Acute Heart Failure: Diagnostic–Therapeutic Pathways and Preventive Strategies—A Real-World Clinician’s Guide

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.


Introduction
AHF is defined as a new onset or recurrence of HF symptoms and signs requiring emergency therapeutic interventions [1,2]. It may occur as the first manifestation of HF, or more frequently as an acute decompensation of chronic HF [3].
Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome [e.g., hemodynamic status (wet/dry-warm/cold) or according to clinical scenario (decompensated heart failure, acute right heart failure, acute pulmonary edema, cardiogenic shock)] [3] (Table 1). AHF is the most frequent cause of unplanned hospital admissions in patients >65 years of age and is associated with poor outcomes, with in-hospital and 1-year mortality rates of~10% and~30%, respectively, with 90-day readmission rates~20-30% [4]. Moreover, it imposes a significant financial burden to health systems, with the total medical cost of annual median hospitalizations estimated at USD~16,000 per patient [5,6].

Epidemiology
The mean age of patients presenting with AHF ranges between 70 and 73 years. About half of patients are male. The majority (65-75%) have a known history of HF. At presentation, most of them have normal or increased blood pressure, while patients presenting with hypotension are generally less than ≤8%, including patients with cardiogenic shock (CS) that represent less than ≤1-2% of cases [7].

Pre-Hospital
AHF patients should immediately ('time-to-treatment' concept) receive appropriate therapy and be rapidly transferred to the nearest hospital, preferably to a site with an intensive cardiology unit (CCU/ICU) [3,14].

Triage
AHF patients admitted to the emergency department (ED) with mild symptoms and signs of congestion, no renal dysfunction, negative troponin values, and very low neuropeptide (NP) levels can be discharged directly home after a small dose of diuretics and adjustments of oral therapy as needed. They should be referred to their physician with the advice to be clinically followed by the HF multidisciplinary outpatient clinic [17].
Search for reversible causes (Table 2) Management starts with the search for specific causes of AHF. These include acute coronary syndromes (ACS), hypertensive emergency, rapid arrhythmias or severe bradycardia/conduction disturbances, acute mechanical causes (i.e., acute valve regurgitation), acute pulmonary embolism (PE), infections, and tamponade (CHAMPIT). Dietary and fluid restriction and medication noncompliance should also be ascertained at this time.
After exclusion of these conditions, which need to be treated/corrected urgently, management of AHF differs according to clinical presentation [3,17]. Step 1 a. Search for reversible causes (Table 2) Management starts with the search for specific causes of AHF. These include acute coronary syndromes (ACS), hypertensive emergency, rapid arrhythmias or severe bradycardia/conduction disturbances, acute mechanical causes (i.e., acute valve regurgitation), acute pulmonary embolism (PE), infections, and tamponade (CHAMPIT). Dietary and fluid restriction and medication noncompliance should also be ascertained at this time.
After exclusion of these conditions, which need to be treated/corrected urgently, management of AHF differs according to clinical presentation [3,17].     [19,20] hs-cTn (I or T), D-dimer TTE Prompt intervention/surgery is needed; transfer to Hub center.
CTA in suspected acute aortic disease Patients with severe hypertension associated with AHF require an urgent reduction of BP with IV drug administration. c.
Assess presenting symptoms and signs The most common symptoms (reflecting pulmonary and/or systemic congestion) include dyspnea during exercise or at rest, orthopnea, fatigue, and reduced exercise tolerance. Clinical signs usually include peripheral oedema, jugular vein distension, the presence of a third heart sound and pulmonary rales [2].
Symptoms and signs such as cold and clammy skin, altered mental status, and oliguria indicate peripheral hypoperfusion-impending CS [2].
Step 2 a.
Lab tests Neuropeptides Cardiovascular biomarkers play a crucial role in the diagnostic-prognostic process of AHF. Upon presentation to the ED, plasma NP levels (BNP, NT-proBNP, or MR-proANP) should be measured (point-of-care assay) in all patients with acute dyspnea. Due to the strong link with hemodynamic intracardiac stress, they may help to differentiate between cardiac and non-cardiac causes of acute dyspnea [35,36].
However, there are many causes of elevated NP levels-both cardiovascular (CV) and non-CV-that might reduce their diagnostic accuracy. These causes include AF, increasing age, and acute or chronic kidney disease. Conversely, NP concentrations may be disproportionately low in obese patients, in patients with pre-left ventricle causes of HF (i.e., mitral stenosis and acute mitral regurgitation), or pericardial diseases.
As a note, NT-pro BNP instead of BNP should be tested in patients taking sacubitrilvalsartan [37].
It should also be highlighted that NP levels are strong predictors of readmissions and death [38].
Troponin In addition to ACS, elevated high-sensitivity troponin I/T (hsTn I/T) levels may be observed in most non-ACS AHF patients and are associated with worse in-hospital and post-discharge outcomes [39].
Others Further lab tests (i.e., BUN (or urea), creatinine, electrolytes, glucose, complete blood count, procalcitonin, PCR, and D-dimer) may be useful to detect and/or to confirm clinically suspected comorbidities and/or end-organ damage [15]. SpO 2 /arterial blood gas (ABG) SpO 2 should be measured routinely at the time of AHF patient presentation and continuous monitoring may be needed in the first hours or days.
Routine ABG is not needed. Specific indications for ABG are: respiratory distress [defined as acute increase in the work of breathing or significant tachypnea (RR > 25 breaths/min)], documented hypoxemia (SpO 2 < 90%) not responsive to supplemental oxygen, and evidence of acidosis or elevated lactate levels. In the case of respiratory failure, ABG may show PaO 2 < 60 mmHg, PaCO 2 > 45 mmHg or PaO 2 /FiO 2 < 300 mmHg. Of note, venous sample might acceptably indicate pH and CO 2 [15].

b. ECG
Routine admission ECG is recommended since it can exclude ACS and arrhythmias. In this regard, careful attention should be paid to ECG changes suggestive of myocardial ischemia. Tachyarrhythmias [i.e., AF (present in 20% to 30% patients), ventricular tachycardia] or bradyarrhythmias (i.e., advanced atrio-ventricular blocks) are also a common trigger for AHF [3,21,22].

c.
Chest X-ray Chest X-ray may reveal lung congestion and/or pleural effusion. Furthermore, it may identify non-cardiac-disease causes of the patient's symptoms (i.e., pneumonia, pneumothorax, widened mediastinum).

d. Transthoracic echocardiography (TTE)
TTE represents the single most useful imaging technique to investigate AHF etiology and to guide related therapeutic interventions.
A "Focus Cardiac Ultrasound" (FoCUS), followed by comprehensive TTE exam, is recommended in all patients to assess LV global systolic (reduced vs. preserved EF) and diastolic function, regional wall abnormalities, valvular heart (stenosis and/or regurgitations) and pericardial disease. In addition, it is of paramount importance to evaluate right heart structure and function, as well as pulmonary pressures, as these are major prognostic determinants [40].
As a note, an E:E' ratio greater than 15 predicts a pulmonary arterial wedge pressure (PAWP) greater than 15 mm Hg, and has been demonstrated to be accurate in the ED and intensive care settings [2,41] (Figure 3).
As a note, an E:E' ratio greater than 15 predicts a pulmonary arterial wedge pressure (PAWP) greater than 15 mm Hg, and has been demonstrated to be accurate in the ED and intensive care settings [2,41] (Figure 3). LUS has emerged as a valuable modality to detect and monitor pulmonary congestion in patients with AHF in a low-cost, portable, real-time, and radiation-free manner.
It outperforms the diagnostic accuracy of the chest radiograph in the detection of pleural water (pleural effusion) and lung water (pulmonary congestion as multiple Blines) [42].
B-lines are well defined (laser-like), hyperechoic, vertical comet-tail artifacts that arise strictly from the pleural line, move in sync with lung sliding and spread to the edge of the screen without fading and erasing A lines. The number of lines is proportional to the severity of congestion and identifies the cardiogenic origin of dyspnea with 85% sensitivity and 92% specificity [43].
The B profile is useful to track dynamic changes in pulmonary congestion in responses to treatment, and its persistence at pre-discharge or in clinically stable outpatients with heart failure is predictive of heart failure hospitalization or death [44].
The amount of pleural effusion can be scored as trivial (<2 mm), small (2 to 15 mm), moderate (15 to 25 mm), or large (>25 mm). Furthermore, LUS represents a guide to thoracentesis in patients with AHF and at least moderate pleural effusion [45]. LUS has emerged as a valuable modality to detect and monitor pulmonary congestion in patients with AHF in a low-cost, portable, real-time, and radiation-free manner.
It outperforms the diagnostic accuracy of the chest radiograph in the detection of pleural water (pleural effusion) and lung water (pulmonary congestion as multiple Blines) [42].
B-lines are well defined (laser-like), hyperechoic, vertical comet-tail artifacts that arise strictly from the pleural line, move in sync with lung sliding and spread to the edge of the screen without fading and erasing A lines. The number of lines is proportional to the severity of congestion and identifies the cardiogenic origin of dyspnea with 85% sensitivity and 92% specificity [43].
The B profile is useful to track dynamic changes in pulmonary congestion in responses to treatment, and its persistence at pre-discharge or in clinically stable outpatients with heart failure is predictive of heart failure hospitalization or death [44].
The amount of pleural effusion can be scored as trivial (<2 mm), small (2 to 15 mm), moderate (15 to 25 mm), or large (>25 mm). Furthermore, LUS represents a guide to thoracentesis in patients with AHF and at least moderate pleural effusion [45].
As a note, the evaluation of "lung sliding" (a horizontal, to-and-fro movement, beginning at the pleural line and synchronous with respiration) is helpful in the differential diagnosis of several parenchymal lung diseases that are present as comorbidities in HF or as causes of dyspnea suspected to be cardiac in origin. For instance, "lung sliding" disappears in pneumothorax and it is reduced or abolished in the case of pneumonia, acute respiratory distress syndrome (ARDS), or pleural adhesions [43].

f. Abdominal ultrasound (AUS)
AUS can be useful for measurement of the inferior vena cava (IVC) diameter as an indirect measure of right atrial pressures (IVC < 21 mm that collapses >50% suggests normal right atrial pressure) [46].
In HF patients, an increased IVC diameter might detect abnormal intravascular volume even prior to any change in symptoms or body weight, and in turn monitor the response to diuretics. AUS can also detect ascites and abdominal aortic aneurysm [46].
Recently, ultrasound techniques have also been implemented to assess renal blood flow [47]. g.
Transesophageal echocardiogram (TEE) TEE may be performed in suspected endocarditis and acute aortic syndromes (AAS). Furthermore, it may be useful to better define heart valve abnormalities and to detect intracardiac shunt and thrombi. Absolute contraindications include: unrepaired tracheoesophageal fistula, esophageal obstruction/stricture, perforated hollow viscus, active gastric/esophageal bleeding, poor airway control, severe respiratory depression, and uncooperative, unsedated patient [48].
Step 3. Additional Non-Invasive and Invasive Tests a.
High-resolution chest computed tomography (Chest HR-CT) Chest HR-CT should be considered when pulmonary parenchymal component is suspected among patients presenting with AHF.
CT can also identify signs of pulmonary edema, such as interlobular septal thickening, fissural thickening, peribronchovascular thickening, perihilar or bat-wing appearance of oedema, increased artery-to-bronchus ratio, pleural effusion, and cardiac enlargement in more advanced HF [49,50].
Furthermore, high-resolution CT provides an effective modality to evaluate patients with suspected COVID-19.

b.
Chest CT angiography (CTA) CTA can be used as a one-step imaging modality (dual rule-out strategy) to exclude PE or AAS. It can be performed with most CT equipment. Furthermore, with state-of-the-art CT equipment, synchronizing image acquisition with the cardiac cycle, it is possible to perform the so-called Triple Rule-Out strategy (TRO). This protocol allows the heart and the coronary arteries to be imaged, allowing the exclusion of ACS in a clinical context where this diagnosis might not be straightforward. The main drawbacks of CTA are the administration of iodinated contrast agent, which may cause acute kidney injury or allergic reactions, even though the amount of contrast material currently required to perform the scan is quite low compared to in the past (i.e., using state-of-the-art CT technology, 50 mL). Furthermore, the use of ionizing radiation should be avoided in younger patients, especially women [51].
Recent CT technology also allows the performance of a full anatomical and functional assessment of cardiac and thoracic structures. Hence, a patient undergoing this kind of assessment will have all heart chamber volumes and functionality assessed, the presence of thrombosis within the cardiac chambers ruled out, the superior and inferior vena cava assessed for patency and distention, the pulmonary artery evaluated for dilatation, and so forth. When COVID-19 is assessed in the context of a TRO protocol, it is referred to as Quadruple Rule-Out [52]. When other causes for the acute settings are included in the evaluation, it can be referred to as Quintuple Rule-Out. Because of this flexibility and wide range of rule-in/rule-out capabilities and its relatively easy access, CT is already, and will become, an increasingly central tool in all acute clinical settings (Figures 4 and 5). evaluation, it can be referred to as Quintuple Rule-Out. Because of this flexibility and wide range of rule-in/rule-out capabilities and its relatively easy access, CT is already, and will become, an increasingly central tool in all acute clinical settings (Figures 4 and 5).  evaluation, it can be referred to as Quintuple Rule-Out. Because of this flexibility and wide range of rule-in/rule-out capabilities and its relatively easy access, CT is already, and will become, an increasingly central tool in all acute clinical settings (Figures 4 and 5).  CIN (contrast induced nephropathy) remains one of the most serious complications of iodinated contrast medium (CM). It is defined as a ≥25% increase in serum creatinine from the baseline value, or an absolute increase of at least 0.5 mg/dL (44.2 µmol/L), 48-72 h after the administration of radiographic contrast media that is not attributable to other causes [53].
Pre-existing renal impairment represents the most important risk factor for CIN. The baseline renal function of patients undergoing contrast studies is best assessed with calculations of glomerular filtration rate (GFR), such as the MDRD or Cockcroft-Gault formulae in adults [53].
Patients at high risk of developing CIN should be identified early and prophylactic measures implemented before the procedure (Table 3). The frequency of allergic-like adverse events related to the intravascular administration of iodinated CM is low and has decreased considerably since the use of nonionic low-osmolality contrast media. However, the majority of adverse side effects to CM are mild non-life-threatening events that usually require only observation, reassurance, and/or supportive measures [54]. Severe reactions (i.e., bronchospasm, laryngeal edema, anaphylaxis) occur rarely and are unpredictable. A frequently recommended premedication oral regimen for elective examinations is shown in Table 4.

Reaction Severity Symptoms Recommendation
Severe Severe edema, including facial and laryngeal edema, anaphylaxis, hypoxia Consider alternative tests. If the test is necessary premedication is recommended Prednisone-50 mg by mouth at 13 h, 7 h, and 1 h before contrast media injection OR Methylprednisolone-32 mg by mouth 12 h and 2 h before contrast media injection PLUS Diphenhydramine-50 mg intravenously, intramuscularly, or by mouth 1 h before contrast medium c.

Coronary angiography
In AHF patients with a clinical picture related to ACS, an immediate coronary angiography, along with revascularization (if needed), should be performed [19,20].

In-Hospital Therapeutic Interventions
The main goals of treatment in AHF consist of alleviating symptoms, improving congestion and organ perfusion, restoring oxygenation, and preventing thromboembolism.  (Table 5) The cornerstone of AHF treatment is represented by diuretics with IV loop diuretics (e.g., furosemide, bumetanide or torasemide) used as first-line therapy in patients with AHF and congestion [3].  The use of an IV dose of diuretics at least equal to the pre-existing oral dose is recommended in those already receiving oral diuretics, and 20-40 mg IV furosemide (or equivalent) in those who are not on regular oral diuretics [3,56].
Furosemide can be given as 2-3 daily boluses or as a continuous infusion. Daily single bolus administrations are discouraged for the possibility of post-dosing sodium retention [3,56].
The diuretic response is evaluated by measuring the urinary volume output and/or spot urinary sodium content, with a satisfactory diuretic response defined as a urine sodium content >50-70 mEq/L at 2 h and/or by a urine output >100-150 mL/h during the first 6 h [56].
If there is an insufficient diuretic response, the loop diuretic IV dose can be doubled. Transition to oral treatment should be started when the patient's clinical condition is stable.
In patients with resistant oedema, dual treatment with a loop diuretic and a thiazide or a thiazide-like diuretic (e.g., metolazone) may be considered to achieve adequate diuresis (so-called "sequential nephron blockade") [56]. (Table 6) Intravenous vasodilators may be considered to relieve AHF symptoms when SBP is >110 mmHg [3].

Vasodilators
They may be started at low doses and up-titrated to achieve clinical improvement and BP control. Nitrates are generally administered with an initial bolus followed by continuous infusion. However, these agents should be avoided in patients with concurrent obstructive valvular disease (i.e., severe aortic stenosis) or restrictive physiology (i.e., hypertrophic cardiomyopathy) [57].

Opiates
Although the routine use of opiates (i.e., morphine) in AHF is not recommended, they may be considered in selected patients, particularly in case of severe pain, anxiety or in the setting of palliation [58,59].

Digoxin
Digoxin is mostly indicated (boluses of 0.25-0.5 mg IV if not used previously, followed by an oral or IV dose of 0.25 mg at least 12 h after the initial dose) in patients with AF and rapid ventricular rate (>110 bpm) despite beta-blockers [3,60].
Caution should be taken in the elderly or in patients with factors affecting digoxin metabolism (i.e., renal failure, drug interaction) [3].
Furthermore, unless the risk of toxicity outweighs the benefit, discontinuation of digoxin is generally discouraged. In this regard, an association between withdrawal of therapy and worsening HF has been well documented [60].

Anticoagulants
AHF patients are at high risk of deep venous thrombosis (DVT) and PE as a direct consequence of higher venous pressures and lower cardiac output. In this regard, current guidelines support the use of thromboprophylaxis [e.g., low-molecular-weight heparin (LMWH) given at 4000 to 5000 units daily, or 2500 to 3000 units twice daily subcutaneously] in all appropriate hospitalized AHF patients, unless contraindicated [61].
In addition, oral anticoagulation [preferring new oral anticoagulants (NOACs) to vitamin K antagonists (VKAs), except in patients with mechanical heart valves or moderatesevere mitral stenosis] is recommended in AHF patients with paroxysmal, persistent, or permanent AF with a CHA2DS2-VASc score ≥ 2 in men and ≥ 3 in women. The HAS-BLED score should be considered to identify patients at high risk of bleeding (HAS-BLED score ≥ 3) for early and more frequent clinical assessments and follow-up [22]. (Table 7) Inotropes [including sympathomimetics/synthetic catecholamines (e.g., dobutamine, adrenaline), phosphodiesterase inhibitors (e.g., milrinone, enoximone), and, more recently, Ca 2+ sensitizers (e.g., levosimendan)] should be reserved for patients with LV systolic dysfunction, low cardiac output and low SBP (e.g., <90 mmHg), resulting in poor vital organ perfusion [2].

Inotropes/Vasopressors
Inotropes improve myocardial contractility, but, especially in the case of the sympathomimetics, also increase myocardial O 2 consumption. As a direct consequence they may trigger supraventricular and ventricular tachyarrhythmias. In this regard, it should be underlined that all patients under inotrope treatment require close monitoring of cardiac rhythm and hemodynamic parameters [62,63]. Of note, while inotropes have been shown to improve symptoms and signs of congestion, these agents have failed to reveal any improvement in mortality in patients with AHF [64].

Future Directions
In the EMPULSE trial, early initiation of SGLT-2 inhibitor empagliflozin in patients hospitalized for AHF led to a statistically significant clinical benefit at 90 days with fewer deaths, improvement in quality of life, lower NT-pro BNP levels, and weight loss [65,66].
The ADVOR trial has reported that, when used in combination with loop diuretic, acetazolamide (a carbonic anhydrase inhibitor) can lead to a greater incidence of successful decongestion [67].
Istaroxime, a novel compound with inotropic and lusitropic positive properties and a dual mechanism of action (activation of the sarcoplasmic reticulum Ca 2+ /ATPase 2a (SERCA2a) and inhibition of the Na + /K + -ATPase), has been shown to increase SBP without activating the adrenergic system, and to improve pulmonary capillary wedge pressure and diastolic cardiac function [68][69][70][71].
Furthermore, in AHF patients, early administration (within 16 h) of serelaxin, a peptide involved in cardiovascular adaptations during pregnancy, has been shown to be associated with a reduction in 5-day worsening HF and markers of renal dysfunction [72].

Management of Chronic HF Therapy
Temporary discontinuation of angiotensin-converting enzyme (ACE), inhibitor/angiotensin receptor blockers (ARB), or beta-blockers may be necessary in the settings of CS or symptomatic hypotension. ACE-I/ARB and mineralocorticoid receptor antagonists (MRAs) may also need to be temporarily held in case of renal dysfunction, oliguria, and/or hyperkalemia [73].
The Initiation of beta-blocker therapy during AHF is contraindicated due to acute negative inotropic effects. However, initiation of beta-blocker in euvolemic patients prior to discharge is safe and associated with increased long-term survival [74].

Mechanical Ventilation
NIV consists of applying positive intrathoracic pressure (PIP) to conscious patients through different interfaces, and can be either continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) [75].
It should be highlighted that NIV has to be started as soon as possible in patients with respiratory distress (respiratory rate >25 breaths/minute, SpO 2 < 90%) to improve gas exchange and reduce the rate of endotracheal intubation [3].
If there is only hypoxemia, CPAP is the treatment of choice. In cases of hypoxemia and hypercapnia, BiPAP is preferred. CPAP is generally started at a pressure of 5 cm H 2 O, which is increased in a stepwise manner to up to 10 cm H 2 O. In BiPAP, it is reasonable to start with an EPAP of 5 cm H 2 O and an IPAP of 10-14 cm H 2 O. EPAP and IPAP can be adjusted further according to the effect on oxygenation and ventilation, respectively [75].
The response to NIV should be assessed after 60 min, and thereafter on a continuous basis. Signs of NIV failure are patient fatigue, progressive worsening of level of consciousness, hemodynamic instability, persistent tachypnoea (>35 breaths/minute), and progressive worsening of respiratory failure with acidosis, hypoxemia, or hypercapnia [75].
Endotracheal intubation and mechanical ventilation are only required in a minority of AHF patients, as most of them will respond to NIV. Agitation or intolerance to NIV with progressive respiratory failure.

Electric Cardioversion
AF patients presenting with a rapid ventricular rate and acute hemodynamic instability (i.e., acute pulmonary oedema, ongoing myocardial ischemia, symptomatic hypotension or CS) require prompt intervention, and emergency electrical cardioversion should be attempted without delay. In this setting, amiodarone may also be considered in order to control heart rate response [3,22].

Mechanical Circulatory Support (MCS)
Short-term MCS (which increases cardiac output and supports end organ damage) may be implemented as a bridge to recovery (BTR), bridge to decision (BTD) or bridge to transplant (BTT) ( Table 8). Intra-aortic balloon pump (IABP) is not routinely recommended [76].

Daily Patient Monitoring
Daily patient monitoring includes: • Weight check along with completion of an accurate fluid balance chart; • Standard non-invasive monitoring of HR, RR, BP; • Renal function and electrolyte measurement.
Invasive monitoring with pulmonary artery catheter failed to show any positive influence on inpatient or follow-up outcomes of patients admitted with AHF, and should be carefully used for selected patients [77].
Indicators of good response to initial therapy that might be considered in discharge include [15]:  Figure 6) In order to reduce hospitalizations and mortality, enrollment in a HF multidisciplinary management program is recommended as it has been shown to improve outcomes based on three main aspects [3,14]:

1.
Patient self-monitoring (i.e., regular weight checks, adherence to therapy, structured exercise program, and dietary sodium and fluid restriction).

2.
Periodic follow-up visits, including monitoring of signs and symptoms of HF, assessment of volume status, BP, HR, and laboratory tests primarily of renal function, electrolytes, iron status, hepatic function, and NP. In patients with minimal symptoms of HF, comparison of NP level with predischarge values should be considered to detect worsening subclinical congestion. At the visit, the physician should also verify that the patient is receiving all guideline-directed chronic HF therapies for which they are eligible. Likewise, laboratory monitoring for corresponding drug adverse effects (i.e., renal insufficiency, electrolyte disturbances) should be considered [3]. Furthermore, planning for additional diagnostic and interventional procedures can be undertaken, including device therapy. It should be highlighted that the 2021 European Society of Cardiology (ESC) HF guidelines recommend the first follow-up outpatient visit within 1 to 2 weeks after discharge [83].

3.
Remote monitoring via telemedicine/teleconsulting evaluations. Home telemonitoring can help maintain quality of care, facilitate rapid access to care when needed, reduce patient travel costs, and minimize the frequency of clinic visits [84]. Remote pulmonary arterial pressure monitoring with implantable pressure sensors, with adjustment of diuretic therapy according to pulmonary arterial pressure measurements, substantially reduced HF hospitalizations and improved outcomes in both patients with HFpEF and HFrEF [85].
ing can help maintain quality of care, facilitate rapid access to care when needed, reduce patient travel costs, and minimize the frequency of clinic visits [84]. Remote pulmonary arterial pressure monitoring with implantable pressure sensors, with adjustment of diuretic therapy according to pulmonary arterial pressure measurements, substantially reduced HF hospitalizations and improved outcomes in both patients with HFpEF and HFrEF [85].

In-Hospital Outcomes
AHF is characterized by relatively low in-hospital mortality but a high rate of recurrent post-discharge events. AHF inpatient mortality ranges between 3% and 7%, with the exception of patients with CS, who have an in-hospital mortality of approximately 40% [5].
At hospital admission, specific predictors of poor prognosis consist of advanced age, HF hospitalization history, decreased kidney function, high NP concentrations, and low BP.
Furthermore, higher degrees of congestion are associated with longer hospital stay [38]. Persistent congestion and high NP levels at discharge are predictors of worse quality of life, recurrent rehospitalization, and higher mortality [86].

Long-Term Outcomes
Approximately 25% of patients hospitalized with HF are readmitted within 30 days of discharge, and mortality during this period can approach 10%. Rates of rehospitalization within 6 months approach 50% in many cohorts, particularly the elderly [83].
In the EVEREST trial, careful adjudication of post-discharge hospitalizations showed that 46% were for HF, 15% for other CV causes, and 39% for non-CV causes.
Of note, approximately half of rehospitalizations are not HF-related, which underscores the high burden of comorbidity as well as the challenges of implementing personalized therapeutic interventions [87].
Median survival in HF patients decreases gradually with the number of hospitalizations, ranging from 2.5 years in patients with one hospital admission to 0.5 years in those with four admissions [88].

MULTIDISCIPLINARY HF MANAGEMENT PROGRAMMES
•

In-Hospital Outcomes
AHF is characterized by relatively low in-hospital mortality but a high rate of recurrent post-discharge events. AHF inpatient mortality ranges between 3% and 7%, with the exception of patients with CS, who have an in-hospital mortality of approximately 40% [5].
At hospital admission, specific predictors of poor prognosis consist of advanced age, HF hospitalization history, decreased kidney function, high NP concentrations, and low BP.
Furthermore, higher degrees of congestion are associated with longer hospital stay [38]. Persistent congestion and high NP levels at discharge are predictors of worse quality of life, recurrent rehospitalization, and higher mortality [86].

Long-Term Outcomes
Approximately 25% of patients hospitalized with HF are readmitted within 30 days of discharge, and mortality during this period can approach 10%. Rates of rehospitalization within 6 months approach 50% in many cohorts, particularly the elderly [83].
In the EVEREST trial, careful adjudication of post-discharge hospitalizations showed that 46% were for HF, 15% for other CV causes, and 39% for non-CV causes.
Of note, approximately half of rehospitalizations are not HF-related, which underscores the high burden of comorbidity as well as the challenges of implementing personalized therapeutic interventions [87].
Median survival in HF patients decreases gradually with the number of hospitalizations, ranging from 2.5 years in patients with one hospital admission to 0.5 years in those with four admissions [88].

Preventive Strategies
The lifetime risk of HF is approximately 20%, and the prevalence and burden of HF will likely continue to increase in developed countries [77].
In all patients, the cornerstone should be counseling on the importance of healthy lifestyle to optimize CV health [89,90].
In this regard, it is essential to assess modifiable HF risk factors, including HTN, elevated body mass index (BMI), physical inactivity, DM, CAD, and tobacco and alcohol use. It should be highlighted that controlling HTN is associated with a lower risk of incident HF, with current guidelines recommending targeting BP < 130/80 mmHg [90].
It is recommended that all patients with HF are regularly screened for anemia and iron deficiency with full blood count, serum ferritin concentration, and transferrin saturation (TSAT). In patients with HF, iron deficiency is defined as either a serum ferritin concentration < 100 ng/mL or 100-299 ng/mL with TSAT < 20% [91].
Ion supplementation with IV ferric carboxymaltose should be considered for the improvement of symptoms, exercise capacity, and quality of life in patients with HF and LVEF < 45%. It should also be considered for the reduction of HF rehospitalizations in patients with LVEF < 50% recently hospitalized for worsening HF [3].
Influenza and pneumococcal vaccination, as well as COVID-19 vaccination, when available, should be considered in patients with HF [92].

Conclusions
AHF is a life-threatening medical emergency requiring immediate therapeutic interventions in order to optimize hemodynamic status. Precipitants and comorbid conditions should be addressed, specifically acute decompensation triggers such as ACS, hypertensive emergency and malignant arrythmia. Multidisciplinary comprehensive follow-up and rehabilitation programs are recommended, along with the implementation of digital health (i.e., remote monitoring, teleconsulting, and implantable device interrogation) in order to reduce the risk of recurrent HF hospitalization and mortality. In the near future, we may expect a major practical change towards personalized care.  Data Availability Statement: The data are available from the corresponding author on reasonable request.