# Early in-hospital treatment of acute heart failure. Part 2
of the international expert opinion series on AHF
management

Anika Naidu, Andrew Ambrosy, Gad Cotter, Edimar Bocchi, Javed Butler, Ovidiu Chioncel, Beth Davison, Anastase Dzudie, Yonathan Freund, Marat Fudim, et al.

► To cite this version:

Anika Naidu, Andrew Ambrosy, Gad Cotter, Edimar Bocchi, Javed Butler, et al. Early in-hospital treatment of acute heart failure. Part 2 of the international expert opinion series on AHF management. ESC Heart Failure, 2025, 10.1002/ehf2.15389. inserm-05353660

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# Early in-hospital treatment of acute heart failure. Part 2 of the international expert opinion series on AHF management

Anika S. Naidu<fnref n="1" /> ID, Andrew P. Ambrosy²,³, Gad Cotter⁴,⁵,⁶, Edimar A. Bocchi⁷, Javed Butler⁸,⁹, Ovidiu Chioncel¹⁰, Beth Davison⁴,⁵,⁶, Anastase Dzudie<fnref n="11" />, Yonathan Freund¹², Marat Fudim¹³,¹⁴, Sivadasanpillai Harikrishnan¹⁵, Ivna G. Cunha⁷, Alexandre Mebazaa⁴,<fnref n="16" />, Robert J. Mentz¹³,¹⁴, Òscar Miró¹⁷, Siti E. Nauli<fnref n="18" />, Mateo Pagnesi¹⁹, Naoki Sato²⁰, Gianluigi Savarese²¹, Karen Sliwa-Hahnle²², Yuhui Zhang²³, Jingmin Zhou²⁴ and Jan Biegus²⁵* ID

## Abstract

Acute heart failure (AHF) remains a major global health challenge, contributing significantly to morbidity, mortality and health-care resource utilization. It is one of the leading causes of hospitalization, with persistently high readmission rates underscoring the need for improved early management strategies. Despite its prevalence, clear and evidence-based guidance for the early evaluation and treatment of AHF is limited. Congestion is the primary reason for emergency admission, making rapid and effective decongestion a top priority, but diuretics are often underdosed in AHF patients. Medications proven to improve mortality are often not started. In this state-of-the-art review, we address this critical gap by outlining a practical, evidence-based framework for the early management of AHF. Key components include early identification of co-existing conditions, bedside haemodynamic profiling, a structured diagnostic approach incorporating both standard and individualized assessments, a stepwise pharmacologic diuretic strategy beginning with high-dose intravenous loop diuretics, and early in-hospital initiation of guideline-directed medical therapy.

<footnote n="1">¹Department of Internal Medicine, Kaiser Permanente Oakland Medical Center, Oakland, California, USA; ²Department of Cardiology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA; ³Division of Research, Kaiser Permanente Northern California, Pleasanton, California, USA; ⁴Université Paris Cité, MASCOT Inserm, Paris, France; ⁵Momentum Research, Durham, North Carolina, USA; ⁶Heart Initiative, Durham, North Carolina, USA; ⁷Heart Failure Clinics, Instituto do Coração Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; ⁸Baylor Scott and White Research Institute, Dallas, Texas, USA; ⁹University of Mississippi, Jackson, Mississippi, USA; ¹⁰Emergency Institute for Cardiovascular Diseases 'Prof C C Iliescu', University of Medicine 'Carol Davila', Bucharest, Romania;</footnote>

<footnote n="11">¹¹Department of Internal Medicine and Subspecialties, Service of Internal Medicine and Cardiology, Douala General Hospital, Douala, Cameroon; ¹²Emergency Department, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France; ¹³Division of Cardiology, Duke University Hospital, Durham, North Carolina, USA; ¹⁴Duke Clinical Research Institute, Durham, North Carolina, USA; ¹⁵Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India;</footnote>

<footnote n="16">¹⁶APHP Hôpitaux Saint Louis and Lariboisière, Paris, France; ¹⁷Emergency Department, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain;</footnote>

<footnote n="18">¹⁸Department of Cardiology and Vascular Medicine, Tangerang District Hospital, Tangerang, Indonesia; ¹⁹Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; ²⁰Department of Cardiovascular Medicine, Kawaguchi Cardiovascular and Respiratory Hospital, Kawaguchi, Japan; ²¹Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden; ²²Cape Heart Institute, University of Cape Town, Johannesburg, South Africa; ²³Heart Failure Center, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, China; ²⁴Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; and ²⁵Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland</footnote>
## Graphical Abstract

This state-of-the-art review outlines a practical, evidence-based framework for early acute heart failure management to address critical gaps in current guidance and improve early treatment outcomes. Key components include early identification of co-existing conditions, bedside haemodynamic profiling, a structured diagnostic approach incorporating both standard and individualised assessments, a stepwise pharmacological diuretic strategy beginning with intravenous loop diuretics adjusted to clinical status and to diuretic/natriuretic response and early in-hospital initiation of guideline-directed medical therapy.

### DAILY ASSESSMENT AND HEMODYNAMIC PROFILING

* Early and daily physical examination focused on congestion and perfusion

* Identify hemodynamic profile

* Consider ultrasound-based assessment

<figure><img src="image_3.png" /></figure>

### IDENTIFY COEXISTING CONDITIONS

* Evaluate for common coexisting conditions

* Early chest radiograph and ECG

* Consider screening for chronic comorbidities

<figure><img src="image_4.png" /></figure>

### DIAGNOSTIC EVALUATION

* Daily serum sodium, potassium, creatinine, BUN

* Telemetry monitoring

* TTE if no prior echocardiogram

* Repeat TTE, right heart catheterization, ischemic evaluation in select cases

<figure><img src="image_5.png" /></figure>

### DECONGESTION

* High-dose IV loop diuretics, with adjunctive agents if necessary

* Measure a post-diuretic uNa⁺

* Introduce SGLT2i early

* Monitor urine output and diuretic response during decongestion

<figure><img src="image_6.png" /></figure>

### GUIDELINE-DIRECTED MEDICAL THERAPY

* GDMT Initiation/uptitration/optimization is the most important intervention

* Initiate/uptitrate GDMT within 3 days of admission

* Prioritize starting multiple GDMT at low doses over optimizing a few

* Up titrate to at least 50% of target doses during hospitalization

<figure><img src="image_7.png" /></figure>

**Keywords** Acute heart failure; Diuretic strategy; Guideline-directed medical therapy; Hospital

Received: 13 May 2025; Revised: 8 July 2025; Accepted: 11 July 2025

*Correspondence to: Jan Biegus, Institute of Heart Diseases, Wroclaw Medical University, 50-556 Wroclaw, Borowska 213, Poland. Email: jan.biegus@umw.edu.pl

## Introduction

Acute heart failure (AHF) is a leading cause of hospitalizations, with over 1 million admissions in the United States and Europe each year, placing a significant burden on the health system.¹ The 30-day readmission rate is around 13%, with rates reaching as high as 26% in the United States.²,³ In elderly patients, 30-day mortality is reportedly 6%–10% in Europe.⁴ These high readmission and mortality rates underscore the need for effective management strategies to improve patient outcomes and reduce the burden of AHF.⁵,⁶ Recent studies have provided evidence to support enhanced

diuresis and in-hospital initiation of guideline-directed medical therapy (GDMT) in AHF. Despite these advancements, AHF management remains challenging for several reasons, including heterogeneity of the AHF population, involvement of multiple specialists in AHF patient care, lack of well-defined and evidence-based clinical practice guidelines, and lack of robust randomized controlled trial (RCT) data to support strategies for the early treatment of AHF.⁷,⁸ Current clinical guidelines primarily focus on chronic HF patients in the outpatient setting, reflecting the high-quality RCT data available for this population. The lack of inpatient guidance contributes to variability in treatment approaches, delays in optimal ther-
apy and potentially worse patient outcomes. We aim to address this unmet need by providing clear, evidence-based (if available) protocols for the early management of AHF with the ultimate goal of improving not only early AHF management but also patient outcomes.

Of note, not all patients with AHF are hospitalized, as between 16% and 36% (depending on the country) of AHF patients presenting to the emergency department (ED) are fully managed in the ED and sent home without hospitalization.⁹,¹⁰ Another paper in this consensus series offers recommendations specifically for emergency physicians managing this subset of patients with mild decompensation. While some overlap exists between these two documents, the guidance presented here is uniquely tailored for hospitalists managing AHF patients admitted to the hospital.

## Case scenario

A classic AHF case is of a 68-year-old male with a history of non-ischaemic HF with reduced ejection fraction (HFrEF) of 35%, stage 3 chronic kidney disease (CKD) and hypertension, hospitalized for AHF after several days of progressive peripheral oedema and dyspnoea (including orthopnoea). NT-proBNP on arrival was 950 pg/mL and lactate was 0.6 mmol/L. The patient's home medications that have been continued during hospitalization include carvedilol 12.5 mg twice per day, eplerenone 25 mg daily and lisinopril 10 mg daily. The patient's home furosemide 40 mg daily was switched to a bolus of intravenous (IV) furosemide 40 mg in the ED. Medical history and clinical presentation suggested a *Worsening Heart Failure* episode requiring hospital admission.¹¹,¹²

## Daily assessment

On hospital day 1, the patient reports that his dyspnoea and orthopnoea have slightly improved. Vitals show a temperature of 37°C, blood pressure of 105/65 mmHg, heart rate of 110 b.p.m., respiratory rate of 22 breaths/min and oxygen saturation of 95% on room air. The patient has a net negative fluid balance of 500 mL. The clinical exam is notable for a persistent warm-wet profile, with pulmonary rales, an S3 gallop, jugular venous pressure (JVP) elevation to 12 cm, bilateral lower extremity oedema and warm extremities. Serum sodium is 133 mmol/L, potassium is 4.1 mmol/L, BUN is 35 mg/dL, and creatinine is 1.3 mg/dL (estimated glomerular filtration rate [eGFR] 58 mL/min). A spot urine sodium (uNa⁺) collected 2 h after receiving IV furosemide 40 mg is 45 mmol/L. An electrocardiogram (ECG) shows sinus tachycardia without ischaemia.

## Treatment adjustment

Because the patient's diuretic regimen was underdosed, the IV furosemide dose is increased to 60 mg twice per day. After 2 h, a post-diuretic uNa⁺ is 95 mmol/L, and after 6 h, the patient has a fluid balance of net negative 1 L. The patient is continued on IV furosemide 60 mg twice per day. In addition to continuing his home beta-blocker and mineralocorticoid receptor antagonist (MRA), his home angiotensin converting-enzyme inhibitor (ACEi) is switched to losartan 50 mg (an angiotensin receptor blocker [ARB]), and he is started on empagliflozin 10 mg (a sodium-glucose cotransporter 2 inhibitor [SGLT2i]).

## Hospital course

The patient's blood pressure is stable in the following days, but potassium levels become slightly low and require repletion every day. Eplerenone is uptitrated to 50 mg. By day 3, the patient appears euvolaemic on clinical exam. On the day of discharge, blood pressure is 110/75 mmHg, heart rate is 70 b.p.m., respiratory rate is 14 breaths/min, and oxygen saturation is 99% on room air. Prior-to-discharge sodium is 140 mmol/L, potassium is 4.0 mmol/L, BUN is 19 mg/dL, creatinine is 0.9 mg/dL, and NT-proBNP is 150 pg/mL. The patient is discharged on carvedilol 12.5 mg twice daily, eplerenone 50 mg daily, sacubitril/valsartan 49/51 mg twice daily (an angiotensin receptor/neprilysin inhibitor [ARNI]), empagliflozin 10 mg daily, and furosemide 40 mg daily.

## Daily assessment and haemodynamic profiling

### Summary of key points

* A daily physical examination, focused on signs of congestion and perfusion, is essential in all AHF patients.

* Identify the patient's haemodynamic profile: warm-wet, warm-dry, cold-wet and cold-dry.

* Consider using ultrasound-based assessments (e.g., pulmonary and cardiac) to identify the haemodynamic profile.

AHF patients should undergo a comprehensive and structured evaluation, comprised of both standard and individualized components. Table 1 presents a highly selective list of tests, clinical assessments, and laboratory evaluations that should be conducted for every hospitalized AHF patient, along with a simplified rationale for their use.

