, was designed to prospectively enroll 2,500 patients with suspected or known SCAD, register clinical information and administrative records, and follow patients for 3 years. Any diagnostic or cardiac imaging modality (including stress tests using electrocardiography, echocardiography, or myocardial perfusion imaging; coronary computed tomographic angiography; and/or invasive coronary angiography with or without fractional flow reserve assessment) is acceptable. Clinical endpoints, such as all-cause mortality, cardiac death, and non-fatal myocardial infarction, will be obtained, along with quality of life assessment using the Seattle Angina Questionnaire. The cost-effectiveness of individual assessment patterns will be quantified by analysis of Diagnosis Procedure Combination (DPC) data, and quality-adjusted life years and the incremental cost-effectiveness ratio will be calculated. Conclusions: J-CONCIOUS is expected to establish a risk-based and cost-effective imaging strategy for the detection and evaluation of functional myocardial ischemia and/or anatomical coronary imaging in Japan.

Muscle wasting, that is, reduction in muscle mass, is frequently observed in patients with chronic heart failure (CHF) and diabetes mellitus (DM).We retrospectively examined 185 patients with CHF (median age of 71 years [interquartile range, 61-78 years]; 64% male) who received a dual-energy X-ray absorptiometry scan for assessment of appendicular skeletal muscle mass index (ASMI).Seventy patients with CHF (38%) had DM. Patients with DM had higher prevalences of ischemic heart disease and hypertension, lower levels of estimated glomerular filtration rate (eGFR) and ASMI, and higher levels of plasma renin activity (PRA) than did patients without DM. In simple regression analyses, ASMI was positively correlated with the Mini Nutritional Assessment Short Form (MNA-SF) score and levels of hemoglobin, eGFR, and fasting plasma insulin and was negatively correlated with levels of N-terminal pro B-type natriuretic peptide, PRA, and cortisol. In multiple linear regression analyses, age, MNA-SF score, DM, fasting plasma insulin level, and PRA were independently associated with ASMI. When multiple linear regression analyses were separately performed in a non-DM group and a DM group, MNA-SF score and fasting plasma insulin level were independent variables for ASMI in both groups. PRA was independently associated with ASMI in the DM group but not in the non-DM group, whereas cortisol concentration was independently associated with ASMI only in the non-DM group.In addition to malnutrition and reduction in plasma insulin, renin-angiotensin system activation may be responsible for the development of muscle wasting in CHF patients with DM.背景: 慢性心力衰竭(chronic heart failure, CHF)和糖尿病(diabetes mellitus, DM)患者常出现肌肉萎缩, 即肌肉质量减少。 方法: 我们回顾了185例CHF患者[中位年龄71岁(四分位数范围61~78岁), 其中64%为男性], 他们接受了双能X线骨密度仪扫描以评估全身四肢骨骼肌质量指数(appendicular skeletal muscle mass index, ASMI)。 结果: 70例CHF患者(38%)合并DM。与非糖尿病患者相比, 糖尿病患者缺血性心脏病和高血压的患病率更高, 肾小球滤过率(estimated glomerular filtration rate, eGFR)和ASMI水平更低, 血浆肾素活性(plasma renin activity, PRA)水平更高。在简单回归分析中, ASMI与MNA-SF(微型营养评估简表)评分、血红蛋白、eGFR和空腹血浆胰岛素水平呈正相关, 与N端B型利钠肽原、PRA和皮质醇水平呈负相关。多元线性回归分析显示, 年龄、MNA-SF评分、糖尿病、空腹血浆胰岛素水平和PRA与ASMI独立相关。在非糖尿病组和糖尿病组分别进行多元线性回归分析时, MNA-SF评分和空腹血浆胰岛素水平是两组ASMI的独立变量。在糖尿病组中, PRA与ASMI独立相关, 而在非糖尿病组中, 皮质醇浓度与ASMI无关, 而皮质醇浓度仅在非糖尿病组中与ASMI独立相关。 结论: 除了营养不良和血浆胰岛素降低外, 肾素-血管紧张素系统激活可能是心力衰竭合并糖尿病患者肌肉萎缩的原因。.

