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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. [ABSTRACT FROM AUTHOR]

• Congestion is a marker of adverse prognosis in patients with heart failure (HF). • BNP, ePVS, BIVA, and BUN/Cr ratio are independent prognostic biomarkers in HF. • Combining BNP, eVPS, BIVA, and BUN/Cr explain the 40% risk of death in HF. Congestion is a marker of adverse prognosis in patients with heart failure (HF). In addition to brain natriuretic peptide (BNP), estimated plasma volume status (ePVS), bioimpedance vector analysis (BIVA), and blood urea nitrogen/creatinine ratio (BUN/Cr) are emerging as new markers for congestion. The aim of this study was to evaluate the prognostic value of BNP, ePVS, BIVA, and BUN/Cr in HF. We analyzed the data from 436 patients with acute or chronic heart failure (AHF, n = 184, and CHF, n = 252, respectively). BNP, ePVS, hydration index (HI%), and BUN/Cr were collected from all patients at admission. The endpoint was all-cause mortality. Ninety-two patients died after a median follow-up of 463 days (IQR: 287–669). The cumulative mortality of all of the patients was 21% (31% and 13% in AHF and CHF, respectively, p < 0.0001). The optimal cut-offs for death occurrence were BNP: >441 pg/mL, ePVS: >5.3 dL/gr, HI: >73.8%, BUN/Cr: >25. Multivariate Cox regression analysis maintained an independent predictive value for mortality (HR 2. 1, HR 2.2, HR 2.1, and HR 1.7; C-index 0.756). AHF status was no longer associated with death. Together, these variables explained 40% of the risk of death (R 2 adjusted = 0.40). Patients with all four parameters below or above their optimal cut-off had mortality rates of 4% and 59%, respectively. BNP, ePVS, BIVA, and BUN/Cr at admission provide independent and complementary prognostic information in patients with HF and, when combined, explain the 40% risk of death in these patients independent from the acute or chronic HF condition. [ABSTRACT FROM AUTHOR]

Background Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). Objectives To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). Methods This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. Results During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79–1.33; p = 0.862) for patients with a BMI of 25.0–29.9 kg/m 2 and 0.83 (95% CIs 0.61–1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m 2 . NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. Conclusions Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories. [ABSTRACT FROM AUTHOR]

Background Acute heart failure is a common cause of hospitalization among older patients. Optimized risk stratification might improve the outcome for this subgroup of patients. Natriuretic peptides have been used in the diagnosis of heart failure and in evaluating the prognosis of patients hospitalized for heart failure. However, their utility in the elderly is still controversial. Objective To evaluate long-term survival and prognostic factors for elderly patients hospitalized for acutely decompensated heart failure and evaluate the prognostic utility of NT-proBNP. Design Retrospective, multicenter cohort study. Setting Two Italian hospitals. Participants Two hundred seventy-nine patients, aged >75 years; hospitalized for decompensation of chronic, established heart failure. Methods Baseline clinical data were recorded at admission. The primary outcome was long-term mortality. Results In-hospital, 12-month and 5-year mortality were, respectively, 10%, 36%, and 77%. NT-proBNP, eGFR, hemoglobin, diabetes, systolic blood pressure, and moderate to severe tricuspid regurgitation were independently associated with long-term prognosis and were entered into a multivariate model, with a C-index of 0.765 for the determination of high-risk patients. The C-index for NT-proBNP to predict mortality at 2 and 12 months was 0.740 and 0.756, respectively. The optimal cutoff point for predicting mortality at 2 and 12 months was 8,444 pg/mL (hazard ratio 5.33) and 8,275 pg/mL (hazard ratio 6.03), respectively. Conclusion Elderly patients hospitalized for acutely decompensated heart failure had a poor long-term outcome, especially in the subgroup with reduced ejection fraction (EF). In addition to EF and comorbidities, NT-pro-BNP remained independently prognostic among elderly patients hospitalized with heart failure. [ABSTRACT FROM AUTHOR]

Background To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF). Methods 1119 patients admitted for AE-CHF and with NT-proBNP levels > 900 pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality. Results During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180 days after admission. Increasing age (p = .012), obesity (p = .037), atrial fibrillation (p = .030), CHD (p = .015), CLD (p = .001), RI (p < .001), and anemia (p < .001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180 days after admission. Male gender was associated with mortality beyond 180 days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission. Conclusions Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions. [ABSTRACT FROM AUTHOR]

Objectives: To assess the incremental prognostic utility of discharge serum creatinine (SCr), systolic blood pressure (SBP), and NT-proBNP and sodium concentrations in hospitalized patients with acutely decompensated chronic heart failure. Background: Whether key prognostic variables at discharge provide incremental prognostic information beyond that provided by a model based on admission variables (referent) remains incompletely defined. Methods: The primary outcome was a composite of death, urgent heart transplantation, or ventricular assist device implantation at 1 year. The gain in predictive performance was assessed using C index, Bayesian Information Criterion, and Net Reclassification Improvement. Results: The best fit was obtained when discharge NT-proBNP was added to the referent model. No interaction between admission and discharge NT-proBNP was found. Discharge SCr, SBP, and sodium did not improve goodness-of-fit. Conclusions: Admission and discharge NT-proBNP provide complementary and independent prognostic information; as such, they should be taken into account concurrently. [ABSTRACT FROM AUTHOR]

Abstract: Background: The clinical utility of different renal function (RF) measures for risk stratification in chronic heart failure (CHF) and the incremental discriminative value of renal dysfunction have not been investigated thoroughly. Methods: We studied 802 patients with systolic CHF. The primary outcome was all-cause mortality. The association of candidate variables and RF measures [serum creatinine (SCr), serum urea nitrogen (SUN), estimated creatinine clearance adjusted for body-surface area (eCrClBSA), and estimated glomerular filtration rate (eGFR)] with mortality was evaluated using Cox proportional-hazards analyses. Recommended metrics of goodness-of-fit and discrimination were calculated. Results: At follow-up (median: 1269days), there were 301 deaths. Age (p<0.001), ischemic etiology (p=0.009), NYHA class (p<0.001), anemia (p<0.001), and left ventricular ejection fraction (p<0.001) independently predicted mortality (reference risk model). On multivariable analysis incorporating one of the measures of RF at a time, each had an independent value for predicting mortality (p<0.001). The addition of each RF measures to the reference model significantly increased the likelihood-ratio χ2 and the models incorporating eCrClBSA or SUN demonstrated the highest probability of being the best. Although changes in C statistic and net reclassification were not significant, the Integrated Discrimination Index was significantly improved by the addition of eCrClBSA. Calibration was improved by all measures of RF expect SUN. The model incorporating eCrClBSA demonstrated both the best goodness-of-fit and discrimination. Conclusions: Our data suggest that renal dysfunction significantly improves risk stratification in a context of established risk factors. eCrClBSA appears to be the most performing measure of RF for this purpose. [Copyright &y& Elsevier]

Abstract: Background: Accurate identification of renal dysfunction (RD) is crucial to risk stratification in chronic heart failure (CHF). Patients with CHF are at special risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr generation. At low levels of SCr, the equations estimating renal function are less accurate. This study was aimed to assess and compare the prognostic value of formulas estimating renal function in CHF patients with normal SCr. Methods: We studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was estimated by the Cockcroft–Gault (eCrCl) and glomerular filtration rate by the 4-variable MDRD equation (eGFR); eCrCl normalized for body-surface area (eCrClBSA) was calculated. The primary outcome was all-cause mortality at 2years. Results: Seventy five patients died. At multivariate Cox regression analysis, only eCrClBSA was significantly associated with mortality (p =0.006); eGFR (p =0.24), eCrCl (p =0.09) and BUN (p =0.14) were not statistically significant predictors. The patients in the lowest eCrClBSA quartile had an adjusted 2.1-fold (CI: 1.06–4.1) increased risk of mortality, compared with those in the referent quartile. Two-year survival was 70.4% in the lowest eCrClBSA quartile and 89.7% in the referent quartile. Other independent predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3–3.5], p =0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51–3.97], p =0.0003), LVEF <0.25 (RR: 3.38 [CI: 1.69–6.75], p =0.014), and anemia (RR: 1.86 [CI: 1.16–2.99], p =0.009). Conclusions: A sizeable proportion of CHF patients have prognostically significant RD despite normal SCr. Such patients represent a high-risk subgroup and can more accurately be identified by the CG formula corrected for BSA than the MDRD. [Copyright &y& Elsevier]

Aims We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes. Methods and results We studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was all-cause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated. Conclusion Heart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF. [ABSTRACT FROM AUTHOR]

Background: reduced renal excretory function (REF) is increasingly being appreciated as a potent prognostic factor in chronic heart failure (CHF). The Cockroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) equations have been recommended to estimate REF. However, limitations for both formulas have been reported in the elderly. Their prognostic performance in older CHF patients has not been investigated. Objectives: to assess the factors independently associated with all-cause mortality and compare the prognostic value of formulas estimating REF in CHF patients aged ⩾70 years. Design: a longitudinal study with a median follow-up of 859 days. The end-point was all-cause mortality. Setting: Division of Cardiology and Cardiac Rehabilitation. Subjects: two hundred and sixty-six patients aged ⩾70 years with systolic CHF. Methods: REF was estimated using the CG (eCrClCG) and the MDRD (eGFRMDRD) formulas. Cox proportional hazards model was used to assess the factors independently associated with mortality and compare the prognostic value of estimating formulas. Receiver-operating characteristic (ROC) curve analysis was also performed. Results: Kaplan-Meier estimates of the rates of death at 1 and 2 years were 85% and 73%, respectively At multivariate analysis, eCrClCG <50 mL/min (P = 0.005), anaemia (P = 0.012), non-prescription of beta-blockers (P = 0.006) and left ventricular ejection fraction (P 0.03) were the only independent predictors of mortality. On ROC analysis, the eCrClCG was significantly more accurate than the eGFRMDRD. Conclusions: among CHF patients aged ⩾70 years, reduced REF is the most powerful independent predictor of survival. The excess in risk conferred by reduced REF is better appraised by means of the CG than the MDRD equation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the prognostic value of change in distance walked in 6 min in chronic heart failure (CHF). Background: The strongest indication for the 6-min walking test (6MWT) is for measuring the response to therapeutic interventions in patients with CHF. Whether the increase in distance walked after a therapeutic intervention translates into improved clinical outcome is largely unknwon. Methods: We studied 476 CHF patients with left ventricular systolic dysfunction who were referred to our institution for adjustment of heart failure therapy because of persisting or worsening symptoms. Adjustment of therapy involved four classes of drugs: angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, beta-blockers, loop diuretics, and aldosterone antagonists. A standardized 6MWT was performed at baseline and at discharge. Results: After 15.2 ± 8 days, the distance walked increased from 326 ± 107 m to 408 ± 109 m (+25%; p = 0.001). During a mean follow-up of 23.9 months, 94 patients died and 12 patients underwent cardiac transplantation. Among a set of variables, New York Heart Association functional class (p = 0.02), serum creatinine concentration (p = 0.01), left ventricular ejection fraction (p = 0.002), distance walked at baseline (p = 0.0002), and change in distance walked (p = 0.002) were significant independent predictors of survival. When the patients were divided into two subgroups according to the median value of the distance walked at baseline, the increase in walking distance was significantly associated with survival only in the subgroup of patients who walked <340 m at baseline. Conclusions: Our data indicate that repeating a 6MWT after drug intervention provides independent prognostic information in CHF patients with more compromised exercise capacity. [Copyright &y& Elsevier]

The prognostic value of change in six-minute walking distance (6MWD) after treatment to predict mortality in heart failure (HF) remains a controversial issue. We assessed the prognostic value of rehabilitation-induced improvement in 6MWD in predicting mortality in patients with HF. We studied 2257 patients admitted to six inpatient rehabilitation facilities after a hospitalization for HF (N. 912) or because of worsening functional capacity and/or deteriorating clinical status (N. 1345). A six-minute walking test was performed at admission and discharge. The primary outcome was 3-year all-cause mortality after discharge from cardiac rehabilitation. We used multivariable Cox proportional hazard modeling to assess the association of increase in 6MWD with 3-year mortality, adjusting for established predictors of mortality. 6MWD significantly increased by 61 m (p <.001) from admission to discharge and 969 patients (42.9%) achieved an increase in 6MWD >50 m. After full adjustment, an increase in 6MWD >50 m was associated with a 22% decreased risk for 3-year mortality (HR 0.78 [95% CI 0.68–0.91]; p =.002). When modeled as a continuous variable, improvement in 6MWD remained independently associated with decreased risk for 3-year mortality (HR per each 50 m increase: 0.92 [95% CI 0.88–0.96]). Rehabilitation–induced improvement in 6MWD was associated with a significantly reduced risk for 3-year mortality. Our data also suggest that an improvement in 6MWD of more than 50 m could represent a clinically meaningful endpoint of cardiac rehabilitation for patients with heart failure. • The prognostic role of improvement in 6-min walk distance in heart failure is a debated issue. • We studied 2250 heart failure patients admitted to inpatient cardiac rehabilitation. • Rehabilitation-induced improvement in 6-min walk distance predicted improved survival. • This finding can contribute to promote cardiac rehabilitation referral for heart failure. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is among the most common comorbidities in patients hospitalized with heart failure and is generally associated with poor outcomes. However, the results of previous studies with regard to increased mortality and risk trajectories were not univocal. We sought to assess the prognostic impact of COPD in patients admitted for acutely decompensated heart failure (ADHF) and investigate the association between use of β-blockers at discharge and mortality in patients with COPD. Methods We studied 1530 patients. The association of COPD with mortality was examined in adjusted Fine-Gray proportional hazard models where heart transplantation and ventricular assist device implantation were treated as competing risks. The primary outcome was 5-year all-cause mortality. Results After adjusting for establisked risk markers, the subdistribution hazard ratios (SHR) of 5-year mortality for COPD patients compared with non-COPD patients was 1.25 (95% confidence intervals [CIs] 1.06–1.47; p =.007). The relative risk of death for COPD patients increased steeply from 30 to 180 days, and remained noticeably high throughout the entire follow-up. Among patients with comorbid COPD, the use of β-blockers at discharge was associated with a significantly reduced risk of 1-year post-discharge mortality (SHR 0.66, 95%CIs 0.53–0.83; p ≤.001). Conclusions Our data indicate that ADHF patients with comorbid COPD have a worse long-term survival than those without comorbid COPD. Most of the excess mortality occurred in the first few months following hospitalization. Our data also suggest that the use of β-blockers at discharge is independently associated with improved survival in ADHF patients with COPD. Highlights • Chronic obstructive pulmonary disease (COPD) is a common comorbidity in acute heart failure. • Comorbid COPD entailed an increased risk of long-term mortality. • Most of the excess mortality occurred in the first few months following hospitalization. • β-blockers reduced the risk of death in patients with comorbid COPD. [ABSTRACT FROM AUTHOR]

Background Still there is conflicting evidence about gender-related differences in prognosis among patients with heart failure. This prognostic uncertainty may have implications for risk stratification and planning management strategy. The aim of the present study was to explore the association between gender and one-year mortality in patients admitted with acute decompensated heart failure (ADHF). Methods We studied 1513 patients. The Cumulative Incidence Function (CIF) method was used to estimate the absolute rate of mortality, heart transplantation (HT)/ventricular assist device (VAD) implantation, and survival free of HT/VAD implantation at 1 year. An interaction analysis was performed to assess the association between covariates, gender, and mortality risk. Propensity score matching and Cox regression were used to compare mortality rates in the gender subgroups. Results The CIF estimates of 1-year mortality, HT/VAD implantation, and survival free of HT/VAD implantation at 1 year were 33.1%, 7.0%, and 59.9% for women and 30.2%, 10.2%, and 59.6% for men, respectively. Except for diabetes, there was no significant interaction between gender, covariates, and mortality risk. In the matched cohort, the hazard ratio of death for women was 1.19 (95% confidence intervals [CIs]: 0.90–1.59; p = .202). After adjusting for age and baseline risk, the hazard ratio of death for women was 1.18 (95% CIs: 0.95–1.43; p = .127). The use of gender-specific predictive models did not allow improving the accuracy of risk prediction. Conclusions Our data strongly suggest that women and men have comparable outcome in the year following a hospitalization for ADHF. [ABSTRACT FROM AUTHOR]

Abstract: Background: NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score. Methods: This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score. Results: One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798–0.880) and the Hosmer–Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711–0.817); the Hosmer–Lemeshow statistic was 2.76 (p=0.251), after recalibration. Conclusions: The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable. [Copyright &y& Elsevier]