A detailed clinical examination is an essential daily step in the treatment of every AHF patient, as AHF presentations are dynamic and can change at any point during the hospitalization. Congestion and hypoperfusion are the major mecha-
nisms of AHF pathophysiology, and therefore, assessing the degree of both pathologies and tracking their trajectory throughout the hospitalization is recommended.¹³ Haemodynamic profiling can guide management during HF hospitalizations by providing a systematic approach to assessing perfusion and congestion. Patients should be classified based on the presence or absence of congestion (wet or dry) and perfusion that is adequate or insufficient (warm or cold) (Figure 1).¹⁴

<table><caption>**Table 1** Simplified, highly selective list of tests, clinical assessments and laboratory evaluations that should be performed for every AHF patient</caption><thead><tr><th>Test</th><th>Clinical information</th></tr></thead><tbody><tr><td>Complete clinical examination and comprehensive history</td><td>The most important initial intervention and diagnosis Guides further diagnosis and therapy</td></tr><tr><td>Systolic blood pressure</td><td>Information about the possible in-hospital trajectory Guides initial and long-term therapy Strong prognostic information</td></tr><tr><td>Serum Na<sup>+</sup>/K<sup>+</sup></td><td>Guide therapy Na<sup>+</sup> provides prognostic information</td></tr><tr><td>Serum creatinine (eGFR), BUN</td><td>Prognostic information Markers of in-hospital trajectory</td></tr><tr><td>uNa<sup>+</sup></td><td>Marker to guide the diuretic therapy Prognostic information</td></tr><tr><td>Natriuretic peptides</td><td>Diagnosis Prognostic information</td></tr><tr><td>Lactate</td><td>Helps assess perfusion A good marker for the follow-up of in-hospital trajectory</td></tr></tbody></table>

Haemodynamic classification can be determined within a 2-min bedside assessment in most patients,¹⁵ although reported accuracy of clinical assessment has been mixed¹⁶ due to limited sensitivity and specificity of clinical signs and exam findings.¹⁷,¹⁸ Subclinical haemodynamic congestion with elevated filling pressures can exist days to weeks before overt signs and symptoms develop.¹⁹ Signs of elevated right-sided filling pressure include the presence of jugular venous distention, hepatojugular reflex, ascites and peripheral oedema.²⁰ Elevated left-sided filling pressure is often underrecognized due to the absence of these classic features¹³ and is instead associated with dyspnoea, orthopnoea, bendopnoea, pulmonary rales and an S3 gallop.²¹⁻²³ Hypoperfusion should be suspected if patients have cool extremities, hypotension, narrow pulse pressure, reduced alertness and/or oliguria.¹⁸,²¹ Early evaluation may also include a serum lactate, which is a useful biomarker of peripheral perfusion.²⁴ An elevated lactate (>2 mmol/L) can identify hypoperfusion in patients without clinical signs of hypoperfusion.²⁴⁻²⁶ It is also a prognostic marker, as an elevated lactate is independently associated with higher mortality rates.²⁴

Identifying the haemodynamic profile helps guide therapy, and patients may transition between multiple profiles during their hospitalization. Congestion without hypoperfusion, the warm-wet profile, is the most common presentation in patients admitted with HF.²¹,²⁷,²⁸ These patients benefit (in the short-term) from continued diuresis with loop diuretics. In practice, clinicians use the degree of clinical congestion and diuretic (natriuretic) response to guide the titration of diuretics.¹³ The cold-wet profile indicates congestion with clinical evidence of hypoperfusion and often necessitates

<figure><img src="image_8.png" /><figcaption>**Figure 1** Haemodynamic profiling in AHF patients with frequencies of each profile. Haemodynamic profiles are warm-wet (most common), warm-dry, cold-wet, and cold-dry. Signs of congestion are elevated JVP, hepatojugular reflex, S3 gallop, pulmonary crackles, peripheral oedema. Signs of inadequate perfusion are cold extremities, decreased mentation, urine output <30 mL/h, lactate >2 mmol/L.</figcaption></figure>
more aggressive interventions, including the use of inotropic agents or vasopressors to improve cardiac output, maintain perfusion pressure and augment diuresis. In patients with hypoperfusion but without cardiogenic shock, if the clinical picture suggests high filling pressure associated with high systemic resistance, IV vasodilators may be used to improve cardiac output.²⁷ The cold-dry profile is rare and can represent patients with hypovolaemia or decreased contractile reserve without fluid retention. These patients might require inotropic support but risk becoming inotrope-dependent.²⁹

Dyspnoea, a common yet highly subjective and multifactorial symptom in the AHF population, must be carefully evaluated during the initial assessment. Because dyspnoea may indicate life-threatening conditions such as cardiogenic shock, pulmonary embolism, or severe pneumonia, it should never be overlooked. The initial patient assessment should therefore include a thorough evaluation of respiratory function. Early evaluation should focus on ruling out respiratory failure and determining the need for respiratory support through clinical examination and, ideally, blood gas analysis. If diagnostic uncertainty persists, additional testing should be conducted promptly.³⁰ Given that continuous monitoring of arterial oxygen saturation alone is insufficient, serial blood gas analyses are particularly important in patients with worsening clinical status or those requiring respiratory support.

When initial clinical assessment is unclear, especially when the overt signs of volume overload resolve, ultrasound-based assessments may be helpful for non-invasive haemodynamic profiling. Lung ultrasound has a high sensitivity and specificity for diagnosing cardiogenic pulmonary edema.³¹ Inferior vena cava respiratory variation on echocardiography can be used to estimate right atrial pressure³² and has shown prognostic value.³³ Doppler echocardiography can estimate pulmonary artery systolic pressure (PASP) from the tricuspid regurgitant jet velocity and left atrial pressure using left atrial volume index, mitral inflow velocities and tissue Doppler imaging.³⁴⁻³⁶ With the expanding use of bedside ultrasound and growing affordability of the technology, randomized trials to prove the benefit of these techniques are a high priority.

## Identifying coexisting conditions

### Summary of key points

* Evaluate AHF patients for common coexisting conditions that may contribute to HF decompensation and be independent targets for intervention.

* All AHF patients should receive a chest radiograph and ECG early in their hospitalization to rule out the most common coexisting conditions (e.g., infection, arrhythmia and ischaemia).

* Consider screening for chronic comorbidities affecting the long-term clinical trajectory of HF that may have been missed in the outpatient setting.

<table><caption>**Table 2** Common coexisting conditions that should be excluded in every AHF patient</caption><thead><tr><th>Coexisting condition</th><th>Frequency</th></tr></thead><tbody><tr><td>Pneumonia/respiratory process</td><td>15.3%</td></tr><tr><td>Arrhythmias</td><td>13.5%</td></tr><tr><td>Acute coronary syndrome</td><td>14.7%</td></tr><tr><td>Uncontrolled hypertension</td><td>10.7%</td></tr><tr><td>Medication non-adherence</td><td>8.9%</td></tr><tr><td>Diet non-adherence</td><td>5.2%</td></tr><tr><td>Worsening renal failure</td><td>6.8%</td></tr><tr><td>Other</td><td>12.7%</td></tr><tr><td colspan="2">Additional cardiac disease (e.g., endocarditis and myopericarditis)</td></tr><tr><td>Non-respiratory acute infection (e.g., UTI)</td><td></td></tr><tr><td>Anaemia</td><td></td></tr><tr><td>Hyper- or hypothyroidism</td><td></td></tr><tr><td>Medications that increase sodium retention (e.g., NSAIDs, thiazolidinediones and steroids)</td><td></td></tr><tr><td>Medications with negative inotropic effect (e.g., verapamil)</td><td></td></tr><tr><td>Excessive alcohol intake or illicit drug use</td><td></td></tr></tbody></table>

Recognizing coexisting conditions that may impact the presentation and trajectory of AHF exacerbation early in a patient's hospitalization is crucial to guide management, inform prognosis, reduce hospital stays and prevent readmissions.¹³,³⁷ Table 2 lists common coexisting clinical scenarios that can play a role in HF decompensation.³⁸⁻⁴³ A patient's management plan should include evaluating these common conditions, as they are potentially reversible and require a targeted intervention.

Most commonly, pneumonia, chronic obstructive pulmonary disease and other primary pulmonary processes leading to inflammatory-mediated myocardial depression can contribute to AHF and require treatment with antibiotics and anti-inflammatory drugs.⁴⁴,⁴⁵ These comorbidities should be proactively identified and treated, especially in patients with persistent dyspnoea or respiratory failure despite improvements in haemodynamics and congestion, as they are linked to poorer outcomes.⁴⁶⁻⁴⁹ Chest radiography is routinely performed to evaluate for pulmonary venous congestion, pleural effusions and cardiomegaly, which are suggestive of HF, and to rule out an underlying pulmonary processes or alternative causes of respiratory distress.¹³,³⁰,⁵⁰ Arrhythmias, including atrial fibrillation, ventricular tachyarrhythmias and bradyarrhythmias, may require medications to control the arrhythmia or procedures to reverse them. Acute coronary syndrome (ACS) is associated with higher mortality and may necessitate urgent reperfusion therapy.³⁷ Early in their hospitalization, all AHF patients should receive a 12-lead electrocardiogram (ECG) to evaluate heart rate and rhythm and for arrhythmias or ischaemia that may have contributed to the AHF.¹³ Uncontrolled hypertension can exacerbate diastolic dysfunction, leading to left-sided congestion. Non-adherence to medications or diet represents only 8.9% and 5.2% of cases, respectively,³⁹ and thorough evaluation
should continue even after one coexisting factor has already been recognized. Addressing these underlying contributors can decrease the risk of future readmissions, such as providing patient education to reduce medication non-adherence.⁴¹ Managing chronic conditions contributing to AHF can also decrease the rehospitalization rate and improve long-term outcomes.⁵¹

Hospitalization is a valuable opportunity to identify and address previously missed chronic comorbidities associated with HF that may not have contributed to the acute exacerbation but can affect the long-term clinical trajectory. In HF patients with iron deficiency (especially in patients with a transferrin saturation <20%), repletion with IV iron has been associated with decreased hospitalizations and improved symptoms, exercise capacity and quality of life, regardless of the presence of anaemia.⁵²⁻⁵⁶ HF patients who have not yet been screened should therefore be tested while hospitalized to identify and treat iron deficiency that may have been missed in the outpatient setting. Patients should also be monitored for sleep-disordered breathing, which affects 50%-80% of HF patients but remains underdiagnosed and can affect the trajectory of the disease.⁴⁶⁻⁴⁸,⁵⁷ Treatment of obstructive sleep apnoea in HFrEF patients with positive airway pressure therapy has been associated with improvement in symptoms, left ventricular ejection fraction (LVEF) and blood pressure.⁵⁸,⁵⁹ Patients suspected to have sleep-disordered breathing should therefore be referred for polysomnography on discharge. Additionally, HF patients are at risk for secondary mitral regurgitation (MR) due to left ventricular remodelling. Patients with chronic, symptomatic secondary MR despite optimized GDMT should be identified, as transcatheter edge-to-edge repair in these patients can reduce HF hospitalizations and all-cause mortality.⁶⁰ Similarly, a widened QRS in HF patients has been linked to higher all-cause mortality and rates of ventricular tachycardia.⁶¹ The initial screening ECG can identify HF patients with a widened QRS who may benefit from cardiac resynchronization therapy, which has been shown to reduce mortality and hospitalizations and improve symptoms and quality of life in select populations.⁶²⁻⁶⁵

## Diagnostic evaluation

### Summary of key points

* Order a daily serum sodium, potassium, creatinine and BUN in AHF patients receiving IV diuretics or undergoing medication titration.

* Do not trend daily NPs but consider collecting a pre-discharge NP.

* Place AHF patients on telemetry monitoring as able to monitor for arrhythmias until clinically stable.

* Patients with no previous echocardiogram should get a TTE.

* Repeat TTE and right heart catheterization should be reserved for select cases where there is a major change in clinical status and/or a low output syndrome.

* Ischaemic evaluation should be performed in patients with concomitant ACS and may be considered in patients with barriers to access outpatient ischaemia testing.

During AHF hospitalizations, a standard diagnostic evaluation should be performed to assess severity and trajectory. Daily labs should include serum electrolytes, creatinine and blood urea nitrogen (BUN) to optimize management and evaluate suitability for treatment options, particularly while receiving IV diuretics or titrating medications that may affect renal function or electrolytes.¹³

B-type natriuretic peptide (BNP) or N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) testing is recommended at admission.¹³ These biomarkers have both diagnostic and prognostic value and have been shown to be a better predictor of outcomes than clinician judgement,⁶⁶ with higher levels correlating to increased risk of all-cause death, cardiovascular death and major cardiovascular events.⁶⁶⁻⁶⁹ Serial natriuretic peptide (NP) testing to guide inpatient management, however, has not been shown to improve outcomes, as changes in NP levels lag behind clinical assessment.⁷⁰,⁷¹ Collecting a pre-discharge NP may be considered as a prognostic tool, as levels correlate with the risk of AHF readmission and death.⁷²,⁷³ This information may be used to guide discussions on prognosis with patients, but more evidence is needed to determine its benefit in routine practice. Although evidence for the diagnostic utility of other biomarkers is limited,⁷⁴ low serum sodium and elevated BUN at discharge also have prognostic value and are associated with higher risk of all-cause mortality.⁷⁵,⁷⁶

AHF patients should be monitored on telemetry as able to evaluate for arrhythmias until clinically stable. Telemetry may identify occult atrial fibrillation, supraventricular tachycardia, or high PVC burden that the initial ECG did not capture and that may have contributed to the AHF episode. AHF is also a risk factor for developing new-onset arrhythmias, which has been associated with higher in-hospital morbidity and mortality.⁷⁷

Additional testing may be indicated in select cases. If clinical concern for specific sequelae of HF exists, further lab testing may include liver function tests for congestive hepatopathy, as these markers also provide prognostic information.⁷⁸⁻⁸² An arterial blood gas should be performed as one of the first evaluations in patients with respiratory distress to assess and monitor respiratory failure and to select or adjust respiratory support. A mixed venous oxygen saturation may be useful for monitoring perfusion.²⁶ Troponin assessment is indicated if there is concern for ACS based on clinical presentation or ECG findings. In patients with newly diagnosed HF or patients with no previous echocardiogram, transthoracic echocardiography (TTE) should be performed to assess cardiac function and identify structural abnormalities to guide treatment.⁸³ However, routine repeat TTE is not needed in the absence of a change in clinical status.¹³,⁸⁴ Similarly, haemodynamic evaluation with right heart catheterization has not shown benefit in routine use,⁸⁵ but may be helpful to guide management decisions when haemodynamics are unclear based on exam or in patients with RV dysfunction or severe/refractory congestion.¹³,²⁹ As AHF is a state of multi-organ dysfunction, the assessment of other
organs that are suspected to be involved in the decompensation may also provide additional information.⁸⁶⁻⁸⁸

Ischaemic evaluation should be considered in patients with HFrEF who are likely to have obstructive CAD and are candidates for coronary revascularization. Ischaemic evaluation is often not necessary during an index hospitalization unless a patient presents with ACS. Additionally, routine ischaemic evaluation and coronary revascularization in patients with HF with preserved EF (HFpEF) is not recommended due to limited evidence, highlighting the need for further investigation in this population. However, early evaluation in patients with new-onset HFrEF is recommended to guide treatment strategies, which differ significantly between ischaemic and non-ischaemic cardiomyopathy. Ischaemic evaluation within 90 days of HFrEF diagnosis has been associated with lower 1-year mortality rates and higher treatment rates with GDMT and coronary revascularization.⁸⁹ Despite this evidence, less than 40% of patients receive ischaemic evaluation within this timeframe,⁹⁰ possibly related to lack of access to or availability of testing modalities, variation in clinical suitability of patients to undergo testing or reperfusion, and lack of outpatient follow-up. Given this underutilization of early CAD testing, HFrEF patients who may not receive timely outpa-

tient ischaemic evaluation should be considered for inpatient testing. Figure 2 depicts an approach to ischaemic evaluation in HFrEF patients.⁹¹ Modalities include the gold standard invasive coronary angiography and several non-invasive alternatives, including coronary computed tomography angiography and stress imaging such as stress echocardiography, single-photon emission computed tomography, positron emission tomography and cardiac magnetic resonance. The modality selection should be based on pre-test probability for CAD and candidacy for coronary revascularization.

## Decongestion strategy

### Summary of key points

* Begin diuresis with an IV loop diuretic at 2.5 times the patient's home oral dose, or IV furosemide 20–40 mg in diuretic-naïve patients.

* Check a post-diuretic uNa⁺ to assess diuretic response (after approximately 2 h). A uNa⁺ < 70 mmol/L suggests inadequate diuretic response.

* Introduce full-dose SGLT2i early during hospitalization.

* If there is inadequate diuresis, serially double the loop diuretic dose to a maximum daily dose of 400–600 mg furosemide equivalents (up to 1000 mg in patients with severely impaired kidney function).

(Continues)

**Figure 2** Diagnostic evaluation of ischaemic cardiomyopathy in heart failure with reduced ejection fraction. ACC, American College of Cardiology; AHA, American Heart Association; CAD, coronary artery disease; CCTA, coronary computed tomography angiography; CMR, cardiac magnetic resonance; ECG, electrocardiogram; ESC, European Society of Cardiology; HFSA, Heart Failure Society of America; HFrEF, heart failure with reduced ejection fraction; ICA, invasive coronary angiography; ICM, ischaemic cardiomyopathy; PET, positron emission tomography; SE, stress echocardiography; SPECT, single-photon emission computed tomography; RWMA, regional wall motion abnormality. **ICM is angiographically defined by the presence of ≥75% stenosis of ≥2 coronary arteries or ≥75% stenosis of either the left main coronary artery or the proximal left anterior descending artery. Reproduced with permission from Chang AJ et al. Med Clin North Am. 2024 May;108(3):553–566.

<figure><img src="image_9.png" /></figure>
## Summary of key points

* If continued poor diuresis, add an adjunctive agent, such as metolazone, hydrochlorothiazide, chlorothiazide or acetazolamide. Use acetazolamide in patients with a serum bicarbonate ≥27 mmol/L and eGFR <45 mL/min.

* Consider using vasodilators, particularly in patients with severe hypertension or acute pulmonary oedema.

* Monitor serum potassium daily and potentially more frequently with aggressive diuresis and electrolyte disturbances.

* Do not discontinue diuretics solely for minor drops in eGFR (particularly if diuretic response is adequate). Continue to monitor eGFR daily and reduce diuretics if eGFR continues to drop.

The initial treatment for AHF patients remains consistent regardless of LVEF, focusing on prompt symptom relief along with initiation and/or optimization of GDMT.

