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Abstract Aims Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care, most HF patients do not receive timely intervention due to the absence of a standardized method for identifying those in need of palliative care. The Needs Assessment Tool: Progressive Disease‐Heart Failure (NAT: PD‐HF) assesses the palliative care needs of patients with HF. However, its validity and reliability have yet to be fully examined. We aimed to assess the validity and reliability of the NAT: PD‐HF in Japanese patients with HF. Methods We prospectively enrolled 106 consecutive patients with chronic HF admitted to our university hospital between February 2023 and July 2023. Their caregivers (n = 95) and healthcare providers (n = 17) were also included. The NAT: PD‐HF was translated from English to Japanese using a forward–backward translation procedure and adapted based on Japanese cultural and medical backgrounds by our professional multidisciplinary team. We assessed the internal consistency of the Japanese NAT: PD‐HF version with Cronbach's alpha coefficient and the inter‐rater and test–retest reliabilities with Cohen's kappa coefficient. After using the tool, all participants were asked to complete a questionnaire about the tool to determine its validity. Results The proportion of female patients in this study was 47 (44%). The median age was 72 years [interquartile range (IQR) 59–81]. The median time spent assessing the patients' and their caregivers' needs using the Japanese NAT: PD‐HF was 14 min (IQR 12–17). The Cronbach's alpha coefficient was 0.82, and the minimum kappa coefficient was 0.77 for inter‐rater reliability and 0.88 for test–retest reliability. In total, 103 patients (97%) and all caregivers responded that the tool was easy to understand. One hundred (94%) patients and 89 (94%) caregivers felt that the tool would improve the quality of care, and 102 (96%) patients and 91 (96%) caregivers indicated that the discussions using this tool allowed them to confide in all their burdens and care needs. All healthcare providers expressed that this tool is helpful in understanding the burden and care needs of both patients and caregivers comprehensively. Conclusions The NAT: PD‐HF is a reliable and valid tool for Japanese patients with HF and their caregivers. This tool was very well accepted by patients, caregivers and healthcare providers to identify burdens and care needs.

Abstract Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT‐conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor‐alpha (TNF‐α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.

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 Aims Iron deficiency (ID) is a common co‐morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF. Methods and results We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT)

Abstract Aims Right‐sided filling pressure is elevated in some patients with heart failure (HF) and preserved ejection fraction (HFpEF). We hypothesized that right atrial pressure (RAP) would represent the cumulative burden of abnormalities in the left heart, pulmonary vasculature, and the right heart. Methods and results Echocardiography was performed in 399 patients with HFpEF. RAP was estimated from inferior vena cava morphology and its respiratory change [estimated right atrial pressure (eRAP)], and patients were divided according to eRAP (3 or ≥8 mmHg). Patients with higher eRAP displayed more severe abnormalities in LV diastolic function as well as right heart structure and function than those with normal eRAP. Cardiac deaths or HF hospitalization occurred in 84 patients over a median follow‐up of 19.0 months (interquartile range 6.7–36.9). The presence of higher eRAP was independently associated with an increased risk of the composite outcome (adjusted hazard ratio 2.20 vs. normal eRAP group, 95% confidence interval 1.34–3.62, P = 0.002). Kaplan–Meier curves separating the patients into four groups based on eRAP and E/e' ratio showed that event‐free survival varied among the groups, providing an incremental prognostic value of eRAP over E/e' ratio. The classification and regression tree analysis demonstrated that eRAP was the strongest predictor of the outcome followed by right ventricular dimension, E/e' ratio, and estimated right ventricular systolic pressure, stratifying the patients into four risk groups (incident rate 8.8–72.2%). Conclusions These data may provide new insights into the prognostic role of RAP in the complex pathophysiology of HFpEF and suggest the utility of eRAP for the risk stratification in patients with HFpEF.

Abstract Aims Increased left ventricular mass index (LVMI) disproportionate to electrocardiographic QRS voltage has been reported to be associated with cardiac fibrosis and amyloid infiltration to myocardium. This study aimed to assess whether the LVMI‐to‐QRS‐voltage ratio predicts clinical outcomes in heart failure with preserved ejection fraction (HFpEF). Methods and results The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of Japanese patients hospitalized with HFpEF (EF ≥ 50%). LVMI was assessed by echocardiography using the cube formula. QRS voltage was assessed by Sokolow–Lyon voltage criteria. We divided 290 patients in the registry who met inclusion criteria into five groups according to the quintile values of their LVMI‐to‐QRS‐voltage ratio. In the highest quintile group (≥71.8 g/m2/mV), approximately 50% of the patients had concentric hypertrophy and 30% had eccentric hypertrophy. These patients had the highest proportion of atrial fibrillation (61.4%) and history of pacemaker implantation (12.1%) among the five groups (P