Background: Obesity increases the risk for development of heart failure (HF) but, when present is likely to be related to better outcomes in patients with HF. This study aimed to clarify the paradoxical prognostic values of visceral obesity in association with cardiac sympathetic function in HF patients. Methods and Results: A total of 653 consecutive patients with systolic HF who underwent visceral adiposity area (VAA) measurements using a computed tomographic technique were divided into 3 groups: VAA 1, area 140 cm(2). Sympathetic innervation was quantified by (123)I-MIBG cardiac activity. Patients were followed up for an average of 22 months with a primary endpoint of lethal cardiac events (CE). The CE group (n=200) had a lower late heart-to mediastinum ratio (HMR) and a smaller VAA than those in the non-CE group. Rates of overall CE/HF death were inversely correlated with VAA: 39.2% ± 6.2% for VAA 1, 27.4% ± 19.9% for VAA 2 and 24.1% ± 15.3% for VAA 3. In addition to sudden cardiac death rate, lethal arrhythmic event rate increased in association with visceral fat obesity: 3.0% for VAA 1, 7.5% for VAA 2 and 8.8% for VAA 3. Late HMR identified high-risk sub-populations in each group. Conclusion: Visceral obesity has paradoxical prognostic implications in terms of HF mortality and lethal arrhythmic/sudden cardiac death events. Cardiac sympathetic denervation and quantitative visceral adiposity are synergistically associated with overall cardiac mortality, contributing to better risk stratification of HF patients.

Background Accurate prediction of mortality in heart failure (HF) patients is crucial for decision-making regarding HF therapies, but a strategy for the prediction of mortality in elderly HF patients has not been established. In addition, although favorable effects of comprehensive cardiac rehabilitation (CR) on clinical outcomes and functional status in HF patients have been demonstrated, a goal of comprehensive CR during hospitalization for reducing mortality remains unclear. Aims We examined whether assessment of basic activities of daily living (ADL) by the Barthel Index (BI), the most widely used tool for assessment of basic ADL, is useful for predicting all-cause mortality in elderly HF patients who received comprehensive CR. Methods This study was a single-center, retrospective and observational study. We retrospectively examined 413 HF patients aged ≥65 years (mean age, 78±7 years; 50% female) who were admitted to our institute for management of HF and received comprehensive CR during hospitalization. Functional status for performing basic ADL ability was assessed by the BI within 3 days before discharge. The clinical endpoint was all-cause death during the follow-up period. Results Of 413 HF patients, 116 patients (28%) died during a follow-up period of median 1.90-years (interquartile range, 1.20–3.23 years). Results of an adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increases in an almost linear fashion as the BI score decreases and that the BI score corresponding the hazard ratio of 1.0 is 85 (Figure A). To minimize the differences in potential confounding factors between patient with low BI ( Conclusion A BI score of Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Japan Society for the Promotion of Science

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.

Background. Left ventricular mechanical dyssynchrony (LVMD), left ventricular hypertrophy, and impaired cardiac sympathetic innervation are closely related to the development of heart failure (HF) and unfavorable outcomes. Methods and Results. A total of 705 consecutive HF patients with reduced left ventricular ejection fraction (EF) &lt, 50% were registered in our hospital HF database. LVMD and left ventricular mass index (LVMI) were evaluated three-dimensionally by gated myocardial perfusion SPECT. LVMD was measured as a heterogeneity index (phase SD) of the regional contraction phase angles calculated by Fourier analysis. Cardiac sympathetic innervation was quantified as a normalized heart-to-mediastinum ratio (HMR) of the 123I-metaiodobenzylguanidine (MIBG) activity. The patients were followed up with a primary end point of lethal cardiac events (CEs) for 42 months. CEs were documented in 246 of the HF patients who had a greater phase SD, greater LVMI, and lower MIBG HMR than those in HF patients without CEs. In the overall multivariate analysis, phase SD, LVMI, and MIBG HMR were identified as significant CE determinants. The three biomarkers were incrementally related to increases in CE risks. Conclusions. Assessment of cardiac sympathetic innervation can further stratify patients with systolic heart failure at increased cardiac risk identified by left ventricular hypertrophy and mechanical dyssynchrony.

BACKGROUND The clinical significance of osteoporosis in chronic heart failure (CHF) remains unclear.Methods and Results:A total of 303 CHF patients (75 years, [interquartile range (IQR) 66-82 years]; 41% female) were retrospectively examined. Bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by using dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when the BMD at any of the 3 sites was

Sedative hypnotics are among the classes of drugs reported to influence falls. However, the effects of the sedative hypnotic drugs, suvorexant and ramelteon, on falls are not well known. Therefore, we conducted this retrospective case-control study to examine the association of the use of these two sedative hypnotics with the risk of falls. Conducted at the Sapporo Medical University Hospital in Japan, our study included 360 patients with fall incidents and 819 randomly selected control patients. Patients in the fall group were significantly older with a lower body mass index, and had a history of falls, disabilities in activities of daily living, cognitive impairment, and delirium. Monovariate analysis revealed that patients in the fall group frequently used ramelteon [odds ratio (OR) 2.38, 95% confidence interval (CI): 1.49-3.81, p

