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Abstract Aims Congestive heart failure (HF) is a common complication in patients with acute myocardial infarction (AMI). The estimated plasma volume status [ePVS = (100 − haematocrit)/haemoglobin] is used as the blood plasma volume index to determine the presence of congestion in patients with HF. However, the clinical impact of ePVS at discharge in patients with AMI remains unclear. This study aimed to investigate whether ePVS at discharge could determine the long‐term prognosis in patients with AMI. Methods and results We retrospectively identified patients with AMI with ePVS measured at discharge between January 2012 and December 2020. The primary endpoint was post‐discharge all‐cause death. The patients were divided into two groups according to an ePVS cut‐off value of 5.5%, which is commonly used in HF. In total, 1012 patients with AMI were included. The median age was 70 years (range, 61–78 years), and 76.4% of the patients were male. The ePVS > 5.5% (high‐ePVS) group included 365 patients (36.1%), and the all‐cause mortality rate in the total cohort was 17.7%. The log‐rank test revealed that the high‐ePVS group had a significantly higher rate of all‐cause death than the ePVS ≤ 5.5% (low‐ePVS) group (P

Abstract This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30–10.8; P 75 years, left ventricular ejection fraction

Abstract Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (

Abstract Aims Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype‐dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model‐based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. Methods and results We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA‐HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian–Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all‐cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m2) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1–3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. Conclusions ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).

Abstract Clinical scenario 1 (CS1) is acute heart failure (HF) characterized by transient systolic blood pressure (SBP) elevation and pulmonary congestion. Although it is managed by vasodilators, the molecular mechanism remains unclear. The sympathetic nervous system plays a key role in HF, and desensitization of cardiac β-adrenergic receptor (AR) signaling due to G protein-coupled receptor kinase 2 (GRK2) upregulation is known. However, vascular β-AR signaling that regulates cardiac afterload remains unelucidated in HF. We hypothesized that upregulation of vascular GRK2 leads to pathological conditions similar to CS1. GRK2 was overexpressed in vascular smooth muscle (VSM) of normal adult male mice by peritoneally injected adeno-associated viral vectors driven by the myosin heavy chain 11 promoter. Upregulation of GRK2 in VSM of GRK2 overexpressing mice augmented the absolute increase in SBP (+ 22.5 ± 4.3 mmHg vs. + 36.0 ± 4.0 mmHg, P

Abstract Diagnosis of calcified nodules (CNs) is critical in the proper management of coronary artery disease, but CNs can be detected only using intracoronary imaging modalities. This study aimed to investigate the ability of coronary computed tomography angiography (CCTA) in predicting CNs detected using optical coherence tomography (OCT). From 138 patients who underwent OCT-guided percutaneous coronary intervention (PCI) after CCTA evaluation, 141 PCI target vessels were retrospectively enrolled and classified into CN (12 vessels/11 patients; CNs in the PCI culprit lesion) and non-CN (129 vessels/127 patients; without CNs) groups based on the OCT analysis. Retrospective CCTA analysis revealed significantly higher coronary artery calcification score (CACS), calcified plaque volume (CPV), and maximum calcified plaque area (MCPA) of the target vessel in the CN group than in the non-CN group. Receiver operating characteristic curve indicated that CACS ≥ 162 (area under the ROC curve (AUC 0.76, sensitivity 83.3%, specificity 54.2%), CPV ≥ 20.1 mm3 (AUC 0.83, sensitivity 100%, specificity 57.3%), and MCPA ≥ 4.51 mm2 (AUC 0.87, sensitivity 91.7%, specificity 78.3%) were the best cutoff values for predicting CNs. MCPA showed the highest AUC among all the CCTA parameters. In conclusion, CCTA is useful for predicting OCT-detected CNs in PCI target vessels.