Diuretics and adjunctive agents in AHF patients have been associated with improvement in physical signs of congestion, symptoms and quality of life,⁹²,⁹³ and early diuretic administration (<1 h) may be associated with decreased hospitalization and mortality rates.⁹⁴,⁹⁵ Figure 3 illustrates a diuretic dosing algorithm. IV loop diuretics (furosemide, torsemide

and bumetanide) are the preferred agents for decongestion in AHF.⁹⁶ The DOSE trial showed that a high-dose loop diuretic strategy at 2.5 times the patient's previous oral dose is associated with greater diuresis and relief of dyspnoea compared with lower doses, despite a transient worsening of renal function.⁹⁷ Patients not taking diuretics at home usually respond adequately to a starting dose of IV furosemide 20–40 mg.⁹⁸⁻¹⁰⁰ Continuous infusion does not show benefit over intermittent boluses,⁹⁷ although it is occasionally employed in cases of poor diuretic response or diuretic resistance, where it may offer clinical value.

Diuretic response should be evaluated with a spot urine sodium (uNa⁺), the best-known objective marker of diuretic response that can significantly help guide diuretic therapy.¹⁰¹⁻¹⁰⁵ Assessment of diuretic effectiveness is commonly based on surrogate measures, including weight loss, urine output, and clinical signs and symptoms, which are not predictive of prognosis.¹⁰⁶,¹⁰⁷ Measuring the natriuretic response with a post-diuretic uNa⁺, on the other hand, has been shown to outperform other estimates as a prognostic indicator, with greater

<figure><img src="image_10.png" /><figcaption>**Figure 3** Algorithm for management of diuretics in AHF patients. SGLT2i, sodium-glucose cotransporter 2 inhibitor; uNa⁺, post-diuretic urine sodium; HTN, hypertension.</figcaption></figure>
sodium excretion and a net negative sodium balance correlat-
ing with better decongestion.¹⁰⁶ Post-diuretic uNa⁺ is a rela-
tively simple, low-cost, non-invasive and objective marker of
diuretic response that can be used to quickly titrate diuretics
during decongestion.¹⁰¹,¹⁰² A spot uNa⁺ of <50–70 mmol/L
measured 2 h after diuretic administration suggests
inadequate diuretic response and should prompt clinicians to
consider escalation of diuretic dosing earlier than waiting 6 h
after diuretic dosing to measure urine response.¹⁰⁸
Natriuresis-guided diuretic protocols have been shown to im-
prove natriuresis and diuresis¹⁰⁵,¹⁰⁹,¹¹⁰ and result in shorter
hospital stays¹⁰⁹ than strategies based on monitoring clinical
signs of congestion on exam or measuring net urine output.
However, they did not impact long-term clinical outcomes.

When there is inadequate diuresis, the next step should be loop diuretic dose escalation, often with a serial doubling of the dose,¹¹¹ up to a maximum daily dose of 400–600 mg furosemide equivalents, and up to 1000 mg in patients with severely impaired kidney function. A high-dose loop diuretic strategy is associated with increased net fluid loss and relief of dyspnoea compared with lower doses.⁹⁷

In patients on high-dose loop diuretics, a stepped pharma-
cological approach with the addition of adjunctive agents has
shown promising results for decongestion.¹¹¹ Sequential
nephron blockade with thiazide diuretics, including
hydrochlorothiazide,¹¹² metolazone or chlorothiazide¹¹³ in-
creases urine output and weight loss, but the diuretic effect
of hydrochlorothiazide decreases in patients with eGFR
<45 mL/min.¹¹² Adjunctive acetazolamide, which reduces
proximal tubule sodium reabsorption, also improves diuretic
response in patients with serum bicarbonate levels
≥27 mmol/L in particular and leads to shorter hospital
stays.¹¹⁴⁻¹¹⁷ Tolvaptan, a vasopressin receptor antagonist,
has also been used as an adjunctive agent, but effects on di-
uresis and symptoms have been mixed.¹¹³,¹¹⁸⁻¹²¹

The initiation of SGLT2i has been linked to increased diuresis and decongestive effects, but the lasting impact of this decongestive benefit is currently disputed (while the longer-term clinical outcome benefits are clear).¹²²⁻¹²⁵ SGLT2i inhibit glucose and sodium reabsorption in the proximal tubule, causing osmotic diuresis and natriuresis. The addition of SGLT2i to standard diuretic therapy increases urine output and decreases required doses of loop diuretics without affecting kidney function.¹²⁶,¹²⁷

Vasodilators, such as nitroglycerin, nesiritide and
clevidipine, can relieve dyspnoea and may be used in patients
with severe high blood pressure and acute pulmonary
oedema, as they can benefit from a swift and controlled
reduction in systemic vascular resistance.¹²⁸⁻¹³⁰ However,
the routine use of vasodilators in other scenarios does not
have clear benefit, and their use is limited by the risk of
hypotension,¹³¹ which is associated with higher mortality
during AHF episodes and should be avoided.¹³² A recent
meta-analysis of vasodilators in AHF did not confirm their

positive impact on survival, but their use was associated with
a lower risk of intubation.¹³³ In the GALACTIC trial, the early
use of vasodilators did not reduce the risk of poor outcomes
during 180 days.¹³¹

The use of inotropes is associated with several risks,
despite augmenting cardiac output. Inotropes, such as
dobutamine and milrinone, can increase myocardial oxygen
demand and are associated with a higher incidence of
arrhythmias.¹³⁴ Inotropic therapy is also linked to higher
in-hospital and all-cause mortality.¹³⁵,¹³⁶ These agents are
therefore reserved for patients with symptomatic hypoperfu-
sion and/or cardiogenic shock.¹³

Several parameters require monitoring during decongestion. Fluid intake should be monitored and managed to achieve a net negative balance. In patients with significant hyponatremia or with inadequate diuresis, fluid intake should be limited to 1–1.5 L/day. Though restricting fluid intake has not been shown to significantly improve mortality or rehospitalization, patients with high fluid intake or who eat food with high water content may display pseudo-diuretic resistance and remain congested despite adequate diuresis. Potassium levels should be measured daily, and potentially more frequently in patients undergoing aggressive diuresis or with electrolyte disturbances. Hypokalaemia is common with increased renal losses of potassium with loop diuretics and often requires potassium repletion. Systolic blood pressure can also drop with decongestion, as increased cardiac output decreases systemic vascular resistance. Asymptomatic hypotension is common, and therapies should not be discontinued unless the patient develops symptoms or there is a concern for hypoperfusion. In addition, diuretic dosage can be safely escalated even with drops in estimated glomerular filtration rate (eGFR), as transient reductions during effective decongestion are common and not linked to long-term kidney dysfunction.¹³⁷,¹³⁸ True worsening renal function should be suspected if eGFR continues to decline over consecutive days, in which case a reduction in diuretic dosage may be necessary.¹³⁷⁻¹⁴⁰

Decongestion endpoints

Summary of key points

* There is a need for sensitive and specific decongestion endpoints to reduce the risk of readmission and mortality. POCUS is emerging as a potential solution, but more trials are critically needed.