Background Although high body mass index (BMI) is a risk factor of heart failure (HF), HF patients with a higher BMI had a lower mortality rate than that in HF patients with normal or lower BMI, a phenomenon that has been termed the “obesity paradox”. However, the relationship between body composition, i.e., fat or muscle mass, and clinical outcome in HF remains unclear. Methods We retrospectively analyzed data for 198 consecutive HF patients (76 years of age; males, 49%). Patients who were admitted to our institute for diagnosis and management of HF and received a dual-energy X-ray absorptiometry scan were included regardless of left ventricular ejection fraction (LVEF) categories. Muscle wasting was defined as appendicular skeletal muscle mass index 2 in males and 2 in females. Increased percent body fat mass (increased FM) was defined as percent body fat > 25% in males and > 30% in females. Results The median age of the patients was 76 years (interquartile range [IQR], 67–82 years) and 49% of them were male. The median LVEF was 47% (IQR, 33–63%) and 33% of the patients had heart failure with reduced ejection fraction. Increased FM and muscle wasting were observed in 58 and 67% of the enrolled patients, respectively. During a 180-day follow-up period, 32 patients (16%) had cardiac events defined as cardiac death or readmission by worsening HF or arrhythmia. Kaplan-Meier survival curves showed that patients with increased FM had a lower cardiac event rate than did patients without increased FM (11.4% vs. 22.6%, p = 0.03). Kaplan-Meier curves of cardiac event rates did not differ between patients with and those without muscle wasting (16.5% vs. 15.4%, p = 0.93). In multivariate Cox regression analyses, increased FM was independently associated with lower cardiac event rates (hazard ratio: 0.45, 95% confidence interval: 0.22–0.93) after adjustment for age, sex, diabetes, muscle wasting, and renal function. Conclusions High percent body fat mass is associated with lower risk of short-term cardiac events in HF patients.

Objective Malnutrition is associated with an increased risk of mortality in heart failure (HF) patients. Here, we examined the hypothesis that assessment of energy intake in addition to nutritional status improves the stratification of mortality risk in elderly HF patients. Methods We retrospectively examined 419 HF patients aged ≥ 65 years (median 78 years, 49% female). Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF), and daily energy intake was calculated from intake during 3 consecutive days before discharge. Results During a median 1.52-year period (IQR 0.96–2.94 years), 110 patients (26%) died. Kaplan–Meier survival curves showed that patients with low tertile of daily energy intake had a higher mortality rate than did patients with high or middle tertile of daily energy intake. In multivariate Cox regression analyses, low daily energy intake was independently associated with higher mortality after adjustment for the model including age, sex, BNP, Charlson Comorbidity Index, history of HF hospitalization, and cachexia in addition to MNA-SF. Inclusion of both MNA-SF and energy intake into the adjustment model improved the accuracy of prediction of the mortality after discharge (continuous net reclassification improvement, 0.355, p = 0.003; integrated discrimination improvement, 0.029, p = 0.003). Results of a fully adjusted dose-dependent association analysis showed that risk of all-cause mortality was lowest among HF patients who consumed 31.5 kcal/kg/day of energy. Conclusions Energy intake during hospital stay is an independent predictor of the mortality in elderly HF patients, and its assessment together with established predictors improves the mortality risk stratification. Graphic abstract

Background Assessment of left ventricular (LV) diastolic function is important because it is possible to detect early sign of myocardial ischemia by this assessment. The purpose of this study was to compare between electrocardiogram (ECG) -gated myocardial perfusion single photon emission computed tomography (G-SPECT) and ultrasound echocardiography in assessment of LV diastolic function in the small heart (SH). Methods The study population consisted of 144 patients who underwent both G-SPECT and ultrasound echocardiography. Peak filling rate (PFR), one-third mean filling rate (1/3 MFR) and the ratio of time to PFR to the RR interval (TPFR/RR) were calculated by quantitative gated SPECT (QGS) and heart risk view-F (HRV-F). Peak early mitral annular velocity (e') was used as the reference standard of LV diastolic function. Results There were 33 patients with end-systolic volume (ESV) of ≤10 ml (SH10), 51 patients with ESV of 11-20 ml (SH 20) and 60 patients with ESV of >20 ml (normal-sized heart: NH). In SH10, PFR calculated by QGS was not correlated with e'. However, that by HRV-F was significantly correlated with e' (r=0.47, p=0.006). On the other hand, 1/3 MFR and TPFR/RR calculated by QGS and HRV-F were not correlated with e' in SH10 and SH20. PFR, 1/3 MFR and TPFR/RR calculated by QGS and HRV-F were correlated with e' in NH.