Abstract Aims Cancer therapy‐related cardiac dysfunction (CTRCD) is commonly reported, but its histopathology, mechanisms, and risk factors are not known. We aimed to clarify the histopathology and mechanisms of CTRCD to identify risk factors. Methods and results We performed myocardial histopathological studies on 13 endomyocardial biopsies from CTRCD patients, 35 autopsied cancer cases with or without cardiac dysfunction, and controls without cancer (10 biopsies and 9 autopsies). Cardiotoxicity risk scores were calculated based on medication; and patient‐related risk factors, fibrosis, and cardiomyocyte changes were scored; and p53 and H3K27ac histone modification were evaluated by histological score (H‐score). In the biopsy cases, all histopathological changes and the p53 evaluation were significantly higher in the CTRCD group than in the controls [p53 H‐score; 63 (9.109) vs. 33 (5.099), P 4.2 years), cellular abnormalities and p53 trended to a positive correlation and cardiotoxicity risk scores and p53 positively correlated (r = 0.95, P

Abstract Background When performing an electrical isolation of ipsilateral pulmonary veins (PVs) for atrial fibrillation, physicians often need additional radiofrequency (RF) ablation in the carina region between the superior and inferior PVs to achieve a right PV isolation because of intercaval bundles between the right PVs and right atrium (RA). We compared the efficacy of a high‐power and short‐duration ablation guided by unipolar signal modification (UM) with the conventional method (CM) for ablating epicardial connections between the right PV carina and RA. Methods The study subjects consisted of patients who underwent an initial box isolation of atrial fibrillation from January 2015 to December 2019 at Nara Medical University Hospital. Among these patients, 94 and 65 patients who met the criteria were assigned to the CM and UM groups, respectively. We retrospectively analyzed the anterior ablation line of the right PV using an electroanatomical mapping system. Patients whose initial ablation line included the right PV carina were excluded. Results Six and seven patients were, respectively, excluded from the CM and UM groups. Among 88 CM group patients, 21 needed additional right PV carina ablation, while among 58 UM group patients, 30 needed additional right PV carina ablation (p = .001). No anatomical factors were associated with the additional right PV carina ablation. Conclusions Compared to the CM group, a box isolation was less achievable without RF ablation at the right PV carina in the UM group. We should consider a long‐duration ablation for epicardial connections between the right PV carina and RA.

Background The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long‐term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all‐cause death. Secondary end points were (1) the composite of all‐cause death and HF readmission, and (2) HF readmission in a time‐to‐event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, 5.5%, ≤5.5%) values at discharge: high‐FEUN/low‐ePVS, high‐FEUN/high‐ePVS, low‐FEUN/low‐ePVS, and low‐FEUN/high‐ePVS groups. During a median follow‐up period of 28.1 months, there were 173 all‐cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan–Meier curve analysis showed that the high‐FEUN/low‐ePVS group had a better prognosis than the other groups (log‐rank test, P

Abstract Aims Patients undergoing dialysis, even those without coronary artery disease or valvular abnormalities, sometimes present with reduced heart function, which resembles dilated cardiomyopathy (DCM). This condition is known as uraemic cardiomyopathy (UCM). The mechanisms of UCM development are not fully understood. Previous studies demonstrated that the balance between placental growth factor (PlGF) and fms‐like tyrosine kinase‐1 (Flt‐1) is correlated with renal function, and PlGF/Flt‐1 signalling is involved in the development of cardiovascular diseases in patients with chronic kidney disease. This study was conducted to evaluate the pathogenesis of UCM and clarify the differences in the mechanisms of UCM and DCM by using human endomyocardial biopsy and blood samples. Methods and results The clinical and pathological features of 30 patients on dialysis with reduced cardiac function [left ventricular ejection fraction (LVEF) ≤50%] (UCM group; mean age: 58.5 ± 9.4 years and LVEF: 39.1 ± 7.2%), 196 DCM patients (DCM group; mean age: 62.7 ± 14.0 years and LVEF: 33.5 ± 8.8%) as controls with reduced cardiac function (LVEF ≤ 45%), and 21 patients as controls with normal cardiac function (control group; mean age: 56.2 ± 19.3 years and LVEF: 67.5 ± 6.7%) were analysed. The percentage of the interstitial fibrosis area in the UCM group was greater than that in the DCM group (P = 0.045). In UCM patients, the percentage of the interstitial fibrosis area was positively correlated with the duration of renal replacement therapy (P

