Heart failure with reduced ejection fraction (HFrEF)

Heart failure with reduced ejection fraction (HFrEF) is defined as a clinical syndrome of symptomatic heart failure associated with a left ventricular ejection fraction (LVEF) of ≤40%, confirmed on echocardiography. It represents the archetypal, historically predominant form of heart failure for which the strongest evidence base for disease-modifying therapy exists. HFrEF carries a prognosis that rivals many advanced malignancies — 50% five-year mortality — yet guideline-directed medical therapy (GDMT) has transformed outcomes over the past three decades.

In Australia, heart failure affects approximately 480,000 people, accounting for more than 50,000 hospitalisations annually. The Australian Institute of Health and Welfare (AIHW) identifies heart failure as the primary diagnosis in approximately 1% of all hospital separations. HFrEF accounts for approximately 40–50% of all heart failure presentations; the remainder comprise heart failure with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF). The age-standardised death rate from heart failure has declined 30% since 2000, reflecting improved implementation of evidence-based therapies. Despite this, heart failure remains the leading cause of hospitalisation in Australians over 65 years and is associated with $1.3 billion AUD annually in direct healthcare costs.

Common Aetiologies of HFrEF in Australia

• Ischaemic cardiomyopathy: Most common cause (~50%). Results from coronary artery disease — either prior myocardial infarction with LV remodelling or chronic ischaemia-related hibernating myocardium. Coronary angiography is essential in all new HFrEF to exclude ischaemic aetiology.
• Dilated cardiomyopathy (DCM): Non-ischaemic cause in ~30%. Genetic (titin, lamin A/C, MYH7 mutations), idiopathic, viral myocarditis, peripartum, autoimmune, or familial. Genetic testing recommended in DCM with family history or early onset (<50 years).
• Hypertensive cardiomyopathy: Chronic pressure overload → concentric hypertrophy → dilation and systolic dysfunction. Aggressive BP control prevents and arrests progression.
• Alcohol-related cardiomyopathy: Dose-dependent cardiotoxicity. Reversible with abstinence if not end-stage. Common in Aboriginal and Torres Strait Islander communities.
• Tachycardia-induced cardiomyopathy: Persistent rapid AF or other tachyarrhythmias → reversible LV dysfunction. Rhythm/rate control leads to recovery.
• Cardiotoxic agents: Anthracyclines (doxorubicin), trastuzumab, tyrosine kinase inhibitors, checkpoint inhibitors. Baseline and surveillance echocardiograms required in oncology patients receiving cardiotoxic therapy.
• Valvular disease: Aortic stenosis, mitral regurgitation, aortic regurgitation — structural correction improves or resolves LV dysfunction.

HFrEF is characterised by progressive LV systolic dysfunction resulting from cardiomyocyte loss, dysfunction, or pathological remodelling. Following an index cardiac injury (MI, myocarditis, prolonged pressure/volume overload), compensatory neurohormonal activation is engaged — initially adaptive, ultimately maladaptive and accelerating disease progression.

Neurohormonal Activation

• Renin-Angiotensin-Aldosterone System (RAAS): Reduced cardiac output → renal hypoperfusion → renin release → angiotensin II generation → systemic vasoconstriction (afterload ↑), sodium retention (preload ↑), aldosterone secretion → myocardial and vascular fibrosis. ACEi, ARBs, ARNI (sacubitril/valsartan) all interrupt RAAS at different levels.
• Sympathetic Nervous System (SNS): Catecholamine excess → tachycardia, vasoconstriction, myocardial toxicity, arrhythmias. Beta-adrenergic receptor downregulation → reduced contractile reserve. Beta-blockers reverse this at cellular level ("beta-blocker paradox" — negative inotropy initially, long-term systolic recovery).
• Vasopressin (ADH): Elevated in HFrEF → free water retention → hyponatraemia (marker of poor prognosis). Targeted by vasopressin antagonists (tolvaptan — limited role, PBS restricted).
• Natriuretic Peptides (BNP/NT-proBNP): Released from ventricular wall stress → natriuresis, vasodilation, counter-regulatory. ARNI (sacubitril/valsartan) augments this pathway by inhibiting neprilysin (BNP-degrading enzyme), amplifying natriuretic peptide effects while blocking RAAS with valsartan.

