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Background Patients with diffuse idiopathic skeletal hyperostosis (DISH) are susceptible to spinal column injuries with neurological deterioration. Previous studies indicated that the prevalence of diabetes mellitus (DM) in patients with DISH was higher than that in patients without DISH. This study investigates the impact of DM on surgical outcomes for spinal fractures in patients with DISH. Methods We retrospectively evaluated 177 spinal fractures in patients with DISH (132 men and 45 women; mean age, 75 ± 10 years) who underwent surgery from a multicenter database. The subjects were classified into two groups according to the presence of DM. Perioperative complications, neurological status by Frankel grade, mortality rate, and status of surgical site infection (SSI) were compared between the two groups. Results DM was present in 28.2% (50/177) of the patients. The proportion of men was significantly higher in the DM group (DM group: 86.0% vs. non-DM group: 70.1%) (p = 0.03). The overall complication rate was 22.0% in the DM group and 19.7% in the non-DM group (p = 0.60). Poisson regression model revealed that SSI was significantly associated with DM (DM group: 10.0% vs. non-DM group: 2.4%, Relative risk: 4.5) (p = 0.048). Change in neurological status, mortality rate, instrumentation failure, and nonunion were similar between both groups. HbA1c and fasting blood glucose level (SSI group: 7.2% ± 1.2%, 201 ± 67 mg/dL vs. non-SSI group: 6.6% ± 1.1%, 167 ± 47 mg/dL) tended to be higher in patients with SSI; however, there was no significant difference. Conclusions In spinal fracture in patients with DISH, although DM was an associated factor for SSI with a relative risk of 4.5, DM did not negatively impact neurological recovery. Perioperative glycemic control may be useful for preventing SSI because fasting blood glucose level was high in patients with SSI.

Sleep disorders and sleep duration have attracted considerable attention as potential modifiable risk factors for the development and progression of heart failure (HF). However, whether these sleep behaviors could aggravate the underlying cardiac condition remains ambiguous. We evaluated the associations between the levels of plasma B-type natriuretic peptide (BNP) and sleep-disordered breathing (SDB), sleep quality and quantity, or daytime sleepiness in cardiovascular diseases (CVD) patients. A total of 1717 consecutive patients with CVD [median age, 66 years (55–74 years); female, 27.5%] were enrolled. SDB was screened by nocturnal pulse oximetry; sleep quality and quantity were determined by Pittsburg Sleep Quality Index, and daytime sleepiness was examined by Epworth Sleepiness Scale. The median plasma BNP level was 54.9 pg/ml (23.5–146.4 pg/ml). Multiple regression analyses showed that the BNP level in the highest quintile (BNP > 181.8 pg/ml) was associated with SDB (severe: OR, 5.88; 95% CI 3.17–10.88; moderate: OR, 3.62; 95% CI 2.17–6.02; mild: OR, 2.22: 95% CI 1.42–3.47). There were no significant associations between other sleep parameters and higher BNP levels. The relationship between SDB and BNP levels was unchanged regardless of the previous history of symptomatic HF. SDB was independently associated with the elevated plasma BNP level in patients with a variety of CVD.

Patients with DISH are susceptible to spinal fractures and subsequent neurological impairment, including after minor trauma. However, DISH is often asymptomatic and fractures may have minimal symptoms, which may lead to delayed diagnosis. The purpose of this study was to identify risk factors for delayed diagnosis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis (DISH).The subjects were 285 patients with DISH surgically treated at 18 medical centers from 2005 to 2015. Cause of injury, imaging findings, neurological status at the times of injury and first hospital examination, and the time from injury to diagnosis were recorded. A delayed diagnosis was defined as that made24 h after injury.Main causes of injury were minor trauma due to a fall from a standing or sitting position (51%) and high-energy trauma due to a fall from a high place (29%) or a traffic accident (12%). Delayed diagnosis occurred in 115 patients (40%; 35 females, 80 males; mean age 76.0 ± 10.4 years), while 170 (60%; 29 females, 141 males; mean age 74.6 ± 12.8 years) had early diagnosis. Delayed group had a significantly higher rate of minor trauma (n = 73, 63% vs. n = 73, 43%), significantly more Frankel grade E (intact neurological status) cases at the time of injury (n = 79, 69% vs. n = 73, 43%), and greater deterioration of Frankel grade from injury to diagnosis (34% vs. 8%, p 0.01). In multivariate analysis, a minor trauma fall (OR 2.08; P 0.05) and Frankel grade E at the time of injury (OR 2.29; P 0.01) were significantly associated with delayed diagnosis.In patients with DISH, it is important to keep in mind the possibility of spinal fracture, even in a situation in which patient sustained only minor trauma and shows no neurological deficit. This is because delayed diagnosis of spinal fracture can cause subsequent neurological deterioration.

Aims The impact of worsening renal function (WRF) on the prognosis of patients with acute heart failure (AHF) remains controversial. We aimed to identify phenotypically distinct subgroups among individuals with both AHF and WRF using cluster analysis. Methods and results Overall, the data of 483 patients with both AHF and WRF enrolled in the West Tokyo Heart Failure Registry were analysed. Using cluster analysis, we identified three phenotypically distinct subgroups (phenogroups 1, 2, and 3). We assessed the impact of WRF on the prognosis of each phenogroup by comparing the incidence of composite endpoints, including all‐cause death and re‐hospitalization due to heart failure, with those of a propensity score‐matched, non‐WRF control group. Participants in phenogroup 1 (N = 122) were the youngest (69.3 ± 13.7 years), had relatively preserved estimated glomerular filtration rate (eGFR, 70.0 ± 27.7 mL/min/1.73 m2), and reduced left ventricular ejection fraction (LVEF) (41.8 ± 13.7%). Conversely, participants in phenogroup 3 (N = 122) were the oldest (81.7 ± 8.5 years), had the worst eGFR (33.0 ± 20.9 mL/min/1.73 m2), and had preserved LVEF (51.7 ± 14.8%). The characteristics of the participants in phenogroup 2 (N = 239) were between those of phenogroups 1 and 3. The propensity score matching analysis showed that WRF was associated with a higher incidence of composite endpoints in phenogroup 1, whereas this association was not observed in phenogroups 2 and 3. Conclusions Using cluster analysis, we revealed three phenotypically distinct subgroups of patients with both AHF and WRF. WRF was associated with worse clinical outcomes in the subgroup of younger patients with reduced LVEF and preserved renal function.

Blood access is a lifeline for dialysis patients. However, serious problems such as stenosis or obstruction of access blood vessels, which are life-threatening conditions in daily clinical practice, still remain. One of the most promising candidates for solving these problems may be Biotube blood vessels. More than 20 years have passed since the development of in-body tissue architecture (iBTA), a technology for preparing tissues for autologous implantation in patients. The tissues obtained by iBTA do not elicit immunological rejection, which is one of the ultimate goals of regenerative medical engineering; however, their practical applications were quite challenging. The seemingly unorthodox iBTA concepts that do not follow the current pre-established medical system may not be readily accepted in general medicine. In contrast, there are many diseases that cannot be adequately addressed even with the latest and most advanced medical technology. However, iBTA may be able to save patients with serious diseases. It is natural that the development of high-risk medical devices that do not fit the corporate logic would be avoided. In order to actively treat such largely unattached diseases, we started Biotube Co., Ltd. with an aim to contribute to society. Biotubes induced by iBTA are collagenous tubular tissues prepared in the patient’s body for autologous implantation. The application of Biotubes as tissues for vascular implantation has been studied for many years. Biotubes may have excellent potential as small-diameter artificial blood vessels, one of the most difficult to clinically achieve. Their possibility is currently being confirmed in preclinical tests. Biotubes may save hundreds of thousands of patients worldwide annually from amputation. In addition, we aim to eliminate the recuring access vascular problems in millions of dialysis patients. This study provides an update on the current development status and future possibilities of Biotubes and their preparation molds, Biotube Makers.

Reflected wave increases after endovascular aortic repair (EVAR) in patients with aortic aneurysm. This affects the left ventricular (LV) diastolic function and leads to a poor prognosis. This study aimed to evaluate the relationship between increased reflected wave amplitude and aortic diameter after EVAR. EVAR was performed in seven healthy goats. We assessed wave intensity (WI), aortic diameter, and stiffness parameter β. Moreover, we evaluated the relationship between negative reflected wave (NW, reflected waves toward the heart from the periphery by WI) and other parameters after EVAR. Results showed an increase in stiffness parameter β (3.5 ± 0.3 vs 15.9 ± 4.7, p = 0.018) and a decrease in the change of aortic diameter (6.9 ± 0.7 vs 2.7 ± 0.4%, p = 0.018) after EVAR. The NW was significantly amplified after EVAR from baseline (−589.8 ± 143.4 to − 1192.3 ± 303.7 mmHg-m/sec3, p = 0.043). The NW showed a significant correlation with maximum aortic diameter (R = 0.707, p = 0.038) and minimum aortic diameter (R = 0.724, p = 0.033). The reflected wave was enhanced after EVAR and was correlated to the aortic diameter at the stent-graft site. It is important to consider that patients with smaller aortic diameters in landing zone who undergo EVAR may develop LV dysfunction.

Aims Clinical guidelines for improving the patients' quality of care vary in clinical practice, particularly in super‐aging societies, like in Japan. We aimed to develop a set of appropriate‐use criteria (AUC) for contemporary heart failure (HF) management to assist physicians in decision making. Methods and results With the use of the RAND methodology, a multidisciplinary writing group developed patient‐based clinical scenarios in 10 selected key topics, stratified mainly by HF stage, age, and renal function. Nine nationally recognized expert panellists independently rated the clinical scenario appropriateness twice on a scale of 1–9, as ‘appropriate’ (7–9), ‘may be appropriate’ (4–6), or ‘rarely appropriate’ (1–3). Decisions were based on clinical evidence and professional opinions in the context of available resource use and costs. An interactive round‐table discussion was held between the first and second ratings; the median score of the nine experts was then assigned to an appropriate‐use category. Most clinical scenarios without strong evidence were evaluated as ‘may be appropriate’. Frailty assessments in elderly patients (age ≥ 75 years), regardless of the HF stage, and advanced care planning in patients with stage C/D HF, regardless of age, were considered ‘appropriate’. For HF with reduced ejection fraction, beta‐blocker administration in elderly patients (age ≥ 75 years) with heart rate

Acute heart failure (AHF) has become a global public health burden largely because of the associated high morbidity, mortality, and cost. The treatment options for AHF have remained relatively unchanged over the past decades. Historically, clinical congestion alone has been considered the main target for treatment of acute decompensation in patients with AHF; however, this is an oversimplification of the complex pathophysiology. Within the similar clinical presentation of congestion, significant differences in pathophysiological mechanisms exist between the fluid accumulation and redistribution. Tissue hypoperfusion is another vital characteristic of AHF and should be promptly treated with appropriate interventions. In addition, recent clinical trials of novel therapeutic strategies have shown that heart failure management is ‘time sensitive’ and suggested that treatment selection based on individual aetiologies, triggers, and risk factor profiles could lead to better outcomes. In this review, we aim to describe the specifics of the ‘time‐sensitive’ approach by the clinical phenotypes, for example, pulmonary/systemic congestion and tissue hypoperfusion, wherein patients are classified based on pathophysiological conditions. This mechanistic classification, in parallel with the comprehensive risk assessment, has become a cornerstone in the management of patients with AHF and thus supports effective decision making by clinicians. We will also highlight how therapeutic modalities should be individualized according to each clinical phenotype.

Infected aortic aneurysm (IAA) is a rare, life-threatening disease with rapid progression and a high mortality rate. An 84-year-old man developed IAA caused by urosepsis owing to extended-spectrum β-lactamase–producing Escherichia coli infection. Considering surgical risk and perioperative mortality, the patient underwent computed tomography–guided percutaneous abscess drainage and continuous irrigation with optimal antibiotic therapy. We controlled his systemic inflammation without surgery; thus, he was discharged. Six months later, we confirmed that the abscess had almost disappeared in the follow-up computed tomography scan. Percutaneous abscess drainage and irrigation may be an effective therapeutic option for surgical high-risk patients with IAA.

