The aim of this study was to evaluate the relationship between anaemia and biomarkers of central/peripheral congestion in heart failure (HF) and the impact on mortality. We retrospectively evaluated 434 acute/chronic HF (AHF/CHF) patients. Anaemia was defined as haemoglobin levels <12 g/dL (women) or <13 g/dL (men). The brain natriuretic peptide (BNP) and hydration index (HI) were measured. The endpoint of the study was all-cause mortality. Anaemia occurred in 59% of patients with AHF and in 35% with CHF (p < 0.001) and showed a significant correlation with the NYHA functional class and renal function. BNP and HI were significantly higher in patients with anaemia than in those without anaemia. Independent predictors of anaemia included BNP, estimated creatinine clearance (eCrCL), and HI. The all-cause mortality rate was 21%, which was significantly higher in patients with anaemia than in those without anaemia (30% vs. 14%, p < 0.001; hazard ratio: 2.6). At multivariate Cox regression analysis, BNP, eCrCL, and HI were independent predictors for mortality (Hazard ratios: 1.0002, 0.97, and 1.05, respectively), while anaemia was not. Anaemia correlates with HF status, functional class, renal function, BNP, and HI. Anaemia was not an independent predictor for mortality, acting as a disease severity marker in congestive patients rather than as a predictor of death.

The estimation of glomerular filtration rate (eGFR) provides prognostic information in patients with heart failure (HF). Bioelectrical impedance analysis may calculate eGFR (Donadio formula). The aim of this study was to evaluate the impact of the Donadio formula in predicting all-cause mortality in patients with HF as compared to Cockroft-Gault, MDRD-4 (Modification of Diet in renal Disease Study), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. Four-hundred thirty-six subjects with HF (52% men; mean age 75 ± 11 years; 42% acute HF) were enrolled. Ninety-two patients (21%) died during the follow-up (median 463 days, IQR 287–669). The area under the receiver operator characteristic curve for eGFR, as estimated by Cockroft-Gault formula (AUC = 0.75), was significantly higher than those derived from Donadio (AUC = 0.72), MDRD-4 (AUC = 0.68), and CKD-EPI (AUC = 0.71) formulas. At multivariate analysis, all eGFR formulas were independent predictors of death; 1 mL/min/1.73 m² increase in eGFR—as measured by Cockroft-Gault, Donadio, MDRD-4, and CKD-EPI formulas—provided a 2.6%, 1.5%, 1.2%, and 1.6% increase, respectively, in mortality rate. Conclusions. eGFR, as calculated with the Donadio formula, was an independent predictor of mortality in patients with HF as well as the measurements derived from MDRD4 and CKD-EPI formulas, but less accurate than Cockroft-Gault.

The role of nitric oxide (NO), soluble guanylate cyclase (sGC), and the cyclic guanosine monophosphate (cGMP) pathway in cardiovascular and renal health and disease is a complex issue. The impact of these biochemical pathways on the vascular tree is well established: the activation of sGC by NO promotes vasodilation and modulates vascular tone. Indeed, additional characteristics exist that lead physicians to believe there is a pleiotropic influence of this pathway on the functional activities and structural characteristics of human tissues and cells. Recently, sGC stimulators have demonstrated clinical efficacy in patients with worsening heart failure with reduced ejection fraction, improving cardiovascular death risk, re-hospitalization for HF, and all-cause mortality. These new outcome data have increased interest in understanding the potential pathophysiological mechanisms. The NO-sGC-cGMP axis may influence endothelial function, kidney performance, and cardiac muscle cell activity. The synergy of these actions could explain the positive effects of vericiguat on worsening HF. The aim of this narrative review was to provide a comprehensive insight into the pathophysiological mechanisms of action of NO-sGC-cGMP axis stimulators on cardiac muscle, endothelial cells, and kidneys.

Circulating parathyroid hormone (PTH) concentrations increase in heart failure (HF) and are related to disease severity. The relationship between PTH and congestion is still a matter of debate. The objective of this analysis was to evaluate the role of PTH as a marker of congestion and prognosis in HF. We enrolled 228 patients with HF. Intact PTH concentrations and HYDRA score (constituted by: B-type natriuretic peptide, blood urea nitrogen–creatinine ratio, estimated plasma volume status, and hydration status) were evaluated. The study endpoint was all-cause mortality. PTH levels were higher in acute compared with chronic HF and in patients with clinical signs of congestion (i.e., peripheral oedema and orthopnea). PTH concentrations significantly correlated with NYHA class and HYDRA score. At multivariate analysis of HYDRA score, estimated glomerular filtration rate (eGFR), and corrected serum calcium were independently determinants of PTH variability. Fifty patients (22%) died after a median follow-up of 408 days (interquartile range: 283–573). Using univariate Cox regression analysis, PTH concentrations were associated with mortality (hazard ratio [HR]: 1.003, optimal cut-off: >249 pg/mL—area under-the-curve = 0.64). Using multivariate Cox regression analysis, PTH was no longer associated with death, whereas HYDRA score, left ventricular ejection fraction, and eGFR acted as independent predictors for mortality (HR: 1.96, 0.97, and 0.98, respectively). Our study demonstrated that intact PTH was related to clinical and subclinical markers of congestion. However, intact PTH did not act as an independent determinant of all-cause death in HF patients.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K⁺ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K⁺ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam–Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients.