What is Heart Failure?
Heart failure (HF) is a clinical syndrome caused by structural or functional cardiac abnormality resulting in reduced cardiac output or elevated intracardiac pressures. It is classified by left ventricular ejection fraction (LVEF): HFrEF (LVEF <40%), HFmrEF (LVEF 40–49%), and HFpEF (LVEF ≥50%). The ESC 2023 guidelines introduced HFpEF as a distinct management target for the first time.
Pathophysiology
Neurohormonal activation — via the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system — drives progressive cardiac remodelling. Compensatory mechanisms become maladaptive over time, leading to ventricular dilatation, hypertrophy, fibrosis, and worsening pump function. SGLT2 inhibitors and ARNIs interrupt these pathways via distinct mechanisms, explaining their complementary benefit in four-pillar therapy.
Clinical Features & Symptoms
- Dyspnoea on exertion or at rest
- Orthopnoea and paroxysmal nocturnal dyspnoea
- Peripheral oedema (bilateral ankle/leg swelling)
- Fatigue and exercise intolerance
- Elevated JVP and hepatojugular reflux
- Third heart sound (S3 gallop)
- Pulmonary crackles on auscultation
- Rapid weight gain (>2 kg over 3 days)
Diagnosis
Diagnosis requires symptoms AND signs of HF AND objective evidence of cardiac dysfunction (typically by echocardiography). BNP >35 pg/mL or NT-proBNP >125 pg/mL supports HF in chronic disease; higher thresholds apply for acute presentations. Echocardiography is the primary imaging modality for LVEF classification, wall motion, and valvular assessment.
Current Treatment Guidelines
ARNI (sacubitril/valsartan)
Class I, Level BPreferred over ACE inhibitor as first-line RAAS blockade in HFrEF. Reduces CV death and HF hospitalisation by 20% vs enalapril (PARADIGM-HF). Initiate at low dose; uptitrate every 2–4 weeks.
Beta-blocker
Class I, Level ABisoprolol, carvedilol, or metoprolol succinate. Reduces all-cause mortality by 34%. Start low, titrate up at 2-weekly intervals to maximum tolerated dose. Do not initiate during acute decompensation.
MRA (mineralocorticoid receptor antagonist)
Class I, Level ASpironolactone or eplerenone. Eplerenone preferred in diabetes or gynaecomastia. Monitor potassium and renal function. Reduces mortality by 30% in RALES and EMPHASIS-HF trials.
SGLT2 inhibitor
Class I, Level ADapagliflozin or empagliflozin. Both reduce risk of worsening HF or CV death regardless of diabetes status (DAPA-HF, EMPEROR-Reduced). First class effective in HFpEF (empagliflozin: EMPEROR-Preserved).
Diuretics for congestion
Class I, Level CLoop diuretics (furosemide, torasemide) for symptom relief of fluid overload. Titrate to achieve euvolaemia; monitor electrolytes and renal function. Not shown to reduce mortality.
CRT / ICD
Class I, Level AICD in LVEF ≤35% on optimal medical therapy with NYHA class II–III. CRT in LVEF ≤35%, LBBB, QRS ≥130 ms. Newer conduction system pacing (His bundle, LBBP) now Class IIa alternative.
Monitoring & Treatment Targets
LVEF reassessment at 3–6 months after initiating therapy. Target: LVEF improvement ≥40%, NT-proBNP reduction, clinical euvolaemia, NYHA class I–II. Renal function and potassium every 1–2 weeks when uptitrating RAAS/MRA. Annual echocardiography in stable patients.
Key Clinical Trials
Sacubitril/valsartan reduced CV death or HF hospitalisation by 20% vs enalapril (HR 0.80, p<0.001)
Dapagliflozin reduced worsening HF or CV death by 26% vs placebo in HFrEF (HR 0.74, p<0.001)
Clinical Guidelines
External Resources
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Frequently Asked Questions
What is the current first-line treatment for heart failure with reduced ejection fraction (HFrEF)?
ESC 2023 guidelines recommend simultaneous initiation of four-pillar therapy at low doses: an ARNI (sacubitril/valsartan, preferred over ACE inhibitor), a beta-blocker (bisoprolol, carvedilol, or metoprolol succinate), an MRA (eplerenone or spironolactone), and an SGLT2 inhibitor (dapagliflozin or empagliflozin). All four have Class I, Level A evidence and should be started together rather than sequentially, then uptitrated to maximum tolerated doses.
What is the role of SGLT2 inhibitors in heart failure?
SGLT2 inhibitors (dapagliflozin, empagliflozin) are now Class I, Level A in both HFrEF and HFmrEF, and Class IIa in HFpEF. They reduce the risk of worsening heart failure hospitalisation and cardiovascular death regardless of whether the patient has type 2 diabetes. This was demonstrated in DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) for HFrEF, and EMPEROR-Preserved for HFpEF.
What BNP or NT-proBNP level confirms heart failure?
BNP >35 pg/mL or NT-proBNP >125 pg/mL supports a chronic heart failure diagnosis in outpatient settings. In acute presentations, higher thresholds are used: BNP >100 pg/mL or NT-proBNP >300 pg/mL. Normal natriuretic peptide levels have high negative predictive value and effectively exclude heart failure as a cause of dyspnoea.
What is the difference between HFrEF, HFmrEF, and HFpEF?
HFrEF (heart failure with reduced ejection fraction): LVEF <40% — most evidence-based treatments exist here. HFmrEF (mildly reduced EF): LVEF 40–49% — ESC 2023 recommends same four-pillar therapy as HFrEF. HFpEF (preserved EF): LVEF ≥50% — fewer proven therapies; SGLT2 inhibitors (Class IIa) and diuretics for symptom relief are current mainstays.
Medical disclaimer: This content is intended for qualified healthcare professionals and does not constitute medical advice. Always apply clinical judgment and refer to current local guidelines and institutional protocols.