Ventricular Remodelling

Adverse LV remodelling encompasses LV dilation, eccentric hypertrophy, reduced sphericity index, mitral annular dilation (→ functional mitral regurgitation), and myocardial fibrosis. Neurohormonal blockade with GDMT reverses remodelling — termed "reverse remodelling" — with improvement in LVEF, LV dimensions, and functional class. The PARADIGM-HF trial demonstrated that sacubitril/valsartan produces greater reverse remodelling and mortality reduction than enalapril alone.

SGLT2 Inhibitor Mechanisms in HFrEF

Beyond glycaemic effects, SGLT2 inhibitors produce haemodynamic, metabolic, and cardioprotective benefits in HFrEF independent of diabetes status. Mechanisms include: osmotic diuresis → preload reduction, natriuresis, haemoconcentration; reduction of cardiac inflammation and oxidative stress; improvement in mitochondrial bioenergetics (cardiac ketone metabolism); reduction in epicardial adipose tissue; and anti-fibrotic effects. DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) each demonstrated ~25% relative risk reduction in CV death or HF hospitalisation in HFrEF, including in non-diabetic patients.

Symptoms

• Dyspnoea: Exertional initially (NYHA II), progressing to dyspnoea at rest (NYHA IV). Orthopnoea (dyspnoea when lying flat — cardinal symptom) and paroxysmal nocturnal dyspnoea (PND) indicate elevated pulmonary capillary wedge pressure.
• Fatigue and reduced exercise tolerance: Low cardiac output → skeletal muscle hypoperfusion. Often the predominant symptom in HFrEF, particularly in those who self-limit activity.
• Oedema: Bilateral ankle/leg oedema → ascites → anasarca with advancing disease. Right heart failure features dominate in severe or longstanding HFrEF.
• Nocturia: Redistribution of interstitial fluid on recumbency → increased renal perfusion → nocturia.
• Cardiac cachexia: Weight loss, muscle wasting in advanced HFrEF — poor prognostic marker.

Signs

• Elevated JVP: Reflects elevated right atrial pressure. Hepatojugular reflux positive. Most specific sign of volume overload in HF.
• Third heart sound (S3): High specificity for elevated LV filling pressure and poor prognosis. Gallop rhythm reflects rapid deceleration of ventricular filling.
• Displaced apex beat: Laterally and inferiorly displaced in LV dilation. Diffuse, heaving character.
• Functional murmurs: Pansystolic murmur of functional mitral regurgitation; TR murmur from RV dilation.
• Pulmonary crackles: Bibasal crepitations from pulmonary oedema — less specific (absent in compensated chronic HF due to lymphatic compensation).
• Peripheral oedema, ascites, hepatomegaly: Right heart failure features.
• Cool peripheries, narrow pulse pressure: Low output state, particularly in acute decompensation.

ESC 2021 Diagnostic Criteria for HFrEF

Essential First-Line Investigations

• Essential
  Echocardiography (TTE)

  Cornerstone of HFrEF diagnosis. Confirms LVEF ≤40%, LV dimensions, wall motion abnormalities (ischaemic pattern), valvular pathology, RV function, and filling pressures (E/e' ratio, tricuspid regurgitant jet velocity). Available at all Australian hospitals. Repeat in 3–6 months after GDMT initiation to assess reverse remodelling. If TTE technically limited, cardiac MRI preferred.
• Essential
  NT-proBNP / BNP

  NT-proBNP >300 ng/L (acute) or >125 ng/L (chronic) supports HF diagnosis. BNP >100 ng/L (acute) or >35 ng/L (chronic). Used for diagnosis, monitoring response to therapy, and risk stratification. Available at all Australian hospitals and many GP practices. Values may be falsely low in obesity or flash pulmonary oedema. Falsely elevated in AF, renal impairment, sepsis.
• Essential
  12-Lead ECG

  Identifies ischaemic changes (Q waves, ST-T changes), arrhythmias (AF — most common HF comorbidity), left bundle branch block (LBBB — CRT candidate marker), LVH, conduction disease. QRS duration critical for device therapy planning. Normal ECG has 98% negative predictive value for LV systolic dysfunction.
• Essential
  Full Blood Count, UEC, LFTs, TFTs, Glucose/HbA1c

