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OverviewAetiologyPathophysiologyClinical features and red flagsInvestigationsDifferential diagnosisManagementComplicationsMonitoring and follow-upSpecial situationsCommon pitfallsQuestionsSources
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Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.

Chronic heart failure with reduced ejection fraction

Cardiology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull

Overview

Diagnose HFrEF, introduce the NICE 2025 four-class treatment package safely and know when to move to ARNI, devices or advanced-heart-failure referral.

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.

Aetiology

01

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.

02

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.

03

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.

04

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.

Pathophysiology

  1. 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. 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. 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. 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. 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.

Clinical features and red flags

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.

Investigations

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 05
    Chest X-ray
    Why
    Assess congestion, heart size and pulmonary alternative diagnoses.

Differential diagnosis

01

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.

02

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.

03

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.

04

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.

05

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.

Management

01First-lineConfirm and stabiliseFirst stepFirst lineSymptoms/signs with raised NT-proBNP or known LV dysfunction+
  1. 1Use NICE NT-proBNP thresholds for specialist assessment and echocardiography; expedite acute symptoms through the acute-HF pathway.
  2. 2Define LVEF, aetiology, rhythm, congestion, BP, renal function, potassium, iron status and comorbidity.
  3. 3Use loop diuretic to achieve euvolaemia and create a written care plan with a named HF coordinator.
  4. 4Refer to the specialist HF MDT for diagnosis and initial optimisation.
02Second-lineIntroduce four classesSecond lineConfirmed stable HFrEF+
  1. 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.

Complications

01

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.

02

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.

03

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.

04

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.

05

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.

Monitoring and follow-up

  • 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.

Special situations

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.

Common pitfalls

  1. 01

    Using an old stepwise plan that delays MRA or SGLT2 inhibitor until ACE inhibitor and beta-blocker are maximised.

  2. 02

    Starting sacubitril/valsartan without stopping ACE inhibitor and allowing the 36-hour washout.

  3. 03

    Withholding a beta-blocker solely because of stable COPD, diabetes, age or peripheral vascular disease.

  4. 04

    Treating oedema with escalating diuretic while omitting disease-modifying therapy.

  5. 05

    Waiting for refractory shock before referring a repeatedly admitted, low-BP patient to advanced-HF services.

Practice

Two practice questions

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Question 1 of 2
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CardiologyOriginal SBA

NICE 2025 core treatment

A stable adult has symptomatic HFrEF with LVEF 32%, BP 118/72 mmHg, HR 78 bpm, potassium 4.4 mmol/L and acceptable renal function. Which treatment concept best matches NICE 2025?

Choose one answer, then submit
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Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources

Sources and review status

National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.

  • NICE NG106: Chronic heart failure in adultsSeptember 2025 diagnosis, four-class treatment, monitoring, devices and referral.
  • NICE NG106 HFrEF visual summaryCurrent core-treatment combinations.
  • ESC 2021 Guidelines for acute and chronic heart failureAetiology, devices and advanced-HF context.
  • Sacubitril/valsartan SmPCLicensed doses, washout and contraindications.
  • Bisoprolol SmPCLicensed HFrEF titration.
  • MHRA: SGLT2 inhibitors during surgery or acute serious illnessInterruption and blood-ketone safety advice.

Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem ·

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.
  • 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+
    1. 1Recheck adherence, volume status, rhythm, ischaemia, valve disease, iron deficiency and non-cardiac causes.
    2. 2Consider replacing ACE inhibitor with sacubitril/valsartan; stop ACE inhibitor and observe a minimum 36-hour washout.
    3. 3Assess ICD/CRT eligibility through NICE TA314 after adequate treatment and repeat ventricular-function assessment.
    4. 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+
    1. 1Refer early to an advanced-HF centre before irreversible renal, hepatic or frailty deterioration.
    2. 2Review valve, coronary, rhythm and device options; do not offer routine coronary revascularisation solely for HFrEF with CAD.
    3. 3Consider transplant or mechanical-support assessment for severe refractory symptoms or refractory cardiogenic shock.
    4. 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.

    Content changes
    Authoring stateComplete draftClinical stateAwaiting reviewJurisdictionUnited Kingdom
    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.