Background Deep vein thrombosis (DVT) develops after major orthopedic surgery despite the current use of prophylaxis. DVT frequently develops in the soleal vein (SV) and might develop easily at the site of SV dilatation because of blood flow stasis. However, whether preoperative SV dilatation detected by ultrasonography predicts DVT after major orthopedic surgery remains unknown. Objective We examined whether SV dilatation detected by preoperative ultrasonography predicts DVT after major orthopedic surgery. Methods Ultrasonography was performed preoperatively and postoperatively in 243 patients with orthopedic diseases (mean age of 67 ± 13 years, 77% women) who underwent total hip arthroplasty (THA, n = 180) or total knee arthroplasty (TKA, n = 63). Presence of DVT was diagnosed by ultrasonography and SV diameter ≥10 mm was defined as SV dilatation. Patients with preoperative DVT were excluded. Results Sixty-nine patients (28%) developed postoperative DVT. SV dilatation was found in 24 patients (10%), and 16 (67%) of those patients had postoperative DVT. Multivariate logistic regression analysis showed that female gender [odds ratio (OR): 4.09, p = 0.004], TKA (OR: 2.52, p = 0.011), and SV dilatation (OR: 6.67, p d -dimer value, independently predict postoperative DVT. Subgroup analyses according to the operation site showed that female gender (OR: 3.27, p = 0.043) and SV dilatation (OR: 3.72, p = 0.022) were independent predictors of postoperative DVT in the THA group. SV dilatation (OR: 12.0, p = 0.027) was an independent predictor of postoperative DVT also in the TKA group. Conclusions In addition to gender and TKA, SV dilatation detected by ultrasonography is an independent predictor of DVT after major orthopedic surgery. Determination of SV diameter by ultrasonography before major orthopedic surgery is useful for assessing the risk of postoperative DVT.

Background Obesity, defined as higher body mass index (BMI), is associated with better prognosis in patients with chronic heart failure (CHF), though the presence of obesity is a risk factor of development of CHF (Obesity paradox). On the other hand, muscle wasting, i.e. reduction in skeletal muscle mass, is frequently observed in CHF, leading to lower exercise capacity and poor cardiovascular outcome. Purpose The aim of this study was to examine whether analysis of body composition improves prediction of short-term readmission rates in patients with CHF. Methods We retrospectively analyzed data for 167 consecutive HF patients who were admitted to our institute for management of HF and received a Dual-energy X-ray absorptiometry (DEXA) scan. Muscle wasting was defined as DEXA-measured appendicular skeletal muscle mass index 25% in male, >30% in female. The primary endpoint was readmission due to cardiac events including worsening heart failure, arrhythmia, and cardiopulmonary arrest during a 180-days follow-up period after discharge. Results The mean age of the patients was 74±13 years and 46% of them were male. The mean BMI was 21.8±3.8 kg/m2. Forty-seven percent of the patients were classified as NYHA functional class III. The most frequent etiology of HF was cardiomyopathy (30%), followed by ischemic heart disease (27%) and valvular heart disease (27%). The prevalence of muscle wasting and that of obesity were 69% and 59%, respectively. Patients with muscle wasting had lower BMI level, higher prevalence of NYHA functional class III and diabetes mellitus compared with those without muscle wasting. On the other hand, patients with obesity had higher prevalence of hypertension and dyslipidemia, higher level of BMI, fasting plasma insulin and triglyceride, and lower level of HDL-cholesterol compared with those without obesity. During the follow-up period, 34 patients (19%) were re-hospitalized due to cardiac events. Kaplan-Meier survival curves showed that patients with obesity had a significantly lower readmission rate during a 180-days follow-up period than did the patients without obesity (14.3% vs. 29.0%, Log-Rank test, p Conclusion Body composition analysis by DEXA enables to find CHF patients with increased fat mass who have lower risk of short-term readmission.