The goal at discharge is euvolaemia,³⁸ but no satisfactory decongestion endpoint exists. Current endpoints used to assess volume status and treatment response, such as resolution of symptoms or attaining a patient’s ‘dry weight’, are inaccurate markers of decongestion with poor correlation to clinical outcomes.¹⁹,¹⁰⁶,¹⁴¹⁻¹⁴³ Persistent congestion at discharge is common, occurring in 25%–48% of patients,²⁷,¹⁴⁴,¹⁴⁵
and is associated with higher readmission and mortality rates.⁷⁶,¹⁴⁶,¹⁴⁷ Unfortunately, we also lack objective markers to guide the transition from IV to oral diuretics, which could be valuable from a practical perspective.

There is a pressing need for new trials to establish more accurate, objective and standardized endpoints for decongestion.¹⁴⁸,¹⁴⁹ Point-of-care ultrasound (POCUS) has emerged as a promising tool in this regard. Lung ultrasound can reveal B-lines indicating pulmonary congestion, and inferior vena cava and Doppler assessments can provide information on intravascular congestion and cardiac filling pressures. However, the role of POCUS in the management of AHF and its effect on outcomes remains unvalidated. Clinical trials are critically needed to validate the use of POCUS in decongestion strategies to inform clinical decision-making and enhance patient outcomes.

# Guideline-directed medical therapy (GDMT) optimization

## Summary of key points

* Initiation/uptitration/optimization of GDMT is the most important and, in a long-term perspective, life-saving intervention that must be performed during an AHF episode.

* GDMT with an evidence-based beta-blocker, RASi or ARNi, MRA, and SGLT2i should be initiated/uptitrated within 3 days of admission (if the patient is not already on optimal dosing).

* Initiation/uptitration/optimization of GDMT should not be delayed by absolute decongestion.

* Prioritize starting multiple GDMT at low doses over uptitrating a few to optimal dosing.

* Home GDMT should be continued and uptitrated to optimal dosing.

* Uptitrate GDMT to at least 50% of the target doses as quickly as tolerated during hospitalization.

Guideline-directed medical therapy (GDMT) for HF have been shown to improve morbidity and mortality and include evidence-based beta-blockers, renin-angiotensin system inhibitors (RASi and ARNi), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). Unlike diuretics, which only target fluid removal, GDMT address the underlying pathophysiological mechanisms involved in HF, including neurohormonal dysregulation and fluid retention.¹⁵⁰,¹⁵¹ In this way, the benefits of GDMT extend beyond immediate symptom relief to significantly improving long-term patient outcomes, and it therefore must be a priority to initiate all four agents in HF patients.

Hospitalization for HFrEF is a critical opportunity to continue, initiate, and further optimize GDMT.¹⁵²⁻¹⁵⁴ Despite strong evidence supporting its role in improving clinical outcomes, in-hospital initiation and uptitration of GDMT remain suboptimal.⁵,⁶,¹⁵⁴⁻¹⁶¹ Early and rapid in-hospital initiation and uptitration of these agents are safe and, in fact, superior to a delayed or slower increase.¹⁶² PIONEER-HF demonstrated

that sacubitril/valsartan was safe to initiate in AHF patients and decreased the composite endpoint of cardiovascular death or rehospitalization compared with enalapril.¹⁶² The EMPULSE trial showed that in-hospital initiation of empagliflozin was well-tolerated and associated with more rapid and sustained decongestion compared with placebo, as well as improvement in a composite endpoint that included death and HF events.¹²³,¹⁶³ The STRONG-HF trial showed that rapid uptitration of GDMT (without SGLT2i) to 50% of the target doses before discharge was associated with reduced symptoms, improved quality of life, and lower risk of death and readmission without increasing the risk of adverse events.¹⁵³,¹⁶⁴⁻¹⁶⁶ Given these facts, initiating, uptitrating, and optimizing GDMT are the most important and, in the long term, life-saving interventions that must be performed during an AHF episode.

Beneficial effects of some GDMT on clinical outcomes are seen early, with event curves separating as early as 12 days (for SGLT2i in HFrEF patients),¹⁶⁷ so any unjustified delays in therapy can result in preventable deaths and hospitalizations.¹⁶⁸ Moreover, post-discharge initiation (for ARNi) cannot reproduce the clinical benefits achieved with early, in-hospital treatment.¹⁶⁹ For these reasons, early GDMT initiation is key, and most trials initiate medications within 2–3 days of admission.¹⁷⁰ GDMT initiation and uptitration should occur as soon as clinical stability is achieved and should not be delayed by absolute decongestion. In fact, rapid initiation of GDMT (excluding beta-blockers) in patients with ongoing congestion is associated with more effective and sustainable decongestion.¹⁵¹ The priority during hospitalization should be to start all four therapies, as each class of medications displays incremental benefits on top of one other. If there is concern for tolerability with multiple agents, they can be initiated at low doses, which still confer benefit.¹⁶⁸ In fact, multitherapy may increase tolerability—for example, SGLT2i may decrease the risk of hyperkalaemia associated with MRAs, or slow the progression of kidney dysfunction and allow better tolerability of RASi and MRAs.¹⁷¹ Additional novel therapeutic agents, such as vericiguat, may be considered in select patients with high-risk HFrEF or worsening HF despite optimized GDMT.¹⁷²

Another reason for suboptimal in-hospital usage rates is that GDMT are often discontinued during hospitalization.¹⁷³,¹⁷⁴ GDMT discontinuation before discharge is associated with increased mortality, readmission, and inpatient adverse events such as worsening renal function and hyperkalaemia.¹⁵⁹,¹⁷⁵⁻¹⁷⁷ Therefore, GDMT should only be held if absolutely necessary. However, 43%–57% of discontinuations do not have clear medical contraindications.¹⁵⁹ Contraindications include severe hypotension, severe bradycardia for beta-blockers, hyperkalaemia refractory to repletion for RASi and MRA, and eGFR <20–30 mL/min for RASi, MRA and SGLT2i.¹⁵⁹ GDMT should not be held for mild or transient
decreases in blood pressure¹⁷⁸ or renal function.¹³,¹⁷⁹ Mild hypotension or hypokalemia are expected side effects of these medications and are often transient. Beta-blockers should not be newly initiated (until euvolaemia is achieved) but can be continued in patients with decompensated AHF.¹⁷⁵,¹⁸⁰ In the case of a medical contraindication requiring discontinuation, GDMT should be resumed early when feasible.