Abstract Aims Although soluble interleukin 2 receptor (sIL‐2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL‐2R was associated with clinical outcomes and to clarify the relationship between sIL‐2R levels and disease activity in patients with CS. Methods and results We examined 83 consecutive patients with CS in our hospital who had available serum sIL‐2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all‐cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18F‐fluorideoxyglucose positron emission tomography/computed tomography. During a median follow‐up period of 2.96 (IQR 2.24–4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL‐2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL‐2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63–8.44, P = 0.002), even after adjustment for significant covariates. sIL‐2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27). Conclusions Increased sIL‐2R is associated with worse long‐term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.

Abstract Aims The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro‐B‐type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF. Methods and results Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP − proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow‐up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P

Abstract Anti‐mitochondrial antibody (AMA)‐positive myositis is an atypical inflammatory myopathy characterized by chronic progressive respiratory muscle weakness, muscular atrophy, and cardiac involvement. Arrhythmias, cardiomyopathy, and myocarditis have been reported as cardiac manifestations. Herein, we present the first report of a patient diagnosed with having AMA‐positive myositis with cardiac involvement mimicking cardiac sarcoidosis.

Abstract Aims The prognostic implication of left ventricular outflow tract velocity time integral (LVOT‐VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT‐VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF. Methods and results We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT‐VTI data on admission, from a prospective HFpEF‐specific multicentre registry. The primary outcome of interest was the composite of all‐cause death and readmission due to heart failure. During a median follow‐up period of 688 (interquartile range 162–810) days, the primary outcome occurred in 83 patients (39%). The optimal cut‐off value of LVOT‐VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT‐VTI was significantly associated with the primary outcome compared with higher LVOT‐VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT‐VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91–0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT‐VTI among clinical parameters (β coefficient = −0.61, P = 0.007). Furthermore, patients with lower LVOT‐VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001). Conclusions Lower admission LVOT‐VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT‐VTI on admission might be useful for categorizing a low‐flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients.

Evaluation of left ventricular filling pressure plays an important role in the clinical management of pulmonary hypertension. However, the accuracy of echocardiographic parameters for the determination of left ventricular filling pressure in the presence of pulmonary vascular lesions has not been fully addressed. We retrospectively investigated 124 patients with pulmonary hypertension due to pulmonary vascular lesions (noncardiac pulmonary hypertension group) and 113 patients with ischemic heart disease (control group) who underwent right heart catheterization and echocardiography. The noncardiac pulmonary hypertension group was subdivided into less-advanced and advanced groups according to median pulmonary vascular resistance. Pulmonary artery wedge pressure was determined as left ventricular filling pressure. As echocardiographic parameters of left ventricular filling pressure, the ratio of early- (E) to late-diastolic transmitral flow velocity (E/A), ratio of E to early-diastolic mitral annular velocity (E/e′), and left atrial volume index were measured. In the less-advanced noncardiac pulmonary hypertension and control groups, positive correlations were observed between pulmonary artery wedge pressure and late-diastolic transmitral flow velocity ( R = 0.41, P = 0.002 and R = 0.71, P

Background There is a limited evidence base to support the volume‐outcome relationship in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease (UPLMD). This study aimed to evaluate the relationship between institutional and operator volume and in‐hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease. Methods and Results We analyzed characteristics and clinical outcomes of 24 320 patients undergoing PCI for unprotected left main coronary artery disease at 1102 hospitals by 7244 operators using data from the Japanese nationwide J‐PCI Registry (National PCI Data Registry) between January 2014 and December 2017. We classified institutions and operators into quartiles based on the mean annual volume of PCI. A generalized linear mixed‐effects model was used to evaluate the association between institutional and operator PCI volume and in‐hospital outcomes. Among the 24 320 patients, 4027 (16.6%), 6147 (25.3%), and 14 146 (58.2%) presented with ST‐segment–elevation myocardial infarction, non–ST‐segment–elevation acute coronary syndrome, and stable ischemic heart disease; their crude in‐hospital mortality was 15%, 3.1%, and 0.3%, respectively. Compared with patients in the lowest quartile of institutional volume (1–216 PCIs/y), the adjusted odds ratio of in‐hospital death in patients in the second (217–323 PCIs/y), third (324–487 PCIs/y), and fourth (488–3015 PCIs/y) quartile of institutional volume was 0.75 (95% CI, 0.51–1.10; P=0.14), 0.87 (95% CI, 0.57–1.34; P=0.54), and 0.51 (95% CI, 0.30–0.86; P=0.01), respectively. These findings were consistent in rates of in‐hospital death or any complication. Conversely, operator PCI volume was not significantly associated with in‐hospital outcomes. Conclusions Institutional rather than operator‐based PCI volume was associated with better in‐hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease.