Background Malnutrition is frequently present and closely associated with poor clinical outcomes in elderly heart failure (HF) patients. Our previous study showed that low energy intake (EI) is associated with worse functional status in elderly HF inpatients after cardiac rehabilitation, but significance of EI in prediction of hospital readmission has not been elucidated fully. Purpose We examined whether low EI is a predictor of readmission for cardiac events in elderly HF patients. Methods We retrospectively retrieved data for 298 HF patients aged ≥65 years (median age of 77 years, interquartile range [IQR]: 71 - 82, female: 53%) who admitted to our institute for diagnosis and treatment of HF. Medical records were reviewed with regard to demography, medical history, comorbidities, medications, laboratory data, echocardiograms, functional status, nutritional status and total energy intake. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF) and total EI per day were calculated at discharge by a registered dietitian and a trained physical therapist. The primary endpoint was readmission due to cardiovascular events including worsening HF, arrhythmia, angina pectoris and myocardial infarction during a 1-year follow-up period. Results The median period of follow-up was 235 days (IQR: 78–365 days). The 1-year readmission rate for cardiovascular events was 54.4%. The cutoff values of MNA-SF score and EI, calculated by ROC curve analysis to predict the primary endpoint, were 7 points (area under the curve [AUC]: 0.59, sensitivity: 0.65, specificity: 0.50) and 31.8 kcal/kg/day (AUC: 0.59, sensitivity: 0.83, specificity: 0.35), respectively. Patients with low MNF-SF score (≤7) or low EI (≤31.8 kcal/kg/day) had significantly higher readmission rate during a 1-year follow-up period than did the patients with high MNF-SF score or EI (MNA-SF: 60.7% vs. 45.6%, p Kaplan-Meier curves of readmission rates Conclusions Low energy intake is a nutritional status-independent predictor of 1-year readmission rate in elderly HF patients.

Aims In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three‐dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF). Methods and results In 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time‐activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non‐CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non‐CE group. Phase SD > 37 and LVMI > 122.7 g/m2 were identified as optimal cut‐off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut‐off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m2 had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024–1.051, P < 0.0001) and 1.005 (CI, 1.001–1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ2 value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI. Conclusions Three‐dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.

Background and Objectives: Idiopathic Pulmonary Fibrosis (IPF), especially with emphysema, reportedly involved with Pulmonary Hypertension (PH). However, it is not elucidated whether pulmonary arterial pressure changes serially during the course and influence on prognosis in IPF. We examined whether serial measurements of Tricuspid Regurgitation Pressure Gradient (TRPG) by echocardiography were meaningful predictors of IPF patient survival. Methods: We retrospectively investigated 83 IPF patients. The echocardiographic TRPG cutoff was set at 30 mmHg, and the subjects were divided into two groups: high TRPG and normal TRPG. We also evaluated the relationship between serial TRPG changes during follow-up. Results: A total of 28 patients were included in the high TRPG group. The high TRPG group showed significantly lower %FVC and %DLco, higher A-aDO 2 , shorter 6-minute walk test distance, and more frequent emphysema than the normal TRPG group. The high TRPG group also had poorer survival than the normal TRPG group. A multivariate Cox proportional hazard model demonstrated that TRPG, %FVC, and A-aDO 2 significantly affected patient survival. Thirty-six patients underwent echocardiography twice. At the time of the second echocardiog- raphy, 7 patients with normal TRPG at baseline (n=22) increased to a TRPG of more than 30 mmHg. These patients had significantly showed poorer survival. Conclusions: TRPG is an independent prognostic factor in IPF. Emphysema involvement, de- creased DLco, and decreased FVC were associated with an increase in TRPG. Serial measure- ments of TRPG are recommended for the early detection of PH and predict prognosis in IPF patients.

Activity of mTOR complex 1 (mTORC1) has been shown to be up-regulated in animal models of heart failure. Here, we investigated the change and role of mTORC1 in human nonischemic dilated cardiomyopathy (NICM).Endomyocardial biopsy specimens were obtained from patients with NICM (n=52) and from Brugada syndrome patients with normal LVEF as controls (n=10). The specimens were stained for phospho-ribosomal protein S6 (p-Rps6) and phospho-p70S6K (p-p70S6K), and the area with p-Rps6 signal was used as an index of mTORC1 activity. Using median mTORC1 activity, patients were divided into a high mTORC1 activity (H-mTOR) group and a low mTORC1 activity (L-mTOR) group.The ratio of p-Rps6-positive area in biopsy samples was 10-fold larger in patients with NICM than in controls (2.0±2.2% vs. 0.2±0.2%, p0.01). p-p70S6K signal level was higher in the H-mTOR group than in the L-mTOR group. The proportion of patients with a family history of cardiomyopathy was higher and the proportion of patients on ACE inhibitors or angiotensin receptor blockers was lower in the H-mTOR group than in the L-mTOR group. The p-Rps6-positive area was correlated with extent of myocardial fibrosis (r=0.46, p0.01). The cardiac event-free survival rate during a 5-year follow-up period tended to be lower in the H-mTOR group than in the L-mTOR group (52.9% vs. 81.6%, P=0.10).Aberrant activation of mTORC1 in cardiomyocytes was associated with myocardial fibrosis and a trend for worse prognosis in patients with NICM, indicating that persistently activated mTORC1 contributes to progression of human heart failure.

