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4 Acute heart failure

Treatment of acute HF was outlined in the recent 2021 ESC HF Guidelines and a Heart Failure Association scientific statement on HF.1,25 Since these publications, trials have been conducted with diuretics, as well as on management strategies for patients with acute HF. The results are summarized here.

4.1 Medical therapy

4.1.1. Diuretics ADVOR was a multicentre, randomized, parallel-group, double-blind, placebo-controlled trial that enrolled 519 patients with acute decompensated HF, clinical signs of volume overload (i.e. oedema, pleural effusion, or ascites), and an NT-proBNP level of >1000 pg/mL or a B-type natriuretic peptide level of >250 pg/mL. They were randomized to receive intravenous (i.v.) acetazolamide (500 mg once daily) or placebo added to standardized i.v. loop diuretic treatment.2 The primary endpoint of successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy, was achieved in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 patients (30.5%) in the placebo group (risk ratio [RR] 1.46, 95% CI 1.17–1.82; P < .001). Rehospitalization for HF or all-cause death occurred in 76 patients (29.7%) in the acetazolamide group and in 72 patients (27.8%) in the placebo group (HR 1.07, 95% CI 0.78–1.48). Length of hospital stay was 1 day shorter with acetazolamide compared with placebo (8.8 [95% CI 8.0–9.5] vs. 9.9 [95% CI 9.1–10.8] days). No difference between the acetazolamide and placebo groups was found for other outcomes and adverse events.2 Although these results may support the addition of acetazolamide to a standard diuretic regimen to aid decongestion, further data on outcomes and safety are needed. The CLOROTIC trial enrolled 230 patients with acute HF and randomized them to oral hydrochlorothiazide (25–100 mg daily, depending on estimated glomerular filtration rate [eGFR]) or placebo, in addition to i.v. furosemide.3 The trial had two co-primary endpoints, change in body weight and change in patient-reported dyspnoea from baseline to 72 h after randomization. Patients on hydrochlorothiazide had a greater decrease in body weight at 72 h compared with those on placebo (−2.3 vs. −1.5 kg; adjusted estimated difference −1.14 kg, 95% CI −1.84 to −0.42 kg; P = .002). Changes in patientreported dyspnoea were similar between the two groups.3 An increase in serum creatinine occurred more frequently in patients on hydrochlorothiazide (46.5%) compared with those on placebo (17.2%) (P < .001). The rates of HF rehospitalization and all-cause death were similar between groups, as was length of stay.3 The lack of an impact on clinical outcomes precludes any recommendation in the current guideline update. Further data on outcomes and safety are needed.

4.1.2 Sodium–glucose co-transporter 2 inhibitors

EMPULSE tested the efficacy of the early initiation of empagliflozin in patients hospitalized for acute HF.9 The primary endpoint was ‘clinical benefit’, defined using a hierarchical composite of death from any cause, number of HF events, and time to first HF event, or a ≥5 point difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire total symptom score at 90 days, assessed using the win-ratio method. HF events were defined as HF hospitalizations, urgent HF visits, and unplanned outpatient HF visits. An event was considered HF-related only if worsening signs and symptoms of HF were present and an intensification of therapy (defined as an increase in oral or i.v. diuretics, augmentation of a vasoactive agent, or starting a mechanical or surgical intervention) was performed.9

Patients were randomized in hospital when clinically stable, with a median time from hospital admission to randomization of 3 days, and were treated for up to 90 days. The primary endpoint was achieved in more patients treated with empagliflozin compared with placebo (stratified win ratio 1.36, 95% CI 1.09–1.68; P = .0054). Efficacy was independent of LVEF and diabetes status. From a safety perspective, the rate of adverse events was similar between the two treatment groups.9 These results are consistent with those shown for SGLT2 inhibitors in patients with chronic HF, regardless of LVEF, and also in those recently hospitalized for HF, once clinically stable.9,26–28 Caution is, however, needed in patients with T2DM at risk of diabetic ketoacidosis, particularly those treated with insulin when carbohydrate intake is reduced or dose of insulin changed.29 SGLT2 inhibitors are not indicated in patients with type 1 diabetes.

4.2 Management strategies

Two large trials have been published since the last guidelines: COACH and STRONG-HF.

4.2.1 Admission phase

The COACH trial was a cross-sectional, stepped-wedge, clusterrandomized trial including 5452 patients (2972 during the control phase and 2480 during the intervention phase) enrolled at 10 centres in Ontario, Canada.4 During the intervention phase, hospital staff used the Emergency Heart Failure Mortality Risk Grade 30 Day Mortality-ST Depression (‘EHMRG30-ST’) score to ascertain whether patients had a low, intermediate, or high risk of death within 7 days or within 30 days. The study protocol recommended that low-risk patients be discharged early (in ≤3 days) and be treated with standardized outpatient care up to 30-day follow-up, whereas it was advised that intermediate- and highrisk patients be admitted to the hospital. Although early discharge occurred at a similar rate in the intervention and control groups (57% vs. 58%), the trial was successful in showing a 12% reduction in the primary outcome of all-cause death or CV hospitalization in the interventional arm compared with the control arm (HR 0.88, 95% CI 0.78–0.99), consistent with a favourable effect of post-discharge care.4 The trial may need further confirmation multinationally before any recommendation on its approach can be offered in a guideline.

4.2.2 Pre-discharge and early post-discharge phases

The importance of pre-discharge and early post-discharge assessment in patients admitted to hospital for an episode of acute HF was already stressed in the original 2021 ESC HF Guidelines.1 The STRONG-HF trial recently showed the safety and efficacy of an approach based on starting and titrating oral medical therapy for HF within 2 days before anticipated hospital discharge and in follow-up visits occurring early after discharge.16 In this trial, 1078 patients hospitalized for acute HF, not already on full doses of evidence-based HF therapies, who were haemodynamically stable, with elevated NT-proBNP concentrations at screening (>2500 pg/mL), and a >10% decrease in concentration between screening and randomization, were randomly assigned, before discharge, to usual care or high-intensity care. Patients in the high-intensity care group received early and rapid intensification of oral HF treatment with ACE-I (or ARB) or ARNI, beta-blockers, and MRA.16 The goal of the first titration visit, which occurred within 48 h before hospital discharge, was to reach at least half of the target doses of recommended medications. Titration to full target doses of oral therapies was attempted within 2 weeks after discharge, with appropriate safety Downloaded from academic.oup.com/eurheartj/article/44/37/3627/7246292 by guest on 07 October 2026