Abstract Aims Patients who survive acute myocardial infarction (AMI) are at risk of being rehospitalized owing to the occurrence of acute decompensated heart failure (HF). However, the clinical characteristics of HF after AMI, especially the frequency of each HF subtype, are unclear. Methods and results We retrospectively studied 1055 patients with AMI. We excluded 257 patients, who were admitted >48 h after the onset of AMI, died during hospitalization or after discharge, and whose echocardiogram data at index hospitalization and follow‐up data were missing. The remaining 798 patients (mean age: 66.5 ± 11.7 years) were investigated for a mean follow‐up period of 4.9 years. All patients underwent emergency coronary angiography. The mean maximum creatine kinase levels were 2898 ± 2627 IU/L, and mean left ventricular ejection fraction (LVEF) was 58.9 ± 10.2%. Eighty‐one patients (10.2%) were rehospitalized because of unexpected worsening of HF. Echocardiography data were available for 74 of the 81 patients during the acute phase of the second hospitalization, of which 30, 20, and 24 patients (41%, 27%, and 32%, respectively) were diagnosed as having HF with preserved LVEF (LVEF ≥ 50%), HF with mid‐range LVEF (40% ≤ LVEF

Abstract Iron is an essential trace element in the body. However, in heart failure (HF), iron is only recognized as the cause of anemia. Actually, iron itself affects myocardial exercise tolerance and cardiac function via mitochondrial function. Therefore, it is necessary to clarify the pathological significance of iron in acute HF, irrespective of concomitant anemia. We investigated the impact of serum iron level at discharge on the prognosis of 615 patients emergently admitted with acute decompensated HF (ADHF). Patients were divided into two groups according to the median level of serum iron (62 µg/dL). The endpoint was the composite outcome, which included all-cause mortality and readmission for HF. During the mean follow-up period of 32.1 months, there were 333 events. Kaplan–Meier analysis showed that the incidence of the composite outcome was significantly higher in the Low iron group (P

Abstract Aims This study aimed to investigate the influence of climatic factors on the onset of Takotsubo syndrome (TTS). Methods and results We performed a retrospective nationwide study among patients registered in the Japanese Registry of All Cardiac and Vascular Diseases and Diagnosis Procedure Combination (JROAD–DPC) discharge database, between 2012 and 2016. Before the analysis, a multicentre validation study was conducted for assessing the accuracy of the JROAD–DPC classification for TTS. First, we investigated the seasonal variation of incidences of TTS. Second, we analysed the associations between the incidence of TTS and climatic factors using the hierarchical Poisson regression modelling, and we also investigated the associations between typhoon landfalls and hospitalization for TTS, using the fixed‐effects conditional Poisson regression model. The sensitivity and specificity for diagnosis were 83% and 100%, respectively. Then we analysed 5643 patients with TTS. The mean patient age was 74 (standard deviation ± 11) years; 79% were female. TTS was diagnosed significantly more frequently in the summer and early autumn. The incidence of TTS was related to higher temperatures; adjusted incidence rate ratios were 1.46 [95% confidence interval (CI): 1.33–1.60, P 25°C, respectively. The incidence rate ratio for the first 2 days after a typhoon landfall was 1.85 (95% CI: 1.07–3.19; P = 0.03). Conclusions This study demonstrates distinct patterns of seasonal variation in the incidence of TTS, as well as a significant association between its onset and climatic factors, including typhoon landfalls.

