Heart failure with mildly reduced or preserved ejection fraction

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

HFpEF is a positive diagnosis of raised filling pressure/structural heart disease in a symptomatic patient, after considering mimics. NICE describes LVEF ≥50% plus at least two structural or functional abnormalities such as left-atrial enlargement, raised E:e', LV hypertrophy or pulmonary hypertension.

The September 2025 NICE update expands treatment beyond diuresis and comorbidity control: SGLT2 inhibition is recommended for consideration in both phenotypes, with MRA in HFpEF and the four HFrEF classes considered in HFmrEF.

Because multimorbidity dominates symptoms and tolerability, the plan must integrate renal function, BP, rhythm, frailty and functional goals rather than chase EF alone.

Key points

NICE defines HFmrEF as symptomatic HF with LVEF 41–49%; HFpEF requires symptomatic HF with LVEF at least 50% plus structural/functional evidence, not a normal EF alone.
For HFmrEF, consider an ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor; use an ARB instead of ACE inhibitor when ACE intolerance applies.
For HFpEF, consider an MRA plus an SGLT2 inhibitor under the NICE 2025 update.
Use diuretics for congestion in every EF phenotype and titrate to the lowest dose that relieves fluid retention.
Search actively for hypertension, AF, obesity, diabetes, CKD, coronary disease, valve disease, sleep-disordered breathing, lung disease and amyloidosis when clues exist.
Natriuretic peptides do not distinguish EF phenotype: echo is required, and obesity can produce deceptively low levels.
Do not routinely restrict salt or fluid; reserve fluid restriction for dilutional hyponatraemia or clearly excessive intake and review the need.
Clinical deterioration follows the same acute-HF pathway regardless of a preserved EF.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Hypertensive and metabolic remodelling

Ageing, hypertension, obesity and diabetes promote ventricular hypertrophy, fibrosis and vascular stiffness. These changes impair relaxation and reserve, forming a common substrate for preserved-ejection-fraction heart failure.

Ischaemic or previously reduced function

Coronary disease may leave mild systolic impairment, while treated HFrEF may recover into the mildly reduced or preserved range. Prior imaging prevents recovered disease being mistaken for a new phenotype.

Atrial fibrillation and valve disease

Atrial fibrillation removes coordinated atrial filling and may cause rapid rates, while valve lesions chronically alter pressure or volume. Both can precipitate congestion despite a relatively preserved ejection fraction.

Specific myocardial disorders

Cardiac amyloidosis and sarcomeric HCM are distinct diseases that can present with a stiff, thick-walled ventricle; other infiltrative or inherited disorders can do likewise. Extracardiac clues, voltage–wall-thickness discordance or unusual imaging should prompt targeted investigation.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Impaired ventricular reserve
HFmrEF includes modest systolic impairment, whereas HFpEF more often reflects hypertrophy, fibrosis and impaired active relaxation. In both phenotypes, ventricular performance may be inadequate during stress even when resting ejection fraction appears only mildly reduced or preserved.
2
Raised filling pressure
When ventricular relaxation or compliance is impaired, accommodating additional blood requires a disproportionate rise in diastolic pressure. Volume expansion or tachycardia can therefore cause marked haemodynamic deterioration.
3
Left-atrial and pulmonary transmission
Elevated ventricular diastolic pressure enlarges the left atrium and transmits backwards into pulmonary veins. Exertional breathlessness and pulmonary congestion follow, while atrial remodelling encourages fibrillation.
4
Impaired cardiovascular reserve
During exercise, limited stroke-volume expansion, abnormal vascular stiffness and sometimes chronotropic incompetence prevent adequate output. Filling pressure rises further, explaining severe exertional symptoms despite only mildly reduced or preserved resting ejection fraction.
5
Right-heart involvement
Persistent pulmonary venous hypertension can increase pulmonary arterial pressure and right-ventricular load. Right-heart dysfunction then adds systemic venous congestion, renal impairment and poorer exercise capacity.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

HFmrEF pattern

Typical HF symptoms/signs with LVEF 41–49%; prior HFrEF with improved EF should be recognised separately because withdrawing established HFrEF therapy may cause relapse.

HFpEF pattern

Exertional dyspnoea, congestion or exercise intolerance with LVEF ≥50% and objective structural/filling-pressure evidence.

Acute decompensationRed flag

Rest dyspnoea, hypoxaemia, rapid oedema/weight change or hypoperfusion needs urgent acute-HF assessment despite preserved EF.

AF and hypertension

Loss of atrial contribution, rapid ventricular rate or uncontrolled BP commonly precipitates symptoms and requires active treatment.

Infiltrative or structural clue

Marked wall thickening, low-voltage ECG, carpal tunnel, neuropathy, valve disease or disproportionate biomarker elevation should prompt specialist cause evaluation.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
NT-proBNPFirst step
Why
Triage suspected HF using the NICE chronic-HF route.
Interpretation and limitations
>2,000 ng/L merits specialist assessment/echo within 2 weeks; 400–2,000 within 6 weeks; <400 untreated makes HF less likely but obesity and HF medicines may suppress it.
02
Expert transthoracic echocardiography
Why
Classify EF and assess LVH, LA volume, E:e', pulmonary pressure, valves and RV.
Interpretation and limitations
HFpEF needs LVEF ≥50% plus structural/functional evidence; HFmrEF is LVEF 41–49% in symptomatic HF.
03
12-lead ECG and ambulatory monitoring when indicated
Why
Identify AF, conduction disease, ischaemia or intermittent arrhythmia.
Interpretation and limitations
Normal sinus rhythm at one visit does not exclude paroxysmal AF; rhythm findings may explain decompensation.
04
FBC, U&E/eGFR, LFT, TFT, HbA1c, lipids, ferritin/TSAT and urinalysis
Why
Find mimics, comorbidity and medicine constraints.
Interpretation and limitations
Renal function and potassium determine MRA/RAAS dosing; anaemia or iron deficiency needs cause-directed evaluation.
05
Chest X-ray and pulmonary testing
Why
Assess congestion and competing lung disease.
Interpretation and limitations
Use spirometry or CT selectively after stabilisation; pulmonary and cardiac disease commonly coexist.
06
Cause-directed CMR, amyloid testing or ischaemia assessment
Why
Clarify infiltrative, hypertrophic, inflammatory or coronary disease.
Interpretation and limitations
Order through specialist pathways when red flags are present; a preserved EF must not end the aetiology work-up.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Obesity and physical deconditioning

Excess weight and low fitness can cause exertional breathlessness without cardiac congestion. Objective structural or filling-pressure abnormalities are required before assigning HFpEF, and both conditions may coexist.

Chronic pulmonary disease

COPD, interstitial lung disease and pulmonary vascular disease produce similar exercise limitation and hypoxaemia. Lung examination, pulmonary testing and the pattern of right-heart findings help separate them.

Anaemia

Reduced oxygen-carrying capacity causes fatigue, tachycardia and exertional dyspnoea. A low haemoglobin and absence of convincing congestion or cardiac structural abnormalities favour anaemia as the principal explanation.

Renal disease and venous oedema

Salt retention from kidney disease or peripheral venous insufficiency may cause swelling without left-sided heart failure. Renal indices, urine findings, local skin changes and cardiac imaging discriminate.

Constrictive pericarditis

A non-compliant pericardium also raises filling pressures with preserved ejection fraction. Respiratory ventricular interdependence and characteristic venous-flow changes support constriction; pericardial thickening or calcification may help but can be absent.

Additional chapter-specific clues

Non-cardiac mimic

Obesity/deconditioning, anaemia, lung disease, renal disease and venous insufficiency may coexist; confirm congestion and cardiac abnormality before labelling HFpEF.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-lineConfirm phenotypeFirst stepFirst lineSuspected HF with LVEF above 40%

1Use NT-proBNP to triage and obtain expert echo; assess structural/filling criteria rather than using EF alone.
2Exclude mimics and identify congestion, AF, BP, valve/coronary disease, renal disease, diabetes, obesity and pulmonary contributors.
3Use a loop diuretic when congested, titrated to the lowest effective dose.
4Create a care plan with specialist HF and primary-care responsibilities and personalised rehabilitation.

02Second-lineHFmrEF disease modificationSecond lineConfirmed symptomatic HF with LVEF 41–49%

1Consider ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor, individualising order, dose and increments.
2Use an ARB when ACE-inhibitor intolerance applies; monitor BP, pulse, renal function and potassium.
3Treat AF, hypertension, coronary/valve disease and diabetes through their NICE pathways.
4Reassess symptoms, congestion and EF trajectory; continue established HFrEF therapy when EF has improved unless specialist review supports change.

03Third-lineHFpEF disease modificationThird lineConfirmed symptomatic HF with LVEF ≥50% and objective cardiac abnormality

1Consider an MRA and an SGLT2 inhibitor under NICE 2025, using renal/potassium and sick-day safety monitoring.
2Control congestion and BP and manage AF, obesity, diabetes, CKD, ischaemia, valve and sleep/lung disease.
3Provide a personalised exercise-based rehabilitation programme with education, psychological support and an accessible delivery format.
4Review response by symptoms, function, admissions and congestion rather than expecting a major EF change.

04EscalationRefractory symptoms or diagnostic uncertaintyEscalationPersistent NYHA III–IV symptoms, recurrent admission or discordant tests

1Reassess volume, adherence, rhythm and non-cardiac limitation; repeat expert echo where physiology may have changed.
2Refer for CMR, stress haemodynamics or amyloid/cardiomyopathy evaluation when red flags or uncertainty remain.
3Use the acute-HF pathway for decompensation and involve renal/pulmonary/valve teams according to the driver.
4Assess palliative needs alongside active care when symptoms remain severe despite specialist optimisation.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

NICE technology-appraisal option considered in HFmrEF and HFpEF, irrespective of diabetes status.

Dapagliflozin

10 mg orally once daily.

Volume depletion, genital infection and rare euglycaemic DKA; interrupt for hospitalised major surgery or acute serious illness, monitor blood ketones and restart only once stable with normal ketones.

MRA considered in both HFmrEF and HFpEF under NICE 2025.

Spironolactone

A typical HF start is 25 mg orally once daily; use lower/alternate-day dosing or cautious titration according to renal function, potassium, BP and frailty.

Hyperkalaemia, renal impairment and gynaecomastia; baseline and 1–2-week renal/potassium monitoring after initiation or increment is essential.

ACE inhibitor considered as part of the HFmrEF four-class combination; not a routine HFpEF disease-modifying requirement solely because of HF.

Ramipril

For HFmrEF when selected, typically start 1.25 mg orally once daily and titrate at 1–2-week intervals toward 10 mg/day as tolerated.

Hypotension, hyperkalaemia, renal dysfunction, pregnancy and angioedema; do not combine with ARB or ARNI.

Beta-blocker considered in HFmrEF and used for another indication such as AF rate control, angina or hypertension in HFpEF.

Bisoprolol

For HFmrEF when selected, start 1.25 mg orally once daily and stepwise titrate toward 10 mg once daily as tolerated.

Start when stable; bradycardia, AV block and hypotension. Dose for AF control is response-led and not necessarily the HFrEF target.

Symptom relief from congestion across all EF phenotypes.

Furosemide

Common oral start 20–40 mg in the morning, adjusted to congestion, renal function and prior exposure; use the lowest dose maintaining euvolaemia.

Volume depletion, renal change, sodium/potassium/magnesium loss and gout; rapid weight change requires clinical context.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Recurrent congestion

Small changes in volume, blood pressure or rhythm can sharply raise filling pressure, causing pulmonary oedema or peripheral fluid retention. Repeated admissions are common and impair function.

Atrial fibrillation

Left-atrial pressure and enlargement promote atrial fibrillation. Loss of atrial contraction and rapid ventricular response further impair filling, while atrial stasis increases thromboembolic risk.

Pulmonary hypertension and right-heart failure

Chronic pulmonary venous pressure can remodel the pulmonary circulation and overload the right ventricle. This adds tricuspid regurgitation, systemic oedema and an adverse prognosis.

Cardiorenal dysfunction

Renal venous congestion and reduced effective perfusion lower filtration, encouraging further sodium retention. Kidney dysfunction also requires closer dosing and laboratory surveillance when diuretics or mineralocorticoid-receptor antagonists are used.

Functional decline

Repeated congestion, poor exercise reserve and multimorbidity promote frailty, muscle loss and loss of independence. A stable ejection fraction therefore does not imply a benign clinical course.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Symptoms, exercise tolerance, orthopnoea, JVP/oedema, weight and admission frequency.
BP including postural symptoms, pulse/rhythm and AF control.
Renal function and electrolytes before ACEi/ARB/MRA, 1–2 weeks after initiation/increments, then every 3–6 months once stable and during illness.
SGLT2 volume status, genital/urinary symptoms and DKA education; blood ketones during treatment interruption for hospitalised surgery/serious illness.
Comorbidity targets: HbA1c, lipids, weight, sleep/lung symptoms, anaemia and iron status.
Repeat echo when clinical status changes or EF trajectory would change the treatment phenotype.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Preserved EF is not normal heart function

High filling pressure and impaired reserve can cause severe HF despite a normal proportion of blood ejected.

NICE requires positive structure/physiology

For HFpEF, LVEF ≥50% is paired with at least two specified structural or functional abnormalities.

BNP cannot phenotype

Natriuretic peptide reflects wall stress and prognosis but does not separate reduced, mildly reduced and preserved EF.

Improved EF is a history

A person whose EF recovered from HFrEF is not necessarily 'cured'; established disease-modifying treatment is generally maintained pending specialist review.

Functional outcomes matter

In HFpEF, success is often fewer congestion episodes and better function, not a rising EF.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing HFpEF from breathlessness plus a normal EF without objective cardiac abnormalities or consideration of mimics.
02
Using natriuretic peptide level to decide the EF phenotype.
03
Continuing the pre-2025 assumption that HFpEF has no disease-modifying medicine options.
04
Using ACE inhibitor and beta-blocker as automatic HFpEF therapy without another indication while omitting MRA/SGLT2 consideration.
05
Stopping established HFrEF therapy simply because EF has improved above 40%.