An excess, long-lasting increase in systemic autonomic function facilitates myocardial injury and heart failure (HF), leading to lethal cardiac outcomes. Cardiac 123 I-labeled metaiodobenzylguanidine (MIBG) imaging enables non-invasive and quantitative evaluation of cardiac sympathetic innervation in human hearts. The independent and incremental prognostic values of this imaging technique in combination with clinical information in chronic HF patients have been shown. Results of recent multicenter MIBG studies performed in North-America, Europe and Japan have further strengthened the prognostic values, facilitating the clinical use of cardiac MIBG imaging in long-term management of chronic HF patients. Cardiac neuroimaging can contribute not only to the riskstratification for lethal events but also to appropriate selection of a therapeutic strategy using drug and device therapies, such as implantable cardioverter defibrillator (ICD) implantation and cardiac resynchronization therapy (CRT), in HF patients. Because of the limitations of current indication criteria, however, some patients undergoing ICD implantation and/or CRT receive no potentially beneficial intervention and, in contrast, some other patients have lethal outcomes without the benefits. Because of increases in medical costs due to noneffective or futile device therapy, the non-negligible number of non-responders to device treatment indicates the need for better selection of high-risk patients who can benefit most from device treatment in a cost-effective manner. Quantitative assessment of cardiac MIBG activity and kinetics can improve the identification of potential candidates for ICD/CRT and reduce costs associated with device treatments with a minimal impact on outcomes. A further large-scale investigation is needed to establish the possibility of cardiac MIBG imaging for more precisely selecting patients at increased risk or at low risk for potentially lethal arrhythmias, sudden cardiac death and/or refractory pump failure so as to optimize therapeutic interventions in patients with heart failure.

Objective Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis. Methods We enrolled 1,150 patients [mean age, 68±12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution. Results The log-GS was significantly larger in men than in women (2.5±1.5 vs. 1.9±1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant. Conclusion A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.

In a polar map display, the LAD originates from an area corresponding to 11 o’clock, and the relationship between localization of the culprit lesion and diagonal arteries can be inferred by the extent of decreased perfusion extending from 12 o’clock towards 1 o’clock. The location of a lesion in the LCX main trunk can be inferred by whether decreased perfusion is observed at any level within 2〜5 o’clock. Infarction volume depends on the anatomical size of the territories of the PD and AV but not on the location of a culprit lesion in the RCA trunk.

Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI 3.89 and TAPSE 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.

Background Whether the short-term effect of cardiac rehabilitation (CR) in elderly patients with heart failure (HF) is influenced by nutritional status is uncertain, so the present study investigated the effect of nutritional status on functional recovery after CR in elderly HF inpatients.Methods and Results:We enrolled 145 patients admitted for treatment of HF who were aged ≥65 years and had a low functional status defined as a Barthel index (BI) score ≤85 points at the commencement of CR. Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF) and total energy intake per day. The primary endpoint was functional status determined by the BI score at discharge. The median CR period was 20 days (interquartile range: 14-34 days), and 87 patients (60%) were functionally dependent (BI score ≤85) at discharge. Multivariate logistic regression analysis showed that MNA-SF score (odds ratio [OR]: 0.76, P=0.02) and total energy intake at the commencement of CR (OR: 0.91, P=0.02) were independent predictors of functional dependence after CR. MNA-SF score ≤7 and total energy intake ≤24.5 kcal/kg/day predicted functional dependence at discharge with moderate sensitivity and specificity. Conclusions MNA-SF score and total energy intake at the commencement of CR are novel predictors of the extent of functional recovery of elderly HF inpatients after in-hospital CR.

Due to many small cycles in factor graphs, detection and decoding over two-dimensional inter-symbol interference (2D-ISI) channels has been considered difficult. It is reported that generalized belief propagation (GBP) detection for 2D-ISI performs much better than BP. However, conventional studies for GBP for 2D-ISI were restricted to the separate uses of detection and decoding. Joint usage of detection and decoding were proposed in [1] but hard-decisions are inserted between detector and decoder. This makes a gap to the optimal performance. In this paper, we study full-joint use of GBP for detector and decoder for 2D-ISI, i.e., we use only soft-messages. Furthermore, we clarify a necessary condition with respect to the region graph that messages converge to a GBP fixed point. We found most of regions graph proposed in the literature do not satisfy the convergence condition. This prevents the full-joint use of GBP for 2D-ISI. Moreover, we propose a method to construct region graphs which satisfy the condition. Numerical experiments show that the proposed joint detector and decoder perform better than the conventional separate detector and decoder [2] in a simple 2D-ISI channels.

