# Therapeutic novelties in acute heart failure and practical perspectives

Benjamin Deniau, Ayu Asakage, Koji Takagi, Etienne Gayat, Alexandre

Mebazaa, Amina Rakisheva

► To cite this version:

Benjamin Deniau, Ayu Asakage, Koji Takagi, Etienne Gayat, Alexandre Mebazaa, et al.. Therapeutic novelties in acute heart failure and practical perspectives. Anaesthesia Critical Care & Pain Medicine, 2025, 44 (2), pp.101481. 10.1016/j.accpm.2025.101481. inserm-05399895

HAL Id: inserm-05399895

https://inserm.hal.science/inserm-05399895v1

Submitted on 5 Dec 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_2.png" /></figure>

## Review article

# Therapeutic novelties in acute heart failure and practical perspectives

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

Benjamin Deniau<sup>a,b,c,d,e,*</sup>, Ayu Asakage<sup>f</sup>, Koji Takagi<sup>g</sup>, Etienne Gayat<sup>a,b,c,d</sup>,
Alexandre Mebazaa<sup>a,b,c,d,e</sup>, Amina Rakisheva<sup>h</sup>

## ARTICLE INFO

Article history:
Available online 21 January 2025

Keywords:
Acute heart failure
Decongestion therapy
Goal directed medical therapy
ESC guidelines
AHA/ACC/HFSA guidelines

## ABSTRACT

Acute Heart Failure (AHF) is a leading cause of death and represents the most frequent cause of unplanned hospital admission in patients older than 65 years. Since the past decade, several randomized clinical trials have highlighted the importance and pivotal role of certain therapeutics, including decongestion by the combination of loop diuretics, the need for rapid goal-directed medical therapies implementation before discharge, risk stratification, and early follow-up after discharge therapies. Cardiogenic shock, defined as sustained hypotension with tissue hypoperfusion due to low cardiac output and congestion, is the most severe form of AHF and mainly occurs after acute myocardial infarction, which can progress to multiple organ failure. Although its prevalence is relatively low, cardiogenic shock complicates 12% of acute myocardial infarction. After a brief summary of the epidemiology of AHF and cardiogenic shock, followed by key pathophysiological points, we detailed current treatments in AHF and cardiogenic shock what every anaesthesiologist and intensivist needs to know, based on the latest guidelines and randomized clinical trials published in recent years.

© 2025 The Author(s). Published by Elsevier Masson SAS on behalf of Société Française d'Anesthésie et de Réanimation (SFAR). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

## Introduction

Acute Heart Failure (AHF) is a leading cause of death and represents the most frequent cause of unplanned hospital admission in patients older than 65 years [1–3]. As congestion represents the pathophysiological cornerstone of AHF, decongestive therapies initiated before or on admission play a central role in the initial management of AHF patients which should be followed, before discharge, by rapid implementation of guideline-directed oral medical therapies (GDMT) for HF [4]. Since the past decade, several randomised clinical trials have highlighted the importance and pivotal role of certain therapeutics, including decongestion by the combination of loop diuretics, the need for rapid GDMT implementation before discharge (i.e., beta-blockers (BBs), renin-

angiotensin system inhibitors (RASi) and mineralocorticoids receptor antagonists (MRAs)), risk stratification and early follow-up after discharge therapies. To date, the major role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is no longer debatable and must be a part of the therapeutic arsenal of AHF patients. Cardiogenic shock (CS), the most severe form of AHF, frequently complicates AHF. Cardiogenic shock is defined as a low-cardiac output state due to cardiac dysfunction with low end-organ perfusion. Although aetiologies of CS are various, pathophysiology comprises overlapping components, notably decreased cardiac output, central haemodynamic alteration, microcirculatory dysfunction and systemic inflammatory response syndrome. The prognosis of CS was greatly improved by the routine use of early revascularisation and the improvement of mechanical devices. After a brief epidemiological summary of AHF, we will detail congestion assessment and current treatments, from the first hours to the days before discharge, based on the latest guidelines

<footnote><sup>a</sup> Department of Anesthesia, Burn and Critical Care, University Hospitals Saint-Louis - Lariboisière, AP-HP, Paris, France</footnote>

<footnote><sup>b</sup> UMR-S 942, INSERM, MASCOT, Paris University, Paris, France</footnote>

<footnote><sup>c</sup> Paris Cité University, Paris, France</footnote>

<footnote><sup>d</sup> FHU PROMICE, Paris, France</footnote>

<footnote><sup>e</sup> INI CRCT Network, Nancy, France</footnote>

<footnote><sup>f</sup> Department of Emergency Medicine and Critical Care, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan</footnote>

<footnote><sup>g</sup> Momentum Research Inc, Durham, NC, United States</footnote>

<footnote><sup>h</sup> City Cardiological Center, Almaty, Kazakhstan</footnote>

<footnote>* Corresponding author.
E-mail address: benjamin.deniau@aphp.fr (B. Deniau).</footnote>
and randomised clinical trials published in recent years. Finally, we will develop a definition, pathophysiology and current treatments of CS that every anaesthesiologist and intensivist needs to know on the subject.

## Definition, epidemiology and prevalence of acute heart failure

Defined as the new onset or recurrence of signs of heart failure (HF), diagnosis of acute heart failure (AHF) is based on the presence of dyspnoea, fatigue, pulmonary rales and distended jugular veins at physical examination. The presentation of AHF can differ according to the patient's medical history. The first situation, the more frequent, is the acutely decompensated HF (with symptoms of congestion) in patients with a known HF history. The second situation, the de novo AHF, corresponds to the occurrence of symptoms of congestion in patients without a history of AHF [3,5]. Acute HF is a major and global public health problem, associated with high morbidity and mortality [1,2,6]. One million patients in Europe and the United States of America are admitted with the diagnosis of AHF each year [7,8]. In a recent prospective analysis involving 18 553 AHF patients, Tromp et al. found that the median age of AHF patients was 67 [IQR 57-77] years, with a minority of women (39%) [1]. In-hospital mortality of AHF is estimated to be 2.5%, reaches 10% within 60 to 90 days after hospital discharge and increases to 25-30% in the year following discharge [9-13]. To note, the in-hospital mortality rate was higher in AHF patients admitted for respiratory infection as a precipitant factor (over 4%) [1]. We observed a steady decrease in mortality related to AHF over the last three decades while readmissions remain unacceptably high (10-30% at 90 days and 46% at one year) [14].

## Congestion: the pathophysiological cornerstone of AHF

The pathophysiology of AHF is complex and not completely resolved, but could be summarized as a vicious circle leading to pulmonary and systemic venous congestion. Thus, left ventricular dysfunction leads to decreased blood pressure with impaired tissue oxygen delivery and neurohormonal activation resulting in systemic venous congestion (Fig. 1). Systemic venous congestion, by decreasing venous return to right cavities (= systemic interstitial fluid accumulation) and by increasing left filling

pressures (= pulmonary fluid accumulation), leads to impaired organ perfusion, notably kidneys, liver, lungs and gut [15]. Moreover, right ventricle dysfunction worsens the decrease of venous return and leads to aggravating systemic congestion. The occurrence of organ dysfunction during AHF is associated with poor outcomes [16]. Thus, decongestive therapy in AHF patients aims to relieve congestion and achieve a state of euvolemia, supporting the central role of diuretics in the therapeutic management of AHF patients. Assessment of congestion is central to correctly to determine optimal diuretic strategy.

### Assessment of congestion

A universally accepted diagnostic algorithm for quantification of congestion and identification of precise therapeutic targets is lacking. Unresolved congestion, occurring in 40% of admitted AHF patients at hospital discharge, is an independent predictor of poor outcomes [17]. However, congestion may be difficult to detect and assess notably when signs are mild [15]. Several tools are available to assess congestion in AHF patients in the acute phase.

* Signs and symptoms of congestion

Although physical signs and symptoms are frequent in AHF patients, only moderate to high levels of congestion can be detected by physical assessment. Clinical findings include dyspnoea, orthopnoea, systemic oedema, jugular veins distension and third heart sound [15]. Unfortunately, signs and symptoms of congestion are late manifestations of increased cardiac filling pressures [18].

* Clinical congestion score

Grading congestion scores could be an interesting tool for daily congestion assessment (including clinic, biological and dynamic manoeuvres items) but needs to be validated before its recommendation [19]. To date, no scores are daily used or clinical assessment of congestion in AHF patients. These scores are often used as prognostic rather than diagnostic tools and their clinical utility needs to be determined.

* Congestion biomarkers

<figure><img src="image_4.png" /><figcaption>**Fig. 1.** Pathophysiology of acute heart failure. BP: blood pressure, LV: left ventricle, RV: right ventricle.</figcaption></figure>
Natriuretic peptides, such as B-type natriuretic peptide (BNP), N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide, are interesting candidates to assess volume status and guide decongestive therapies but fluid overload may not the sole cause of increased levels of these biomarkers [20,21]. Interestingly, a decrease greater than 30% at day 5 of natriuretic peptides in AHF patients after fluid removal with a discharge value < 1500 pg/mL are good prognostic markers [22]. Due to the large use of sacubitril/valsartan in HF and its interpretation, NT-proBNP is likely to become the standard natriuretic peptide to use in AHF patients. Finally, apart from natriuretic peptides, renal (in case of worsening renal function) and liver function markers (cholestatic liver injury due to congestion) are interesting markers of congestion and can drive an optimal decongestive therapy.

* Imaging tools

In AHF patients, chest X-ray signs of AHF include peri-bronchial cuffing, cardiomegaly, pulmonary venous congestion and pleural effusion [15]. Transthoracic echocardiography is considered the gold standard for the evaluation of volume status and left ventricular filling pressures [23], set on the transmitral flow and diastolic tissue wave (E/e'). Lung ultrasound by using the analysis of B-line artefacts [24–26], can be considered for the diagnosis of pulmonary oedema in AHF patients with a good sensitivity (94%) and specificity (92%) [27]. Recent studies found that change in lung ultrasound congestion scoring in AHF congestive patients was associated with readmission-free survival [28]. Some authors proposed inferior vena cava diameter and per cent change to guide decongestion in AHF patients. Data are inconsistent and need to be confirmed [29].

## Therapeutic management and treatments of AHF in the first hours

* Identification of etiology and precipitant factor

Rapid diagnosis and identification of precipitant(s) factor(s) are central in the first hours of AHF. Aetiologies of AHF are various and determine the patient's management [30]: acute coronary syndrome, hypertensive emergency, rapid arrhythmias or severe bradycardia/conduction disturbance, acute mechanical causes (e.g. pulmonary embolism), infection (e.g. myocarditis, endocarditis) and tamponade. All the aetiologies are regrouped under the CHAMPIT acronym [6]. Thus, specific etiological therapies should be implemented as early as possible. Recent clinical trials and meta-analyses, from the acute to the post-discharge phase, have redefined the objectives and the management of AHF patients [30].

* Risk stratification and patient placement

Before admission in a specialized department (critical care or cardiology), AHF patients are often cared for in the emergency department (ED), where the decision to admit the patient or discharge at home is often based on clinical judgment. Unfortunately, the risk of discharge at home of a high-risk AHF patient is important, with the possibility of serious adverse events or death [31]. To improve clinical decisions, risk stratification is a tool that could help ED physicians [31]. Recently, by combining a validated point-of-care tool for risk stratification [31–33] in the ED to support clinicians' decisions about admissions or discharge of AHF

patients, with the provision of standardized transitional care, Lee et al. observed a reduction of 12% in the risk of death from any cause or hospitalization for cardiovascular causes within 30 days after AHF episode [34]. This risk remained lower at 20 months after the AHF episode. Implementation of these tools may provide a pathway for early and safe discharge from the hospital or ED. However, these results need to be confirmed by large international cohorts before recommendations in guidelines.

* Decongestive therapy and diuretics

As congestion is the pathophysiological cornerstone of AHF, decongestive therapies are recommended to treat fluid overload and quickly achieve optimal fluid status [6,35]. The latest guidelines recommend that AHF patients with evidence of significant fluid overload should be treated with intravenous loop diuretics to improve symptoms and reduce morbidity [35]. Moreover, therapy with diuretics should be titrated to resolve clinical evidence of congestion to reduce symptoms and rehospitalizations [35].

o Loops diuretics and diuretics combination

Two major and recent clinical trials on decongestive therapies recently published provide important insights on decongestive therapy in AHF patients. Firstly, a recent, multicentre, randomized, double-blind, clinical trial assessing the diuretic effects of acetazolamide in decompensated HF showed that the association of intravenous acetazolamide was associated with a greater incidence of successful decongestion within 3 days after initiation of decongestive therapy [36,37]. However, the authors did not find a reduction in death from any cause in the group of AHF patients treated by the combination of diuretics [36]. Secondly, a multicentre placebo-controlled randomized trial showed the beneficial effect of addition of hydrochlorothiazide to loop diuretics in AHF patients on weight loss, with no changes in patient-reported dyspnoea 72 hours after initiation of decongestive therapy [38]. However, the authors did not find any difference in mortality and rehospitalization rates between groups [38]. Due to the lack of impact on clinical outcomes, this combination was not recommended in the latest guidelines update [30]. Thus, further data are needed.

Guidelines recommend the use of intravenous loop diuretics in AHF patients [6]. Concerning the time-to-intravenous loop diuretics, data suggest that delaying the administration of intravenous furosemide could increase mortality with inconclusive results. Ouwerkek et al. found no association between longer time-to-diuretics and in-hospital mortality but found an association with 30-day mortality [39]. Further studies are needed to confirm these results. Concerning the mode of injection of loop diuretics, a recent clinical trial showed the absence of difference in improved global assessment of dyspnoea between continuous infusion versus bolus injection in AHF patients [40]. To note, in the case of bolus injections, a 6-h interval is needed between two doses to maximize the time the diuretic tubular concentration is adequate to trigger a natriuretic response [23].

o Evaluation of diuretic response and management of diuretic resistance

Weight loss is a surrogate measure of diuretic response, but remains insensitive and accurate [41,42]. According to the mode of action of certain diuretics, natriuresis measurements could be an interesting marker to assess the response of decongestion therapy but also a potential treatment to target. Studies found an association between insufficient natriuresis and increased risk of
mortality and rehospitalization [43,44]. The diuretic response should be quickly assessed after the start of decongestive therapy, by performing a spot urine sodium content measurement after 2-6 h and/or by measuring the hourly urine output. An objective of urine sodium content >50-70 mEq/L at 2 h and/or by a urine output >100-150 mL/h during the first 6 hours is considered a satisfactory diuretic response [6,41]. In case of insufficient diuretic response, dose of loop diuretics should be doubled. If the diuretic response remains inadequate despite optimal doses, association with alternative tubular sites of action may be considered (e.g. acetazolamide or thiazides) [36].

* Sodium-glucose co-transporter 2 inhibitors (SGLT2i)

Initially used for type 2 diabetes mellitus, studies highlighted the pivotal of SGLT2i in chronic HF patients' prognosis improvement [30,35,45-47]. Sodium-glucose co-transporter 2 inhibitors act by inhibiting the SGLT-2 proteins expressed in the renal proximal tubules to reduce the reabsorption of filtered glucose and promote urinary glucose excretion. However, exact mechanisms remain elusive notably in HF. In 2022, Voors et al. authors found that the treatment of clinically stable AHF patients by empagliflozin 10 mg by day until day 90 was associated with a better clinical benefit at 90 days when compared to placebo [48]. The efficacy of the treatment was independent of left ventricular ejection fraction and diabetes status, with a rate of events similar between the two arms [48]. Moreover, Biegus et al. found that treatment by empagliflozin in AHF patients resulted in an early, effective and sustained decongestion associated with clinical benefit at day 90 [49]. Although these treatments are promising in AHF, the efficacy of SGLT2i needs to be confirmed by large randomized clinical trials.

* Vasodilators

Results on the benefits of intravenous infusion of vasodilators on long-term outcomes are inconclusive despite the clinical evidence of hemodynamic and clinical improvement. In a recent clinical trial including older patients admitted to the emergency department (ED) for AHF, Freund et al. the use of intravenous nitrate boluses and management of precipitating factors did not result in a reduced number of days alive at 30 days compared to the usual care [50]. By treating AHF patients with intensive vasodilation compared to usual care, recent findings suggest no benefit in all-cause mortality and AHF rehospitalization at 180 days of this strategy [51]. Recent ESC guidelines recommend the use of intravenous vasodilators (e.g. nitroglycerine 1-2 mg boluses) in case of high systolic blood pressure (systolic blood pressure > 110 mmHg), started at low doses and up-titrated to achieve clinical improvement and blood pressure control (Class IIb, Level B) [6].

* Iron supplementation therapies

Iron deficiency affects more than 50% of AHF patients and is associated with poor outcomes conferring an increased risk of rehospitalizations and death [52,53]. Therefore, diagnosis and treatment of iron deficiency with ferric carboxymaltose or ferric derisomaltose after an AHF episode are highly recommended by the latest guidelines [6,30]. Two major randomized clinical trials were recently published on the subject and recommend the use of intravenous iron treatment to reduce the risk of hospital admission for HF after an episode of AHF [54,55].

* Other measures

* Non-invasive ventilation

Non-invasive ventilation (NIV) is considered a major point of the therapeutic management of AHF patients, commonly used since the 1980s. By applying positive pressure by three modalities (continuous positive airway pressure (CPAP), pressure support ventilation (NIPSV) or high-flow nasal cannula (HFNC)) in conscious AHF patients, NIV reduces the need for endotracheal intubation and decreases the risk of ventilator-associated pneumonia [56]. The latest ESC guidelines recommended NIV as a Class IIa recommendation with a level of evidence B in AHF patients with respiratory distress (defined as respiratory rate > 25/min and/or SpO₂ < 90%) [6]. Although randomized clinical trials and meta-analyses highlighted the benefits of NIV in AHF patients when compared to conventional oxygen therapy, data on mortality and long-term outcomes are inconclusive. Large randomized clinical trials are needed to confirm these results. In addition, the delay of the beginning of the NIV remains an important question, because some studies found that an early application of NIV in AHF patients was associated with a reduced requirement for mechanical ventilation [57-59]. Finally, NIV was historically contraindicated in acute pulmonary oedema in the setting of acute myocardial infarction after the results of two studies suggested that NIPSV could precipitate acute myocardial infarction [60,61]. These results have never been confirmed by other studies. Thus, because of the absence of a relationship between NIV and the risk of acute myocardial infarction, NIV is a safe technique to consider in this type of patient. However, further studies are needed in this indication of NIV. A close clinical and biological monitoring of AHF patients when NIV is used is needed to ensure the success of the technique. Respiratory rate, oxygen saturation, pH and PaCO₂ are the most common and easy parameters to monitor in patients under NIV. One of the keys to the success of NIV is the optimal synchronisation between the patient's breathing and the ventilator [62-64]. The most common cause of asynchrony is air leakage, which can be prevented by an optimal adjustment of the facial mask, a shortening inspiration time, a change in pressure support and modification of inspiratory and expiratory triggers.

In AHF patients, NIV must be continued until a satisfactory recovery has been achieved and needs to be stopped in case of the presence of criteria of mechanical ventilation (e.g., cardiac or respiratory arrest, worsening of altered mental status, progressive worsening of pH, PaCO₂, PaO₂, signs of fatigue, need to protect the airway, persistent haemodynamic instability, agitation and/or intolerance to NIV) or in case of contraindications [65]. Weaning of NIV in AHF patients is ensured by a decrease of FiO₂, positive end-expiratory pressure and ventilation setting. The use of high flow nasal cannula must be considered in case of predicted difficulty of NIV weaning [66,67]. However, data are needed to confirm the benefits of HFNC in NIV weaning in AHF patients.

* Morphine and anxiolytic treatments

Sedative treatments such as morphine and short half-life benzodiazepines (e.g. midazolam) could have potential indications in AHF to reduce anxiety and dyspnoea. However, clinical trials failed to show the benefits of sedative treatments on the mortality of patients admitted for AHF in the ED [68]. Moreover, serious adverse events were more common in the morphine group, confirming the results of previous studies [69-71]. Further studies are needed but routine use of opiates in AHF patients is currently not recommended [6].

## Oral long-lasting therapies to implement before discharge

* Goal directed medical therapies
The latest North American and European guidelines for chronic HF recommended that GDMT for HF includes BBs, angiotensin-converting enzyme inhibitors (ACEi) and MRAs for HFrEF and SGLT2i for all HF patients regardless of LVEF [72]. Research after discharge of AHF patients has recently progressed during recent years. Acute HF is characterised by a significant neurohormonal inflammatory activation strongly associated with increased adverse outcomes, whose extension and persistence is called the "vulnerable" period, persisting 3 to 6 months after AHF episode [73,74]. This period is a high risk of serious adverse events, rehospitalisation and death [74]. Interestingly, recent studies found that post-discharge intervention implemented before discharge (i.e., SGLT2i, angiotensin receptor-neprilysin inhibitors (ARNi), ACEi, angiotensin receptors blockers (ARBs), BBs and MRAs) and prolonged during the vulnerable phase, are cornerstones to improving AHF patients' outcomes. Recently, major randomised clinical trials focused on GDMT before and after discharge AHF patients were published [4,48,75-77].

To date, based on the latest European guidelines for the diagnosis and treatment of AHF, an intensive strategy of initiation and rapid up-titration of GDMT before discharge and during frequent and careful follow-up visits in the first 6 weeks following HF hospitalization is recommended (Class I, Level B) to reduce the risk of HF rehospitalization or death [30]. Latest guidelines recommend intravenous iron supplementation in symptomatic patients with HF and iron deficiency (Class I, Level A) and intravenous ferric carboxymaltose or ferric carbomaltose should be considered in symptomatic HF patients with iron deficiency to reduce the risk of HF hospitalization (Class IIa, Level A).

Fig. 2 summarizes therapeutics measures for AHF based on the latest randomized clinical trials and guidelines.

## Acute heart failure and anesthetic management

Every year, up to 5% of the worldwide population requires major surgery [78], and up to half of adults > 45 years requiring non-cardiac (NC) major surgery present at least 2 or more cardiovascular risk factors, testifying of the growing prevalence of cardiac peri-operative morbidity. Decompensated or untreated HF is associated with a high peri-operative risk, including peri-operative myocardial infarction/injury, stent thrombosis, AHF, relevant arrhythmias, stroke and death [79]. The surgical procedure leads to increased catecholamines release as stress response, neuro-endocrine and sympathovagal imbalance. Moreover, vascular resistances could be modified during surgery due to variations in body core temperature, blood loss and fluid shifts decompensating an already precarious state. Anaesthetic management of HF patients depends on 1/ the degree of HF, 2/ the cause of cardiomyopathy and 3/ the surgical procedure. Of course, in the case of AHF, and as far as possible, surgical procedures should be postponed for the purpose of medical therapy, modification of risk factors and cardiac investigations if needed [80]. A multidisciplinary approach, including anaesthesiologists/intensivists, surgeons and cardiologists is always requested.

### Clinical risk assessment

Perioperative cardiovascular morbidity and mortality are determined by patient (age, cardiovascular risk factors and comorbidities) and surgical procedure risk factors. Initial patient cardiovascular assessment should evaluate accurate history, physical examination and standard laboratory tests (e.g. haemoglobin and renal function). An electrocardiogram and measure of cardiovascular biomarkers (e.g. cardiac troponin and/or NT-

<figure><img src="image_5.png" /><figcaption>**Fig. 2.** Therapeutics measures and treatments in acute heart failure based on the latest major clinical trials and recent ESC AHA/ACC/HFSA guidelines. AHF: acute heart failure, ACEi: angiotensin-converting enzyme inhibitors, ARB: antagonist receptor blocker, ARNi: angiotensin receptor neprilysin inhibitors, BB: beta-blocker, CPAP: continuous positive airway pressure, eGFR: estimated glomerular filtration rate, EI: endotracheal intubation, GDMT: goal-directed medical therapies, IV: intravenous, K+: kaliemia, MRA: mineralocorticoid receptor antagonist, MV: mechanical ventilation, NIPSV: non-invasive pressure support ventilation, NT-proBNP: N terminal pro brain natriuretic peptide, SGLT2i: sodium-glucose co-transporter 2 inhibitor.</figcaption></figure>
proBNP) depends on the patient-related and surgery-related risk (Class I, Level B). In non-emergency situation, and in case of poor functional capacity and/or high NT-proBNP/BNP levels detected before high-risk NC surgery, the latest ESC guidelines recommend the realisation of transthoracic echocardiography (Class I, Level B) [79].

The surgical-related risk is determined by the urgency, and the type (ESC guidelines classified surgery into three groups: low surgical risk (<1%), intermediate surgical risk (1–5%) and high surgical risk (>5%)) and the duration of the procedure. Acute procedures are associated with higher cardiovascular peri-operative risk, reason why the optimal timing of NC surgery should be as multidisciplinary and discussed as possible. Concerning the type of surgical approach, new techniques (laparoscopy, vascular and endovascular procedures and video-assisted NC surgery) have been introduced to replace open surgery and to reduce overall risk. These techniques cause less tissue trauma and intestinal paralysis and are associated with reduced pain, better postoperative pulmonary function and diminished fluid shifts [79]. However, precautions with these procedures should be taken in decompensated or acute HF patients. Indeed, pneumoperitoneum induced by laparoscopy increases intra-abdominal abdominal pressure with direct consequences such as the reduction of venous return, and the risk of reducing cardiac output already decreased during AHF. Thus, the latest ESC guidelines recommend endovascular or video-assisted procedures for patients with high cardiovascular risk for patients undergoing vascular or pulmonary surgery (Class IIa, Level B) [79].

Before surgery, smoking cessation and control of CV risk factors are always recommended in AHF patients, as it is associated with reduced postoperative complications and mortality. When surgery

is postponed, the question of continuation and discontinuation of HF medications should be answered. Table 1 summarises the latest recommendations for pharmacological cardiovascular treatments in AHF patients before NC surgery. Antiplatelets and oral anticoagulants are not included as they are subject to specific recommendations.

## Perioperative management and anaesthesia

Routine use of intra-operative monitoring improves the safety of surgical outcomes without data available on prognosis relevance. Indeed, no strong evidence on invasive arterial and central venous monitoring and outcomes in AHF patients is available. However, invasive monitoring helps anesthesiologists to anticipate or limit hemodynamic changes. Minimal cardiovascular monitoring should include blood pressure (non-invasive or invasive), electrocardiogram and pulse oximetry [79]. Transthoracic echocardiography is used in case of decompensated or AHF in major surgery to monitor cardiac output or during cardiac surgery. The decision to implement cardiovascular monitoring depends on individual patient-directed assessment. Cardiac monitoring by arterial pulmonary catheter is not routinely recommended.

Anaesthetic technique (general vs. locoregional technique) should be discussed with surgeons. In the case of general anaesthesia, the choice of anaesthetic agents is of major importance, notably by limiting the risk of hypotension and end-organ perfusion, already impaired in decompensated and AHF. Findings suggest no association between volatile or intravenous anaesthetic agents and post-operative cardiac events in NC surgery [79]. Finally, locoregional could be an alternative to general anaesthesia in certain cases. However, neuraxial blockade induced

<table><caption>**Table 1**
Management of pharmacological cardiovascular treatments in AHF patients before non-cardiac surgery.</caption><thead><tr><td>Pharmacological treatment</td><td>Indications/benefits</td><td>Recommendations</td></tr></thead><tbody><tr><td>Beta-blockers</td><td><ul><li>Reducing myocardial oxygen consumption by reducing contractile force and heart rate (cardioprotection)</li><li>Reducing acute inflammatory responses (metoprolol)</li></ul></td><td>Pre-operative initiation before high-risk NC surgery must be considered in patients with ≥2 risk factors (Class IIb, Level A)<br>Peri-operative continuation if chronic treatment (Class I, Level B)</td></tr><tr><td>Amiodarone</td><td><ul><li>Prevention of post-operative atrial fibrillation</li></ul></td><td>No recommendation</td></tr><tr><td>Statins</td><td><ul><li>Reducing cholesterol biosynthesis</li><li>Anti-atherosclerotic effects</li></ul></td><td>Peri-operative continuation (Class I, Level B)</td></tr><tr><td>Renin-angiotensin-aldosterone system inhibitors</td><td><ul><li>Reducing systemic inflammation</li><li>Nephroprotection</li><li>Reducing of all-cause mortality in HF patients</li></ul></td><td>Data inconclusive<br>Peri-operative continuation in stable HF patients should be considered (Class IIb, Level C)<br>Data inconclusive</td></tr><tr><td>Calcium channel blockers</td><td><ul><li>Improving balance between myocardial oxygen supply and demand</li></ul></td><td>Peri-operative continuation but withholding the dose on the day of surgery<br>No recommendation</td></tr><tr><td>Alpha-2 receptors agonists</td><td><ul><li>Reducing post-operative ganglionic noradrenaline output</li><li>Reducing catecholamines surge during surgery</li></ul></td><td>No recommendation</td></tr><tr><td>Diuretics</td><td><ul><li>Reducing systemic congestion</li></ul></td><td>For patients on chronic diuretics to treat hypertension, discontinuation of diuretics on the day of surgery should be considered (Class IIa, Level B)<br>No recommendation</td></tr><tr><td>Ivabradine</td><td><ul><li>Alternative to beta-blockers</li><li>Reducing heart rate without hypotensive effect</li></ul></td><td>No recommendation</td></tr><tr><td>Sodium-glucose co-transporter-2 inhibitors</td><td><ul><li>Inhibiting the SGLT-2 proteins expressed in the renal proximal tubules to reduce reabsorption of filtered glucose</li><li>Promoting urinary glucose excretion</li></ul></td><td>Interruption for at least 3 days before surgery (Class IIa, Level B)</td></tr></tbody></table>
sympatholysis with a high risk of severe hypotension [80]. Analgesic effects accelerated recovery, and decreased postoperative complications are interesting benefits of locoregional anaesthesia in AHF patients but need to be confirmed. Moreover, no data are available on the benefit of locoregional vs. general anaesthesia on HF patient's prognosis.

## Management of AHF in the intensive care unit

Intensive care unit admission of AHF patients varies from 5% to 45.4% of overall AHF, according to registries, and is associated with a high risk of death [14,81]. Indications of ICU admission are broad and notably rely on the existence of organ failure [82]. As described for AHF, management of AHF in ICU is mainly based on decongestive therapy, associated with the preservation of end-organ perfusion for adequate systemic perfusion. To reach this goal, intensivists should consider pharmacological and non-pharmacological interventions. In case of evolution to cardiogenic shock, early treatment by mechanical circulatory (MCS) support should be considered.

Management of decongestive therapy in AHF admitted in ICU does not differ from standard decongestive therapy for AHF, but the maintenance of normovolemia to prevent reduced end-organ perfusion following hypovolemia is challenging and often requires cardiovascular monitoring and progressive escalation therapy. Loops diuretics are the molecule of choice in this indication. In case of acute kidney injury, (particularly when accompanied by hyperkaliemia or metabolic acidosis) or insufficient response to loop diuretics despite optimal doses (as described above), renal replacement therapy for decongestion should be quickly considered. Other than this indication, the benefits of renal replacement therapy vs. diuretics for decongestion are unclear [83–85]. To reduce left and right-sided filling pressures, vasodilators and inotropes should be considered. As described above, although intravenous vasodilators reduce preload, decrease afterload and increase cardiac output, their clinical benefits have never been demonstrated in AHF patients with normal blood pressure. However, they allowed a rapid control of high blood pressure if necessary. Concerning the use of inotropes (e.g., beta-adrenergic receptor agonists, phosphodiesterase III inhibitors and calcium sensitisers) in AHF patients admitted to ICU, findings suggest an

increase in short and long-term survival by improving impaired cardiac output and end-organ perfusion [86]. Data on the superiority of one inotrope over another in this indication are lacking, but norepinephrine is the most studied molecule in this indication [87]. Finally, oxygen therapy should be considered in patients with $SpO_2 < 90$% by implementing NIV in patients with acute pulmonary oedema [65]. In case of persistent hypoxemia or hypercapnia, intubation should be quickly considered.

## Cardiogenic shock

### Definition

Cardiogenic shock (CS) is a low-cardiac output state and life-threatening syndrome due to cardiac dysfunction and is defined as a shock state with sustained reduced systolic blood pressure ($<90$ mmHg or need of pharmacological or mechanical support to maintain systolic blood pressure $> 90$ mmHg) with low end-organ perfusion [88,89]. Cardiogenic shock remains the most severe form of AHF, with a high in-hospital (30–50%) and one-year mortality (50–60%) [88–90]. Although its prognosis is terrific, outcomes of CS patients (complicating 4–12% of the acute coronary syndrome) was improved thanks to the routine use of early revascularisation and improvement of hemodynamic mechanical devices [88,91]. Although CS is more common during ST-elevation myocardial infarction than non-ST-elevation myocardial infarction, CS could be observed in non-ischaemic aetiology (e.g., myocarditis, Takotsubo syndrome, cardiomyopathies, peripartum cardiomyopathy, valves lesion, post-cardiac surgery, intoxication).

### Pathophysiology of CS (Fig. 3)

The diagnosis of CS is based on the association of low systolic blood pressure $< 90$ mmHg, combined with end-organ hypoperfusion (cold extremities, confusion, oliguria), increased lactate level $> 2$ mmol/L and reduced cardiac index $< 2.2$ L/min/m$^2$. Although aetiologies are various, the pathophysiology of CS shares overlapping components, including reduced cardiac output due to depressional contractility, haemodynamic alterations with low blood pressure, increased left and right ventricles pressures, microcirculatory dysfunction, systemic inflammatory response

<figure><img src="image_6.png" /><figcaption>**Fig. 3.** Pathophysiology of cardiogenic shock. eNOS: endothelial nitric oxide synthase, iNOS: inducible nitric oxide synthase, LV: left ventricle, SBP: systolic blood pressure, SVR: systemic vascular resistances.</figcaption></figure>
and safest pharmacological agent for cardioversion in critically ill patients [98].

### o Inotropes and vasopressors

Dobutamine and milrinone, the two main inotropic agents prescribed during CS, are used to manage hypoperfusion [88]. By stimulating β-receptors to increase cardiac contractility and relaxing vascular smooth muscle to reduce afterload, dobutamine causes severe hypotension. Milrinone, a phosphodiesterase-3 inhibitor, increases intracellular calcium levels, myocardial contractility and cardiomyocyte relaxation, this drug causes arterial and venous vasodilation [88]. Used at the lowest doses for the shortest duration, inotropes should be used with progressive titration, and are indicated in case of persistent low cardiac output and hypotension related to left ventricle systolic dysfunction [95].

Vasopressors, including high-dose dopamine, norepinephrine and epinephrine, present α-receptor vasoconstricting properties and promote myocardial contractility. A randomised clinical trial comparing dopamine versus norepinephrine as the first-line vasopressor to manage CS after acute myocardial infarction did not observe a difference in 28-day mortality [99]. In addition, sub analysis of overall CS patients highlights an increased mortality in patients receiving dopamine when compared to norepinephrine, with more arrhythmic events [99]. Levosimendan, an inodilator combining calcium sensitisation, phosphodiesterase inhibition and vasodilating properties has been evaluated in CS patients with inconsistent results [100–103]. While levosimendan seems to be a promising drug in CS, further studies are needed to specify which patients could benefit from its use. To note, the SURVIVE study observed reduced mortality in CS patients who received levosimendan when compared to dobutamine [104]. To date, the target blood pressure to reach in CS patients is unknown and still debated, the latest recommendations suggest an objective of 65 mmHg of mean blood pressure [95].

### o Mechanical circulatory support

To date, robust randomised clinical trials on evidence of mechanical circulatory support (MCS) in CS patients are lacking. Mechanical circulatory support is indicated in CS patients to improve end-organ perfusion when inotropic support is insufficient, leading to tissue hypoperfusion in severe to refractory CS [105]. However, evidence of MCS for survival benefits of CS is limited [105–108]. Available devices for MCS are usually classified as right ventricle support, left ventricle support and biventricular support, providing partial or full circulatory support (Table 2). No data on the benefits of one device on another are available. The choice depends on CS types and local expertise [98]. These techniques should be considered in the absence of any irreversible cardiac failure, to allow heart recovery (bridge to recovery), transplantation (bridge to transplantation) or long-term MCS. Further studies are needed to determine the exact indication of MCS in CS patients.

## Conclusion

The latest guidelines from the European and North American cardiology and HF societies have specified the place of main therapeutic measures of AHF. Concerning therapeutic novelties in AHF, SGLT2i take a large part of the discussion in terms of potential benefits on mortality and prevention of readmission, but clinical data are lacking. Ongoing trials may confirm these interesting results. The most severe form of AHF, CS, remains associated with poor outcomes, despite recent advances in therapeutic manage-

ment, notably in the case of CS-induced by acute myocardial infarction. Recent classification of CS should enable better prognosis of these patients and need to be evaluated in large cohorts. The place of MCS in the therapeutic management of CS patients needs to be precise.

## Disclosure of interest

AM received speaker's honoraria from Orion, Otsuka, Philips, Roche and Servier, received fee as member of advisory board and/or Steering Committee and/or research grant from 4TEEN4. EG declared competing interest with Baxter, Mindray as past consultancy and research grants from Philipps, Edwards and Deltex. Other authors declared no competing of interest.

## Funding

This work did not receive any grant from funding agencies in the public, commercial, or not-for-profit sectors.

## Author contributions

All authors attest that they meet the current International Committee of Medical Journal Editors (ICMJE) criteria for Authorship.

## References

[1] Tromp J, Beusekamp JC, Ouwerkerk W, van der Meer P, Cleland JGF, Angermann CE, et al. Regional differences in precipitating factors of hospitalization for acute heart failure: insights from the REPORT-HF registry. Eur J Heart Fail 2022;24:645–52. http://dx.doi.org/10.1002/ejhf.2431.

[2] Tromp J, Bamadhaj S, Cleland JGF, Angermann CE, Dahlstrom U, Ouwerkerk W, et al. Post-discharge prognosis of patients admitted to hospital for heart failure by world region, and national level of income and income disparity (REPORT-HF): a cohort study. Lancet Global Health 2020;8:e411–22. http://dx.doi.org/10.1016/S2214-109X(20)30004-8.

[3] Arrigo M, Jessup M, Mullens W, Reza N, Shah AM, Sliwa K, et al. Acute heart failure. Nat Rev Dis Primers 2020;6:16. http://dx.doi.org/10.1038/s41572-020-0151-7.

[4] Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet 2022;1938–52. http://dx.doi.org/10.1016/S0140-6736(22)02076-1. S0140-6736(22)02076-1.

[5] Chioncel O, Mebazaa A, Harjola V-P, Coats AJ, Piepoli MF, Crespo-Leiro MG, et al. Clinical phenotypes and outcome of patients hospitalized for acute heart failure: the ESC Heart Failure Long-Term Registry. Eur J Heart Fail 2017;19:1242–54. http://dx.doi.org/10.1002/ejhf.890.

[6] McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–726. http://dx.doi.org/10.1093/eurheartj/ehab368.

[7] Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, et al. The global health and economic burden of hospitalizations for heart failure. J Am Coll Cardiol 2014;63:1123–33. http://dx.doi.org/10.1016/j.jacc.2013.11.053.

[8] Crespo-Leiro MG, Anker SD, Maggioni AP, Coats AJ, Filippatos G, Ruschitzka F, et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur J Heart Fail 2016;18:613–25. http://dx.doi.org/10.1002/ejhf.566.

[9] Filippatos G, Khan SS, Ambrosy AP, Cleland JGF, Collins SP, Lam CSP, et al. International REgistry to assess medical Practice with IOnitudinal obseRva-tion for Treatment of Heart Failure (REPORT-HF): rationale for and design of a global registry. Eur J Heart Fail 2015;17:527–33. http://dx.doi.org/10.1002/ejhf.262.

[10] Gheorghiade M, Zannad F, Sopko G, Klein L, Piña IL, Konstam MA, et al. Acute heart failure syndromes: current state and framework for future research. Circulation 2005;112:3958–68. http://dx.doi.org/10.1161/CIRCULATIO-NAHA.105.590091.

[11] Cleland JGF, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar JC, et al. The EuroHeart Failure survey programme– a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J 2003;24:442–63. http://dx.doi.org/10.1016/S0195-668x(02)00823-0.

[12] Sliwa K, Davison BA, Mayosi BM, Damasceno A, Sani M, Ogah OS, et al. Readmission and death after an acute heart failure event: predictors and outcomes in sub-Saharan Africa: results from the THESUS-HF registry. Eur Heart J 2013;34:3151–9. http://dx.doi.org/10.1093/eurheartj/eht393.

[13] Abraham WT, Fonarow GC, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, et al. Predictors of in-hospital mortality in patients hospitalized for heart failure: insights from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). J Am Coll Cardiol 2008;52:347–56. http://dx.doi.org/10.1016/j.jacc.2008.04.028.
[14] Kimmoun A, Takagi K, Gall E, Ishihara S, Hammoum P, El Bêze N, et al. Temporal trends in mortality and readmission after acute heart failure: a systematic review and meta-regression in the past four decades. Eur J Heart Fail 2021;23:420–31. http://dx.doi.org/10.1002/ejhf.2103.

[15] Girerd N, Seronde M-F, Coiro S, Chouihed T, Bilbault P, Braun F, et al. Integrative assessment of congestion in heart failure throughout the patient journey. JACC Heart Fail 2018;6:273–85. http://dx.doi.org/10.1016/j.jichf.2017.09.023.

[16] Mentz RJ, O'Connor CM. Pathophysiology and clinical evaluation of acute heart failure. Nat Rev Cardiol 2016;13:28–35. http://dx.doi.org/10.1038/nrcardio.2015.134.

[17] Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, et al. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur J Heart J 2013;34:835–43. http://dx.doi.org/10.1093/eurheartj/ehs444.

[18] Abraham WT, Adamson PB, Hasan A, Bourge RC, Pamboukian SV, Aaron MF, et al. Safety and accuracy of a wireless pulmonary artery pressure monitoring system in patients with heart failure. Am Heart J 2011;161:558–66. http://dx.doi.org/10.1016/j.ahj.2010.10.041.

[19] Gheorghiai M, Follath F, Ponikowski P, Barsuk JH, Blair JEA, Cleland JG, et al. Assessing and grading congestion in acute heart failure: a scientific statement from the Acute Heart Failure Committee of the Heart Failure Association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 2010;12:423–33. http://dx.doi.org/10.1093/eurjhf/hfg045.

[20] Bayes-Genis A, Lupón J, Jaffe AS. Can natriuretic peptides be used to guide therapy? EJFCC 2016;27:208–16.

[21] Felker GM, Ahmad T, Anstrom KJ, Adams KF, Cooper LS, Ezekowitz JA, et al. Rationale and design of the GUIDE-IT study: guiding evidence based therapy using biomarker intensified treatment in heart failure. JACC Heart Fail 2014;2:457–65. http://dx.doi.org/10.1016/j.jichf.2014.05.007.

[22] Cohen-Solal A, Logear D, Huang B, Cai D, Niemenin MS, Mebazaa A. Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. J Am Coll Cardiol 2009;53:2343–8. http://dx.doi.org/10.1016/j.jacc.2009.02.058.

[23] Deniau B, Costanzo MR, Sliwa K, Asakage A, Mullens W, Mebazaa A. Acute heart failure: current pharmacological treatment and perspectives. Eur Heart J 2023;44:ehad617. http://dx.doi.org/10.1093/eurheartj/ehad617.

[24] Price S, Platz E, Cullen L, Tavazzi G, Christ M, Cowie MR, et al. Expert consensus document: echocardiography and lung ultrasonography for the assessment and management of acute heart failure. Nat Rev Cardiol 2017;14:427–40. http://dx.doi.org/10.1038/nrcardio.2017.56.

[25] Platz E, Campbell RT, Claggett B, Lewis EF, Groarke JD. Docherty KF, et al. Lung ultrasound in acute heart failure: prevalence of pulmonary congestion and short- and long-term outcomes. JACC Heart Fail 2019;7:849–58. http://dx.doi.org/10.1016/j.jichf.2019.07.008.

[26] Pang PS, Russell FM, Ehrman R, Ferre R, Gargani L, Levy PD, et al. Lung ultrasound-guided emergency department management of acute heart failure (BLUSHED-AHF): a randomized controlled pilot trial. JACC Heart Fail 2021;9:638–48. http://dx.doi.org/10.1016/j.jichf.2021.05.008.

[27] Martindale JL, Wakai A, Collins SP, Levy PD, Diercks D, Hiestand BC, et al. Diagnosing acute heart failure in the emergency department: a systematic review and meta-analysis. Acad Emerg Med 2016;23:223–42. http://dx.doi.org/10.1111/acem.12878.

[28] Harrison NE, Ehrman R, Collins S, Desai AA, Duggan NM, Ferre R, et al. The prognostic value of improving congestion on lung ultrasound during treatment for acute heart failure differs based on patient characteristics at admission. J Cardiol 2024;83:121–9. http://dx.doi.org/10.1016/j.jicc.2023.08.003.

[29] Tsutsui RS, Borowski A, Tang WHW, Thomas JD, Popović ZB. Precision of echocardiographic estimates of right atrial pressure in patients with acute decompensated heart failure. J Am Soc Echocardiogr 2014;27:1072–1078.e2. http://dx.doi.org/10.1016/j.echo.2014.06.002.

[30] McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023;44:3627–39. http://dx.doi.org/10.1093/eurheartj/ehad195.

[31] Lee DS, Lee JS, Schull MJ, Borgundvaag B, Edmonds ML, Ivankovic M, et al. Prospective validation of the emergency heart failure mortality risk grade for acute heart failure. Circulation 2019;139:1146–56. http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035509.

[32] Lee DS, Stitt A, Austin PC, Stukel TA, Schull MJ, Chong A, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med 2012;156:767–75. http://dx.doi.org/10.7326/0003-4819-156-11-201206050-00003. W-261, W-262.

[33] Greig D, Austin PC, Zhou L, Tu JV, Pang PS, Ross HJ, et al. Ischemic electrocardiographic abnormalities and prognosis in decompensated heart failure. Circ Heart Fail 2014;7:986–93. http://dx.doi.org/10.1161/CIRCHEARTFAULURE.114.001460.

[34] Lee DS, Straus SE, Farkouh ME, Austin PC, Taljaard M, Chong A, et al. Trial of an intervention to improve acute heart failure outcomes. N Engl J Med 2023;388:22–32. http://dx.doi.org/10.1056/NEJMoa2211680.

[35] Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: execu-

tive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:1757–80. http://dx.doi.org/10.1016/j.jacc.2021.12.011.

[36] Mullens W, Dauw J, Martens P, Meekers E, Nijst P, Verbrugge FH, et al. Acetazolamide in decompensated heart failure with volume overload trial (ADVOR): baseline characteristics. Eur J Heart Fail 2022;24(9). http://dx.doi.org/10.1002/ejhf.2587.

[37] Martens P, Dauw J, Verbrugge FH, Nijst P, Meekers E, Augusto SN, et al. Decongestion with acetazolamide in acute decompensated heart failure across the spectrum of left ventricular ejection fraction: a prespecified analysis from the ADVOR trial. Circulation 2023;147:201–11. http://dx.doi.org/10.1161/CIRCULATIONAHA.122.062486.

[38] Trullàs JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sánchez-Martelees M, Conde-Martel A, et al. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J 2022;44(5):ehac689. http://dx.doi.org/10.1093/eurheartj/ehac689.

[39] Ouwerkerk W, Tromp J, Cleland JGF, Angermann CE, Dahlstrom U, Ertl G, et al. Association of time-to-intravenous furosemide with mortality in acute heart failure: data from REPORT-HF. Eur J Heart Fail 2023;25:43–51. http://dx.doi.org/10.1002/ejhf.2708.

[40] Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011;364:797–805. http://dx.doi.org/10.1056/NEJMoa1005419.

[41] Mullens W, Damman K, Harjola V-P, Mebazaa A, Brunner-La Rocca H-P, Martens P, et al. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019;21:137–55. http://dx.doi.org/10.1002/ejhf.1369.

[42] ter Maaten JM, Valente MAE, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy. Nat Rev Cardiol 2015;12:184–92. http://dx.doi.org/10.1038/nrcardio.2014.215.

[43] Hodson DZ, Griffin M, Mahoney D, Raghavendra P, Ahmad T, Turner J, et al. Natriuretic response is highly variable and associated with 6-month survival: insights from the ROSE-AHF trial. JACC Heart Fail 2019;7:383–91. http://dx.doi.org/10.1016/j.jichf.2019.01.007.

[44] Damman K, Ter Maaten JM, Coster JE, Krikken JA, van Deursen VM, Krijnen HK, et al. Clinical importance of urinary sodium excretion in acute heart failure. Eur J Heart Fail 2020;22:1438–47. http://dx.doi.org/10.1002/ejhf.1753.

[45] Tomasoni D, Fonarow GC, Adamo M, Anker SD, Butler J, Coats AJS, et al. Sodium-glucose co-transporter 2 inhibitors as an early, first-line therapy in patients with heart failure and reduced ejection fraction. Eur J Heart Fail 2022;24:431–41. http://dx.doi.org/10.1002/ejhf.2397.

[46] Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 2021;384:117–28. http://dx.doi.org/10.1056/NEJMoa2030183.

[47] Cunningham JW, Vaduganathan M, Claggett BL, Kulac IJ, Desai AS, Jhund PS, et al. Dapagliflozin in patients recently hospitalized with heart failure and mildly reduced or preserved ejection fraction. J Am Coll Cardiol 2022;80:1302–10. http://dx.doi.org/10.1016/j.jacc.2022.07.021.

[48] Voors AA, Angermann CE, Teerlink JR, Collins SP, Kosiborod M, Biegus J, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022;28:568–74. http://dx.doi.org/10.1038/s41591-021-01659-1.

[49] Biegus J, Voors AA, Collins SP, Kosiborod MN, Teerlink JR, Angermann CE, et al. Impact of empagliflozin on decompensation in acute heart failure: the EMPULSE trial. Eur Heart J 2023;44:41–50. http://dx.doi.org/10.1093/eurheartj/ehac530.

[50] Freund Y, Cachanado M, Delannoy Q, Laribi S, Yordanov Y, Gorlicki J, et al. Effect of an emergency department care bundle on 30-day hospital discharge and survival among elderly patients with acute heart failure: the ELISABETH randomized clinical trial. JAMA 2020;324:1948–56. http://dx.doi.org/10.1001/jama.2020.19378.

[51] Kozhuharov N, Goudev A, Flores D, Maeder MT, Walter J, Shrestha S, et al. Effect of a strategy of comprehensive vasodilatation vs usual care on mortality and heart failure rehospitalization among patients with acute heart failure: the GALACTIC randomized clinical trial. JAMA 2019;322:2292–302. http://dx.doi.org/10.1001/jama.2019.18598.

[52] Jankowska EA, Kasztura M, Sokolski M, Bronisz M, Nawrocka S, Oleśkowska-Florek W, et al. Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J 2014;35:2468–76. http://dx.doi.org/10.1093/eurheartj/ehu235.

[53] Núñez J, Comín-Colet J, Miñana G, Núñez E, Santas E, Mollar A, et al. Iron deficiency and risk of early readmission following a hospitalization for acute heart failure. Eur J Heart Fail 2016;18:798–802. http://dx.doi.org/10.1002/ejhf.513.

[54] Ponikowski P, Kirwan B-A, Anker SD, McDonagh T, Dorobantu M, Drozdz J, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet 2020;396:1895–904. http://dx.doi.org/10.1016/S0140-6736(20)32339-4.

[55] Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA, Squire IB, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective,
randomised, open-label, blinded-endpoint trial. Lancet 2022;400:2199-209. http://dx.doi.org/10.1016/S0140-6736(22)02083-9.

[56] Girou E, Brun-Buisson C, Taillé S, Lemaire F, Brochard L. Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema. JAMA 2003;290:2985-91. http://dx.doi.org/10.1001/jama.290.22.2985.

[57] Ducros L, Logeart D, Vicaut E, Henry P, Plaisance P, Collet J-P, et al. CPAP for acute cardiogenic pulmonary oedema from out-of-hospital to cardiac intensive care unit: a randomised multicentre study. Intensive Care Med 2011;37:1501-9. http://dx.doi.org/10.1007/s00134-011-2311-4.

[58] Plaisance P, Pirracchio R, Berton C, Vicaut E, Payen D. A randomized study of out-of-hospital continuous positive airway pressure for acute cardiogenic pulmonary oedema: physiological and clinical effects. Eur Heart J 2007;28:2895-901. http://dx.doi.org/10.1093/eurheartj/ehm502.

[59] Foti G, Sangalli F, Berra L, Sironi S, Cazzaniga M, Rossi GP, et al. Is helmet CPAP first line pre-hospital treatment of presumed severe acute pulmonary edema? Intensive Care Med 2009;35:656-62. http://dx.doi.org/10.1007/s00134-008-1354-7.

[60] Mehta S, Jay GD, Woolard RH, Hipona RA, Connolly EM, Cimini DM, et al. Randomized, prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med 1997;25:620-8. http://dx.doi.org/10.1097/00003246-199704000-00011.

[61] Sharon A, Shpirer I, Kaluski E, Moshkovitz Y, Milovanov O, Polak R, et al. High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema. J Am Coll Cardiol 2000;36:832-7. http://dx.doi.org/10.1016/s0735-1979(00)00785-3.

[62] Hess DR. Patient-ventilator interaction during noninvasive ventilation. Respir Care 2011;56:153-65. http://dx.doi.org/10.4187/respcare.01049. discussion 165-167.

[63] Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med 2006;32:1515-22. http://dx.doi.org/10.1007/s00134-006-0301-8.

[64] Vignaux L, Vargas F, Roeseler J, Tassaux D, Thille AW, Kossowsky MP, et al. Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study. Intensive Care Med 2009;35:840-6. http://dx.doi.org/10.1007/s00134-009-1415-6.

[65] Maspí J, Peacock WF, Price S, Cullen L, Martin-Sanchez FJ, Seferovic P, et al. Indications and practical approach to non-invasive ventilation in acute heart failure. Eur Heart J 2018;39:17-25. http://dx.doi.org/10.1093/eurheartj/ehx580.

[66] Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA 2016;316:1565-74. http://dx.doi.org/10.1001/jama.2016.14194.

[67] Hernández G, Vaquero C, González P, Subira C, Frutos-Vivar F, Rialp G, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial. JAMA 2016;315:1354-61. http://dx.doi.org/10.1001/jama.2016.2711.

[68] Domínguez-Rodríguez A, Suero-Mendez C, Burillo-Putze G, Gil V, Calvo-Rodríguez R, Piñera-Salmeron P, et al. Midazolam versus morphine in acute cardiogenic pulmonary oedema: results of a multicentre, open-label, randomized controlled trial. Eur J Heart Fail 2022;24:1953-62. http://dx.doi.org/10.1002/ejhf.2602.

[69] Iakobishvili Z, Cohen E, Garty M, Behar S, Shotan A, Sandach A, et al. Use of intravenous morphine for acute decompensated heart failure in patients with and without acute coronary syndromes. Acute Card Care 2011;13:76-80. http://dx.doi.org/10.3109/17482941.2011.575165.

[70] Miró O, Gil V, Martín-Sánchez FJ, Herrero-Puente P, Jacob J, Mebazaa A, et al. Morphine use in the ED and outcomes of patients with acute heart failure: a propensity score-matching analysis based on the EAHFE registry. Chest 2017;152:821-32. http://dx.doi.org/10.1016/j.chest.2017.03.037.

[71] Caspi O, Naami R, Halfin E, Aronson D. Adverse dose-dependent effects of morphine therapy in acute heart failure. Int J Cardiol 2019;293:131-6. http://dx.doi.org/10.1016/j.ijcard.2019.06.015.

[72] Tsao CW, Lyass A, Enserro D, Larson MG, Ho JE, Kizer JR, et al. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail 2018;6:678-85. http://dx.doi.org/10.1016/j.jchf.2018.03.006.

[73] Greene SJ, Fonarow GC, Vaduganathan M, Khan SS, Butler J, Gheorghiade M. The vulnerable phase after hospitalization for heart failure. Nat Rev Cardiol 2015;12:220-9. http://dx.doi.org/10.1038/nrcardio.2015.14.

[74] Cotter G, Davison B, Cohen-Solal A, Freund Y, Mebazaa A. Targeting the "vulnerable" period - first 3-6 months after an acute heart failure admission - the light gets brighter. Eur J Heart Fail 2022;5:30-5. http://dx.doi.org/10.1002/ejhf.2754.

[75] Kosiborod MN, Angermann CE, Collins SP, Teerlink JR, Ponikowski P, Biegus J, et al. Effects of empagliflozin on symptoms, physical limitations, and quality of life in patients hospitalized for acute heart failure: results from the EMPULSE trial. Circulation 2022;146:279-88. http://dx.doi.org/10.1161/CIRCULATIONAHA.122.059725.

[76] Morrow DA, Velazquez EJ, DeVore AD, Desai AS, Duffy CI, Ambrosy AP, et al. Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF trial.

Circulation 2019;139:2285-8. http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039331.

[77] Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z, et al. Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. Eur J Heart Fail 2019;21:998-1007. http://dx.doi.org/10.1002/ejhf.1498.

[78] Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008;372:139-44. http://dx.doi.org/10.1016/S0140-6736(08)60878-8.

[79] Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J 2022;43:3826-924. http://dx.doi.org/10.1093/eurheartj/ehac270.

[80] Kotzé A, Howell SJ. Heart failure: pathophysiology, risk assessment, community management and anaesthesia. Contin Educ Anaesth Crit Care Pain 2008;8:161-6. http://dx.doi.org/10.1093/biaceacpp/mkn028.

[81] Chioncel O, Mebazaa A. Characteristics of intensive care in patients hospitalized for heart failure in Europe. Heart Fail Clin 2015;11:647-56. http://dx.doi.org/10.1016/j.hfc.2015.07.005.

[82] Sheehan M, Sokoloff L, Reza N. Acute heart failure: from the emergency department to the intensive care unit. Cardiol Clin 2024;42:165-86. http://dx.doi.org/10.1016/j.ccl.2024.02.005.

[83] Bart BA, Goldsmith SR, Lee KL, Givertz MM, O'Connor CM, Bull DA, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med 2012;367:2296-304. http://dx.doi.org/10.1056/NEJMoa1210357.

[84] Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2007;49:675-83. http://dx.doi.org/10.1016/j.jacc.2006.07.073.

[85] Costanzo MR, Saltzberg MT, Jessup M, Teerlink JR, Sobotka PA, Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) Investigators. Ultrafiltration is associated with fewer rehospitalizations than continuous diuretic infusion in patients with decompensated heart failure: results from UNLOAD. J Card Fail 2010;16:277-84. http://dx.doi.org/10.1016/j.cardfail.2009.12.009.

[86] Rossinen J, Harjola V-P, Siirila-Waris K, Lassus J, Melin J, Peuhkurinen K, et al. The use of more than one inotrope in acute heart failure is associated with increased mortality: a multi-centre observational study. Acute Card Care 2008;10:209-13. http://dx.doi.org/10.1080/17482940802263276.

[87] Cheshire C, Bhagra CJ, Bhagra SK. A review of the management of patients with advanced heart failure in the intensive care unit. Ann Transl Med 2020;8. http://dx.doi.org/10.21037/atm-20-1048. 828-828.

[88] Samsky MD, Morrow DA, Proudfoot AG, Hochman JS, Thiele H, Rao SV. Cardiogenic shock after acute myocardial infarction: a review. JAMA 2021;326:1840-50. http://dx.doi.org/10.1001/jama.2021.18323.

[89] van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, et al. Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association. Circulation 2017;136:e232-68. http://dx.doi.org/10.1161/CIR.0000000000000525.

[90] Chioncel O, Parissis J, Mebazaa A, Thiele H, Desch S, Bauersachs J, et al. Epidemiology, pathophysiology and contemporary management of cardiogenic shock - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2020;22:1315-41. http://dx.doi.org/10.1002/ejhf.1922.

[91] Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 1999;341:625-34. http://dx.doi.org/10.1056/NEJM9908263410901.

[92] Baran DA, Grines CL, Bailey S, Burkhoff D, Hall SA, Henry TD, et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019. Catheter Cardiovasc Interv 2019;94:29-37. http://dx.doi.org/10.1002/cvd.28329.

[93] Hill KL, Rustin MA, Asche MA, Bennett CE, Patel PC, Jentzer JC. Cardiogenic shock classification and associated mortality risk. Mayo Clinic Proc 2023;98:771-83. http://dx.doi.org/10.1016/j.mayocp.2022.12.007.

[94] Zweck E, Thayer KL, Helgestad OKL, Kanwar M, Ayyouty M, Garan AR, et al. Phenotyping cardiogenic shock. J Am Heart Assoc 2021;10e020085. http://dx.doi.org/10.1161/JAHA.120.020085.

[95] Levy B, Bastien O, Karim B, Cariou A, Chouih T, Combes A, et al. Experts' recommendations for the management of adult patients with cardiogenic shock. Ann Intensive Care 2015;5:52. http://dx.doi.org/10.1186/s13613-015-0052-1.

[96] Thiele H, Akin I, Sandri M, Fuernau G, de Waha S, Meyer-Saraei R, et al. PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med 2017;377:2419-32. http://dx.doi.org/10.1056/NEJMoa1710261.

[97] Hochman JS, Sleeper LA, White HD, Dzavik V, Wong SC, Menon V, et al. One-year survival following early revascularization for cardiogenic shock. JAMA 2001;285:190-2. http://dx.doi.org/10.1001/jama.285.2.190.
[98] Laghlam D, Benganem S, Ortuno S, Bouabdallaoui N, Manzo-Silberman S, Hamzaoui O, et al. Management of cardiogenic shock: a narrative review. Ann Intensive Care 2024;14:45. http://dx.doi.org/10.1186/s13613-024-01260-y.

[99] Levy B, Clere-Jehl R, Legras A, Morichau-Beauchant T, Leone M, Frederique G, et al. Epinephrine versus norepinephrine for cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol 2018;72:173-82. http://dx.doi.org/10.1016/j.jacc.2018.04.051.

[100] Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA 2007;297:1883-91. http://dx.doi.org/10.1001/jama.297.17.1883.

[101] Uhlig K, Efremov L, Tongers J, Frantz S, Mikolajczyk R, Sedding D, et al. Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev 2020;11CD009669. http://dx.doi.org/10.1002/14651858.CD009669.pub4.

[102] Packer M, Colucci W, Fisher L, Massie BM, Teerlink JR, Young J, et al. Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. JACC Heart Fail 2013;1:103-11. http://dx.doi.org/10.1016/j.jchf.2012.12.004.

[103] Landoni G, Biondi-Zoccai G, Greco M, Greco T, Bignami E, Morelli A, et al. Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Crit Care Med 2012;40:634-46. http://dx.doi.org/10.1097/CCM.0b013e318232962a.

[104] Mebazaa A, Nieminen MS, Filippatos GS, Cleland JG, Salon JE, Thakkar R, et al. Levosimendan vs. dobutamine: outcomes for acute heart failure patients on beta-blockers in SURVIVE. Eur J Heart Fail 2009;11:304-11. http://dx.doi.org/10.1093/eurjhf/hfn045.

[105] Geller BJ, Sinha SS, Kapur NK, Bakitas M, Balsam LB, Chikwe J, et al. Escalating and de-escalating temporary mechanical circulatory support in cardiogenic shock: a scientific statement from the American Heart Association. Circulation 2022;146:e50-68. http://dx.doi.org/10.1161/CIR.0000000000001076.

[106] Thiele H, Zeymer U, Neumann F-J, Ferenc M, Olbrich H-G, Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012;367:1287-96. http://dx.doi.org/10.1056/NEJMoa1208410.

[107] Thiele H, Zeymer U, Neumann F-J, Ferenc M, Olbrich H-G, Hausleiter J, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet 2013;382:1638-45. http://dx.doi.org/10.1016/S0140-6736(13)61783-3.

[108] Thiele H, Zeymer U, Thelemann N, Neumann F-J, Hausleiter J, Abdel-Wahab M, et al. Intraaortic balloon pump in cardiogenic shock complicating acute myocardial infarction: long-term 6-year outcome of the randomized IABP-SHOCK II Trial. Circulation 2019;139:395-403. http://dx.doi.org/10.1161/CIRCULATIONAHA.118.038201.