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Aim: Evidence on healthcare resource utilization (HCRU) for hospitalized patients with heart failure (HF) and reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction is limited., Methods and Results: We analysed HCRU in relation to left ventricular ejection fraction (LVEF) phenotypes, clinical features and in-hospital and 12-month outcomes in 16 943 patients hospitalized for HF in a worldwide registry. HFrEF was more prevalent (53%) than HFmrEF (17%) or HFpEF (30%). Patients with HFmrEF and HFpEF were older, more often women, with milder symptoms and more comorbidities, but differences were not pronounced. HCRU was high in all three groups; two or more in- and out-of-hospital services were required by 51%, 49% and 52% of patients with HFrEF, HFmrEF and HFpEF, respectively, and intensive care unit by 41%, 41% and 37%, respectively. Hospitalization length was similar (median, 8 days). Discharge prescription of neurohormonal inhibitors was <80% for each agent in HFrEF and only slightly lower in HFmrEF and HFpEF (74% and 67%, respectively, for beta-blockers). Compared to HFrEF, 12-month all-cause and cardiovascular mortality were lower for HFmrEF (adjusted hazard ratios 0.78 [95% confidence interval 0.59-0.71] and 0.80 [0.70-0.92]) and HFpEF (0.64 [0.59-0.87] and 0.63 [0.56-0.71]); 12-month HF hospitalization was also lower for HFpEF and HFmrEF (21% and 20% vs. 25% for HFrEF). In-hospital mortality, 12-month non-cardiovascular mortality and 12-month all-cause hospitalization were similar among groups., Conclusions: In patients hospitalized for HF, overall HCRU was similarly high across LVEF spectrum, reflecting the subtle clinical differences among LVEF phenotypes during hospitalization. Discharge prescription of neurohormonal inhibitors was suboptimal in HFrEF and lower but significant in patients with HFpEF and HFmrEF, who had better long-term cardiovascular outcomes than HFrEF, but similar risk for non-cardiovascular events., (© 2023 European Society of Cardiology.)

Cognitive impairment (CI) is an important comorbidity in patients with heart failure (HF). Its prevalence parallels the severity of heart failure, while it is an independent prognostic marker of adverse events. Various factors contribute to cognitive decline in HF, influencing self-care. There are no standardized screening methods for the diagnosis and management of these patients. The aim of the present manuscript is to provide an overview of the impact of cognitive impairment in HF, describe the utility of assessment tools and imaging methods for the evaluation of CI, and propose a comprehensive diagnostic and management approach., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin-angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum., Methods and Results: We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF <40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50-99%, 1-49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49-0.74), P < 0.001; 50-99%: 0.56 (0.46-0.68), P < 0.001; 1-49%: 0.71 (0.59-0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%., Conclusion: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%., (© 2021 European Society of Cardiology.)

Aims: Oral sucrosomial iron (SI) combines enhanced bioavailability and tolerance compared to conventional oral iron along with similar efficacy compared to intravenous iron in several conditions associated with iron deficiency (ID)., Methods and Results: In this non-randomized, open-label study, we sought to evaluate prospectively the effects of SI on clinical parameters, exercise capacity and quality of life in 25 patients with heart failure (HF) with reduced ejection fraction (HFrEF) and ID, treated with SI 28 mg daily for 3 months, in comparison to 25 matched HFrEF controls. All patients were on optimal stable HF therapy. Patients were followed for 6 months for death or worsening HF episodes. There were no differences in baseline characteristics between groups. At 3 months, SI was associated with a significant increase in haemoglobin, serum iron and serum ferritin levels (all P ≤ 0.001) along with a significant improvement in 6-min walked distance and Kansas City Cardiomyopathy Questionnaire (all P < 0.01), even after adjustment for baseline parameters; these differences persisted at 6 months. Over the study period, there were no deaths, while 10 patients (20%) in total (four in the SI group and six in the control group), experienced worsening HF (odds ratio 0.51, 95% confidence interval 0.41-6.79, P = 0.482). Drug-associated diarrhoea was reported by one patient in the SI group and led to drug discontinuation; no other adverse events were reported., Conclusions: In this proof-of-concept study, SI was well tolerated and improved exercise capacity and quality of life in HFrEF patients with ID. Randomized studies are required to further investigate the effects of this therapy., (© 2021 European Society of Cardiology.)