  FBC: anaemia (worsens HF — treat iron deficiency preferentially); UEC: renal function (guides GDMT initiation/titration, electrolytes — hypokalaemia and hyperkalaemia critical in GDMT); LFTs: hepatic congestion (elevated ALP, GGT, bilirubin); TFTs: hypo/hyperthyroidism as HFrEF aetiology; HbA1c: diabetes (guides SGLT2i use).
• Essential
  Iron Studies (serum iron, ferritin, transferrin saturation)

  Iron deficiency (ferritin <100 µg/L OR ferritin 100–299 µg/L + TSAT <20%) affects 30–50% of HFrEF patients. Treat with IV ferric carboxymaltose (AFFIRM-AHF). Improves symptoms, exercise capacity, and reduces HF hospitalisation independent of anaemia.
• Available
  Chest X-Ray

  Cardiomegaly (cardiothoracic ratio >0.5), pulmonary venous congestion, interstitial oedema (Kerley B lines), alveolar oedema, pleural effusions. Normal CXR does not exclude HF. Useful in acute presentations to quantify pulmonary oedema and guide diuretic therapy.
• Available
  Coronary Angiography (invasive or CT)

  Indicated in all new HFrEF without a clear non-ischaemic aetiology. CT coronary angiography appropriate first-line in low-intermediate pre-test probability. Invasive angiography for high probability ischaemic aetiology or if revascularisation is being considered (viable myocardium on stress imaging or CMR).
• Specialist
  Cardiac MRI (CMR)

  Gold standard for LVEF measurement and myocardial characterisation. Late gadolinium enhancement (LGE) pattern differentiates ischaemic (subendocardial/transmural scar) from non-ischaemic (mid-wall/epicardial) aetiology. T1/T2 mapping for myocarditis, amyloid, sarcoidosis, haemochromatosis. Extracellular volume (ECV) quantification. Available at major Australian tertiary centres.
• Specialist
  Genetic Testing

  Recommended in: DCM with family history, DCM onset <50 years, DCM + conduction disease (suspect lamin A/C mutation), DCM + skeletal myopathy. Familial DCM genetic panel (titin, lamin A/C, MYH7, SCN5A, FLNC) available via cardiogenetics services at major centres. First-degree relatives require cascade screening.

NYHA Functional Classification

ACC/AHA Heart Failure Stages

Prognostic Assessment

The MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) risk score predicts 1- and 3-year mortality based on age, LVEF, systolic BP, BMI, creatinine, NYHA class, sex, smoking, diabetes, COPD, first diagnosis versus established HF, and beta-blocker use. An online calculator is available at www.heartfailurecalculator.net. High-risk patients (predicted 1-year mortality >15%) should be referred to advanced heart failure services for transplant/LVAD evaluation. Peak VO₂ <12 mL/kg/min and BNP >300 ng/L despite GDMT are transplant listing criteria.

Pillar 1: ARNI / ACEi / ARB — RAAS Blockade

Pillar 2: Beta-Blockers

Pillar 3: Mineralocorticoid Receptor Antagonists (MRA)

Pillar 4: SGLT2 Inhibitors

Additional Medical Therapies

• Ivabradine (Coralan®): If-channel blocker. Reduces HR without negative inotropy. PBS Authority for HFrEF (LVEF ≤35%) in sinus rhythm with resting HR ≥70 bpm despite maximally tolerated beta-blocker. Starting dose 5 mg BD; target 7.5 mg BD. SHIFT trial: 18% reduction in CV death/HF hospitalisation. Avoid in AF — ineffective.
• Hydralazine + Isosorbide Dinitrate (ISDN): Alternative vasodilator strategy if ARNI/ACEi/ARB contraindicated (bilateral renal artery stenosis, severe renal impairment, prior angioedema, intolerant of all RAAS agents). A-HeFT trial: mortality benefit in African-American patients. Start hydralazine 25 mg TDS + ISDN 20 mg TDS; titrate to hydralazine 75 mg TDS + ISDN 40 mg TDS.
• Loop diuretics (frusemide, bumetanide): For symptomatic fluid overload. No mortality benefit — use minimum effective dose. Frusemide 20–40 mg daily; uptitrate for persistent oedema. IV frusemide for decompensation (see Acute Management section). Avoid over-diuresis (worsening renal function, electrolyte derangement, RAAS activation).
• IV Ferric Carboxymaltose (Ferinject®): For iron deficiency (ferritin <100 µg/L or ferritin 100–299 + TSAT <20%). AFFIRM-AHF: 26% reduction in HF hospitalisation post-acute HF. Dose by body weight and Hb. PBS restricted benefit — check current listing criteria.
• Anticoagulation in AF + HFrEF: All HFrEF + AF patients should receive anticoagulation unless contraindicated. Prefer DOAC (apixaban or rivaroxaban) over warfarin — equal/superior efficacy, fewer interactions. HFrEF itself is NOT an indication for anticoagulation in sinus rhythm.

Implantable Cardioverter-Defibrillator (ICD)

• Primary prevention ICD (Class I): LVEF ≤35% after ≥3 months GDMT optimisation + NYHA II–III + expected survival >1 year. Reduces sudden cardiac death (SCD) by ~50%. Evidence: MADIT-II, SCD-HeFT trials. Consider wearable defibrillator (LifeVest) as bridge in newly diagnosed HFrEF (LVEF ≤35%) awaiting GDMT response assessment.
• Post-MI ICD (Class I): LVEF ≤30–35% ≥40 days post-MI + NYHA I (MADIT-II) or NYHA II–III (SCD-HeFT). Note: ICD does not reduce mortality in NYHA IV (death from pump failure dominates over SCD).
• Secondary prevention ICD (Class I): Survivors of sustained VT/VF or VF cardiac arrest without reversible cause.

Cardiac Resynchronisation Therapy (CRT / CRT-D)

• CRT indications (Class I): LVEF ≤35% + LBBB morphology + QRS ≥150 ms + NYHA II–IV on GDMT. Resynchronises dysynchronous LV contraction → improved LVEF, reduced MR, reverse remodelling, mortality benefit (CARE-HF, COMPANION trials).
• CRT in non-LBBB (Class IIa): Non-LBBB pattern QRS ≥150 ms (RBBB, IVCD) — moderate evidence, less benefit than LBBB. Consider in NYHA III–IV after careful patient selection.
• CRT-D vs CRT-P: CRT-D (defibrillator) preferred in patients with primary prevention ICD indication + CRT criteria. CRT-P (pacemaker only) appropriate for NYHA IV (palliative intent, low SCD risk relative to pump failure) or patient preference/frailty.
• Conduction system pacing (His bundle / left bundle branch area pacing): Emerging alternative to biventricular pacing in selected patients, particularly with CRT non-response. Refer to specialist electrophysiologist.

Advanced Heart Failure — Stage D

Stage D HFrEF (refractory NYHA IV despite optimised GDMT and device therapy) requires referral to an advanced heart failure centre for consideration of mechanical circulatory support, cardiac transplantation, or palliative care. Typical triggers for referral: recurrent HF hospitalisations (>2 in 12 months), progressive renal dysfunction, cardiac cachexia, inotrope dependence.

• Left Ventricular Assist Device (LVAD): Durable mechanical LV support. Used as bridge to transplant (BTT), bridge to candidacy (BTC), or destination therapy (DT) in transplant-ineligible patients. MOMENTUM 3 trial: HeartMate 3 centrifugal-flow LVAD demonstrated superior outcomes to axial-flow device. LVAD centres: Alfred, St Vincent's (Sydney/Melbourne), Prince Charles Hospital (Brisbane), Fiona Stanley (Perth).
• Cardiac Transplantation: Gold standard for eligible end-stage HFrEF. 5-year survival ~75% post-transplant. Australia performs ~70–90 transplants/year (ANZCOTR data). Contraindications: fixed pulmonary hypertension (PVR >5 WU), active infection, malignancy, irreversible organ failure, significant frailty, psychosocial issues.
• Palliative Care Integration: For transplant/LVAD-ineligible NYHA IV patients. Symptom management (opioids for dyspnoea, diuretics for comfort), ICD deactivation discussion, advance care planning, community palliative care coordination.

Initial Assessment — Haemodynamic Profile

Classify ADHF by haemodynamic profile ("wet/dry" and "warm/cold") to guide therapy:

Acute Pharmacotherapy

• IV Frusemide: 40–80 mg IV bolus (2× oral dose if on maintenance frusemide). Onset 30–60 minutes. May require infusion (5–10 mg/hr) in refractory cases or severe renal impairment. Target urine output ≥0.5–1 mL/kg/hr. Add metolazone 5–10 mg oral 30 minutes before frusemide for sequential nephron blockade in diuretic resistance.
• GTN (Glyceryl Trinitrate): IV infusion starting 5–10 mcg/min, titrate to SBP ≥90 mmHg. Venodilator → preload reduction. Avoid if SBP <90 mmHg. Sublingual GTN 300–600 mcg while IV access established in APO. Tolerance develops within 24 hours — consider breaks.
• BiPAP / CPAP: Non-invasive ventilation reduces intubation rates and improves mortality in acute pulmonary oedema (3CPO trial). CPAP 5–10 cmH₂O or BiPAP IPAP 10–12/EPAP 4–6 cmH₂O. Contraindicated in: vomiting, facial trauma, GCS <8, haemodynamic instability.
• Dobutamine: Inotrope for cardiogenic shock/low output state (systolic BP <90 mmHg, cold peripheries, renal failure). Starting dose 2.5 mcg/kg/min IV; titrate to 5–20 mcg/kg/min. Monitor for tachycardia, arrhythmias. Bridge to definitive therapy only — not used long-term (increases mortality).
• Morphine: Historically used in APO — current evidence does not support routine use and may be harmful (nausea, respiratory depression, vasodilation). Use with extreme caution; prefer non-opioid measures first.

GDMT During Hospitalisation

Continue background GDMT during ADHF hospitalisation where haemodynamics allow. Do NOT routinely stop beta-blockers — dose reduce if haemodynamically unstable, but complete cessation is associated with worse outcomes (OPTIMIZE-HF registry). Hold MRA and RAAS agents if hyperkalaemia (K+ >5.5) or AKI (creatinine rise >50%). Restart and uptitrate GDMT before discharge. Ensure SGLT2 inhibitor is withheld during acute admission (DKA risk) and restarted post-discharge when clinically stable.

Routine Outpatient Monitoring Schedule

Key Safety Monitoring Parameters

• Potassium: Target K+ 4.0–5.0 mmol/L in HFrEF. Hypokalaemia (<3.5) worsens arrhythmia risk — supplement. Hyperkalaemia (>5.5) — reduce/withhold MRA and RAAS. Consider patiromer (Veltassa®) or sodium zirconium cyclosilicate (Lokelma®) to enable continued GDMT use in hyperkalaemia-prone patients.
• Renal function: Accept up to 20–30% creatinine rise with RAAS initiation (benign, reflects reduced intraglomerular pressure). Stop if creatinine rises >50% or eGFR falls below 20. AKI monitoring — hold nephrotoxins (NSAIDs, contrast), adjust SGLT2i during illness.
• Weight monitoring: Daily home weights — patient education essential. Weight gain >2 kg in 48–72 hrs = fluid retention → increase diuretic, contact HF nurse/GP urgently.
• Device monitoring: ICD/CRT interrogations every 3–6 months or via remote monitoring platform. Alert thresholds: daily activity, heart rate trends, intrathoracic impedance (fluid detection). Documented antitachycardia pacing (ATP) or shock delivery requires urgent cardiology review.

🤰 Pregnancy and Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) presents in the last month of pregnancy or first 5 months postpartum — LVEF typically <45%, often <35%. Most cases occur in women aged >30 years, multiparous, with hypertensive disorders of pregnancy. Recovery occurs in ~50% within 6 months; persistent LVEF <35% at 6 months associated with poor prognosis.

• ACEi/ARBs/ARNI: Absolutely contraindicated in all trimesters — fetotoxic (oligohydramnios, renal agenesis, pulmonary hypoplasia). Immediately postpartum (non-breastfeeding): initiate ACEi/ARNI as soon as possible — use ramipril or perindopril, transition to sacubitril/valsartan at 4–6 weeks.
• Beta-blockers: Metoprolol succinate (Toprol-XL) considered safest in pregnancy — monitor neonate for bradycardia/hypoglycaemia. Continue postpartum. Carvedilol preferred postpartum (not breastfeeding).
• MRA: Spironolactone contraindicated in pregnancy (anti-androgenic). Avoid in breastfeeding. Initiate postpartum.
• SGLT2 inhibitors: Contraindicated in pregnancy and breastfeeding — insufficient safety data. Initiate at least 4–6 weeks postpartum in non-breastfeeding women.
• Anticoagulation: LMWH (enoxaparin) in pregnancy. DOAC contraindicated in pregnancy. All PPCM patients with LVEF <30% should receive anticoagulation for thromboembolic prophylaxis (high LV thrombus risk).
• Bromocriptine: May promote recovery in PPCM via prolactin inhibition (evidence from BOARD trial — 2.5 mg daily for 8 weeks). Used off-label in Australia; requires multidisciplinary decision. Requires anticoagulation if used.
• Subsequent pregnancy: Advise against further pregnancy if LVEF has not fully recovered (<50%). Even with LVEF recovery, recurrence risk ~20–30% in subsequent pregnancies.

👴 Elderly Patients (≥75 years)

HFrEF in elderly patients is managed with all four GDMT pillars — trials included patients up to 85–90 years. Frailty, polypharmacy, falls risk, cognitive impairment, and CKD require careful dose titration and monitoring. Benefits of GDMT persist in elderly populations.

• ARNI/ACEi: Start low (sacubitril/valsartan 24/26 mg BD, ramipril 1.25 mg). Hypotension risk — check sitting and standing BP. Renal function may limit titration.
• Beta-blockers: Falls risk from bradycardia and hypotension — start bisoprolol 1.25 mg (less hypotension than carvedilol at equivalent doses). Target HR 60–70 bpm in elderly.
• SGLT2 inhibitors: Safe and effective in elderly; eGFR ≥20 allows initiation. Volume depletion risk — review concomitant diuretics. Genital hygiene important (UTI/mycotic infections).
• Diuretics: Minimum effective dose. Avoid over-diuresis — orthostatic hypotension, falls, worsening renal function. Daily weight monitoring with carer involvement.
• ICD in elderly: Individual risk-benefit discussion — competing mortality risks from non-cardiac disease. Generally ICD not beneficial if life expectancy <1 year from non-cardiac causes. CRT-P (without defibrillator) appropriate for frail elderly with CRT criteria.

🫘 Chronic Kidney Disease (CKD)

Cardiorenal syndrome type 2 (chronic HFrEF causing CKD) affects 30–50% of HFrEF patients. GDMT use is feasible in most CKD patients with appropriate monitoring.

• RAAS agents: Accept creatinine rise up to 30%. Avoid if bilateral renal artery stenosis. Dose reduce in eGFR <30 (ramipril 1.25–2.5 mg, perindopril 2.5 mg). Sacubitril/valsartan: avoid eGFR <30.
• SGLT2 inhibitors: Reno-protective beyond HF benefit (CREDENCE, DAPA-CKD). Initiate at eGFR ≥20. Initial eGFR dip of 3–5 mL/min is benign and expected — do not stop.
• MRA: Avoid spironolactone/eplerenone if eGFR <30 or K+ >5.0 — hyperkalaemia risk. Finerenone (non-steroidal MRA — FIDELIO-DKD trial) may have a future role with safer potassium profile in CKD + HF.
• Diuretics: Frusemide doses often need escalation as GFR falls (reduced tubular secretion reduces diuretic efficacy). IV frusemide or combination diuretic therapy may be required in CKD stage 4–5.

🦺 Ischaemic HFrEF Post-MI

Early revascularisation (primary PCI for STEMI, urgent PCI for NSTEMI) reduces infarct size and subsequent HFrEF development. In established ischaemic HFrEF, viability assessment (stress echo, nuclear perfusion, CMR) guides revascularisation decision — hibernating/stunned myocardium can recover function post-revascularisation (HEART trial data).

• Antiplatelet therapy: Dual antiplatelet (aspirin + P2Y12 inhibitor for 12 months post-ACS). Long-term aspirin 100 mg daily for all ischaemic HFrEF. Ensure no interaction with DOAC/anticoagulation if AF coexists.
• Statins: High-intensity statin (atorvastatin 40–80 mg, rosuvastatin 20–40 mg) for all ischaemic HFrEF. LDL target <1.8 mmol/L (or <1.4 in very high cardiovascular risk). Add ezetimibe or PCSK9 inhibitor if target not reached.

Medicines to Avoid or Use with Caution in HFrEF

• NSAIDs (ibuprofen, naproxen, diclofenac, celecoxib, ketorolac): Cause sodium and water retention, reduce renal response to diuretics, increase HF hospitalisation risk, worsen renal function. Absolutely contraindicated in symptomatic HFrEF. Paracetamol is preferred for analgesia. If unavoidable, use lowest dose for shortest duration with intensified fluid and renal monitoring.
• Non-dihydropyridine calcium channel blockers (verapamil, diltiazem): Negative inotropes — contraindicated in HFrEF (LVEF ≤40%). Can cause acute decompensation. Amlodipine and felodipine (dihydropyridines) are safe if CCB required for BP or angina management.
• Thiazolidinediones (pioglitazone, rosiglitazone): Cause fluid retention and worsen HF. Contraindicated in NYHA II–IV HF. Avoid in HFrEF regardless of NYHA class.
• Saxagliptin (DPP-4 inhibitor): SAVOR-TIMI trial showed increased HF hospitalisation. Avoid in HFrEF — if DPP-4 inhibitor required, sitagliptin preferred. Consider switching to SGLT2i (cardioprotective and glucose-lowering).
• Class I antiarrhythmics (flecainide, propafenone): Proarrhythmic in structural heart disease — avoid in HFrEF. Amiodarone is the preferred antiarrhythmic for AF/VT in HFrEF if needed (negative inotropy minimal at low doses).
• Dronedarone: Increases mortality in HFrEF (PALLAS trial). Absolutely contraindicated in NYHA III–IV or recently decompensated HF.
• Trastuzumab and other HER2-targeted therapies: Monitor LVEF at baseline, every 3 months during therapy. Withhold if LVEF falls >10% to <50% — cardio-oncology referral. GDMT can partially protect against cardiotoxicity.
• Corticosteroids: Sodium and fluid retention → HF exacerbation. Minimise; if essential, intensify diuretic monitoring.

NHFA/CSANZ Quality Indicators for HFrEF

• Echocardiogram with LVEF documented at diagnosis
• ACEi/ARB/ARNI prescribed or contraindication documented
• Beta-blocker prescribed or contraindication documented
• MRA prescribed or contraindication documented (NYHA II–IV)
• SGLT2 inhibitor prescribed or contraindication documented (eGFR ≥20)
• ICD referral made if LVEF ≤35% after 3 months GDMT
• Iron studies performed; IV iron given if deficiency confirmed
• Post-discharge cardiology/GP follow-up within 7–14 days arranged before discharge

Heart Failure Disease Management Programmes

Structured heart failure disease management programmes (HFDMPs) with nurse-led coordination reduce all-cause mortality by ~20% and HF readmissions by ~30% (systematic review, Stewart et al.). All patients hospitalised with HFrEF should be enrolled in a HFDMP on discharge. Components include: specialist nurse-led HF clinic follow-up, patient education (symptoms, daily weights, medication adherence, dietary sodium restriction <2 g/day), telephone monitoring, and telemonitoring (remote weight/BP/symptom tracking). Programmes available at most major Australian hospitals and via community nursing services (e.g., RDNS, Silver Chain).

Cardiac Rehabilitation

• Exercise training: HF-ACTION trial: supervised aerobic exercise training reduces all-cause mortality/hospitalisation by 11% (modest but significant) in stable HFrEF. Improves peak VO₂, 6-minute walk distance, NYHA class, and quality of life. Recommend supervised cardiac rehabilitation 3–5 sessions/week. Medicare-rebatable (MBS item numbers via Phase 3 cardiac rehabilitation).
• Resistance training: Moderate resistance training safe and effective for muscle wasting/cachexia in HFrEF. Supervised by exercise physiologist. Avoid Valsalva manoeuvre — risk of haemodynamic instability.
• Inspiratory muscle training: Benefits dyspnoea and exercise tolerance, particularly in patients unable to participate in conventional aerobic exercise (severe NYHA III–IV, LVAD). Simple home-based device (Threshold IMT).

Prevention of Progression and Hospitalisation

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