Search

Background Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver‐synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin‐A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin‐A in connecting cardiac–hepatic–peripheral interaction. Methods and Results We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin‐A by ELISA. Correlation analysis revealed a negative association between fetuin‐A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin‐A levels. During a median follow‐up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high‐risk subgroup with lower fetuin‐A (

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.

BackgroundThe Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) thrombotic risk score has been proposed to estimate the risk of stent thrombotic events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS thrombotic risk score for long term all-cause and cardiac mortalities, as well as hospitalization due to heart failure, has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS thrombotic risk score for all-cause and cardiac mortalities and hospitalization due to heart failure following PCI.Methods and resultsConsecutive 1,061 patients who underwent PCI were divided into three groups based on PARIS thrombotic risk score; low- (n = 320), intermediate- (n = 469) and high-risk (n = 272) groups. We followed up on all three groups for all-cause mortality, cardiac mortality and hospitalization due to heart failure. Kaplan-Meier analysis showed that all outcomes were highest in the high-risk group (P < 0.001, P = 0.022 and P < 0.001, respectively). Multivariate Cox proportional hazard analysis, adjusted for confounding factors, showed that the risk of all-cause mortality and hospitalization due to heart failure of the high-risk group were higher than those of the low-risk group (hazard ratios 1.76 and 2.14, P = 0.005 and P = 0.017, respectively).ConclusionThe PARIS thrombotic risk score is a significant prognostic indicator for all-cause mortality and hospitalization due to heart failure in patients after PCI.

Aims: We aimed to assess the associations of CAVI with exercise capacity in heart failure (HF) patients. In addition, we further examined their prognosis.Methods: We collected the clinical data of 223 patients who had been hospitalized for decompensated HF and had undergone both CAVI and cardiopulmonary exercise testing.Results: For the prediction of an impaired peak oxygen uptake (VO2) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. In the multivariate logistic regression analysis for predicting impaired peak VO2, high CAVI was found to be an independent factor (odds ratio 2.343, P = 0.045). We divided these patients based on CAVI: the low-CAVI group (CAVI < 8.9, n = 145) and the high-CAVI group (CAVI ≥ 8.9, n = 78). Patient characteristics and post-discharge cardiac events were compared between the two groups. The high-CAVI group was older (69.0 vs. 58.0 years old, P < 0.001) and had lower body mass index (23.0 vs. 24.1 kg/m2, P = 0.013). During the post-discharge follow-up period of median 1,623 days, 58 cardiac events occurred. The Kaplan–Meier analysis demonstrated that the cardiac event rate was higher in the high-CAVI group than in the low-CAVI group (log–rank P = 0.004). The multivariate Cox proportional hazard analysis revealed that high CAVI was an independent predictor of cardiac events (hazard ratio 1.845, P = 0.035).Conclusion: High CAVI is independently associated with impaired exercise capacity and a high cardiac event rate in HF patients.

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes. [ABSTRACT FROM AUTHOR]