Heart Failure ❤️ with Reduced Ejection Fraction

Related Subjects: | AP of the Coronary Arteries |Atherosclerosis |Ischaemic heart disease |Acute Coronary Syndrome (ACS): Complications |Acute Coronary Syndrome (ACS) |Assessing Chest Pain |ACS - General |ACS - STEMI |ACS - NSTEMI |ACS - GRACE Score |ACS - ECG Changes |Cardiac Troponins |ACS: Right Ventricular Infarction

Heart failure with reduced ejection fraction, abbreviated HFrEF, is a clinical syndrome in which impaired left ventricular systolic contraction results in an inadequate cardiac output and increased cardiac filling pressures. HFrEF is generally defined as heart failure with a left ventricular ejection fraction of 40% or less. Unlike HFpEF, where ventricular filling and increased diastolic pressures are central abnormalities, HFrEF is characterised primarily by impaired systolic contraction. In practice, however, patients with HFrEF usually have abnormalities of both systolic contraction and diastolic filling.

🫀 What is the ejection fraction?

The left ventricular ejection fraction is the proportion of blood present in the left ventricle at the end of diastole that is ejected during systole. It can be expressed approximately as:

Ejection fraction = stroke volume ÷ end-diastolic volume × 100

A normal left ventricular ejection fraction is usually approximately 50–70%.

• HFrEF: LVEF 40% or less
• HFmrEF: LVEF 41–49%
• HFpEF: LVEF 50% or greater

Ejection fraction is useful but does not completely describe ventricular function. The severity of symptoms does not always correlate directly with the numerical ejection fraction.

⚙️ Pathophysiology

The fundamental abnormality in HFrEF is impaired left ventricular contraction. Myocardial injury causes loss or dysfunction of functioning cardiac muscle. The ventricle cannot generate normal contractile force, stroke volume falls and end-systolic volume increases. Over time the ventricle commonly undergoes pathological remodelling.

• Left ventricular dilatation
• Increasing ventricular wall stress
• More spherical ventricular geometry
• Functional mitral regurgitation
• Progressive deterioration in systolic function

The initial fall in cardiac output activates several compensatory mechanisms. These may maintain blood pressure and organ perfusion in the short term but become harmful when chronically activated.

🧠 Sympathetic nervous system activation

A reduction in cardiac output activates the sympathetic nervous system. Noradrenaline increases heart rate, myocardial contractility and peripheral vasoconstriction. Initially this helps maintain blood pressure and cardiac output. Chronic sympathetic activation is harmful because it increases myocardial oxygen demand, promotes arrhythmias, causes vasoconstriction and contributes to adverse ventricular remodelling. This provides an important physiological explanation for the benefit of beta-blockers in HFrEF.

💧 Renin-angiotensin-aldosterone system

Reduced renal perfusion activates the renin-angiotensin-aldosterone system.

• Renin production increases
• Angiotensin II causes vasoconstriction
• Aldosterone promotes sodium and water retention
• Preload increases
• Afterload increases
• Myocardial fibrosis and remodelling are promoted

These responses temporarily support blood pressure but ultimately worsen congestion and increase the workload of the failing ventricle. This explains why inhibition of the renin-angiotensin-aldosterone system is such an important component of HFrEF treatment.

🩸 Increased preload and afterload

Fluid retention increases venous return and ventricular filling pressure. Initially, increasing preload may increase stroke volume through the Frank-Starling mechanism. However, the failing ventricle eventually operates on the flatter portion of the Frank-Starling curve. Additional filling then produces little improvement in cardiac output but substantially increases pulmonary and systemic venous pressure. Increased afterload also makes it more difficult for the failing ventricle to eject blood. Reducing excessive preload relieves congestion, while reducing afterload can improve forward cardiac output.

🫁 Why does HFrEF cause breathlessness?

When the left ventricle cannot empty normally, left ventricular end-diastolic pressure rises. This increased pressure is transmitted backwards through the left atrium into the pulmonary veins and pulmonary capillaries.

• Left ventricular filling pressure rises
• Left atrial pressure rises
• Pulmonary venous pressure rises
• Fluid moves into the pulmonary interstitium
• Pulmonary oedema may develop
• Breathlessness results

Initially breathlessness occurs during exertion. As heart failure progresses, orthopnoea, paroxysmal nocturnal dyspnoea and breathlessness at rest may occur.

🦵 Why does peripheral oedema occur?

Advanced left ventricular failure may eventually cause pulmonary hypertension and right ventricular dysfunction.

Systemic venous pressure then rises and fluid accumulates in dependent tissues.

• Ankle and sacral oedema
• Raised jugular venous pressure
• Hepatic congestion
• Ascites
• Gut oedema

Renal sodium and water retention further contributes to fluid accumulation.

⚠️ Causes of HFrEF

HFrEF is a syndrome rather than a single disease. Identifying the underlying cause is important because some causes are reversible or have specific treatments.

Common causes include:

• Ischaemic heart disease
• Previous myocardial infarction
• Dilated cardiomyopathy
• Long-standing hypertension
• Valvular heart disease
• Myocarditis
• Alcohol-related cardiomyopathy
• Cardiotoxic chemotherapy
• Tachycardia-induced cardiomyopathy
• Genetic cardiomyopathy
• Peripartum cardiomyopathy
• Endocrine and metabolic disorders

🫀 Ischaemic heart disease

Coronary artery disease is one of the most important causes of HFrEF.

Myocardial infarction permanently destroys functioning cardiomyocytes. The damaged region becomes scar tissue and the remaining myocardium must compensate.

Large or repeated infarctions may therefore produce progressive ventricular dilatation and systolic dysfunction.

Ongoing myocardial ischaemia can also produce dysfunctional but potentially viable myocardium.

🧬 Dilated cardiomyopathy

Dilated cardiomyopathy is characterised by left ventricular or biventricular dilatation with impaired systolic function that cannot be explained solely by abnormal loading conditions or coronary artery disease. Potential causes include:

• Genetic disease
• Previous myocarditis
• Alcohol
• Cardiotoxic drugs
• Pregnancy
• Tachyarrhythmias
• Endocrine disease

In many patients no single cause is identified.

🍷 Alcohol and cardiomyopathy

Prolonged excessive alcohol consumption can cause dilated cardiomyopathy and HFrEF. Alcohol-related myocardial dysfunction may improve substantially if alcohol is stopped before irreversible myocardial damage has occurred.

💓 Tachycardia-induced cardiomyopathy

Persistent rapid tachyarrhythmias can cause ventricular dilatation and impaired systolic function. Atrial fibrillation with a persistently rapid ventricular response is a common example. This is particularly important because ventricular function may improve dramatically when the arrhythmia is controlled.

🧪 Symptoms of HFrEF

Symptoms arise from pulmonary congestion, systemic venous congestion and reduced cardiac output.

• Exertional breathlessness
• Reduced exercise tolerance
• Fatigue
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• Ankle swelling
• Rapid weight gain due to fluid retention
• Nocturnal cough
• Reduced appetite
• Abdominal distension
• Dizziness

Severe disease may cause hypotension, confusion, oliguria and cardiogenic shock.

🩺 Clinical signs

Clinical findings vary according to the degree of congestion and cardiac output.

• Tachycardia
• Low blood pressure in advanced disease
• Raised jugular venous pressure
• Displaced apex beat
• Third heart sound
• Functional mitral regurgitation
• Basal pulmonary crackles
• Peripheral oedema
• Hepatomegaly
• Ascites
• Cool peripheral extremities in low-output states

🔊 Third heart sound

A third heart sound may be heard in patients with significant systolic heart failure.

It occurs during rapid ventricular filling into a dilated ventricle and, in an older adult, usually indicates significant ventricular dysfunction or volume overload.

🔎 Diagnosis

The diagnosis requires a compatible clinical syndrome together with objective evidence of cardiac dysfunction.

Assessment usually includes:

• Clinical history and examination
• BNP or NT-proBNP
• 12-lead ECG
• Echocardiography
• Full blood count
• Renal function and electrolytes
• Liver function
• Thyroid function
• Glucose or HbA1c
• Lipid profile
• Iron studies where appropriate
• Chest imaging when indicated

🧪 BNP and NT-proBNP

BNP and NT-proBNP are released in response to increased myocardial wall stress.

Low concentrations make clinically significant heart failure less likely, while elevated concentrations support the diagnosis and should prompt cardiac assessment.

Natriuretic peptide concentrations are influenced by several factors.

• Levels increase with age
• Levels increase in renal impairment
• Levels increase in atrial fibrillation
• Levels may be reduced by obesity

The concentration should therefore always be interpreted in the clinical context.

🖥️ Echocardiography

Echocardiography is the central imaging investigation in HFrEF.

Typical abnormalities include:

• Reduced left ventricular ejection fraction
• Global or regional hypokinesis
• Left ventricular dilatation
• Left atrial enlargement
• Functional mitral regurgitation
• Right ventricular dysfunction
• Pulmonary hypertension

Echocardiography also identifies important underlying conditions such as valvular heart disease.

🧲 Cardiac MRI

Cardiac magnetic resonance imaging can provide valuable information when the cause of cardiomyopathy is uncertain. It can assess ventricular volumes and function and may identify patterns of myocardial scar, previous infarction, myocarditis, infiltrative disease or other cardiomyopathies.

💊 Treatment of HFrEF

Modern HFrEF treatment should not be thought of simply as giving a diuretic and then slowly adding other drugs. Several drug classes alter the underlying biology of heart failure and substantially reduce hospitalisation and mortality. The aim is to establish disease-modifying therapy early and titrate treatment according to blood pressure, renal function, potassium, heart rate and tolerability.

⭐ The four pillars of HFrEF treatment

Current UK treatment centres around four major classes of disease-modifying therapy.

• ACE inhibitor or appropriate renin-angiotensin system therapy
• Evidence-based beta-blocker
• Mineralocorticoid receptor antagonist
• SGLT2 inhibitor

These treatments act through different physiological pathways and their benefits are complementary.

1️⃣ ACE inhibitors

ACE inhibitors reduce production of angiotensin II and aldosterone.

The effects include:

• Reduced vasoconstriction
• Reduced afterload
• Reduced sodium and water retention
• Reduced pathological ventricular remodelling
• Reduced heart failure hospitalisation
• Improved survival

Examples include ramipril, lisinopril and enalapril.

Renal function and potassium should be checked before treatment and monitored after initiation and dose increases.

💊 ARBs

An angiotensin receptor blocker may be used when an ACE inhibitor cannot be tolerated, particularly because of persistent ACE inhibitor-associated cough. Examples include candesartan and valsartan.

2️⃣ Beta-blockers

Evidence-based beta-blockers counter chronic sympathetic nervous system activation. They reduce heart rate, decrease arrhythmic risk, improve ventricular function over time and improve survival. Commonly used agents include:

• Bisoprolol
• Carvedilol
• Nebivolol in selected older patients

Beta-blockers should usually be introduced when the patient is clinically stable rather than during severe fluid overload or cardiogenic shock.

Treatment is usually started at a low dose and increased according to heart rate, blood pressure and tolerability.

3️⃣ Mineralocorticoid receptor antagonists

Mineralocorticoid receptor antagonists block the effects of aldosterone.

Examples include:

• Spironolactone
• Eplerenone

They reduce sodium retention, myocardial fibrosis, cardiovascular mortality and heart failure hospitalisation. Potassium and renal function must be monitored because hyperkalaemia and renal dysfunction may occur.

4️⃣ SGLT2 inhibitors

SGLT2 inhibitors are now a core component of HFrEF treatment irrespective of whether the patient has diabetes.

Examples include:

• Dapagliflozin
• Empagliflozin

They reduce worsening heart failure and cardiovascular events and have important renal benefits. Their mechanism in heart failure is multifactorial and extends well beyond glucose lowering.

🔄 Sacubitril/valsartan

Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor, usually abbreviated ARNI. Sacubitril inhibits neprilysin, increasing concentrations of beneficial natriuretic peptides. Valsartan blocks the angiotensin II receptor. The combined effect promotes natriuresis and vasodilatation while suppressing harmful renin-angiotensin signalling. In current UK practice, sacubitril/valsartan may replace ACE inhibitor therapy in appropriate symptomatic patients despite established guideline-directed therapy or where ACE inhibition is not tolerated for reasons other than angioedema. An ACE inhibitor must not be given simultaneously with sacubitril/valsartan because of the risk of angioedema.

💧 Diuretics

Loop diuretics such as furosemide relieve pulmonary and peripheral congestion.

They improve symptoms but should be distinguished from the principal disease-modifying treatments that improve survival.

The aim is to use the lowest dose required to maintain euvolaemia.

• Monitor body weight
• Monitor renal function
• Monitor sodium and potassium
• Assess oedema and JVP
• Reduce the dose if the patient becomes volume depleted

🩸 Iron deficiency

Iron deficiency is common in HFrEF and can worsen fatigue and exercise intolerance even when the haemoglobin concentration is relatively preserved. Iron studies should therefore be considered in symptomatic patients. Intravenous iron can improve symptoms and exercise capacity in appropriately selected iron-deficient patients and may reduce recurrent heart failure admissions.

💓 Atrial fibrillation

Atrial fibrillation commonly accompanies HFrEF.

Management includes:

• Appropriate ventricular rate control
• Consideration of rhythm control in selected patients
• Anticoagulation according to thromboembolic risk
• Identification of tachycardia-induced cardiomyopathy

In selected patients with HFrEF, particularly where AF is driving ventricular dysfunction, catheter ablation may substantially improve ventricular function and clinical outcomes.

💊 Digoxin

Digoxin may be used in selected patients with HFrEF, particularly where additional rate control is required in atrial fibrillation. It may reduce heart failure hospitalisation but does not provide the mortality benefit of the principal disease-modifying therapies. Toxicity is more likely in older people, renal impairment and hypokalaemia.

🚫 Drugs that may worsen HFrEF

Drugs that should be avoided or used cautiously include:

• NSAIDs
• Most non-dihydropyridine calcium-channel blockers such as verapamil and diltiazem
• Thiazolidinediones
• Drugs causing significant sodium retention
• Potentially cardiotoxic drugs where alternatives exist

NSAIDs are particularly important because they may cause sodium retention, renal dysfunction and loss of response to diuretics.

⚡ Implantable cardioverter defibrillator

Patients with severe persistent left ventricular systolic dysfunction are at increased risk of ventricular tachyarrhythmias and sudden cardiac death. An implantable cardioverter defibrillator can detect and terminate life-threatening ventricular arrhythmias. Selected patients with persistently reduced LVEF despite optimal medical treatment should therefore be assessed for ICD therapy.

🔌 Cardiac resynchronisation therapy

Some patients with HFrEF have electrical dyssynchrony, particularly left bundle branch block.

This means different regions of the ventricle contract at different times, making an already impaired ventricle even less efficient.

Cardiac resynchronisation therapy stimulates both ventricles in a coordinated manner.

In appropriately selected patients it can:

• Improve symptoms
• Increase ejection fraction
• Reverse ventricular remodelling
• Reduce hospitalisation
• Improve survival

🫀 Revascularisation

Patients with HFrEF caused by significant coronary artery disease should be assessed for myocardial ischaemia and appropriate coronary intervention. Selected patients may benefit from PCI or coronary artery bypass grafting depending on symptoms, coronary anatomy and viability of myocardium.

🏃 Exercise and cardiac rehabilitation

Stable patients should usually be encouraged to exercise rather than advised to rest. Cardiac rehabilitation and structured exercise improve functional capacity and quality of life. Prolonged inactivity promotes skeletal muscle deconditioning and can substantially worsen exercise intolerance.

🧂 Salt and fluid

Routine severe salt or fluid restriction is not necessary for every patient with stable HFrEF.

Advice should be individualised according to congestion, renal function, serum sodium and clinical circumstances.

Patients should understand how to recognise increasing fluid retention, particularly rapid increases in body weight and worsening peripheral oedema or breathlessness.

🚑 Acute decompensated HFrEF

Acute deterioration is frequently triggered by another clinical event.

Common precipitants include:

• Acute coronary syndrome
• Infection
• Atrial fibrillation or another tachyarrhythmia
• Uncontrolled hypertension
• Renal deterioration
• Medication non-adherence
• NSAID use
• Excess sodium or fluid intake
• Anaemia
• Pulmonary embolism

Treatment requires both correction of congestion and identification of the precipitating cause.

Intravenous loop diuretics are commonly used when significant congestion is present.

⚠️ Cardiogenic shock

Severe ventricular failure may result in an inadequate cardiac output to maintain tissue perfusion.

Features include:

• Hypotension
• Cold peripheries
• Confusion
• Oliguria
• Metabolic acidosis
• Elevated lactate

This is a medical emergency requiring urgent specialist management and identification of potentially reversible causes such as acute myocardial infarction or mechanical complications.

👴 HFrEF in older people

Older patients frequently have HFrEF together with chronic kidney disease, frailty, postural hypotension, atrial fibrillation and polypharmacy.

This does not mean that disease-modifying treatment should automatically be withheld.

The challenge is to introduce effective therapy while monitoring physiological reserve and adverse effects carefully.

• Start treatment thoughtfully
• Monitor blood pressure including postural blood pressure
• Monitor renal function and potassium
• Review polypharmacy
• Assess frailty and mobility
• Avoid excessive diuresis
• Do not stop effective therapy solely because of chronological age

🔄 Heart failure with improved ejection fraction

Some patients treated for HFrEF subsequently show substantial recovery of left ventricular systolic function. This is sometimes termed heart failure with improved ejection fraction. Improvement in ejection fraction does not necessarily mean that the underlying myocardial disease has been cured. Disease-modifying treatment is generally continued because withdrawal may be followed by recurrent ventricular dysfunction.

📈 Prognosis

HFrEF is a serious chronic condition associated with recurrent hospitalisation, ventricular arrhythmias and increased mortality. However, prognosis has improved substantially with contemporary multidrug treatment and appropriate device therapy. A central concept is therefore to establish effective disease-modifying therapy rather than relying solely on symptomatic treatment with diuretics.

🧠 HFrEF versus HFpEF

• HFrEF has an LVEF of 40% or less
• HFpEF generally has an LVEF of 50% or greater
• HFrEF is characterised predominantly by impaired systolic contraction
• HFpEF is characterised predominantly by abnormal filling and increased filling pressures
• HFrEF often produces ventricular dilatation
• HFpEF frequently has concentric hypertrophy and a relatively small stiff ventricle
• Both can produce pulmonary congestion and peripheral oedema
• Both have important disease-modifying treatments, although the evidence base differs

⭐ Key Points

• HFrEF is heart failure with a left ventricular ejection fraction of 40% or less
• The primary abnormality is impaired left ventricular systolic contraction
• Reduced cardiac output activates the sympathetic nervous system and renin-angiotensin-aldosterone system
• These compensatory systems initially maintain circulation but subsequently drive adverse remodelling and disease progression
• Ischaemic heart disease and cardiomyopathy are major causes
• Echocardiography confirms reduced systolic function and helps identify the underlying cause
• Natriuretic peptides are useful in the diagnostic pathway
• Modern treatment should include the major disease-modifying drug classes as early as tolerated
• The four core treatments are renin-angiotensin system inhibition, beta-blocker, mineralocorticoid receptor antagonist and SGLT2 inhibitor
• Diuretics relieve congestion but are not a substitute for disease-modifying therapy
• Selected patients benefit from sacubitril/valsartan, ICD or cardiac resynchronisation therapy
• Iron deficiency, atrial fibrillation, coronary disease and other comorbidities should be actively identified and treated
• Improvement in ejection fraction does not normally mean that heart failure treatment can simply be stopped