BACKGROUND Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683.2±237.3 to 560.3±238.7 dyn·s/cm5(P

Whether different patterns of ventricular ballooning in takotsubo cardiomyopathy (TCM) reflect differences in trigger mechanisms or clinical outcomes is unclear. Here we examined differences in the clinical characteristics of typical and atypical forms of TCM. TCM patients (n = 251) in the BOREAS Registry were enrolled for comparison of TCM with apical ballooning (type A, n = 217) and TCM with non-apical ballooning (type non-A, n = 34). The percentage of females was significantly lower in the type non-A group (58.8 vs. 75.6 %), while other demographic parameters and triggers of TCM were similar in the two groups. Rate of mid-ventricular obstruction (MVO) was lower (2.9 vs. 14.3 %) in the type non-A group than in the type A group, though left ventricular ejection fractions in the two groups were comparable. During a follow-up period of 2.6 ± 2.8 years, TCM recurred in 2.9 % of the patients and cardiac death occurred in 4.0 %. Cox proportional hazard analysis indicated that body mass index (hazard ratio [HR]: 0.75, 95 % confidence interval [CI] 0.54-0.99) and MVO (HR: 14.71, CI 1.87-304.66) were determinants of TCM recurrence and that advanced age (HR: 1.09, CI 1.02-1.17) and cardiogenic shock (HR: 4.27, CI 1.07-18.93) were significantly associated with cardiac death. In conclusion, approximately 20 % of TCM patients show non-apical left ventricular ballooning, and female sex and MVO are less frequent in this type than in apical ballooning type TCM. Low body mass index and MVO are risk factors of recurrence, and advanced age and cardiogenic shock are risk factors of cardiac death in TCM.

The autonomic nervous system has pivotal roles in pathophysiology and prognosis in patients with heart failure. Cardiac (123)I-labeled metaiodobenzylguanidine (MIBG) imaging enables noninvasive and quantitative assessment of cardiac sympathetic innervation in cardiology practice. Several investigations have demonstrated independent and incremental prognostic values of this imaging technique in combination with clinical information in patients with heart failure. Cardiac MIBG imaging may help cardiologists evaluate cardiac sympathetic nerve function and predict lethal event risk in heart failure. It can contribute not only to the identification of low-risk or high-risk probability for lethal events but also to the selection of the appropriate therapeutic strategy, such as medical and device therapy in patients at greater risk for lethal outcomes due to pump failure or sudden arrhythmic events. Thus, precise risk stratification through cardiac MIBG imaging may contribute to more effective use of medical resources and more appropriate selection of therapeutic strategy in heart failure patients.

Detecting myocardial ischemia in hemodialysis patients is crucial given the high incidence of silent ischemia and the high cardiovascular mortality rates. Abnormal myocardial fatty acid metabolism as determined by imaging with (123)I-labeled BMIPP (β-methyl iodophenyl-pentadecanoic acid) might be associated with cardiac-derived death in hemodialysis patients.Prospective observational study.Asymptomatic hemodialysis patients with one or more cardiovascular risk factors, but without known coronary artery disease, were followed up for 3 years at 48 Japanese hospitals (406 men, 271 women; mean age, 64 years).Baseline BMIPP summed scores semiquantified using a 17-segment 5-point system (normal, 0; absent, 4).Cardiac-derived death, including cardiac and sudden death.HRs were estimated using a Cox model for associations between BMIPP summed scores and cardiac-derived death, adjusting for potential confounders of age, sex, body mass index, dialysis duration, and cardiovascular risk factors.Rates of all-cause mortality and cardiac-derived death were 18.5% and 6.8%, respectively. Cardiac-derived death (acute myocardial infarction [n = 10], congestive heart failure [n = 13], arrhythmia [n = 2], valvular heart disease [n = 1], and sudden death [n = 20]) accounted for 36.8% of all-cause deaths. Cardiac-derived death (n = 46) was associated with age, history of heart failure, and BMIPP summed scores of 4 or higher (HR, 2.9; P0.001). Three-year cardiac-derived death-free survival rates were 95.7%, 90.6%, and 78.8% when BMIPP summed scores were 3 or lower, 4-8, and 9 or higher, respectively. BMIPP summed score also was a predictor of all-cause death (HR, 1.6; P = 0.009).Sudden death of unknown cause was considered to have been cardiac derived, although a coronary origin was not confirmed.Abnormal myocardial fatty acid metabolism is associated with cardiac-derived death in hemodialysis patients. BMIPP single-proton emission computed tomography appears clinically useful for predicting cardiac-derived death in this population.

