Chronic heart failure with reduced ejection fraction

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

HFrEF diagnosis requires symptoms/signs plus objective cardiac dysfunction; natriuretic peptide triages suspected cases, while echocardiography establishes phenotype and aetiology. Very high NT-proBNP (>2,000 ng/L) needs specialist assessment and echo within 2 weeks; 400–2,000 ng/L within 6 weeks.

The September 2025 NICE update moves away from a slow staircase. ACE inhibition, beta-blockade, MRA and SGLT2 inhibition should all be introduced according to BP, pulse, renal function, potassium, congestion, frailty and preference.

Optimisation includes cause treatment, education, rehabilitation, vaccination, rhythm and iron assessment, device eligibility and advance-care conversations—not medicines alone.

Key points

NICE defines HFrEF as symptomatic heart failure with LVEF 40% or less.
For HFrEF, offer an ACE inhibitor, evidence-based beta-blocker, MRA and SGLT2 inhibitor; individualise order and timing rather than fully titrating one before introducing the next.
If symptoms persist on the maximum tolerated four classes, consider replacing the ACE inhibitor with an ARNI; primary-care prescribers should consider specialist advice before starting ARNI.
Never combine ACE inhibitor with ARNI; allow at least a 36-hour washout after the last ACE-inhibitor dose before sacubitril/valsartan.
Use loop diuretic for congestion at the lowest dose that maintains euvolaemia; it improves symptoms but is not a substitute for disease-modifying treatment.
Check renal function/electrolytes before ACE inhibitor/ARNI/ARB/MRA, then 1–2 weeks after starting and each increment, every 3–6 months once stable and whenever renal function may be compromised.
Do not start or up-titrate beta-blocker during acute decompensation; once stable, avoid withholding it solely because of age, COPD, diabetes or peripheral vascular disease.
Persistent symptoms, low EF, arrhythmia, worsening end-organ function or repeated admission should trigger specialist review for ICD/CRT, valve/coronary options or advanced therapy.

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

Ischaemic myocardial injury

Previous infarction or chronic coronary disease can replace functioning myocardium with scar and cause adverse remodelling. Regional wall-motion abnormality and an ischaemic history support this mechanism.

Pressure or volume overload

Longstanding hypertension and important valve disease increase ventricular work. Persistent pressure or regurgitant volume eventually promotes hypertrophy, dilatation, fibrosis and systolic failure.

Primary or acquired cardiomyopathy

Genetic susceptibility, alcohol, cardiotoxic treatment, inflammation and peripartum disease can directly injure myocardium. Exposure, family and temporal history guide targeted investigation.

Persistent tachyarrhythmia

Sustained rapid atrial or ventricular rhythm can depress contractility and dilate the ventricle. Improvement after durable rate or rhythm control supports a tachycardia-mediated contribution.

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

1
Contractile impairment
Myocyte loss, dysfunction or chronic overload reduces ventricular force and ejection. Stroke volume may fall, while residual end-systolic volume often rises, increasing chamber size and wall stress.
2
Compensatory activation
Reduced effective arterial filling activates sympathetic, renin–angiotensin–aldosterone and vasopressin pathways. Tachycardia, vasoconstriction and fluid retention initially support pressure but raise myocardial demand.
3
Loading and remodelling
Increased preload and afterload promote ventricular dilatation, hypertrophy and fibrosis. Functional mitral regurgitation may develop as the ventricle and annulus enlarge.
4
Congestion
Rising left-sided filling pressure drives pulmonary venous congestion and breathlessness. Right-sided involvement or secondary pulmonary pressure elevation causes raised jugular venous pressure, oedema and hepatic congestion.
5
Progressive low output
Continued remodelling and neurohormonal stress reduce reserve further. Renal, hepatic and skeletal-muscle perfusion deteriorate, contributing to fatigue, frailty and intolerance of otherwise beneficial treatment.

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

Typical syndrome

Breathlessness, orthopnoea, fatigue, reduced exercise tolerance, raised JVP, crackles or oedema; absence of oedema does not exclude chronic HFrEF.

Urgent decompensationRed flag

Rest dyspnoea, pulmonary oedema, hypotension, confusion, oliguria or rapid weight gain needs same-day acute-HF assessment.

Low-output intolerance

Cool peripheries, narrow pulse pressure, symptomatic hypotension, worsening renal/liver function or inability to tolerate prognostic medicines suggests advanced disease.

Aetiology clue

Angina/MI, valve murmur, alcohol/toxin exposure, tachyarrhythmia, family history, pregnancy, chemotherapy or inflammatory illness should direct further testing.

Advanced-HF marker

NYHA III–IV despite treatment, recurrent admission, escalating diuretic, ventricular arrhythmia/ICD shock, SBP below 90 mmHg or end-organ dysfunction warrants early specialist-centre referral.

Medicine toxicity

Hyperkalaemia, symptomatic hypotension, bradycardia/heart block, dehydration or euglycaemic ketoacidosis symptoms require prompt review without indiscriminately abandoning all four classes.

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 chronic HF for specialist assessment and echocardiography.
Interpretation and limitations
>2,000 ng/L: urgent specialist assessment/echo within 2 weeks; 400–2,000: within 6 weeks; <400 untreated makes HF less likely, but obesity and HF medicines can suppress the level.
02
Transthoracic echocardiography
Why
Measure LVEF and evaluate structure, valves, RV and filling.
Interpretation and limitations
LVEF ≤40% with symptomatic HF defines HFrEF under NICE; reassess after optimisation when device decisions depend on EF.
03
12-lead ECG
Why
Identify rhythm, QRS duration/morphology, prior infarction and conduction disease.
Interpretation and limitations
AF changes anticoagulation/rate strategy; broad QRS/LBBB may create CRT eligibility after specialist assessment.
04
FBC, ferritin/TSAT, U&E/eGFR, LFT, TFT, HbA1c, lipids and urinalysis
Why
Find cause, comorbidity, iron deficiency and treatment constraints.
Interpretation and limitations
Treat contributors; eGFR ≤45 may require lower starting doses/smaller increments, and eGFR <30 prompts HF–renal liaison consideration.
05
Chest X-ray
Why
Assess congestion, heart size and pulmonary alternative diagnoses.
Interpretation and limitations
A normal film does not exclude stable chronic HF.
06
Cause-directed imaging or coronary assessment
Why
Clarify ischaemia, infiltrative disease, myocarditis or poor echo windows.
Interpretation and limitations
Use CMR, TOE, CT or angiography only when the result will refine cause or intervention; do not routinely revascularise HFrEF solely to treat HF.

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

Heart failure with preserved ejection fraction

This produces similar congestion and natriuretic-peptide elevation but systolic ejection is preserved. Echocardiography instead shows relevant diastolic, structural or filling-pressure abnormalities.

Chronic lung disease

COPD, asthma or interstitial lung disease can cause exertional breathlessness and crackles. Respiratory history, spirometry and imaging may explain symptoms without left-ventricular systolic dysfunction.

Anaemia or deconditioning

Reduced oxygen carriage or physical reserve commonly causes fatigue, tachycardia and exertional breathlessness. Blood count and functional history help identify these potentially reversible contributors.

Renal, hepatic or venous oedema

Kidney disease, cirrhosis and chronic venous insufficiency can produce peripheral swelling. Distribution, jugular venous pressure, protein or liver abnormalities and echocardiography clarify the dominant cause.

Constrictive pericarditis

Predominantly right-sided congestion with a pericardial risk history, Kussmaul sign or respiratory ventricular interaction suggests constriction. Preserved myocardial tissue velocities and cross-sectional imaging help distinguish it.

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

01First-lineConfirm and stabiliseFirst stepFirst lineSymptoms/signs with raised NT-proBNP or known LV dysfunction

1Use NICE NT-proBNP thresholds for specialist assessment and echocardiography; expedite acute symptoms through the acute-HF pathway.
2Define LVEF, aetiology, rhythm, congestion, BP, renal function, potassium, iron status and comorbidity.
3Use loop diuretic to achieve euvolaemia and create a written care plan with a named HF coordinator.
4Refer to the specialist HF MDT for diagnosis and initial optimisation.

02Second-lineIntroduce four classesSecond lineConfirmed stable HFrEF

1Offer ACE inhibitor, evidence-based beta-blocker, MRA and SGLT2 inhibitor; choose order and starting doses from BP, pulse, renal function, potassium, frailty and preference.
2Do not wait to reach the target dose of one class before starting every other class; arrange early monitoring after each change.
3AlternativeIf ACE inhibitor causes non-angioedema intolerance, use the NICE ARNI-based alternative with specialist support; after ACE-inhibitor angioedema, avoid ARNI and consider the ARB route.
4Keep titrating toward licensed/evidence-based target or maximum tolerated doses while maintaining euvolaemia.

03Third-linePersistent symptomsThird lineSymptoms despite maximum tolerated ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor

1Recheck adherence, volume status, rhythm, ischaemia, valve disease, iron deficiency and non-cardiac causes.
2Consider replacing ACE inhibitor with sacubitril/valsartan; stop ACE inhibitor and observe a minimum 36-hour washout.
3Assess ICD/CRT eligibility through NICE TA314 after adequate treatment and repeat ventricular-function assessment.
4Offer personalised exercise-based cardiac rehabilitation with education and psychological support.

04EscalationAdvanced or refractory HFrEFEscalationRepeated admission, refractory congestion, low output, ventricular arrhythmia or end-organ dysfunction

1Refer early to an advanced-HF centre before irreversible renal, hepatic or frailty deterioration.
2Review valve, coronary, rhythm and device options; do not offer routine coronary revascularisation solely for HFrEF with CAD.
3Consider transplant or mechanical-support assessment for severe refractory symptoms or refractory cardiogenic shock.
4Integrate palliative-needs assessment according to need, not a prognostic score alone, while continuing appropriate HF care.

Key medicines and prescribing safety6 treatments · regimens, roles and cautions

First-line renin–angiotensin inhibition within the NICE four-class HFrEF package.

Ramipril

For stable chronic HF, a typical licensed start is 1.25 mg orally once daily, doubling every 1–2 weeks toward 10 mg/day (once daily or divided) as tolerated; lower or slower dosing may be required.

BP, creatinine/eGFR and potassium monitoring; pregnancy and prior ACE-inhibitor angioedema contraindicate. Do not combine with ARNI or ARB.

Evidence-based beta-blocker for stable HFrEF.

Bisoprolol

Start 1.25 mg orally once daily for 1 week, then 2.5 mg once daily for 1 week, 3.75 mg once daily for 1 week, 5 mg once daily for 4 weeks, 7.5 mg once daily for 4 weeks, then 10 mg once daily as maintenance if each stage is tolerated.

Start only when clinically stable; assess ECG, pulse, BP and HF symptoms after increments. Avoid without pacing in second/third-degree block or HR <50 bpm; reduce gradually if stopping rather than withdrawing abruptly.

MRA component of four-class HFrEF therapy.

Spironolactone

Usually 25 mg orally once daily; may increase to 50 mg once daily if symptoms persist and potassium/renal function permit, or reduce to 25 mg on alternate days if not tolerated.

Hyperkalaemia, renal impairment and gynaecomastia; check potassium/creatinine at baseline and after every initiation/increment.

SGLT2 inhibitor for symptomatic chronic HF, with benefit independent of diabetes status.

Dapagliflozin

10 mg orally once daily.

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

Replace ACE inhibitor when symptoms persist on maximum tolerated four-class therapy, or as the NICE alternative for non-angioedema ACE-inhibitor intolerance.

Sacubitril/valsartan

Usually 49/51 mg orally twice daily, doubled after 2–4 weeks to 97/103 mg twice daily; start 24/26 mg twice daily for low prior ACEi/ARB exposure, SBP 100–110 mmHg or relevant renal/hepatic impairment.

Never combine with ACE inhibitor; wait at least 36 hours. Avoid with previous ACE-inhibitor- or ARB-related angioedema, hereditary/idiopathic angioedema, SBP <100 mmHg or potassium >5.4 mmol/L; monitor renal function, potassium and BP.

Symptom relief from fluid retention; not a mortality-modifying substitute for the four classes.

Furosemide

A common oral start for oedema is 40 mg in the morning, then titrate up or down to the lowest dose that maintains euvolaemia; dose is congestion- and renal-function dependent.

Dehydration, hypotension, renal change, hyponatraemia, hypokalaemia and hypomagnesaemia; teach a clear weight/symptom action plan where used.

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

Acute decompensation

Infection, ischaemia, arrhythmia or treatment disruption may abruptly raise filling pressures, causing pulmonary oedema, hypoxaemia and systemic congestion. Severe episodes can progress to cardiogenic shock.

Arrhythmia and sudden death

Fibrosis and chamber dilatation create atrial and ventricular arrhythmic substrates. Atrial fibrillation worsens filling and embolic risk, while ventricular tachyarrhythmia may cause syncope or sudden death.

Thromboembolism

Atrial fibrillation or marked ventricular akinesis can promote intracardiac thrombus. Embolisation may cause stroke or systemic infarction, although risk varies with rhythm and anatomy.

Cardiorenal and hepatic dysfunction

Low perfusion and venous congestion impair kidney and liver function. Electrolyte disturbance, diuretic resistance and reduced tolerance of disease-modifying treatment can follow.

Advanced heart failure

Repeated admission, escalating congestion, low blood pressure, cachexia and end-organ injury indicate declining reserve. Delayed referral may reduce eligibility for device or advanced-heart-failure options.

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

Clinical status, NYHA/function, congestion, weight, BP including posture, pulse/rhythm, cognition and nutrition at each review.
Renal function and electrolytes before ACEi/ARNI/ARB/MRA, 1–2 weeks after starting and each increment, every 3–6 months once stable and during intercurrent renal risk.
ECG before beta-blocker and heart rate/clinical status after each increment; repeat ECG if symptomatic bradycardia.
SGLT2 adverse effects, volume status and sick-day/surgery interruption knowledge; blood ketones during hospitalised acute illness or major surgery.
Haemoglobin and iron status, medication adherence and adverse effects at the HF review.
Repeat LVEF after treatment optimisation when ICD/CRT or recovery phenotype would change management; primary care recall at least every 6 months.

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

Four classes, flexible sequence

NICE 2025 emphasises early access to all four classes and does not require full titration of one before introducing another.

ARNI is a replacement

Sacubitril/valsartan replaces ACE inhibition; simultaneous use creates unacceptable angioedema risk.

NT-proBNP still works with ARNI

BNP is a neprilysin substrate and may rise with ARNI, whereas NT-proBNP remains interpretable for prognosis/trajectory.

Potassium substitutes are risky

NICE advises people with HF to avoid potassium-containing salt substitutes, especially relevant with ACEi/ARNI/MRA.

Refer before collapse

Advanced-HF assessment is most useful before irreversible end-organ dysfunction or frailty removes transplant/MCS options.

11Common pitfallsFrequent interpretation and management errors.

01
Using an old stepwise plan that delays MRA or SGLT2 inhibitor until ACE inhibitor and beta-blocker are maximised.
02
Starting sacubitril/valsartan without stopping ACE inhibitor and allowing the 36-hour washout.
03
Withholding a beta-blocker solely because of stable COPD, diabetes, age or peripheral vascular disease.
04
Treating oedema with escalating diuretic while omitting disease-modifying therapy.
05
Waiting for refractory shock before referring a repeatedly admitted, low-BP patient to advanced-HF services.