Activation of the classical complement pathway plays a major role in regulating atherosclerosis progression, and it is believed to have both proatherogenic and atheroprotective effects. This study focused on C1q, the first protein in the classical pathway, and examined its potentialities of plaque progression and instability and its relationship with clinical outcomes. To assess the localization and quantity of C1q expression in various stages of atherosclerosis, immunohistochemistry, western blotting, and real-time polymerase chain reaction (PCR) were performed using abdominal aortas from eight autopsy cases. C1q immunoreactivity in relation to plaque instability and clinical outcomes was also examined using directional coronary atherectomy (DCA) samples from 19 patients with acute coronary syndromes (ACS) and 18 patients with stable angina pectoris (SAP) and coronary aspirated specimens from 38 patients with acute myocardial infarction. C1q immunoreactivity was localized in the extracellular matrix, necrotic cores, macrophages and smooth muscle cells in atherosclerotic lesions. Western blotting and real-time PCR illustrated that C1q protein and mRNA expression was significantly higher in advanced lesions than in early lesions. Immunohistochemical analysis using DCA specimens revealed that C1q expression was significantly higher in ACS plaques than in SAP plaques. Finally, immunohistochemical analysis using thrombus aspiration specimens demonstrated that histopathological C1q in aspirated coronary materials could be an indicator of poor medical condition. Our results indicated that C1q is significantly involved in atherosclerosis progression and plaque instability, and it could be considered as one of the indicators of cardiovascular outcomes.

Placental growth factor (PlGF) and its receptor, fms-like tyrosine kinase-1 (Flt-1), are important regulators involved in angiogenesis, atherogenesis, and inflammation. This review article focuses on the function of PlGF/Flt-1 signaling and its regulation by soluble Flt-1 (sFlt-1) in chronic kidney disease (CKD). Elevation of circulating sFlt-1 and downregulation of sFlt-1 in the vascular endothelium by uremic toxins and oxidative stress both exacerbate heart failure and atherosclerosis. Circulating sFlt-1 is inconsistent with sFlt-1 synthesis, because levels of matrix-bound sFlt-1 are much higher than those of circulating sFlt-1, as verified by a heparin loading test, and are drastically reduced in CKD.

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long‐term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post‐discharge all‐cause death. Patients were divided into two groups according to a FEUN cut‐off value of 35%, commonly used in pre‐renal failure. The FEUN

LMNA is one of the leading causative genes of genetically inherited dilated cardiomyopathy (DCM). Unlike most DCM-causative genes, which encode sarcomeric or sarcomere-related proteins, LMNA encodes nuclear envelope proteins, lamin A and C, and does not directly associate with contractile function. However, a mutation in this gene could lead to the development of DCM. The molecular mechanism of how LMNA mutation contributes to DCM development remains largely unclear and yet to be elucidated. The objective of this study was to clarify the mechanism of developing DCM caused by LMNA mutation.Methods and Results: We assessed cardiomyocyte phenotypes and characteristics focusing on cell cycle activity in mice with Lmna mutation. Both cell number and cell size were reduced, cardiomyocytes were immature, and cell cycle activity was retarded in Lmna mutant mice at both 5 weeks and 2 years of age. RNA-sequencing and pathway analysis revealed “proliferation of cells” had the most substantial impact on Lmna mutant mice. Cdkn1a, which encodes the cell cycle regulating protein p21, was strongly upregulated in Lmna mutants, and upregulation of p21 was confirmed by Western blot and immunostaining. DNA damage, which is known to upregulate Cdkn1a, was more abundantly detected in Lmna mutant mice. To assess the proliferative capacity of cardiomyocytes, the apex of the neonate mouse heart was resected, and recovery from the insult was observed. A restricted cardiomyocyte proliferating capacity after resecting the apex of the heart was observed in Lmna mutant mice.Conclusions: Our results strongly suggest that loss of lamin function contributes to impaired cell proliferation through cell cycle defects. The inadequate inborn or responsive cell proliferation capacity plays an essential role in developing DCM with LMNA mutation.

