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The aim of this study was to identify by classification and regression tree (CART) analysis groups of patients with different survival patterns in a population of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) by using standard methods of heart function assessment, as well as well as utilizing non-traditional approaches for determining hydration and nutritional status in HF patients—lung ultrasonography (LUS) and bioimpedance spectroscopy (BIS) analysis. Eligible patients with a left ventricular ejection fraction (LVEF) below 45% were identified via the daily echocardiography assessments. LUS was performed with patients in the supine position, for a total of 28 sites per complete examination. The hydration state and the body composition were assessed using a portable whole-body BIS device. Our study included 151 patients (69.2% males) with a mean age of 67.1 years. During the follow-up 53 (35.1%) patients died. Using the CART algorithm, we identified five groups based on serum sodium, the severity of NYHA class, serum urea and systolic blood pressure. When comparing the two models, the model derived from the CART analysis showed better predictive power than the conventional Cox model (c-index 0.790, 95% CI 0.723–0.857 vs. 0.736, 95%CI 0.664–0.807, p

Background and Aims Despite impressive improvements in treatment strategies, heart failure (HF) morbidity and mortality remain substantially high worldwide. Pulmonary congestion is considered the leading cause for hospital admissions and death among patients with HF. The aim of this study is to investigate if the effect of fluid status, as assessed by bioimpedance spectroscopy (BIS) on lung congestion is mediated by renal function, inflammation or cardiac function. Method This was a prospective observational study of outpatient adults referred for clinically indicated transthoracic echocardiograms at an academic hospital between 2016 and 2018. A left ventricular ejection fraction (LVEF) below 45% was required for inclusion (HFrEF). Mediation is the process through which an exposure causes disease. We hypothesized that some of the total effect of extracellular water (ECW) to intracellular water (ICW) (as assessed by bioimpedance) ratio on lung congestion (as assessed by lung ultrasonography) is mediated by C-reactive protein (CRP), left atrium volum index (LAVI) or estimated glomerular filtration rate (eGFR) – the mediators. Results Our study included 153 patients. The mean age and eGFR values of the population at baseline were 67.1 years and 66.5 ml/min/1.73m2. The mean median value for CRP was 25.6 (IQR 9.0-56.4) mg/L. Figure 1 depicts the structural equation models with the calculated magnitude of the direct and indirect effects of ECW/ICW on the B-lines number in our population. In this model, the fluid status has both direct and indirect effects on lung congestion. Specifically, it has a direct effect on LAVI and eGFR, which in turn have a direct effect on the number of B-lines. Therefore, the indirect effect mediated by LAVI and eGFR accounts for a significant proportion of 27.6% of the total effect of ECW/ICW on lung congestion Although ECW/ICW has a direct effect on inflammation, this doesn’t have any effect on renal function or lung congestion. Conclusion We show that eGFR and LAVI partly mediate the effect of ECW/ICW on lung congestion in patients with HFrEF. While the deleterious effects of fluid overload on lung congestion have long been recognized, this study provides evidence for a relationship of significant magnitude linking fluid overload with decreased eGFR and increased LAVI, which in turn lead to elevations in the B-lines number. This work was supported by a grant of the Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1.1-PD-2016-0287, within PNCDI III and by a grant of the “Grigore T. Popa” University of Medicine and Pharmacy, contract number 27505/2018.

Background and Aims Ferritin, is commonly used as a surrogate marker of iron storage in haemodialysis (HD) patients. However, besides being an indicator of iron storage, serum ferritin levels are closely influenced by non-iron related factors, such as systemic inflammation. The aim of this study is to assess the combined effect of serum ferritin and C-reactive protein (CRP) levels on all-cause and cardiovascular (CV) mortality in a large national cohort of HD patients. Method This is a retrospective study which included all patients that were on standard HD therapy in 34 Romanian Fresenius dialysis units at January 1st 2014. The main outcomes were all-cause and CV mortality. Patients were censored at December 31st 2016. Results Our study included 1255 patients. The mean age of the population at baseline was 59 years. The median values for CRP and ferritin levels were 4.8 (IQR 1.9-11.0) mg/dL and 696.0 (IQR 448.5-996.8) ng/mL, respectively. Using the tertiles categories for CRP (8.1 mg/dL) and ferritin (876.1 ng/mL) our population was categorized into 9 groups of patients: Group 1 CRP Group 2 CRP Group 3 CRP 2.7-8.1mg/dL, ferritin >876.1 ng/mL; Group 4 CRP 2.7-8.1 mg/dL, ferritin Group 5 CRP 2.7-8.1 mg/dL, ferritin 536.6-876.1ng/mL; Group 6 2.7-8.1 mg/dL, ferritin >876.1 ng/mL; Group 7 CRP>8.1 mg/dL, ferritin Group 8 CRP>8.1 mg/dL, ferritin 536.6-876.1ng/mL; Group 9 CRP>8.1 mg/dL, ferritin >876.1 ng/mL; During the follow-up (mean 1.75, median 1.94 years), 204 patients (16.25%) died with 103 (8.21%) from CV disease. The central point of our investigation was to assess the combined effect of CRP and ferritin levels on the two outcomes (Table 1). For the all-cause mortality, after adjustment for different demographic, clinical and biological risk factors, only patients with CRP levels in the highest tertile (CRP>8.1 mg/dL), irrespectively of ferritin levels (Groups 7, 8 and 9), remained significantly associated with this outcome. When considering the CV mortality, in the adjusted analysis, only patients from Groups 4 (2nd tertile CRP, 1st tertile ferritin) and 7 (3rd tertile CRP, 1st tertile ferritin) remained associated with a higher risk for the outcome as compared with patients from Group 1. Conclusion We show that increased levels of CRP are associated with an increased risk for all-cause mortality in the HD population, irrespective of ferritin levels. However, increasing CRP levels are associated with CV mortality only for the lowest tertile of ferritin levels. This work was supported by a grant of the Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1.1-PD-2016-0287, within PNCDI III and by grants of the “Grigore T. Popa” University of Medicine and Pharmacy, contract numbers 27495/2018 and 27505/2018.

IntroductionChronic heart failure (HF) represents a major global public health problem, and despite significant advances in diagnosis and management over the past two decades, HF patients still have a poor prognosis. The aim of the study was to evaluate the relationship between lung congestion, as assessed by lung ultrasonography (LUS), bioimpedance spectroscopy, body fluid compartments, and echocardiographic parameters, and to determine the effect of these associations on all-cause mortality in HF patients.Material and methodsEligible patients with a left ventricular ejection fraction (LVEF) below 45% were identified via daily echocardiography assessments. Lung ultrasonography was performed with patients in the supine position, for a total of 28 sites per complete examination. The extracellular water (ECW) was determined using a BIS device.ResultsOur study included 122 patients (67.2% males) with a mean age of 67.2 years. In the multivariable linear regression analysis, including all the univariable predictors of lung congestion, only New York Heart Association (NYHA) class, ECW, estimated glomerular filtration rate (eGFR), and LVEF levels maintained an independent association with the number of B-lines. During the follow-up, 33 patients died. In multivariable Cox analysis, a B-line number of at least 15 remained significantly associated with all-cause mortality, independently of age, sex, diabetes, LVEF, estimated glomerular filtration rate, C-reactive protein, N-terminal pro-brain natriuretic peptide, or ECW values (adjusted HR = 3.84, 95% CI: 1.12–13.09).ConclusionsWe show for the first time in HF patients that pulmonary congestion, as assessed by LUS, is associated with the severity of NYHA class, LVEF, eGFR, and ECW, and it identifies those at increased risk of death.