Aims Impairment of cardiac sympathetic innervation is a potent prognostic marker in heart failure, while left ventricular mechanical dyssynchrony (LVMD) has recently been noted as a novel prognosis determinant in heart failure patients with reduced LV ejection fraction (HFrEF). This study was designed to determine the correlation between cardiac sympathetic innervation quantified by metaiodobenzylguanidine (MIBG) activity and LVMD measured by electrocardiogram-gated myocardial perfusion imaging and to evaluate their incremental prognostic values in HFrEF patients. Methods and results A total of 570 consecutive HFrEF patients were followed up for 19.6 months with a primary endpoint of lethal cardiac events (CE) such as sudden cardiac death, death due to pump failure and appropriate ICD shock against life-threatening ventricular tachyarrhythmias. Cardiac sympathetic function and innervation were quantified as heart-to-mediastinum ratio (HMR) and washout kinetics of cardiac MIBG activity. LVMD was assessed by a standard deviation (SD) of systolic phase angle in gated myocardial perfusion imaging. Patients with CE (n = 166, 29%) had a significantly lower HMR and a significantly greater phase SD than did non-CE patients: 1.46 ± 0.28 vs. 1.63 ± 0.29, P

Several studies have shown the utility of left atrial (LA) function determined by two-dimensional or three-dimensional speckle tracking echocardiography (2D- or 3D-STE) for identifying patients with paroxysmal atrial fibrillation (AF). However, whether 3D-STE is applicable for prediction of the recurrence of AF after catheter ablation (CA) remains unknown. We examined whether any 3D-STE parameters are better than 2D-STE parameters for the prediction of AF recurrence. Forty-two patients with paroxysmal AF (58 ± 10 years old, 69% male) underwent 2D- and 3D-STE within 3 days before first-time CA. The global peak LA longitudinal, circumferential, and area strains during systole (3D-GLSs, -GCSs, and -GASs, respectively) and those just before atrial contraction (3D-GLSa, -GCSa, and -GASa, respectively) were determined by 3D-STE and standard deviations of times to peaks of regional LA strains were calculated as indices of LA dyssynchrony. In 2D-STE, global LA longitudinal strains during systole and just before atrial contraction (2D-GLSs and -GLSa) were determined. During follow-up of 441 ± 221 days, 12 patients (29%) had AF recurrence. In the univariate Cox proportional hazard analysis, age [hazard ratio (HR): 1.08, p = 0.04], 3D-GCSs (HR: 0.91, p = 0.03), and 3D-GASs (HR: 0.95, p = 0.01) were predictors of AF recurrence, though associations of recurrence with 2D-STE parameters, indices of LA synchrony, and LA volume were not significant. Multivariable analysis showed that 3D-GASs was an independent predictor of AF recurrence (HR: 0.96, p = 0.048). LA strain determined by 3D-STE is a novel and better predictor of AF recurrence after CA than that determined by 2D-STE or other known predictors.

An iterative reconstruction method in combination with resolution recovery, attenuation and scatter corrections (IR-RASC) can improve image quality. It, however, is undetermined whether this technique can improve the detection of coronary artery disease (CAD) when automated quantitative analysis is used. This study evaluated diagnostic values of IR-RASC in combination with automated quantitative analysis in stress myocardial perfusion imaging (MPI) in the CAD detection. This study enrolled consecutive 64 patients (mean age 66.2 ± 17.3 years, 39 males) who had undergone both 99mTc-labeled tetrofosmin stress MPI and coronary angiography within 3 months. Stress MPI abnormalities quantified as summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS) by Heart Risk View-S (HRV-S) and Quantitative Perfusion SPECT (QPS) softwares using IR-RASC images were compared with those by using conventional filtered back-projection method (FBP) images and angiographic findings. Based on expert visual assessment, SSS and SRS by HRV-S/QPS softwares with IR-RASC were significantly lower than those by HRV-S/QPS softwares with FBP at mid- and basal left ventricular segments. Receiver-operating characteristics analysis showed that areas under the curve assessed by HRV-S (0.687) and QPS (0.678) with IR-RASC were nearly identical to those (0.717–0.724) by expert assessment with FBP, and were significantly (P