Background Although multiorgan networks are involved in the pathophysiology of heart failure (HF), interactions of the heart and the liver have not been fully understood. Hepatokines, which are synthesized and secreted from the liver, have regulatory functions in peripheral tissues. Here, we aimed to clarify the clinical impact of the hepatokine selenoprotein P in patients with HF. Methods and Results This is a prospective observational study that enrolled 296 participants consisting of 253 hospitalized patients with HF and 43 control subjects. First, we investigated selenoprotein P levels and found that its levels were significantly higher in patients with HF than in the controls. Next, patients with HF were categorized into 4 groups according to the presence of liver congestion using shear wave elastography and liver hypoperfusion by peak systolic velocity of the celiac artery, which were both assessed by abdominal ultrasonography. Selenoprotein P levels were significantly elevated in patients with HF with liver hypoperfusion compared with those without but were not different between the patients with and without liver congestion. Selenoprotein P levels were negatively correlated with peak systolic velocity of the celiac artery, whereas no correlations were observed between selenoprotein P levels and shear wave elastography of the liver. Kaplan‐Meier analysis demonstrated that patients with HF with higher selenoprotein P levels were significantly associated with increased adverse cardiac outcomes including cardiac deaths and worsening HF. Conclusions Liver‐derived selenoprotein P correlates with hepatic hypoperfusion and may be a novel target involved in cardiohepatic interactions as well as a useful biomarker for predicting prognosis in patients with HF.

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obstructive sleep apnea (OSA). CPAP is strongly recommended for patients with an apnea hypopnea index (AHI) ≥30, patients with an AHI ≥15 who have prior CVD history, and/or CVD risks or clinical symptoms due to SDB (class I, evidence level B). 15 However, after the 2010 JCS guidelines were published, a recent randomized controlled trial (RCT) focusing on treatment using CPAP, published in 2016, failed to demonstrate a beneficial prognostic impact on the primary or secondary setting of CVD. 16-20 In addition, adaptive servo-ventilation (ASV) is globally used to treat central sleep apnea (CSA) in HF patients, 21 and was originally used to manage congestive HF in Japan. Due to the evidence from the treatment of sleep-disordered breathing with predominant central sleep apnea by adaptive servo ventilation in patients with heart failure (SERVE-HF) S leep-disordered breathing (SDB) is a major health problem worldwide, and it is related to a high risk of cardiovascular disease (CVD), including sudden death, atrial fibrillation (AF), stroke, and coronary artery disease (CAD), leading to heart failure (HF). 1-9 SDB is highly prevalent 10-14 and is associated with an elevated risk of serious cardiovascular outcomes. 2,3,5 In consideration of high concurrent risk of CVD with SDB, the Japanese Circulation Society (JCS) has published the "Guidelines for Diagnosis and Treatment of Sleep-Disordered Breathing in Cardiovascular Medicine (the 2010 JCS guidelines)", and appropriate screening, management and treatment of SDB in patients with CVD have been recommended. 15 With regard to treatment for SDB, continuous positive airway pressure (CPAP) is the gold standard therapy for

Background: It has recently been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition, which excludes 6 rare criteria, is comparable to the original ARC-HBR definition in predicting major bleeding in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention. In this study, we investigated whether the simplified ARC-HBR definition could be applied to patients with heart failure (HF) to identify those at high bleeding risk (HBR). Methods and Results:In all, 2,437 patients hospitalized for HF were enrolled in this study. Patients were divided into 2 groups based on the simplified ARC-HBR definition: those at HBR (n=2,026; 83.1%) and those not (non-HBR group; n=411; 16.9%). The HBR group was older (72.0 vs. 61.0 years; P<0.001) and had a lower prevalence of CAD (31.1% vs. 36.5%; P=0.034) than the non-HBR group. Kaplan-Meier analysis showed that post-discharge bleeding events defined as hemorrhagic stroke or gastrointestinal bleeding were more frequent in the HBR than non-HBR group (log-rank P<0.001). The simplified ARC-HBR definition accurately predicted bleeding events (Fine-Gray model; hazard ratio 2.777, 95% confidence interval 1.464-5.270, P=0.001). Conclusions:The simplified ARC-HBR definition predicts a high risk of bleeding events in patients with HF.

Background: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC). Methods and Results:This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25-35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality. Conclusions:Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.