Abstract Background As the transvenous defibrillator lead is fragile and its failure may cause a life‐threatening event, reliable insertion techniques are required. While the extrathoracic puncture has been introduced to avoid subclavian crush syndrome, the reports on the long‐term defibrillator lead survival using this approach, especially the comparison with the cephalic cutdown (CD), remain scarce. We aimed to evaluate the long‐term survival of the transvenous defibrillator lead inserted by the extrathoracic subclavian puncture (ESCP) compared with CD. Methods Between 1998 and 2011, 324 consecutive patients who underwent an implantable cardioverter‐defibrillator (ICD) implantation in Hokkaido University Hospital were included. ICD leads were inserted by CD from 1998 to 2003 and by contrast venography‐guided ESCP thereafter. Lead failure was defined as a nonphysiologic high‐rate oversensing with abnormal lead impedance or highly elevated sensing and pacing threshold. Results Of 324 patients, CD was used in 37 (11%) and ESCP in 287 patients (89%). During the median follow‐up of 6.2 years (IQR:3.2‐8.3), 7 leads (2 in CD and 5 leads in ESCP group) failed. All patients with lead failure in ESCP group were implanted with either SJM Riata (n = 1) or Medtronic Fidelis lead (n = 4). Five‐year lead survival was 93.8% (CI95%:77.3‐98.4%) in CD compared with 99.1% (CI95%:96.6‐99.8%) in ESCP group (P = 0.903). Univariate Cox regression analysis showed that the use of Fidelis or Riata lead was the strong predictor of the ICD lead failure (HR 13.8, CI95%:2.9‐96.5; P = 0.001). Conclusions Contrast venography‐guided extrathoracic puncture ensures the reliable long‐term survival in the transvenous defibrillator leads.

Abstract Background Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. Methods The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J‐ACNES) trial was designed as a prospective, multicenter, randomized, open‐label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine‐18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. Results The results of this study are currently under investigation. Conclusion The J‐ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

Abstract Background Exercise intolerance is a common clinical feature and is linked to poor prognosis in patients with heart failure (HF). Skeletal muscle dysfunction, including impaired energy metabolism in the skeletal muscle, is suspected to play a central role in this intolerance, but the underlying mechanisms remain elusive. Lysine acetylation, a recently identified post‐translational modification, has emerged as a major contributor to the derangement of mitochondrial metabolism. We thus investigated whether mitochondrial protein acetylation is associated with impaired skeletal muscle metabolism and lowered exercise capacity in both basic and clinical settings of HF. Methods We first conducted a global metabolomic analysis to determine whether plasma acetyl‐lysine is a determinant factor for peak oxygen uptake (peak VO2) in HF patients. We then created a murine model of HF (n = 11) or sham‐operated (n = 11) mice with or without limited exercise capacity by ligating a coronary artery, and we tested the gastrocnemius tissues by using mass spectrometry‐based acetylomics. A causative relationship between acetylation and the activity of a metabolic enzyme was confirmed in in vitro studies. Results The metabolomic analysis verified that acetyl‐lysine was the most relevant metabolite that was negatively correlated with peak VO2 (r = −0.81, P < 0.01). At 4 weeks post‐myocardial infarction HF, a treadmill test showed lowered work (distance × body weight) and peak VO2 in the HF mice compared with the sham‐operated mice (11 ± 1 vs. 23 ± 1 J, P < 0.01; 143 ± 5 vs. 159 ± 3 mL/kg/min, P = 0.01; respectively). As noted, the protein acetylation of gastrocnemius mitochondria was 48% greater in the HF mice than the sham‐operated mice (P = 0.047). Acetylproteomics identified the mitochondrial enzymes involved in fatty acid β‐oxidation (FAO), the tricarboxylic acid cycle, and the electron transport chain as targets of acetylation. In parallel, the FAO enzyme (β‐hydroxyacyl CoA dehydrogenase) activity and fatty acid‐driven mitochondrial respiration were reduced in the HF mice. This alteration was associated with a decreased expression of mitochondrial deacetylase, Sirtuin 3, because silencing of Sirtuin 3 in cultured skeletal muscle cells resulted in increased mitochondrial acetylation and reduced β‐hydroxyacyl CoA dehydrogenase activity. Conclusions Enhanced mitochondrial protein acetylation is associated with impaired FAO in skeletal muscle and reduced exercise capacity in HF. Our results indicate that lysine acetylation is a crucial mechanism underlying deranged skeletal muscle metabolism, suggesting that its modulation is a potential approach for exercise intolerance in HF.

Background: Amiodarone is associated with a number of significant adverse effects, including elevated transaminase levels, pulmonary fibrosis, arrhythmia, and thyroid dysfunction. Although thyroid dysfunction is considered to be a common and potentially serious adverse effect of amiodarone therapy, the exact pathogenesis remains unknown because of its complex manifestations. Therefore, the prevalence of, and risk factors for, amiodarone-induced thyroid dysfunction in Japanese patients were investigated in the present study. Methods: A retrospective analysis of patients treated with amiodarone between January 2012 and December 2013 was performed. A total of 317 patients with euthyroidism, or subclinical hyperthyroidism or hypothyroidism, were enrolled in this study. Results: After being treated with amiodarone, 30 (9.5%) and 60 patients (18.9%) developed amiodarone-induced hyperthyroidism and amiodarone-induced hypothyroidism, respectively. Ten (33.3%) patients with amiodarone-induced hyperthyroidism and 40 (66.6%) with amiodarone-induced hypothyroidism were diagnosed within two years of the initiation of amiodarone therapy. Dilated cardiomyopathy (DCM) [Adjusted odds ratio (OR) 3.30 (95% confidence interval (CI): 1.26–8.90)], and cardiac sarcoidosis [Adjusted OR 6.47 (95% CI: 1.60–25.77)] were identified as predictors of amiodarone-induced hyperthyroidism. The baseline free thyroxine (T4) level [Adjusted OR 0.13 (95% CI: 0.03–0.68)], and thyroid-stimulating hormone (TSH) level [Adjusted OR1.47 (95% CI: 1.26–1.74)] were identified as predictors of amiodarone-induced hypothyroidism. Conclusion: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism.

Background Early detection for worsening renal function (WRF) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B‐type or brain natriuretic peptide (BNP) molecular form is associated with the occurrence of WRF. Methods and Results Circulating levels of proBNP, the NT‐proBNP (N‐terminal proBNP), and total BNP (proBNP+mature BNP) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (emBNP) concentration was calculated by subtracting proBNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One‐way repeated‐measures ANOVA was used to compare the changes of variables between the patients with and without WRF. In patients with acute decompensated HF (New York Heart Association class III–IV; 96%) hospitalized for HF, NT‐proBNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, emBNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT‐proBNP/emBNP molar ratios were elevated on day 3 after admission in the patients with WRF, before estimated glomerular filtration rate declined, but were unchanged in patients without WRF. On day 3 after hospital admission, NT‐proBNP/emBNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. Conclusions These findings suggest that elevation of NT‐proBNP/emBNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.

Background The JROAD‐DPC (Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination) is a nationwide claims database comprised of the Japanese DPC/Per Diem Payment System. This study aimed to investigate the relationship between prescription rates of guideline‐directed medications in each hospital and in‐hospital mortality among patients with acute myocardial infarction. Methods and Results A total of 61 838 Japanese patients from 741 hospitals with acute myocardial infarction between 2012 and 2013 were enrolled. The relationship between prescription rates of 4 guideline‐directed medications for acute myocardial infarction and in‐hospital mortality was analyzed. There were variations in the prescription ratio of β‐blockers on admission (median prescription rate 23% [interquartile range 11% to 38%]) and at discharge (51% [36% to 63%]), and of angiotensin converting enzyme/receptor blocker (60% [47% to 70%]). The highest prescription rate quartile of each medication was associated with a significantly lower mortality compared with the lowest prescription rate quartile (aspirin on admission, incidence rate ratio 0.67 [95% CI 0.61‐0.74], P

