Background: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. Methods: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. Results: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P <0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P <0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P <0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P =0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P =0.852). Conclusions: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). Conclusions This discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations.

Epicardial adipose tissue (EAT) is an endocrine and paracrine organ constituted by a layer of adipose tissue directly located between the myocardium and visceral pericardium. Under physiological conditions, EAT exerts protective effects of brown-like fat characteristics, metabolizing excess fatty acids, and secreting anti-inflammatory and anti-fibrotic cytokines. In certain pathological conditions, EAT acquires a proatherogenic transcriptional profile resulting in increased synthesis of biologically active adipocytokines with proinflammatory properties, promoting oxidative stress, and finally causing endothelial damage. The role of EAT in heart failure (HF) has been mainly limited to HF with preserved ejection fraction (HFpEF) and related to the HFpEF obese phenotype. In HFpEF, EAT seems to acquire a proinflammatory profile and higher EAT values have been related to worse outcomes. Less data are available about the role of EAT in HF with reduced ejection fraction (HFrEF). Conversely, in HFrEF, EAT seems to play a nutritive role and lower values may correspond to the expression of a catabolic, adverse phenotype. As of now, there is evidence that the beneficial systemic cardiovascular effects of sodium-glucose cotransporter-2 receptors-inhibitors (SGLT2-i) might be partially mediated by inducing favorable modifications on EAT. As such, EAT may represent a promising target organ for the development of new drugs to improve cardiovascular prognosis. Thus, an approach based on detailed phenotyping of cardiac structural alterations and distinctive biomolecular pathways may change the current scenario, leading towards a precision medicine model with specific therapeutic targets considering different individual profiles. The aim of this review is to summarize the current knowledge about the biomolecular pathway of EAT in HF across the whole spectrum of ejection fraction, and to describe the potential of EAT as a therapeutic target in HF.

Cognitive impairment is a central feature of schizophrenia and has shown to play a crucial role in the psychosocial function of the disorder. Over the past few years, several cognitive remediation (CR) interventions have been developed for schizophrenia, whose effectiveness has also been widely demonstrated by systematic reviews and meta-analysis studies. Despite these evidences, many questions remain open. In particular, the identification of CR response predictors in patients with schizophrenia is still a topic with equivocal findings and only a few studies have looked for the relationship between CR response or resistance and the biological, socio-demographic, clinical and cognitive features in schizophrenia. The current knowledge on positive or negative response predictors to CR treatment in schizophrenia include: age, duration of illness, premorbid adjustment, baseline cognitive performance, intrinsic motivation, hostility, disorganized symptoms, neurobiological reserve, genetic polymorphisms, the amounts of antipsychotics, the type of CR, etc. The aim of this review is to identify neurobiological, psychopathological, cognitive, and functional predictors of CR response or resistance in schizophrenia, taking into account both cognitive and functional outcome measures. The information obtained could be very useful in planning integrated and personalized interventions, also with a better use of the available resources.

Cardiogenic shock represents one of the most dramatic scenarios to deal with in intensive cardiology care and is burdened by substantial short-term mortality. An integrated approach, including timely diagnosis and phenotyping, along with a well-established shock team and management protocol, may improve survival. The use of the Swan-Ganz catheter could play a pivotal role in various phases of cardiogenic shock management, encompassing diagnosis and haemodynamic characterisation to treatment selection, titration and weaning. Moreover, it is essential in the evaluation of patients who might be candidates for long-term heart-replacement strategies. This review provides a historical background on the use of the Swan-Ganz catheter in the intensive care unit and an analysis of the available evidence in terms of potential prognostic implications in this setting.