Abstract Aims Heart failure (HF) is classified into three types according to left ventricular ejection fraction (EF). The effect of blood pressure (BP) on the pathogenesis of each type is assumed to be different. However, the association between the prognosis of each type of HF and abnormal BP variations assessed by ambulatory BP monitoring (ABPM), such as nocturnal hypertension and the riser pattern, remains unclear. Methods and results We studied 325 consecutive patients with decompensated HF who were acutely admitted to our hospital and underwent ABPM at discharge. During a mean follow‐up of 30.0 months, 52 cardiovascular and 112 all‐cause deaths occurred. The Cox proportional hazards model showed that the mean values of 24 h, awake, and sleep‐time systolic BP (SBP), and abnormal 24 h ABPM patterns, such as nocturnal hypertension and non‐dipper pattern, were not associated with either all‐cause or cardiovascular mortality in patients with HF with reduced EF (HFrEF), HF with mid‐range EF (HFmrEF), or HF with preserved EF (HFpEF), except for sleep‐time SBP in HFrEF. However, the riser pattern was a significant and independent predictor of all‐cause and cardiovascular deaths in patients with HFpEF (hazard ratio, 2.01; 95% confidence interval, 1.12–3.62; 0.0200; and hazard ratio, 2.48; 95% confidence interval, 1.08–5.90; 0.0332, respectively). Sleep‐time pulse rate was similarly decreased in both the riser and non‐riser groups. Conclusions The riser pattern of SBP was associated with an increased risk of adverse outcomes among patients with HFpEF but not HFrEF or HFmrEF.

Background Insulin beneficially affects myocardial functions during myocardial ischemia. It increases glucose‐derived ATP production, decreases oxygen consumption, suppresses apoptosis of cardiomyocytes, and promotes the survival of cardiomyocytes. Patients with chronic heart failure generally have high insulin resistance, which is correlated with poor outcomes. The role of insulin in acute decompensated heart failure (ADHF) remains unclear. This study aimed to investigate the prognostic value of serum insulin level at the time of admission for long‐term outcomes in patients with ADHF. Methods and Results We enrolled 1074 consecutive patients who were admitted to our department for ADHF. Of these 1074 patients, we studied the impact of insulin on the prognosis of ADHF in 241 patients without diabetes mellitus. The patients were divided into groups according to low, intermediate, and high tertiles of serum insulin levels. Primary end points were all‐cause death and cardiovascular death. During a mean follow‐up of 21.8 months, 71 all‐cause deaths and 38 cardiovascular deaths occurred. Kaplan–Meier analysis showed that all‐cause and cardiovascular mortality was significantly higher in the low‐insulin group than those in the intermediate‐ and high‐insulin groups (log‐rank P=0.0046 and P=0.038, respectively). Moreover, according to the multivariable analysis, low serum insulin was an independent predictor of all‐cause and cardiovascular mortality (hazard ratio, 2.37 [95% CI, 1.24–4.65; P=0.009] and 2.94 [95% CI, 1.12–8.19; P=0.028], respectively). Conclusions Low serum insulin levels were associated with increased risk of all‐cause and cardiovascular death in ADHF patients without diabetes mellitus.

Background Little evidence is available about the number of cardiologists required for appropriate treatment of heart failure (HF). Our objective was to determine the association between the number of cardiologists per cardiology beds for treating patients with acute HF and in‐hospital mortality. Methods and Results This was a cross‐sectional study, and we used the Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination discharge database. The data of patients with HF on emergency admission from April 1, 2012, to March 31, 2014, were extracted. The patients were categorized into 4 groups by the quartiles of the numbers of cardiologists per 50 cardiovascular beds (first group: median, 4.4 [interquartile range, 3.5–5.0]; second group: median, 6.7 [interquartile range, 6.5–7.5]; third group: median, 9.7 [interquartile range, 8.8–10.1]; and fourth group: median, 16.7 [interquartile range, 14.0–23.8]). Using multilevel mixed‐effect logistics regression, we determined adjusted odds ratios for in‐hospital mortality. We identified 154 290 patients with HF on emergency admissions. There were 29 626, 36 587, 46 451, and 41 626 patients in the first, second, third, and fourth groups, respectively. HF severity, on the basis of New York Heart Association classification, was similar in the 3 groups. Adjusted odds ratios (95% CIs) for in‐hospital mortality were 0.92 (0.82–1.04; P=0.20), 0.82 (0.72–0.92; P