## Conclusion

Despite growing evidence supporting effective management strategies for AHF, real-world practice continues to be hindered by suboptimal patient evaluation, inadequate medication dosing, and insufficient follow-up—factors that contribute to poor outcomes. In this review, we propose a comprehensive approach to early AHF management focused on key interventions shown to improve clinical outcomes. These include daily assessment with bedside haemodynamic profiling, prompt identification and treatment of coexisting conditions, a diuretic strategy starting with high-dose IV diuretics, and early in-hospital use of GDMT. To support clinical implementation, we provide practical algorithms designed to standardize and streamline early AHF care. Looking ahead, future research should prioritize developing validated tools to assess congestion and perfusion, define actionable endpoints for decongestion, evaluate diagnostic modalities such as ultrasound, and design systems of care that promote timely and effective initiation of GDMT during hospitalization.

## Conflict of interest

Dr. Ambrosy has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159 and R01AG091005), the American Heart Association (2nd Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc., Bayer Pharma AG, Cordio Medical, Edwards Lifesciences LLC, Esperion Therapeutics, Inc., Merck, and Novartis and has been a consultant to Corstasis, Merck, Novo Nordisk, scPharma, and SQ Innovation. Dr. Cotter and Dr. Davison are employees of Momentum Research, which has received grants for research from the Heart Initiative, Corteria Pharmaceuticals, Windtree Therapeutics, Echosens, and 4TEEN4 Pharmaceuticals. Dr. Bocchi has received consulting fees from Servier, AstraZeneca, Boehringer Ingelheim; subsidized travel/registration fees/hotel fees from Servier; membership in steering committees from Servier, Novartis, Boehringer

Ingelheim; research grant support through the Heart Institute from Jansen, Bayer/Merck, AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Cardiol Therapeutics, Eurofarma; and honoraria from Servier, Novartis, AstraZeneca and Boehringer Ingelheim. Dr. Butler has been a consultant at Abbott, Adaptyx, American Regent, Amgen, AskBio, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CSL Vifor, CVRx, Cytokinetics, Daxor, Diastol, Edwards, Element Sciences, Faraday, Idorsia, Impulse Dynamics, Imbria, Innolife, Intellia, Inventiva, Levator, Lexicon, Eli Lilly, Mankind, Medtronic, Merck, New Amsterdam, Novartis, NovoNordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Reprieve, Roche, Rycarma, Saillent, Salamandra, Salubris, SC Pharma, SQ Innovation, Secretome, Sequanna, Transmural, TekkunLev, Tenex, Tricog, Ultromic, Vera, and Zoll. Dr. Fudim has received support from the NIH, Alleviant, Gradient, Reprieve, Sardocor, Tenax, and Doris Duke and has been a consultant and/or has ownership interest in Abbott, Acorai, Ajax, Alio Health, Alleviant, Artha, Astellas, Audicor, AxonTherapies, Bodyguide, Bodyport, Boston Scientific, Broadview, Cadence, Cardiosense, Cardioflow, Clinical Accelerator, CVRx, Daxor, Edwards LifeSciences, Echosens, Endotronix, Feldschuh Foundation, Fire1, FlowMod, FutureCardia, Gradient, Hatteras, Hemodynamiq, Impulse Dynamics, ISHI, Lumia Health, Medtronic, NovoNordisk, NucleusRx, Omega, Orchestra, Parasym, Pharmacosmos, Presidio, Procyreon, Proton Intelligence, Puzzle, ReCor, Scirent, SCPharma, Shifamed, Splendo, Summacor, SyMap, Terumo, Vifor Pharma, Vironix, Viscardia, and Zoll. Dr. Harikrishnan has received research grants from the Indian Council of Medical Research. Dr. Mebazaa has received research contracts from 4TEEN4, Roche, Sphingotec, Abbott Diagnostics, Windtree; consulting fees from Roche, Corteria, Adrenomed, Fire, Johnson&Johnson; honoraria for lectures from Merck, Novartis, Roche, Bayer; is co-inventor of a patent owned by S-Form Pharma on combined therapies to treat dyspnoea; and is a committee member for the Secret-HF trial sponsored by the French Government, S-Form Pharma, 4TEEN4, Echosens, and Implicity. Dr. Nauli has received honoraria from Otsuka, Astra Zeneca, Boehringer Ingelheim, Merck, Servier, Novartis, and Bayer for lectures and participation in advisory boards. Dr. Pagnesi reports personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics and Vifor Pharma, all outside the submitted work. Dr. Sato has received honoraria or consulting fees from Otsuka, Novartis, BMS, Bayer, Terumo, Boehringer-Ingelheim, Daiichi-Sankyo, Ono, AstraZeneca, Roche, and Abiomed. Dr. Savarese reports grants and personal fees from CSL Vifor, Boehringer Ingelheim, AstraZeneca, Servier, Novartis, Cytokinetics, Pharmacosmos, Medtronic, Bayer, and personal fees from Roche, Abbott, Edwards Lifescience, TEVA, Menarini, INTAS, GETZ, Laboratori Guidotti, and grants from Boston Scientific, Merck, all out-
side the submitted work. Dr. Biegus has received honoraria from Bayer, Boehringer Ingelheim, and AstraZeneca for lectures and from Alleviant Medical, Reprieve Cardiovascular, and WhiteSwell for participation in clinical trial advisory boards and is a member of the Editorial Board of ESC Heart Failure and Heart Failure Reviews. All other authors report no conflicts of interest.

## Funding

This manuscript was financed by a grant from Wroclaw Medical University IDUB.A46B.24.002. The presented manuscript was funded by the Development Strategy of the Wroclaw Medical University entitled 'UMW in the Light of Scientific Excellence 2024-26'.

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