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Introduction: This study aimed to evaluate the association between the NephroCheck® test AKIRisk® score, diuretic efficiency (DE), and the odds of worsening kidney function (WKF) within the first 72 h of admission in patients hospitalized for acute heart failure (AHF)., Methods: The study prospectively enrolled 125 patients admitted with AHF. NephroCheck® test was obtained within the first 24 h of admission. DE was defined as net fluid urine output per 40 mg of furosemide equivalents., Results: The median AKIRisk® score was 0.11 (IQR 0.06-0.34), and 38 (30.4%) patients had an AKIRisk® score >0.3. The median cumulative DE at 72 h was 1,963 mL (IQR 1317-3,239 mL). At 72 h, a total of 10 (8%) patients developed an absolute increase in sCr ≥0.5 mg/dL (WKF). In a multivariable setting, there was an inverse association between the AKIRisk® score and DE within the first 72 h. In fact, the highest the AKIRisk® score (centered at 0.3), the higher the likelihood of poor DE (below the median) and WKF at 72 h (odds ratio [OR] 2.04; 95%; CI: 1.02-4.07; p = 0.043, and OR 3.31, 95% CI: 1.30-8.43; p = 0.012, respectively)., Conclusion: In patients with AHF, a higher NephroCheck® AKIRisk® score is associated with poorer DE and a higher risk of WKF at 72 h. Further research is needed to confirm the role of urinary cell cycle arrest biomarkers in the AHF scenario., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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., Competing Interests: Disclosures Dr Dauw received speaker fees from AstraZeneca, Boehringer-Ingelheim, and Bayer; Dr Lelonek received speaker and consulting fees from Novartis, Novo Nordisk, Servier, AstraZeneca, Boehringer-Ingelheim, Bausch Health, Bayer, Ewopharma, and Gedeon Richter and was involved in clinical trials from Amgen, Novartis, Novo Nordisk, and Boehringer-Ingelheim; Dr Borbély received speaker fees from Astra Zeneca, Bayer, Boehringer-Ingelheim, and Novartis; Dr Cobo-Marcos received speaker fees from Astra Zeneca, Boehringer-Ingelheim, Novartis, Vifor Pharma, Novo Nordisk, and Bayer; Dr Barge-Caballero received travel grants and speaker fees from Astra Zeneca, Boehringer-Ingelheim, Novartis, Viatris, and Pfizer and received research grants from Pfizer; Dr Barker received speaker fees from AstraZeneca, Novartis, and Medtronic; Dr Doghmi received speaker fees from Novartis, Boehringer-Ingelheim, and Pfizer; Dr Nijst received speaker fees from Novartis, Boehringer-Ingelheim, and Bayer; and Dr Martens received consultancy fees from Novartis and CLS Vifor and is supported by a research grant from the Belgian American Educational Foundation and the Frans Van de Werf Fund. The other authors report no conflicts.

Aims: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively., Methods and Results: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization., Conclusions: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: In acute heart failure (AHF), early assessment of spot urinary sodium (UNa) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot UNa predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot UNa in patients with AHF and concomitant renal dysfunction (RD)., Methods: This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] <60 mL/min/1.73 m2) were included. Diuretic efficiency was calculated as the net fluid output produced per 40 mg of furosemide equivalents in 24 h. The association between early spot UNa and diuretic efficiency and clinical variables associated with UNa were evaluated using multivariate linear regression analysis. The contribution of the exposures in the predictability of the models was assessed with the coefficient of determination (R2)., Results: The mean age of the study population was 78 ± 8 years. The median (interquartile range) diuretic efficiency, early spot UNa, aminoterminal pro-brain natriuretic peptide, and eGFR were 747 (490-1,167) mL, 90 mmol/L (65-111), 7,765 pg/mL (3,526-15,369), and 33.7 ± 11.3 mL/min/1.73 m2, respectively. In a multivariate setting, lower UNa was significantly and nonlinearly associated with lower diuretic efficiency (p = 0.001), explaining the 44.4% of the model predictability. Natremia and surrogates of congestion emerged as the main factors related to UNa., Conclusions: In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency., (© 2020 S. Karger AG, Basel.)

Aims: Optimal diuretic treatment of patients with refractory congestive heart failure (CHF) remains to be elucidated. In this work, we aimed to evaluate the serial changes of functional class and surrogates of fluid overload (weight and antigen carbohydrate 125) after addition of oral acetazolamide in patients with refractory CHF. Likewise, serial changes in renal function, serum electrolytes and pH were evaluated., Method: This is an observational retrospective study in which 25 ambulatory patients with refractory CHF that received acetazolamide in addition to standard intensive diuretic strategy were evaluated. Longitudinal assessment of New York Heart Association (NYHA) functional class and biomarkers was analyzed using joint modelling of longitudinal and survival data., Results: All patients showed NYHA class III/IV at baseline. After prescription of acetazolamide, a total of 125 outpatient visits were recorded [median visits per patient: 6 (IQR = 3-7)] during a median follow-up of 152 days (IQR = 80-353). A significant decrease in NYHA class, weight, and antigen carbohydrate 125 was observed. On the other hand, estimated glomerular filtration rate increased over time. No significant changes in systolic blood pressure, serum sodium, potassium, amino-terminal pro-brain natriuretic peptide, and pH occurred., Conclusion: In a cohort of patients with refractory CHF treated with an intensive diuretic treatment, the addition of acetazolamide was associated with improvement in functional class and surrogates of fluid overload., (© 2018 John Wiley & Sons Ltd.)

Introduction and Objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1., Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days., Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation., Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)