BackgroundUrinary neutrophil gelatinase‐associated lipocalin (U‐NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U‐NGAL on the first day of admission for the occurrence of acute kidney injury and long‐term outcomes in acute decompensated heart failure patients. Methods and ResultsWe studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U‐NGAL in 24‐hour urine samples collected on the first day of admission. Primary end points were all‐cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U‐NGAL levels (32.5 μg/gCr). The high‐U‐NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low‐U‐NGAL group (P=0.0012). Kaplan‐Meier analysis revealed that the high‐U‐NGAL group exhibited a worse prognosis than the low‐U‐NGAL group in all‐cause death (hazard ratio 2.07; 95%CI 1.38‐3.12, P=0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28‐4.24, P=0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13‐2.77, P=0.0119). The addition of U‐NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all‐cause mortality (P=0.0083). ConclusionsIn acute decompensated heart failure patients, an elevated U‐NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis.

Danon disease, an X-linked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A total of 39 patients (17 males, 22 females) from 20 families were identified in the analysis. All patients had cardiomyopathy. Of the 21 patients who died, 20 (95%) died of cardiac failure or sudden cardiac arrest. Most patients had hypertrophic cardiomyopathy. Wolf⁻Parkinson⁻White syndrome was present at a comparatively high incidence (54% in males, 22% in females). Only one female patient received a heart transplant, which is the most effective therapy. Histopathologically, all male patients showed autophagic vacuoles with sarcolemmal features in muscle. Half of the probands showed de novo mutations. Male patients showed completely absent LAMP-2 expression in muscle. In contrast, female patients showed decreased LAMP-2 expression, which is suggested to reflect LAMP-2 haploinsufficiency due to a heterozygous null mutation. In conclusion, Danon disease is an extremely rare muscular disorder in Japan. Cardiomyopathy is the most significant prognostic factor and the main cause of death. Our findings suggest that the present survey can extend our understanding of the clinical features of this rare disease.

Objective: This study aimed to reveal the clinical characteristics of patients with severe Takotsubo syndrome (TTS) who needed catecholamine support (CS) or mechanical support (MS) and to identify factors associated with serious illness and in-hospital mortality.Methods: This was a nationwide retrospective study that used claims data from the Japanese registry of all cardiac and vascular diseases and the diagnosis procedure combination registry, from April 2012 to March 2016. The patients with TTS were divided into severe TTS and mild TTS groups. The severe group was defined as patients who needed CS and/or MS.Results: Among 6169 patients with TTS, 1148 (18.6%) had severe TTS. No significant difference in age was found between the two groups; however, the number of female patients was significantly lower in the severe group than in the mild group. Among 130 patients who underwent MS, 22 and 108 patients required MS alone and both MS and CS, respectively. The 30-day mortality rate was significantly higher in the severe group than in the mild group (11.4% vs 2.6%, p<0.01) and increased with age. Of the patients with severe TTS, 65.6% died within 7 days. Multivariable analysis showed that male sex (OR 1.22, p=0.03), higher Charlson scores (OR 1.11, p<0.01), comorbid pneumonia (OR 1.68, p<0.01), comorbid sepsis (OR 6.02, p<0.01) and ambulance use (OR 2.01, p<0.01) were associated with severe TTS.Conclusions: The rate of severe TTS was 18.6% among 6169 patients registered in the Japanese nationwide database, and the 30-day mortality was higher in patients with severe TTS than in those with mild TTS (11.4% vs 2.6%). [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV) to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac; further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease.