Chapter 1

Acute Heart Failure

Definition

Acute heart failure (AHF) can be described as the sudden appearance of new or exacerbated signs and symptoms associated with heart failure in a broader context.[7]

Pathophysiology

AHF is generally caused by an underlying pathological condition. This underlying condition is cardiac impairment (including acute damage to the heart muscle and remodelling) along with systemic and pulmonary vessel malfunction that ultimately causes severe acute hemodynamic abnormalities. The cause of these is unclear, but several generalized conditions such as neurohormonal activation, oxidative stress and inflammatory processes are hypothesized to be involved. [8] Dysfunction of other organs like kidneys, liver has been also found to cause acute heart failure. Various other factors like arrhythmia, hypertension, ischemia, and administered drugs can also lead to acute heart failure.

Neurohormonal System

To counter the vascular congestion and hypoperfusion various neurohormonal pathways get activated.[9,10] In response to these, the sympathetic system gets activated which releases norepinephrine and increases contractility, vasoconstriction and heart rate. An increased level of norepinephrine in blood is correlated with poor prognosis and high mortality.[10] Furthermore, it stimulates the secretion of renin. Another physiological response to this event is the activation of the renin-angiotensin-aldosterone system. Consequently, the renin levels in the bloodstream increase, leading to the vasoconstriction of the efferent arteriole, which, in turn, raises the filtration fraction. So, the concentration of aldosterone increases which results in retention of salt and water. Although it is effective in the short term but it is responsible for increased mortality.[11] Aldosterone also contributes in causing ventricular remodelling.[12]

Inflammatory Damage and Oxidative Stress

The chronic nature of heart failure, coupled with its repercussions on other organs, initiates inflammation, oxidative stress, and endothelial dysfunction. These elements collectively play a role in the development of heart failure’s underlying mechanisms.[13]

The first discovered inflammatory molecule related to HF was C-reactive protein[10]. Subsequently, a range of additional inflammatory substances, such as tumor necrosis factor α and specific interleukins (particularly IL-1, IL-6, and IL-18), have been identified as contributors that incite inflammatory reactions within the heart. The endothelium also holds significant importance in responding to congestion through the generation of various free radicals and vasoactive peptides.[13]

These inflammatory responses are marked by rise in oxidative stress which decreases the bio-availability of NO. This excess oxygen and reduction in NO, intensify the myocardial necrosis[14] and promotes remodelling.

Systemic Congestion

Congestion in acute heart failure can be recognized through symptoms like orthopnea, dyspnea, jugular venous distension, ascites, hepatomegaly, and lung crackles. Two theories are linked to the development of congestion in AHF. The initial hypothesis revolves around the concept of congestion caused by the accumulation of sodium and water, leading to increased effective circulatory volume. Another recent theory says that it is due to the abrupt displacement of the splanchnic reservoir into general circulation, triggered by increased sympathetic stimulation due to cardiac decompensation.

Hemodynamic Overload and Adaption

In conditions of myocardial deficit, a decline in ejection fraction coupled with an escalation in LV end-diastolic volume and end-diastolic pressure, prompts increased atrial contraction to maximize cardiac reserve.

Acute RV overload, such as in cases of tamponade, pulmonary thromboembolism, or acute valvular heart disease, disrupts effective left ventricular filling, leading to decreased cardiac output. Consequently, this condition causes hypoxemia and inadequate right ventricular perfusion, exacerbating its dysfunction. This sets off a harmful cycle that can swiftly progress to a fatal outcome.

Coming to the analysis of these control systems shows that once there is deviation from the normal physiological process, we tend to have a negative feedback or feedback opposite to the initiating factor (when compared to positive feedback) for getting back to normal homeostasis. When positive feedback or feedback in the same direction of initiating response tends to occur like shock causes more shock, it eventually leads to death of the patient. Thus, negative feedback is in favour of correcting homeostasis in a critically ill patient.

Symptoms

Mainly, left ventricular dysfunction (volume or pressure overload), elevates pulmonary pressure, resulting in pulmonary congestion. This condition leads to symptoms like dyspnea and tachypnea, often accompanied by fluid transudation and pulmonary crackles. Simultaneously, decreased peripheral circulation (forward failure) gives rise to renal dysfunction, peripheral malperfusion, and poor absorption of nutrients. These factors collectively contribute to the manifestation of cardiac cachexia. The other symptoms can be:

1. Persistent coughing or wheezing
2. Edema
3. Fatigue
4. Lack of appetite

The major site of dysfunction includes the left side, right side, or both ventricles (biventricular) which has a considerable impact on the clinical manifestation of HF.

Diagnosis

The diagnosis of acute heart failure takes the symptoms and clinical findings into account. Appropriate tests such as an ECG, imaging, laboratory testing and echocardiography are used to support the diagnosis.[15]

An ECG in acute heart failure can show any arrhythmias and help identify the reason of HF such as in acute coronary syndrome (ACS). The ECG almost always shows abnormalities in acute heart failure.[16] Furthermore, it can aid in identifying causative or precipitating factors and left versus right sided cardiac pathology.[15]

Imaging techniques are very important in diagnosing AHF. A chest x-ray in acute heart failure should be done early to assess pre-existing conditions and look for lung congestion. An x-ray can help figure out if there is any pulmonary congestion, pleural effusion, edema or cardiomegaly, yet it can also be normal in acute heart failure.[17] If aortic dissection is suspected, a CT scan or transesophageal echocardiography should be done.[15]

Laboratory testing is another important aspect of diagnosing AHF. Biomarkers and arterial blood gas should be done in all cases.[15] BNP and NT-proBNP are essential biomarkers used as the gold standard to complement the clinical diagnosis of acute heart failure.[18] Blood glucose, urea, creatinine, BUN, electrolyte levels, estimated glomerular filtration rate, transaminases, and C-reactive protein, TSH can give important diagnostic clues for underlying pathologies leading up to acute heart failure.[16]

Echocardiography is used to assess the function of the ventricles and valves.[15] It can provide important information such as an underlying ischemia, tamponade or valvular disease that may be contributing to the sudden heart failure.[16]

Risks and Prevention

Acute heart failure can have detrimental complications on patient health. Since the outcome of acute heart failure is grim, especially among the elderly population, prevention is a very important aspect. Cardiovascular and non-cardiovascular conditions, along with patient-related factors and iatrogenic factors, facilitates to the onset of AHF.[19] Early identification and treatment of cardiovascular risk factors and heart disease are crucial to prevent the incidence of AHF. Making sure patients have a good grasp on their heart failure medication, compliance with therapy and patient education are important factors that can help mitigate acute heart failure.[19] The morbidity, mortality and healthcare cost from acute heart failure is extensive.[18] Therefore, risk stratification and preventative measures are essential.

Treatment Options, Complications and Long-Term Management

In the treatment of AHF, there are three distinguishable stages: pre-hospital, in-hospital, and prior to discharge. If possible, non-invasive monitoring techniques such as continuous ECG, pulse oximetry, blood pressure measurement, and monitoring heart and respiratory rates should be employed.[20] Clinical judgement can be utilised to decide whether oxygen therapy should be administered, however oxygen saturation < 90% warrants its administration. Non-invasive ventilation should be initiated when patients exhibit signs of respiratory distress, such as a respiratory rate exceeding 25 breaths/min and oxygen saturation dropping below 90%.[21,22] Research studies with randomized controls have not yet established Enhanced pre-hospital care efficiency could influence the clinical results of
AHF patients.[23]

Management primarily begins with figuring out the specific causes of a patient presenting with AHF.[20] Causes of AHF include: hypertensive emergency, ACS, fast arrhythmias or severe bradycardia, acute pulmonary embolism, acute valve regurgitation, infection e.g., myocarditis, tamponade. Once these conditions are excluded or treated urgently, AHF can be managed based on clinical presentation.

It is not advised to administer oxygen routinely in non-hypoxemic patients due to eventual vasoconstriction and cardiac output reduction.[24] In cases with oxygen saturation < 90% or PaO2 < 60 mm Hg, O2 is recommended to correct hypoxaemia. Nevertheless, it is crucial to highlight that in individuals with a prior diagnosis of chronic obstructive pulmonary disease, excessive oxygenation can lead to ventilation suppression and subsequently hypercapnia.

Constant positive airway pressure and pressure support, (both forms of non-invasive positive pressure ventilation enhance oxygenation and pH levels while reducing the partial pressure of carbon dioxide and the effort required for
breathing. It also improves respiratory failure. Meta-analyses demonstrate an improvement in dyspnoea and reduced intubation and mortality, in comparison to traditional oxygen therapy.[25] Patients experiencing respiratory distress (oxygen saturation < 90%, respiratory rate >25) may show enhanced gas exchange and a reduced requirement for endotracheal intubation through the application of non-invasive positive pressure ventilation.[25] If oxygen therapy or non-invasive ventilation proves ineffective in managing worsening respiratory failure, intubation is recommended.[21]

The fundamental aspect of AHF treatment involves administration of intravenous diuretics. Diuretics are prescribed to manage fluid overload and congestion in individuals with AHF. Loop diuretics are frequently employed because of rapid onset of action. The diuretic treatment protocol typically begins with an initial intravenous dose of furosemide or an equivalent dose of bumetanide or torasemide. Patients who were not previously on oral diuretics are recommended to start with a dose of 20–40 mg of furosemide or a bolus of 10–20 mg IV torasemide.[20,26] Loop diuretic IV dose can be doubled should there be insufficient diuretic response.[26] An inadequate diuretic response (e.g.
< 100 mL hourly diuresis), resistant oedema or symptoms/signs of congestion despite increasing the dose of loop diuretics and simultaneously administering diuretics that act on different sites of the nephron e.g., thiazides, aldosterone antagonist e.g., spironolactone, eplerenone is advised. When the patient’s clinical condition stabilizes, oral treatment should be initiated.

Other alternative drug treatments include intravenous vasodilators, especially nitrates or nitroprusside. These medications cause decrease in venous return to heart, therefore less congestion. Intravenous vasodilators are useful to relieve acute heart failure symptoms when the systolic blood pressure is > 110 mmHg. In severely hypertensive cases having acute pulmonary oedema, nitroglycerine can be given as 1–2 mg boluses.[27] However, this can cause extreme reduction in preload and afterload which can eventually lead to hypotension and therefore it is advised for careful monitoring of haemodynamic parameters.[28]

Patients exhibiting a low systolic blood pressure (BP) (< 90 mmHg) and signs of hypoperfusion may be considered for inotropic agents like dobutamine if they Do not exhibit a positive response to conventional therapies like fluid
challenges.[29] This approach enhances peripheral perfusion and preserves end-organ function. In cases of cardiogenic shock, vasopressors, preferably norepinephrine, can be contemplated to raise BP and improve end-organ perfusion.[30,31] To mitigate the risk of deep venous thrombosis and pulmonary embolism, thromboembolism prophylaxis (e.g., using low molecular weight heparin) is advised for cases not currently on anticoagulation.[32,33] While the daily use of opiates in AHF is discouraged, they might be suitable in situations where patients are enduring severe pain or anxiety, or under palliative care.[34,35]

Patients experiencing cardiogenic shock should be evaluated for short-term mechanical circulatory assistance. While cases with CS may suitable for an intra-aortic balloon pump, which is generally not recommended for those who have recently had a myocardial infarction.[36,37]

Complications of AHF include arrythmias, which is frequently triggered by arrythmias, especially atrial fibrillation.[38,39] Use of nitrates such as glyceryl trinitrate may cause headache and hypotension. Worsening renal function, hypotension, and hypokalaemia and over activation of the renin-angiotensin system and sympathetic system can result from over-diuresis. If faced with worsening renal impairment attributed to over-diuresis, the diuretic dose should be decreased. Cases of severe renal impairment will mean that the diuretic should be withheld and patient assessment occurring daily, and diuretics re-introduced at lower doses.

Long-term management can occur once the acute episode is stabilised and depends on the left ventricular ejection fraction (LVEF). Establishing the aetiology of HF is essential, for examples patients with hypertensive cardiomyopathy should have an aggressive antihypertensive treatment regime, those with alcoholic cardiomyopathies will benefit from cessation of alcohol consumption and those with ischaemic cardiomyopathies will may benefit from revascularisation. In patients with reduced ejection fraction i.e., LVEF ≤ 40% patients will benefit from pharmacological therapies. They should be started on an ACE inhibitor (or an angiotensin-II receptor antagonist if an ACE inhibitor is not tolerated). The recommended approach is to initiate treatment with a minimal dose and then gradually increase it as necessary. Beta-blockers are recommended in this group of patients e.g., bisoprolol.[40] Aldosterone antagonist is also given alongside ACE inhibitors and beta-blockers. Regardless of whether a patient has diabetes or not, patients are initiated on sodium-glucose co-transporter 2 (SGLT2) inhibitors e.g., dapagliflozin or empagliflozin.[40] Patients with symptoms or signs of congestion should be considered for an oral diuretic.

Early involvement of the specialist heart failure team, who may consider additional treatments, enables optimisation of outcomes. The treatment options that the team may consider are:[40]

1. Ivabradine
2. Isosorbide dinitrate plus hydralazine
3. Digoxin
4. Cardiac resynchronization treatment
5. Implantable cardioverter defibrillator
6. Transplantation or MCS

Cardiac rehabilitation is recommended to patients before they are discharged. This can be exercised-based and personalised, whilst also addressing educational and psychological aspects.

Patients with higher LVEF (i.e., beyond 41%) are referred to specialists, cardiac rehabilitation and diuretics.

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