Background The diagnosis of cardiac sarcoidosis (CS) is challenging because endomyocardial biopsy has only a 20% to 30% sensitivity rate for diagnosis and it presents with similar clinical features of idiopathic dilated cardiomyopathy (DCM). Lymphatic vessel proliferation in pulmonary sarcoidosis has been previously demonstrated. In this study, we compared endomyocardial biopsy samples obtained from patients with CS and DCM to determine whether lymph vessel counts using D2‐40 immunostaining can be utilized as a complementary tool to distinguish CS from DCM. Methods and Results Endomyocardial biopsy tissues were obtained from 62 patients with CS (30 patients with a diagnosis made histologically, 32 patients with a diagnosis made clinically), and hematoxylin/eosin, Masson trichrome, and D2‐40 immunostaining were performed. Their results were compared with those from 53 patients with DCM. The histological CS group showed significantly increased lymphatic vessels (12.0 [4.0–40.0] versus 2.6 [1.9–3.4], P

Background: Landiolol effectively controls rapid heart rate in atrial fibrillation or flutter (AF/AFL) patients with left ventricular (LV) dysfunction. However, predicting landiolol Responders and Non-Responders and patients who will experience adverse effects remains a challenge. The aim of this study was to clarify the potential applicability of landiolol for rapid AF/AFL and refractory ventricular tachyarrhythmias (VTs) in patients with heart failure. Methods: A total of 39 patients with AF/AFL with ventricular response ≥120 bpm and 12 VTs were retrospectively enrolled. Landiolol Responders for rapid AF/AFL were defined as patients whose ventricular response was suppressed to less than 110 bpm or decreased by ≥20% from the initial heart rate after administration of landiolol. Responders for VTs were defined as patients with no recurrent VTs during the 24 h after the initiation of landiolol. Results: For AF/AFL, 29 patients (74%) were Responders. In nine patients (31%), AF was spontaneously terminated after starting landiolol. Eight Non-Responders (80%) needed to have AF terminated by cardioversion. Left ventricular ejection fraction (LVEF) at baseline was significantly associated with landiolol efficacy. For VTs, seven patients (58%) were Responders, and smaller LV diastolic and systolic diameters were associated with landiolol efficacy. Hypotension after landiolol treatment occurred in 5 of 51 patients, and lower LV systolic function was associated with the development of adverse events. Conclusions: Landiolol is effective in patients with heart failure not only due to rapid AF/AFL but also due to VTs. However, preserved LVEF is important for efficacy and safety in landiolol treatment.

Background: There is little evidence of the efficacy and safety of dabigatran in Japanese patients with non-valvular atrial fibrillation (NVAF). Methods and Results: We evaluated 300 consecutive patients with NVAF (68±11 years old, 209 men, 180 paroxysmal) who received 220 mg/day (203 patients) or 300 mg/day dabigatran (97 patients) at our hospital. Most patients (84%) had lower CHADS2 (congestive heart failure, hypertension, age>75 years, diabetes, stroke/transient ischemic attack) scores of 0 (n=60), 1 (n=114), or 2 (n=78) and lower HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition) scores of 0 (n=39), 1 (n=114), or 2 (n=103). The estimated creatinine clearance was 77±24 mL/min, which was inversely correlated to age (r2=0.48, p

Abstract Background Cardiac resynchronization therapy (CRT) has been widely used for the treatment of refractory heart failure (HF). However, the efficacy of CRT is not well established in class IV HF patients on inotropic support. Methods Twenty‐six patients (age 55±18 years, 73% men) with inotrope‐dependent HF were reviewed to evaluate the effectiveness of CRT in class IV HF patients on inotropic support. Results Intravenous inotropic therapy was administered for 72±56 days before CRT and consisted of dobutamine (n=24; 3.0±1.2 μg kg−1 min−1), dopamine (n=2; 4.5±2.1 μg kg−1 min−1), and/or milrinone (n=16; 0.12±0.09 μg kg−1 min−1). CRT did not produce significant reverse remodeling in eligible patients (left ventricular ejection fraction 23±7% to 25±9%; p=0.23, left ventricular end‐diastolic diameter 70±9 mm to 68±9 mm; p=0.14). After CRT device implantation, 13 (50%) patients experienced 1 or more episodes of ventricular tachyarrhythmia or sudden cardiac death. Twenty (77%) patients survived to hospital discharge with weaning from inotropic support (70±70 days after CRT implantation). The 1‐year survival rate was 81%. However, data from long‐term follow‐up showed that 68% of the study patients who attained survival discharge had an HF hospitalization event within the follow‐up period. Conclusion CRT did not result in significant reverse remodeling in patients with inotrope‐dependent class IV end‐stage HF. However, it contributed to dramatically improve the cardiovascular outcomes at least in the short‐term period in some patients.

BackgroundThe histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. Methods and ResultsThe numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209+ DC and CD68+ macrophages were more frequently observed (P