To examine the relationship between handgrip strength and leg extension power, walking speed, and intermittent claudication for lumbar spinal stenosis (LSS) using computed tomography. We examined patients who underwent laminectomy for LSS from June 2015 through March 2018. Before spine surgery, we evaluated walking distance, handgrip strength, leg extension power (LEP), 10-m walk test (time and steps), psoas muscle index (PMI), and the area of both total and multifidus muscle using plain computed tomography imaging at the third lumbar level. Handgrip strength was compared with comorbidities including anemia, diabetes, hypertension, marital status, etc. There were 183 patients (55 female, 128 male) with a mean age of 70.5 years. Handgrip strength significantly correlated with LEP (P

Aims Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low‐dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy‐proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7–96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9–83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P

Study design Prospective multi-center study. Objective The aim of this study was to evaluate the effectiveness of surgical treatment in reducing falls and fall-related neurological deterioration in a prospective cohort of patients undergoing surgery for degenerative cervical myelopathy (DCM). Summary of background data Current evidence is limited for the effectiveness of surgical interventions for DCM in reducing the risk of fall-related neurological deterioration. Methods Patients with DCM scheduled for surgical treatment were enrolled prospectively at eight participating institutes. At the time of enrollment, participants were given diaries to record details of their falls, to be returned at the 1-year postoperative follow-up. In the fall diary, patients were asked whether they had experienced any deterioration in neurological symptoms at each fall episode. Deterioration of neurological symptoms was categorized as follows: only deterioration of sensory function in the limbs; or deterioration of motor deficits. The incidence rate of falls was calculated separately for the preoperative and postoperative periods, as the total number of falls divided by the time over which falls were monitored (100 person-years). Functional outcome was assessed with the Japanese Orthopaedic Association (JOA) score and Neck Disability Index. Results Of the initial 168 participants, 159 completed the 1-year follow-up, and 132 fall diaries were retrieved and analyzed. Of these 132 patients, 65 (49%) reported at least one fall during the survey period. The incidence rate of falls decreased significantly from 497.4 to 90.3 falls per 100 person-years after surgery. The incidence of motor deterioration per fall decreased significantly from 34% to 8% after surgery. Patients who experienced preoperative fall-related motor deterioration had a significantly lower JOA score compared with patients without fall-related motor deterioration at 1-year follow-up. Conclusion Surgical intervention for DCM is effective not only in reducing the frequency of falls, but also in reducing the risk of fall-related deterioration of motor deficits. Level of evidence 2.

Aims The blood urea nitrogen (BUN)/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF). However, the clinical impact of a high BUN/creatinine ratio at discharge with respect to renal dysfunction, neurohormonal hyperactivity, and different responsiveness to decongestion therapy remains unclear. Herein, we examined (i) the predictive value of a high BUN/creatinine ratio at discharge and (ii) its haemoconcentration‐dependent effects, in patients with ADHF. Methods and results The West Tokyo Heart Failure registry was a multicentre, prospective cohort registry‐based study that enrolled patients hospitalized with a diagnosis of ADHF. The endpoint was post‐discharge all‐cause death. Based on the degree of haemoconcentration, patients (n = 2090) were divided into four subcategories. In multivariate proportional hazard analyses, a higher BUN/creatinine ratio was independently associated with higher all‐cause mortality in the total population and in the extreme haemodilution (ΔHaemoglobin ≤ −0.9 g/dL) and haemoconcentration (0.8 g/dL ≤ ΔHaemoglobin) subcategories, but not in the modest haemodilution/haemoconcentration subcategories. Conclusions A higher BUN/creatinine ratio at discharge was independently associated with higher post‐discharge all‐cause mortality in patients with ADHF. The predictive value of a high BUN/creatinine ratio at discharge was haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution.

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) &gt, 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP &lt, 100 mmHg and CONUT score &gt, 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use.

Background Lower heart rate (HR) is associated with more favourable long-term outcome in patients with heart failure with reduced ejection fraction (HFrEF). However, an optimal threshold of HR remains unclear. Targeted HR (THR), defined by echocardiographic deceleration time (DCT) to eliminated overlap of E and A waves, may aid in risk stratification of HFrEF patients. Purpose In this study, we aimed to clarify the impact of on long-term clinical outcome in patients with HFrEF. Methods In the multicenter WET-HF registry, 4000 consecutive patients hospitalized for acute decompensated HF (ADHF) were registered between 2006 and 2017. Among them, the patients with EF ≥40% or a history of atrial fibrillation were excluded. THR was calculated based on their DCT value measured in compensated HF phase during the index admission. The following formula was applied; THR (bpm)=93 - 0.13 × deceleration time (DCT, msec). A total of 876 patients with HFrEF were included in the present analysis (age: 72 [60–81], male: 69%) and the patients were divided into the 2 groups of HR at discharge ≤ THR (L group) and > THR (H group). The primary endpoint (PE) was defined as the composite of all-cause death and ADHF re-admission. Results Compared to the H group, the L group showed higher prevalence of males (74% vs. 66%, P=0.025) with higher body mass index (BMI, 23.2 vs. 22.2, P=0.016), hemoglobin (Hb, 12.9 vs. 12.4, P=0.031), albumin (Alb, 3.7 vs. 3.6, P=0.039) and larger left atrial diameter (LAD, 44 mm vs. 41 mm, P=0.002) and tricuspid regurgitation pressure gradient (TRPG, 29 mmHg vs. 27 mmHg, P=0.012). Age, estimated glomerular filtration rate (eGFR), LVEF (29% vs. 30%, P=NS) and E/e' (17.7 vs. 16.8, P=NS) were similar for both groups. At discharge, HR was lower in L group (66 [60–71] bpm vs. 80 [74–86] bpm, P In the survival analysis, the L group showed a significantly lower rate of PE (P=0.03), whereas there was no significant difference in the incidence of PE between the patients with HR at discharge ≥70 bpm and Multivariate Cox hazard analysis showed that HR at discharge ≤ THR was an independent predictor of PE (hazard ratio 0.67 [0.46–0.97], P=0.037), even after adjusting for confounding factors including age, sex, BMI, Hb, Alb, and b-blocker prescription, whereas HR at discharge Conclusion THR was associated with long-term outcomes in patients with HFrEF after acute decompensation, suggesting that it may aid in tailored treatment for HR reduction in these patients. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background: Malnutrition is common in patients with heart failure with reduced ejection fraction (HFrEF) and may influence the long-term prognosis and allocation of guideline-directed medical therapy (GDMT).Methods and Results: We reviewed 1,231 consecutive patient-level records from a multicenter Japanese registry of hospitalized HFrEF patients. Nutritional status was assessed using the geriatric nutritional risk index (GNRI). GDMTs were categorized based on the use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists. The composite outcome of all-cause death and HF rehospitalization was assessed. The mean age was 72.0±14.2 years and 42.6% patients were malnourished (GNRIConclusion: Malnutrition assessed by GNRI score predicts long-term adverse outcomes among hospitalized HFrEF patients. However, its prognosis may be modified with GDMT.

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-reported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %sedentary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p &lt, 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sedentary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.

Thrombosis, especially venous thromboembolism, is a complication often associated with COVID-19. However, there have been relatively few reports of arterial thrombosis. Here, we describe a case of non-severe COVID-19 in a patient with dilated cardiomyopathy. After admission, symptoms, laboratory data, and imaging findings improved, but D-dimer levels gradually increased. Contrast computed tomography (CT) and echocardiography revealed a left ventricular thrombus. Anti-coagulant treatment diminished the thrombus, and the patient recovered and was discharged. Although a left ventricular thrombus is a rare COVID-19 complication, performing appropriate diagnostic tests could improve COVID-19 mortality in patients with dilated cardiomyopathy., A 56-year-old man with dilated cardiomyopathy was admitted to our hospital with non-severe COVID-19 and heart failure. Symptoms, laboratory data, and imaging findings improved rapidly, but the D-dimer levels gradually increased. Contrast CT scan and echocardiography revealed a left ventricular thrombus, which was treated by anticoagulant treatment.

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction &lt, 50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044, non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.

Noonan syndrome is known to have various cardiovascular defects, which include pulmonary artery stenosis. Pulmonary artery stenosis is characterized by obstruction of pulmonary artery blood flow that can cause elevated pulmonary artery pressure and ventilation-perfusion inequality, which can cause dyspnea on exertion and eventually, heart failure. Although the etiology of pulmonary artery stenosis related to congenital diseases is still unknown, balloon pulmonary angioplasty has being reported to be effective to selected patients with Alagille and Williams syndromes, but not from Noonan syndrome despite of modest prevalence of pulmonary artery stenosis. Here, we report the first Noonan syndrome patient with pulmonary artery stenosis who underwent successful balloon pulmonary angioplasty. The strategy used in balloon pulmonary angioplasty was planned with careful morphologic evaluation by computed tomographic angiography, and performed with scoring balloons in a graded approach with multiple sessions. After balloon pulmonary angioplasty, we confirmed maintained dilation of lesions and symptom alleviation, suggesting that balloon pulmonary angioplasty can be performed safely on pulmonary artery stenosis in a Noonan syndrome patient.

Spinal cord injury (SCI) is caused by an initial mechanical insult followed by a series of deleterious events that promote the progressive damage of affected tissues. Fibrinolysis, the process by which plasmin degrades cross-linked fibrin clots, has numerous functions in the central nervous system. However, the roles of the fibrinolytic system in SCI pathophysiology remain unknown. We investigated the roles of fibrinolysis in SCI, and explored therapeutic applications targeting fibrinolysis. Plasminogen-deficient (Plg−/−) mice exhibited significantly improved locomotor function in the early phase of SCI (the first 7 days post injury), with significant inhibition of bleeding and vascular permeability, but failed to demonstrate conclusive functional recovery. Consistent with these findings, the short-term administration of tranexamic acid (TXA) in wild-type mice over the first 3 days post injury significantly improved locomotor function after SCI, whereas prolonged TXA administration did not. Prolonged TXA administration resulted in significantly lower levels of matrix metalloproteinase activities in the spinal cord, suggesting that inhibition of the fibrinolytic system impaired tissue remodeling. Our results indicate that the fibrinolytic system has time-dependent biphasic actions following SCI. The temporally optimised modulation of fibrinolytic activity may thus be a novel therapeutic strategy to improve functional outcomes after SCI.

Patients having heart failure with midrange ejection fraction (HFmrEF: 40% ≤ EF50%) are increasingly being considered a new subset of the population with heart failure. Despite recent advances in heart-failure treatment strategies, the prognosis of these patients has not improved substantially over time. In addition, the significance of this new phenotype in hospitalized patients with acute decompensated heart failure (ADHF), another population whose prognosis has not improved, also remains poorly understood. This study aimed to describe the clinical characteristics, prognosis and treatment responses of patients with HFmrEF hospitalized for ADHF.On the basis of consecutive inpatient data from a multicenter ADHF registry, 651 of 3572 patients (17.1%) were classified as having HFmrEF. Prognostic factors predicting composite outcomes, defined as all-cause death and heart failure readmission, as well as all-cause death alone, were analyzed.In the median follow-up duration of 724 days, both composite endpoints and all-cause death alone were comparable in those with heart failure with preserved ejection fraction, HFmrEF and heart failure with reduced ejection fraction. Age, anemia, hyponatremia, elevated blood urea nitrogen, chronic kidney disease, and elevated plasma brain natriuretic peptide levels were significant predictors of composite outcomes in HFmrEF.Roughly one-sixth of the patients with ADHF had HFmrEF. The long-term prognosis of patients with HFmrEF was not significantly different from that of patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in the population with ADHF. Risk factors for adverse outcomes in HFmrEF were also similar to those for heart failure with preserved ejection fraction and HFmrEF in the hospitalized population with ADHF.

Background: The concept of Clinical Scenario (CS) classification has been widely utilized to aid in choosing appropriate management strategies for acute decompensated heart failure (ADHF). Methods and Results: The West Tokyo-Heart Failure (WET-HF) Registry is a multicenter, prospective cohort registry enrolling consecutive hospitalized ADHF patients. Based on systolic blood pressure (SBP) at admission, 4,000 patients enrolled between 2006 and 2017 were classified into 3 groups: CS1, SBP ≥140 mmHg; CS2, 100≤SBP

Purpose Although guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) should be treated with renin-angiotensin system (RAS) inhibitors, the long-term efficacy of RAS inhibitors in HFrEF patients with moderate-to-severe chronic kidney disease (CKD) remains unclear. Methods The present study included consecutive patients hospitalized for acute heart failure across five Japanese teaching hospitals. The impact of RAS inhibitors on 2-year all-cause mortality was evaluated in patients with an ejection fraction ≤40% and CKD, defined as an estimated glomerular filtration rate (eGFR) Results Overall, 553 patients (age, 76 ± 11 years; 68% male) were included. RAS inhibitors were prescribed more frequently in 227 patients with stage 3B (71.2%) than in 107 patients with stage 4 or 5 CKD (45.7%). All-cause mortality was recorded in 119 patients (23.4%) (55 [18.5%] patients with stage 3B; 64 [30.3%] patients with stage 4 or 5 CKD), within the median follow-up period of 609 (220–983) days. After many-to-one propensity score matching (87 pairs in stage 3; 60 pairs in stage 4 or 5 CKD), those with RAS inhibitors had reduced mortality rate in stage 3B (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.19–0.83) but not in stage 4 or 5 CKD (HR, 1.08; 95% CI, 0.57–2.03). Conclusions In HFrEF patients with CKD, RAS inhibitors are associated with reduction in mortality in stage 3B CKD, but the association is less clear in stage 4 or 5 CKD.

Patient-reported quality of life (PRQL) is a primary therapeutic target for patients with chronic heart failure (HF) and is associated with long-term prognosis. However, its utility in hospitalized HF (HHF) patients in the acute setting remains unclear. We aimed to assess the utility of PRQL (the Kansas City Cardiomyopathy Questionnaire [KCCQ]) in HHF patients and its association with long-term prognosis as well as with the clinical risk score (Get With The Guidelines-Heart Failure [GWTG-HF] risk score). PRQL was evaluated using the KCCQ in consecutive 114 HHF patients. Its association with the composite outcome of all-cause mortality or HF readmission within the first year after discharge was analyzed. Furthermore, its distribution by the clinical risk score (GWTG-HF) was evaluated using Pearson's correlation coefficient. The median KCCQ was 34.9, but was widely distributed (interquartile range 23.7-56.8). After adjustment for known prognostic indicators, the KCCQ was not an independent predictor of the composite outcome within the first year (group with high vs. low KCCQ scores: hazard ratio, 0.67; 95% confidence interval 0.26-1.71). There was no significant correlation between the KCCQ and the GWTG-HF risk score. In conclusion, PRQL during the acute phase of HF was significantly impaired and also varied widely, irrespective of patient characteristics or severity. PRQL assessment and risk prediction for HHF patients in the acute setting seemed to provide two distinct types of information for health care providers.

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years, men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed, borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes.

As shown in cases of photosensitive epilepsy, audio-visual stimuli can have various effects on the human body. However, until now, there have been no reports investigating the effect of television commercials on the human body. In this study, for which we obtained ethical approval, we are the first ones to investigate the effect of television commercials on the human cardiovascular and autonomic nervous systems. Cardiovascular and autonomic nervous functions were evaluated using the human face blood flow analyzing system invented in Tohoku University (Jpn.Pt. 4789203, 5161671, 5390851, 5408751). No epilepsy and no patho-physiological reactions were observed after viewing of soft TV commercials including commercials from the advertising awards. Autonomic nerve responses were shown to be altered depending on the interests and preferences of the viewer. Our results suggest that assessing the response of the human body to TV commercials will become a key aspect of the process of creating TV commercials.

Background: Whether machine-learning-based (ML) models improve the predictability of adverse periprocedural events compared with traditional risk-scoring systems remains unknown. Methods: We extracted data from a Japanese, multicenter PCI registry for patients with coronary artery disease who underwent PCI in accordance with the NCDR-CathPCI registry. We developed logistic regression (LR) and extreme gradient descent boosting (XGB) models to predict periprocedural acute kidney injury (AKI), bleeding, and in-hospital mortality, incorporating the same covariates as the original NCDR-CathPCI risk score models. The hyperparameters of the XGB models were tuned using a stratified 3-fold cross-validation. Model discrimination was evaluated using the area under receiver-operating characteristic (AUROC) curves, and the calibration was evaluated using a calibration plot. Results: In the analytic cohort, the median age was 70 (interquartile range 62, 77) years and predominantly men (79·3%). AKI, bleeding, and in-hospital mortality occurred in 9·6%, 7·8%, and 2·3%, respectively. The NCDR-CathPCI risk scores demonstrated good discrimination for each outcome with good calibration (AUROC of 0·79, 0·76, and 0·92 for AKI, bleeding, and in-hospital mortality). Compared with the NCDR-CathPCI risk scores, the LR and XGB models modestly improved model discrimination for AKI and bleeding (AUROC of 0·80, and 0·77 in LR models; 0·81, and 0·79, in XGB models) but not for in-hospital mortality (AUROC of 0·92 in LR models, and 0·93 in XGB models, respectively).The calibration curve demonstrated that the XGB model for in-hospital mortality overestimated the risk in low-risk patients. Conclusion: All of the original NCDR-CathPCI risk models for periprocedural adverse events showed an adequate discrimination and calibration within our cohort. Discrimination of bleeding and AKI risk improved modestly when ML-based models were incorporated, but whether the improvement in overall performances by ML-based models was clinically significant was unclear. Funding: The present study was funded by the Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKENHI; Nos. 16KK0186, 16H05215, 18K17332, and 20H03915 https://kaken.nii.ac.jp/ja/index/). Declaration of Interest: Dr. Shiraishi is affiliated with an endowed department by Nippon Shinyaku Co., Ltd., Medtronic Japan Co., Ltd., and BIOTRONIK JAPAN Inc., and received research grants from the SECOM Science and Technology Foundation and the Uehara Memorial Foundation and honoraria from Otsuka Pharmaceuticals Co., Ltd. and Ono Pharmaceuticals Co., Ltd.; Dr Kohsaka reported receiving grants from Daiichi Sankyo during the conduct of the study; and grants from Bayer and personal fees from Bristol Bayer, Bristol-Myers Squibb, and Pfizer outside the submitted work. Ethical Approval: The protocol of this study was under the principles of the Declaration of Helsinki and approved by the committee of each participating hospital.

Introduction Several report showed the association between ambient air pollution including particular matter under 2.5um (PM2.5) and increasing rate of hospitalization for heart failure. However, these report analyzed mainly cross-sectional, epidemiological data, thus the reports regarding association between vulnerability to PM2.5 and specific populations in acute heart failure (AHF) were scarce. Purpose 1. To analyze the association between air pollution and rate of hospitalization for AHF 2. To analyze whether the vulnerability to air pollution differ between specific populations in AHF. Methods A case-cross over analysis was conducted to 4980 consecutive patients registered for multicenter acute heart failure registry in 2017 in our city Japan. This registry enrolled patients transferred to cardiovascular care unit (80 institutions) via emergency medical services across our city area. Logistic regression analysis were conducted to estimate percentage changes in the rate of acute heart failure hospitalization associated with per 1μg/m3 PM2.5 concentration increase. We also conducted subgroup analysis for patients stratified by age, gender, comorbidities, left ventricular ejection fraction, and clinical scenario. Results An increase in 1 μg/m3 PM2.5 concentration corresponded to 2.9% (95% CI 1.2–4.6%) increase in AHF hospitalization. Patients with age younger than 75, without prior heart failure hospitalization, without history of hypertension, without anemia, and with reduced ejection fraction were more susceptible to increase in PM2.5 concentration (Figure). Conclusions Increase in PM2.5 concentration was associated with increased rate of AHF hospitalization. Effect of PM2.5 may differ across specific AHF subpopulations. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Tokyo Metropolitan Government

Early and rapid risk stratification of patients with acute heart failure (AHF) is crucial for appropriate patient triage and outcome improvements. We aimed to develop an easy-to-use, in-hospital mortality risk prediction tool based on data collected from AHF patients at their initial presentation. Consecutive patients&rsquo, data pertaining to 2006&ndash, 2017 were extracted from the West Tokyo Heart Failure (WET-HF) and National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registries (n = 4351). Risk model development involved stepwise logistic regression analysis and prospective validation using data pertaining to 2014&ndash, 2015 in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure Syndrome (REALITY-AHF) (n = 1682). The final model included data describing six in-hospital mortality risk predictors, namely, age, systolic blood pressure, blood urea nitrogen, serum sodium, albumin, and natriuretic peptide (SOB-ASAP score), available at the time of initial triage. The model showed excellent discrimination (c-statistic = 0.82) and good agreement between predicted and observed mortality rates. The model enabled the stratification of the mortality rates across sixths (from 14.5% to &lt, 1%). When assigned a point for each associated factor, the integer score&rsquo, s discrimination was similar (c-statistic = 0.82) with good calibration across the patients with various risk profiles. The models&rsquo, performance was retained in the independent validation dataset. Promptly determining in-hospital mortality risks is achievable in the first few hours of presentation, they correlate strongly with mortality among AHF patients, potentially facilitating clinical decision-making.

With the progress of surgical technology, the survival rate after resection of esophageal and tongue carcinomas has improved. However, the surgical protocol for esophageal and tongue surgery is complex, and surgery for elderly esophageal and tongue carcinoma patients with cardiopulmonary dysfunction is difficult. Using an artificial tongue and esophagus will be helpful for patients. However, peristalsis of foods depends on food size, taste, and viscosity. This study developed and evaluated a new diagnosis machine for drinking and peristalsis motion. Before clinical evaluation, animal experiments were performed on healthy adult goats using a stereo camera. After a feasibility study of the diagnosis system for peristalsis, clinical evaluation was conducted on healthy normal volunteers. We observed no aspiration pneumonia. The foods and drinks tested were safe. There was no mis-swallowing, but the participants’ feeling with regard to taste differed. Overall, the results indicated that the quantitative swallowing and peristalsis diagnosis system is safe. Evaluation of the visual imaging and spectral analysis gave us useful information about peristalsis, which will help us design an artificial tongue and esophagus with a good control mechanism in the near future.

Repair of dissected aorta requires remodeling the structure of the media. Modeling approaches specific to endovascular stenting for aortic dissection have been reported. We created a goat model of descending thoracic aortic dissection and reproduced its morphological characteristics in a mock circulatory system. The purpose of this study was to examine a newly developed aortic stent which was capable of installing to the aortic dissected lesion for biomedical hemodynamics point of view. In this study, we examined the changes in hemodynamics of dissected lesions and the amelioration by endovascular stent intervention. Firstly, we performed animal experiments with the dissected aorta and examined the effects of stenting on volumetric changes in the false lumen. Secondly, we made several types of 3-D stereolithographic dissected aortic models with silicone rubber membrane between the false and the true lumens. Then, the hemodynamic characteristics in each model were evaluated in the pulsatile flow conditions in a mock circulatory system. These modelling approaches enabled the quantitative examination of post-therapeutic effects of stenting followed by elucidating of hemodynamic changes in the vicinity of stents, which may follow the management of clinical amelioration of interventional treatment with aortic stenting.Clinical Relevance— This study represents a modelling approach of the dissected aorta for endovascular intervention using stenting followed by the examination of false lumen volumetric changes resulting in the deterioration of pressure increase in diseased lesions.

Background Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier. Methods Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared. Results Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure. Conclusions More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.

In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, an early invasive strategy did not decrease mortality compared to a conservative strategy for stable ischemic heart disease (SIHD) patients with moderate-to-severe ischemia, and the role of revascularization would be revised. However, the applicability and potential influence of this trial in daily practice remains unclear. Our objective was to assess the eligibility and representativeness of the ISCHEMIA trial on the patients with percutaneous coronary intervention (PCI). From a multicenter registry, we extracted a consecutive 13,223 SIHD patients with PCI (baseline cohort). We applied ISCHEMIA eligibility criteria and compared the baseline characteristics between the eligible patients and the actual study participants (randomized controlled trial (RCT) patients). In 3463 patients with follow-up information (follow-up cohort), the 2 year composite of major adverse cardiac events was evaluated between the eligible patients and RCT patients, as well as eligible and non-eligible patients in the registry. In the baseline cohort, 77.3% of SIHD patients with moderate-to-severe ischemia were eligible for the ISCHEMIA. They were comparable with RCT patients for baseline characteristics and outcomes unlike the non-eligible patients. In conclusion, the trial results seem applicable for the majority of PCI patients with moderate-to-severe ischemia except for the non-eligible patients.

BackgroundRisk prediction for hospitalised heart failure (HF, HHF) patients remains suboptimal. We aimed to determine the prognostic value of hospital food intake (FI) immediately before discharge among HHF patients.MethodWe analysed the data of 255 HHF patients extracted from the records of a single university hospital. The FI percentage of the three meals the day before hospital discharge was averaged. Patients were stratified into adequate FI (100% consumption) and inadequate FI (less than 100% consumption) groups. The primary outcome was the composite of all-cause mortality and/or HF readmission within 1 year.ResultsOnly 49.3% of HHF patients consumed 100% of their meals. Patients with inadequate FI were older; predominantly women; and had a lower body mass index, higher brain natriuretic peptide levels and Clinical Frailty Scale scores at discharge than those with adequate FI. Inadequate FI was significantly associated with adverse outcomes after adjustments (HR 2.00; 95% CI 1.09 to 3.67; p=0.026). The effect of interaction by ejection fraction (EF) was highly significant: HF with preserved EF (≥40%) was significantly associated with inadequate FI with adverse outcomes (HR 4.95; 95% CI 1.71 to 14.36; p=0.003) but HF with reduced EF (ConclusionsThe hospital FI assessment might be a simple, useful tool for predicting and stratifying risk for HHF patients.

Background Although 30‐day readmission is thought to be an important quality indicator in patients with hospitalized heart failure, its prognostic impact and comparison of patients who were readmitted beyond 30 days has not been investigated. We assessed early (0–30 days) versus midrange (31–90 days) readmission in terms of incidence and distribution, and elucidated whether the timing of readmission could have a different prognostic significance. Methods and Results We examined patients with hospitalized heart failure registered in the WET ‐ HF (West Tokyo Heart Failure) registry. The primary outcomes analyzed were all‐cause death and HF readmission. Data of 3592 consecutive patients with hospitalized heart failure (median follow‐up, 2.0 years [interquartile range, 0.8–3.1 years]; 39.6% women, mean age 73.9±13.3 years) were analyzed. Within 90 days after discharge, HF readmissions occurred in 11.1% patients. Of them, patients readmitted within 30 and 31 to 90 days after discharge accounted for 43.1% and 56.9%, respectively. Independent predictors of 30‐ and 90‐day readmission were almost identical, and after adjustment, readmission for HF within 90 days (including both early and midrange readmission) was an independent predictor of subsequent all‐cause death (hazard ratio, 2.36; P Conclusions Among patients readmitted within 90 days after index hospitalization discharge, ≈60% of readmission events occurred beyond 30 days. Patients readmitted within 90 days had a higher risk of long‐term mortality, regardless of the temporal proximity of readmission to the index hospitalization.

Background Depression and anxiety are common mental health problems that are strongly associated with sleep disturbances, according to community-based researches. However, this association has not been investigated among patients admitted for cardiovascular diseases (CVDs). We examined the prevalence of depression and anxiety in inpatients with various CVDs and their association with sleep disturbances. Materials and methods This cross-sectional study included 1294 patients hospitalized for CVDs in a Japanese university hospital were evaluated for their mental status using the Hospital Anxiety and Depression Scale (HADS), for sleep-disordered breathing (SDB) using pulse oximetry, and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). Results Patient characteristics were as below: mean age, 63.9±14.7 years; 25.7% female. Overall, 18.9% had depression (HADS-depression≥8) and 17.1% had anxiety (HADS-anxiety≥8). The presence of depression was associated with female sex, older age, higher plasma brain natriuretic peptide level, lower estimated glomerular filtration rate, and the prevalence of heart failure. Overall, 46.5% patients were categorized as having a poor sleep quality (PSQI>5), and 28.5% patients had SDB (3% oxygen desaturation index>15). Although depression and anxiety were not associated with SDB, they were independently associated with poor sleep quality (OR = 3.09, 95% CI 2.19–4.36; OR = 3.93, 95% CI 2.71–5.69, respectively). Conclusions Depression and anxiety were not uncommon in patients with CVDs. Poor sleep quality could be an important risk factor linked to psychological disturbances.

Background Heart failure (HF) is a highly prevalent, heterogeneous, and life-threatening condition. Precise prognostic understanding is essential for effective decision making, but little is known about patients’ attitudes toward prognostic communication with their physicians. Methods and Results We conducted a questionnaire survey, consisting of patients’ prognostic understanding, preferences for information disclosure, and depressive symptoms, among hospitalized patients with HF (92 items in total). Individual 2-year survival rates were calculated using the Seattle Heart Failure Model, and its agreement level with patient self-expectations of 2-year survival were assessed. A total of 113 patients completed the survey (male 65.5%, median age 75.0 years, interquartile range 66.0–81.0 years). Compared with the Seattle Heart Failure Model prediction, patient expectation of 2-year survival was matched only in 27.8% of patients; their agreement level was low (weighted kappa = 0.11). Notably, 50.9% wished to know “more,” although 27.7% felt that they did not have an adequate prognostic discussion. Compared with the known prognostic variables (eg, age and HF severity), logistic regression analysis demonstrated that female and less depressive patients were associated with patients’ preference for “more” prognostic discussion. Conclusions Patients’ overall prognostic understanding was suboptimal. The communication process requires further improvement for patients to accurately understand their HF prognosis and be involved in making a better informed decision.

Background: Worsening renal function (WRF) during the hospitalization has been recognized as a predictor for worse outcomes in patients with acute heart failure (AHF). However, in recent years, elevation of serum creatinine during the acute phase of the treatment is accepted as a sign of efficient decongestion. Herein, we aimed to evaluate the phenotypic difference in this heterogeneous phenomenon by using clustering analysis. Methods: A total of 4000 patient data from the West-Tokyo Heart Failure Registry, a multicenter, prospective registry for consecutive AHF hospitalization were analyzed. Within 632 patients identified to have WRF (17%; defined as elevation of eGFR over 20 percent during the hospitalization), we applied two-step clustering analysis of phenotypic data (37 variables) to define and characterize phenotypically distinct population. After identification of phenotypically distinct subgroups, survival analysis with Cox proportional hazard was conducted to elucidate the impact of the classification on composite outcomes of heart failure re-hospitalization and all cause death. Results: The analysis identified four distinct populations (group 1-4) that distinctly differed in terms of clinical characteristics: Group1 composed of patients with reduced ejection fraction (EF), while group 2 to 4 were composed of patients with mid-range and preserved EF. Group 1 patients also had lowest eGFR and blood pressure at the time of admission. Group 1 and 2 patients were younger, but had higher plasma BNP compared to 3 and 4. Among these subgroups, group 1 had the worst, and group 2 had the most favorable prognosis. The difference in prognosis between these two groups was significant after adjustments with known prognostic factors (hazard ratio, 0.58; 95 percent confidence interval, 0.35-0.97). Conclusion: WRF represents heterogeneous condition; our clustering analysis revealed four phenotypically distinct population with significant difference in their prognosis. Further investigation is needed to assess its therapeutic implication.

IMPORTANCE: Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear. OBJECTIVE: To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). DESIGN, SETTING, AND PARTICIPANTS: This study used data from the Japan Cardiovascular Database–Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score–matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019. EXPOSURES: Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI. MAIN OUTCOMES AND MEASURES: Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition. RESULTS: Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight

This observational study aimed to examine the extent of early invasive strategy (EIS) utilization in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) according to the National Cardiovascular Data Registry (NCDR) CathPCI risk score, and its association with clinical outcomes. Using a prospective multicenter Japanese registry, 2968 patients with NSTE-ACS undergoing percutaneous coronary intervention within 72 hours of hospital arrival were analyzed. Multivariable logistic regression analyses were performed to determine predictors of EIS utilization. Additionally, adverse outcomes were compared between patients treated with and without EIS. Overall, 82.1% of the cohort (n = 2436) were treated with EIS, and the median NCDR CathPCI risk score was 22 (interquartile range: 14&ndash, 32) with an expected 0.3&ndash, 0.6% in-hospital mortality. Advanced age, peripheral artery disease, chronic kidney disease or patients without elevation of cardiac biomarkers were less likely to be treated with EIS. EIS utilization was not associated with a risk of in-hospital mortality, yet, it was associated with an increased risk of acute kidney injury (AKI) (adjusted odds ratio: 1.42, 95% confidence interval: 1.02&ndash, 2.01) regardless of patients&rsquo, in-hospital mortality risk. Broader use of EIS utilization comes at the cost of increased AKI development risk, thus, the pre-procedural risk-benefit profile of EIS should be reassessed appropriately in patients with lower mortality risk.

Background: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators. Methods: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality. Results: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P=0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures. Conclusions: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators. Trial registration: UMIN-CTR identifier, UMIN000013128

In diffuse idiopathic hyperostosis (DISH), the ankylosed spine becomes susceptible to spinal fractures and spinal cord injuries due to the long lever arms of the fractured segments that make the fracture extremely unstable. The aim of this retrospective multicenter study was to examine the differences in DISH-affected spine fractures according to fracture level. The data of 285 cases with fractures of DISH-ankylosed segments diagnosed through computed tomography (CT) imaging were studied and the characteristics of 84 cases with cervical fractures were compared to 201 cases with thoracolumbar fractures. Examination of the CT images revealed that cervical fracture cases were associated with ossification of the posterior longitudinal ligament and had fractures at the intervertebral disc level, while thoracolumbar fracture cases were associated with ankylosing of the posterior elements and had fractures at the vertebral body. Neurologically, cervical fracture cases had a higher ratio of spinal cord injury leading to higher mortality, while thoracolumbar fracture cases had lower rates of initial spinal cord injury. However, a subset of thoracolumbar fracture cases suffered from a delay in diagnosis that led to higher rates of delayed neurological deterioration. Some of these thoracolumbar fracture cases had no apparent injury episode but experienced severe neurological deterioration. The information provided by this study will hopefully aid in the education of patients with DISH and raise the awareness of clinicians to potential pitfalls in the assessment of DISH trauma patients.

Diuretics are the cornerstone therapy for acute heart failure (AHF) but can lead to various electrolyte disturbances and inversely affect the patients' outcome. We aimed to evaluate whether (1) the dose of loop diuretics could predict hospital-acquired hyponatremia (HAH) during AHF treatment, (2) addition of thiazide diuretics could affect development of HAH, and (3) assess their impact on long-term outcomes.We analyzed the subjects enrolled in the multicenter AHF registry (WET-HF). Risk of HAH, defined as hyponatremia at discharge with normonatremia upon admission, was evaluated based on oral non-potassium-sparing diuretics via multivariate logistic regression analysis. Additionally, we performed one-to-one matched analysis based on propensity scores for thiazide diuretics use and compared long-term mortality.Of total 1163 patients (mean age 72.6±13.6 years, male 62.6%), 92 (7.9%) had HAH. Compared with low-dose loop diuretics users (40mg; without thiazide diuretics), risks for developing HAH were significantly higher in patients with thiazide diuretics, regardless of the dose of loop diuretics (OR 2.67, 95% CI 1.13-6.34 and OR 2.31, 95% CI 1.50-5.13 for low- and high-dose loop diuretics, respectively). The association was less apparent in patients without thiazide diuretics (OR 1.29, 95% CI 0.73-2.27 for high-dose loop diuretics alone). Among 206 matched patients, all-cause and cardiac mortality rate was 27% and 14% in non thiazide diuretics users and 50% and 30% in thiazide diuretics users, respectively (HR 2.46, 95% CI 1.29-4.69, p=0.006 and HR 2.50, 95% CI 1.10-5.67, p=0.028, respectively) during a mean 19.3 months of follow-up.Thiazide diuretics use, rather than loop diuretics dose, was independently associated with HAH; and mortality was higher in thiazide diuretics users even after statistical matching.

Aims: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan. Methods and results: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in‐hospital (4.8% vs. 2.5%) and 180‐day (20.7% vs. 9.5%) mortality. The model c‐statistics for the published/derivation (range 0.70–0.76) and Japanese (range 0.75–0.77) cohorts were similar and higher than for the UK (0.62–0.75) but models consistently overestimated mortality in Japan. For in‐hospital mortality, the OPTIMIZE‐HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c‐indices: 0.75 (0.74–0.77); 0.75 (0.68–0.81) and 0.77 (0.70–0.83), respectively], and least overestimated mortality in Japan. For 180‐day mortality, the c‐statistics for the ASCEND‐HF model were similar in published/derivation (0.70) and UK [0.69 (0.64–0.74)] cohorts but higher in Japan [0.75 (0.71–0.79)]; calibration was good in the UK but again overestimated mortality in Japan. Conclusion: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.

Background:\ud \ud Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK.\ud Methods:\ud \ud Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP.\ud Results:\ud \ud Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years; p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m2; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg; p

Study design Retrospective analysis of prospective data. Objective The aim of this study was to reveal baseline predictors of persistent postlaminoplasty neck pain. Summary of background data Axial neck pain is one of the most common complications after cervical laminoplasty; however, baseline predictors of persistent postlaminoplasty neck pain are unclear. Methods We analyzed data from 156 patients who completed a 2-year follow-up after double-door laminoplasty for degenerative cervical myelopathy. Patients rated the average intensity of axial neck pain in the last month using an 11-point numerical rating scale preoperatively and at the 2-year follow-up. The dependent variable was the presence of moderate-to-severe neck pain (numerical rating scale ≥4) at the 2-year follow-up. The independent variables included patient characteristics, baseline radiological parameters, surgical variables, baseline axial neck pain intensity, and baseline functions, which were measured by the Japanese Orthopaedic Association score and the Short Form-36 survey (SF-36). Logistic regression analysis was performed to identify independent predictors of moderate-to-severe neck pain after laminoplasty. Results At the 2-year follow-up, 51 patients (32%) had moderate-to-severe neck pain, and 106 patients (68%) had no or mild pain. Univariate analysis revealed that the ratio of cervical anterolisthesis, ratio of current smoking, baseline neck pain intensity, and baseline SF-36 Mental Component Summary differed significantly between the groups. Multivariate logistic regression analysis showed that independent predictors of moderate-to-severe neck pain at the 2-year follow-up include the presence of anterolisthesis, current smoking, moderate-to-severe baseline neck pain, and lower SF-36 Mental Component Summary. The presence of anterolisthesis and moderate-to-severe baseline neck pain were also associated with significantly poorer physical function after surgery. Conclusion The presence of anterolisthesis was associated not only with the highest odds ratio of persistent neck pain but also with significantly poorer functional outcomes. Indications for cervical laminoplasty should be carefully determined in patients with cervical anterolisthesis. Level of evidence 4.

Both the obesity paradox and blood pressure (BP) paradox remain ill defined. Because both obesity and hypertension are well-known predictors of coronary artery disease (CAD) and acute heart failure (HF), in the present study, we compared the obesity paradox and the BP paradox between patients with acute HF with and without a history of CAD. A multicenter retrospective study was conducted on 3,204 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; multivariate Cox regression analysis with backward stepwise selection was then used to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 27% of patients had a history of CAD, and the all-cause in-hospital mortality rate was 5%. In-hospital mortality was significantly lower for patients with obesity than in those without obesity (log-rank, p = 0.033). However, this obesity paradox disappeared in the group with HF and CAD (log-rank, p = 0.740). In contrast, in-hospital mortality was significantly lower for patients with high BP at admission, regardless of the presence of a history of CAD (log-rank, p 0.001 for both groups). In conclusion, a history of CAD canceled the obesity paradox in patients with acute HF, whereas the BP paradox persisted regardless of a history of CAD.