Heart failure (HF) has been classified in chronic HF (CHF) and acute HF (AHF). The latter has been subdivided in acutely decompensated chronic HF (ADCHF) defined as the deterioration of preexisting CHF and de novo AHF defined as the rapid development of new symptoms and signs of HF that requires urgent medical attention. However, ADCHF and de novo AHF have fundamental pathophysiological differences. Most importantly, the typical illness trajectory of HF, which is similar to that of other chronic organ diseases including lung, renal, and liver failure, features a gradual decline, with acute episodes usually related to disease evolution followed by partial recovery. Thus, ADCHF should be considered part of the natural history of CHF and renamed CHF exacerbation (CHFE) in accordance with the appropriate terminology used in chronic obstructive pulmonary disease. AHF, in turn, should include only acute de novo HF. The clinical implications of this paradigm shift will be in CHFE the change in focus from in-hospital to optimal ambulatory CHF management aiming at primary and secondary CHFE prevention, while in AHF, the institution of measures for in-hospital limitation of cardiac injury and prevention or retardation of symptomatic CHF development.

Acute heart failure (AHF) is a common clinical challenge that a wide spectrum of physicians encounters in every practice. In many cases, AHF is due to decompensation of chronic heart failure. This decompensation may be triggered by various reasons, with sepsis being a notable one. Sepsis is defined as a life-threatening organ dysfunction caused by the dysregulated host response to infection and is associated with a very high mortality, which may reach 25%. Alarmingly, the increase in the mortality rate of patients with combined cardiac dysfunction and sepsis is extremely high (may reach 90%). Thus, these patients need urgent intervention. Management of patients with AHF and sepsis is challenging since cornerstone interventions for AHF may be contraindicated in sepsis and vice versa (e.g., diuretic treatment). Unfortunately, no relevant guidelines are yet available, and treatment remains empirical. This review attempts to shed light on the intricacies of the available interventions and suggests routes of action based on the existing bibliography.

Background and Aims: Increased sodium intake is associated with increased risk of decompensation in patients with heart failure. This non-randomized, open-label, controlled study aimed to examine the feasibility, preliminary safety and efficacy of a low sodium-potassium enriched salt substitute compared to regular table salt in patients with heart failure with reduced ejection fraction (HFREF)., Methods: Fifty patients (68% male, NYHA I/II/III 6%/68%/26%, mean age 70 ± 9 years, LVEF 31 ± 5%, median BNP 112 pg/ml) were included. Of these, 30 patients received the salt substitute (maximum consumption of 2 g daily), who were prospectively compared to a control group of 20 age/sex/NYHA class-matched HFREF patients who consumed regular salt (maximum consumption of 2 g daily). Consumption of regular salt was prohibited in the salt substitution group. All patients were followed for 12 weeks., Results: Patient groups did not differ by sex, age, LVEF, NYHA class, 6MWD, and BNP at baseline. In primary safety analysis, no significant differences were detected between groups regarding SBP (p = 0.052), DBP (p = 0.159), HR (p = 0.246), serum potassium (p = 0.579), serum sodium (p = 0.125), and eGFR (p = 0.710) throughout the 12 weeks. Secondary efficacy analysis revealed a statistically significant difference in 6MWD at 12 weeks between the salt substitute and regular salt groups after adjustment for baseline 6MWD (mean difference±SEM, 4.7 ± 2.1 m, F = 4.92, p = 0.031)., Conclusions: In this pilot study, a low sodium-potassium enriched salt substitute was found to be safe compared to regular salt in HFREF patients, while it resulted in a small albeit significant improvement in exercise capacity, possibly justifying further investigation with randomized clinical studies., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)