Heart Failure ❤️ with Preserved 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 preserved ejection fraction, usually abbreviated HFpEF, is a clinical syndrome in which the patient has symptoms and signs of heart failure despite a left ventricular ejection fraction that is usually 50% or greater. The older term "diastolic heart failure" is useful but incomplete. Many patients with HFpEF have impaired ventricular relaxation and increased ventricular stiffness, but the disorder also involves abnormalities of the left atrium, pulmonary circulation, right ventricle, vascular system, kidneys and skeletal muscle. HFpEF is therefore best regarded as a systemic clinical syndrome rather than simply a problem with ventricular diastole.

🫀 What happens in HFpEF?

During diastole the normal left ventricle relaxes rapidly and fills at relatively low pressure. In HFpEF the ventricle is often hypertrophied, fibrotic or otherwise stiff and does not relax normally. A stiff ventricle requires a higher filling pressure to achieve an adequate end-diastolic volume. This increased pressure is transmitted backwards to the left atrium and pulmonary veins.

• Left ventricular filling pressure rises
• Left atrial pressure rises
• Pulmonary venous pressure rises
• Pulmonary congestion develops
• The patient becomes breathless

The ejection fraction can remain normal because ejection fraction describes the proportion of ventricular blood ejected rather than the absolute volume of blood pumped. A small, thick-walled ventricle may therefore eject 60% of a relatively small end-diastolic volume while still producing an inadequate stroke volume.

💡 Preserved EF does not mean normal cardiac function

A normal ejection fraction should never be interpreted as meaning that heart failure has been excluded. In HFpEF the principal abnormality is often an inability of the ventricle to fill normally without an excessive rise in filling pressure. This becomes especially important during exercise. Increasing venous return requires the ventricle to accommodate more blood. A compliant ventricle does this with little increase in pressure, whereas a stiff ventricle develops a marked rise in left ventricular and left atrial pressures. This explains why many patients with HFpEF may appear relatively comfortable at rest but become markedly breathless during exertion.

👵 Who develops HFpEF?

HFpEF becomes increasingly common with age and is particularly common among older adults with multiple cardiovascular and metabolic conditions.

Common associations include:

• Increasing age
• Hypertension
• Left ventricular hypertrophy
• Obesity
• Type 2 diabetes
• Atrial fibrillation
• Chronic kidney disease
• Coronary artery disease
• Obstructive sleep apnoea
• Pulmonary hypertension
• Valvular heart disease

HFpEF is often the final cardiac manifestation of several interacting disorders rather than a single disease.

🩸 Hypertension

Long-standing hypertension is one of the most important causes of HFpEF. Chronic pressure loading causes concentric left ventricular hypertrophy. The thicker myocardium becomes less compliant and requires progressively higher filling pressures. The left atrium subsequently dilates because it is chronically exposed to increased filling pressure. Good blood pressure control is therefore central to both prevention and treatment of HFpEF.

⚖️ Obesity and HFpEF

Obesity is increasingly recognised as an important HFpEF phenotype rather than simply an associated risk factor. Obesity promotes systemic inflammation, insulin resistance, plasma volume expansion, ventricular remodelling and abnormal ventricular-vascular coupling. Epicardial and visceral adipose tissue may also contribute to myocardial inflammation and fibrosis. Obese patients can have substantial HFpEF despite relatively low natriuretic peptide concentrations, making diagnosis more difficult. Weight reduction, physical activity and treatment of associated diabetes, hypertension and sleep apnoea are therefore particularly important.

💓 Atrial fibrillation

Atrial fibrillation and HFpEF commonly coexist and each can worsen the other. The stiff ventricle is particularly dependent on atrial contraction for late diastolic filling. Loss of this "atrial kick" may therefore produce a substantial increase in symptoms. Rapid ventricular rates also shorten diastolic filling time and can further increase left atrial and pulmonary venous pressures. Management should include appropriate rate or rhythm control and anticoagulation according to thromboembolic risk.

🧬 Cardiac amyloidosis

Cardiac amyloidosis is an important and frequently overlooked cause of HFpEF, particularly in older patients. Amyloid protein is deposited within the myocardium, producing increased ventricular wall thickness and progressive myocardial stiffness. Wild-type transthyretin amyloid cardiomyopathy becomes increasingly important with advancing age. Features that should raise suspicion include:

• HFpEF with unexplained increased ventricular wall thickness
• Disproportionately low ECG voltages
• Bilateral carpal tunnel syndrome
• Peripheral or autonomic neuropathy
• Unexplained hypotension
• Conduction disease
• Aortic stenosis with marked ventricular thickening
• Poor tolerance of conventional heart failure medication

An apparently hypertrophied ventricle on echocardiography combined with unexpectedly low ECG voltage is particularly suggestive. Technetium-labelled bone scintigraphy, commonly using 99mTc-DPD in the UK, plays an important role in identifying transthyretin cardiac amyloidosis. However, AL amyloidosis must be excluded using serum and urine testing for a monoclonal protein and serum free light chains before a non-biopsy diagnosis of ATTR cardiac amyloidosis is made.

🫁 Symptoms

The dominant symptom is usually exertional breathlessness.

Other symptoms include:

• Reduced exercise tolerance
• Fatigue
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• Peripheral oedema
• Abdominal swelling
• Rapid weight gain during fluid retention
• Palpitations, particularly with atrial fibrillation

Patients may have remarkably few signs when euvolaemic and may only become symptomatic when filling pressures rise during exercise.

🩺 Clinical signs

Clinical examination may be normal when the patient is compensated.

During congestion there may be:

• Raised jugular venous pressure
• Basal pulmonary crackles
• Peripheral oedema
• Tachycardia
• Hypertension
• An irregular pulse from atrial fibrillation
• A displaced or sustained apex associated with LV hypertrophy
• Features of an underlying valvular disorder

🔎 Diagnosing HFpEF

HFpEF should not be diagnosed simply because a breathless patient has a normal ejection fraction. The diagnosis requires evidence that the patient's symptoms are caused by heart failure together with objective evidence of abnormal cardiac structure, function or raised filling pressures.

Assessment usually includes:

• Clinical history and examination
• ECG
• BNP or NT-proBNP
• Echocardiography
• Blood tests
• Chest imaging where appropriate
• Investigation for underlying and alternative causes

🧪 Natriuretic peptides

BNP and NT-proBNP are released when myocardial wall stress increases and are useful in the assessment of suspected heart failure. An elevated natriuretic peptide concentration supports the diagnosis but is not specific for HFpEF. Levels may also be increased by:

• Atrial fibrillation
• Chronic kidney disease
• Increasing age
• Pulmonary hypertension
• Acute coronary syndromes

Conversely, obesity can suppress natriuretic peptide concentrations. A relatively low BNP or NT-proBNP therefore does not completely exclude HFpEF, particularly in an obese patient.

🖥️ Echocardiography

Echocardiography is central to the assessment of suspected HFpEF. Typical findings include:

• Preserved left ventricular ejection fraction
• Concentric left ventricular hypertrophy
• Increased ventricular wall thickness
• Left atrial enlargement
• Abnormal mitral inflow
• Abnormal tissue Doppler velocities
• Evidence of increased left ventricular filling pressure
• Pulmonary hypertension
• Right ventricular abnormalities in more advanced disease

No single echocardiographic measurement reliably establishes HFpEF.

📊 E/e′ and tissue Doppler

Tissue Doppler measures the velocity of movement of the mitral annulus during early ventricular filling, known as e′.

The relationship between transmitral E velocity and tissue Doppler e′ velocity, expressed as E/e′, provides an estimate of left ventricular filling pressure.

An increased E/e′ supports increased filling pressure, but the measurement should not be interpreted in isolation.

🏃 Why exercise testing can be important

Some patients have normal or borderline filling pressures at rest but develop markedly abnormal pressures during exercise. When the diagnosis remains uncertain, diastolic stress echocardiography or invasive haemodynamic exercise testing may demonstrate an abnormal rise in filling pressures. This illustrates an important feature of HFpEF: the cardiovascular system may compensate adequately at rest but fail when challenged.

📋 HFA-PEFF and H2FPEF scores

Diagnostic scoring systems can help estimate the likelihood of HFpEF when the diagnosis is uncertain.

The HFA-PEFF approach incorporates:

• Functional echocardiographic abnormalities
• Structural cardiac abnormalities
• Natriuretic peptide concentrations

The H2FPEF score incorporates clinical and echocardiographic characteristics including obesity, hypertension, atrial fibrillation, pulmonary pressure and age.

These scores support clinical reasoning but do not replace clinical assessment.

🩻 Important differential diagnoses

Breathlessness in an older patient with preserved ejection fraction should not automatically be attributed to HFpEF. Important alternatives and contributors include:

• COPD
• Interstitial lung disease
• Pulmonary embolic disease
• Anaemia
• Obesity and physical deconditioning
• Coronary artery disease
• Valvular heart disease
• Pulmonary hypertension
• Thyroid disease
• Chronic kidney disease
• Cardiac amyloidosis

💊 Treatment of HFpEF

Treatment of HFpEF has changed substantially in recent years. The principal aims are to:

• Relieve congestion
• Reduce heart failure admissions
• Treat the underlying cause
• Treat important comorbidities
• Improve exercise tolerance and quality of life
• Reduce cardiovascular risk

💧 Diuretics

Loop diuretics are used when there is pulmonary or peripheral congestion. The aim is to achieve euvolaemia rather than to administer a predetermined dose. Patients with HFpEF can be particularly sensitive to excessive preload reduction because their stiff ventricle may require relatively high filling pressure to maintain stroke volume. Excessive diuresis may therefore cause:

• Hypotension
• Dizziness
• Acute kidney injury
• Reduced cardiac output

The dose should therefore be adjusted to clinical congestion, body weight, blood pressure, renal function and symptoms.

⭐ SGLT2 inhibitors

Sodium-glucose cotransporter-2 inhibitors are now a major disease-modifying treatment for HFpEF.

Dapagliflozin and empagliflozin reduce the risk of worsening heart failure and heart failure hospitalisation across a broad range of left ventricular ejection fractions.

Their heart failure benefit is present whether or not the patient has diabetes.

SGLT2 inhibitors have therefore fundamentally changed HFpEF management, which previously had very few treatments supported by robust randomised trial evidence.

💊 Mineralocorticoid receptor antagonists

Mineralocorticoid receptor antagonists such as spironolactone may be considered in suitable patients with HFpEF.

Renal function and serum potassium must be monitored because treatment can cause hyperkalaemia and worsening renal function.

Evidence also continues to develop for newer non-steroidal mineralocorticoid receptor antagonists such as finerenone in patients with mildly reduced or preserved ejection fraction.

🩸 Treat hypertension

Hypertension increases ventricular afterload and promotes ventricular hypertrophy, myocardial fibrosis and progressive diastolic dysfunction.

Blood pressure should therefore be actively controlled using treatment appropriate to the individual patient and their comorbidities.

💓 Beta-blockers

Beta-blockers are not a specific disease-modifying treatment for HFpEF simply because the patient has heart failure.

They are useful where there is another indication, including:

• Atrial fibrillation requiring rate control
• Angina
• Previous myocardial infarction
• Hypertension in selected patients

Excessive rate slowing can occasionally worsen exercise intolerance because some patients with HFpEF rely on an increase in heart rate to augment cardiac output during exercise.

💊 ACE inhibitors, ARBs and ARNIs

Renin-angiotensin system treatments may be appropriate for hypertension, chronic kidney disease, coronary disease or another specific indication. The benefits seen with these drugs in HFrEF cannot simply be assumed to apply equally to all patients with HFpEF. Sacubitril/valsartan may have benefit in selected patients towards the lower end of the preserved ejection fraction spectrum, but it is not the universal cornerstone of HFpEF treatment that it is in HFrEF.

💊 Digoxin

Digoxin is not routinely indicated for HFpEF in sinus rhythm. It may have a role in selected patients with atrial fibrillation where additional ventricular rate control is required.

🏃 Exercise and cardiac rehabilitation

Exercise intolerance in HFpEF is not solely a cardiac phenomenon. Skeletal muscle abnormalities, obesity, vascular dysfunction and physical deconditioning contribute substantially. Regular structured exercise can improve functional capacity and quality of life. Patients should therefore be encouraged to remain physically active within the limits imposed by their symptoms and comorbidity.

⚖️ Weight management

Weight management is especially important in obesity-related HFpEF.

Weight reduction reduces haemodynamic load and can improve exercise capacity, metabolic health and symptoms. Modern incretin-based therapies have also demonstrated important improvements in symptoms, physical limitations and weight in selected patients with obesity-related HFpEF, making obesity an increasingly treatable component of the syndrome.

🫁 Treat sleep apnoea and lung disease

Obstructive sleep apnoea, COPD and other respiratory disorders frequently coexist with HFpEF and may substantially contribute to breathlessness. Identifying and treating these conditions is an important part of HFpEF management.

🧠 HFpEF in the older patient

HFpEF is particularly relevant to geriatric medicine because many patients are older, frail and multimorbid.

The dominant clinical problem may not be fluid overload alone but the interaction between heart failure, sarcopenia, renal impairment, anaemia, atrial fibrillation, obesity, cognitive impairment and loss of physiological reserve.

Management should therefore focus on the patient rather than simply the ejection fraction.

• Review polypharmacy
• Avoid unnecessary hypotension
• Avoid excessive diuresis
• Monitor renal function
• Assess mobility and frailty
• Look for iron deficiency and anaemia
• Optimise nutrition
• Encourage appropriate physical activity
• Consider cardiac amyloidosis where appropriate

🚑 Acute decompensated HFpEF

Patients with HFpEF may develop acute pulmonary oedema despite retaining a normal ejection fraction.

Common precipitants include:

• Uncontrolled hypertension
• Atrial fibrillation with rapid ventricular response
• Myocardial ischaemia
• Infection
• Renal deterioration
• Excess salt or fluid intake
• Stopping medication
• Anaemia

Treatment is directed at congestion and the precipitating cause. Intravenous loop diuretics are commonly required when significant fluid overload is present.

📈 Prognosis

HFpEF is not a benign form of heart failure. It is associated with recurrent hospital admission, declining exercise capacity, reduced quality of life and substantial mortality. Many deaths in patients with HFpEF are related not only to progressive heart failure but also to sudden cardiac death and non-cardiovascular disease, reflecting the high burden of multimorbidity in this population.

🧠 HFpEF versus HFrEF

• HFpEF usually has an LVEF of 50% or greater
• HFrEF is characterised by reduced left ventricular systolic function
• HFpEF commonly involves impaired relaxation and increased ventricular stiffness
• HFrEF is typically characterised by impaired systolic contraction
• Both can cause pulmonary congestion, oedema and severe breathlessness
• Both are associated with substantial morbidity and mortality
• The evidence-based drug treatment differs considerably between the two syndromes

⭐ Key Points

• HFpEF is heart failure despite a preserved left ventricular ejection fraction
• A normal ejection fraction does not mean normal cardiac function
• The fundamental haemodynamic abnormality is often increased ventricular filling pressure
• Symptoms may be predominantly exercise-induced
• Hypertension, ageing, obesity, diabetes, AF and CKD are major associations
• Cardiac amyloidosis should be considered particularly in older patients with unexplained ventricular thickening
• Echocardiography and natriuretic peptides are central to diagnosis
• A normal or modestly elevated natriuretic peptide does not completely exclude HFpEF, particularly in obesity
• Diuretics treat congestion but should not be used excessively
• SGLT2 inhibitors are now a major disease-modifying treatment
• Mineralocorticoid receptor antagonists may also be considered
• Beta-blockers are used for specific indications rather than routinely for HFpEF itself
• Management of hypertension, AF, obesity, diabetes, renal disease and other comorbidities is fundamental
• HFpEF is a heterogeneous systemic syndrome and not simply "diastolic dysfunction"