Key Facts

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterised by signs and symptoms of heart failure, preserved LVEF (≥50%), and evidence of structural heart disease and/or diastolic dysfunction. It was previously termed 'diastolic heart failure.'

Epidemiology

• Accounts for ~50% of all heart failure cases (proportion increasing)
• Prevalence increases significantly with age: >10% in those >80 years
• Female predominance (~60% women)
• Strongly associated with hypertension, obesity, diabetes, and atrial fibrillation
• Hospital admission rates similar to HFrEF

Aetiology

• Hypertension (most common cause)
• Obesity and metabolic syndrome
• Diabetes mellitus
• Ageing and senescent myocardium
• Atrial fibrillation
• Coronary artery disease
• Hypertrophic cardiomyopathy
• Infiltrative diseases: cardiac amyloidosis, Fabry disease
• Restrictive cardiomyopathy
• Constrictive pericarditis (mimics HFpEF)

Pathophysiology

• Impaired LV relaxation and increased passive stiffness
• Concentric LV remodelling/hypertrophy → reduced compliance
• Elevated LV end-diastolic pressure → raised LA pressure → pulmonary congestion
• Systemic microvascular endothelial inflammation (driven by comorbidities)
• Myocardial fibrosis and altered titin phosphorylation reduce distensibility
• Often provoked by exercise, AF, or volume overload

Typical Presentation

• Exertional dyspnoea (most common symptom)
• Exercise intolerance and fatigue
• Peripheral oedema
• Often elderly woman with hypertension and atrial fibrillation

Clinical Features

• Bilateral crepitations
• Elevated JVP
• Peripheral oedema
• Third/fourth heart sounds
• Features indistinguishable from HFrEF on clinical examination alone

Distinguishing Features from HFrEF

• More likely to be female, older, obese
• Concentric LV remodelling rather than dilatation
• Normal or near-normal EF on echo
• Symptoms often provoked by AF, exercise, or volume shifts

Red Flags

• Cardiac amyloidosis: consider if HFpEF with LVH + low-voltage ECG
• Fabry disease: consider in young patients with LVH
• Constrictive pericarditis: may mimic HFpEF

Bedside

• ECG: LVH, AF, low voltage (consider amyloid)
• Observations: HR, BP, SpO₂

Bloods

• NT-proBNP/BNP: elevated but may be lower than in HFrEF (especially in obesity — BNP may be falsely low in obese patients)
• FBC, U&Es, LFTs, TFTs, HbA1c, iron studies: standard HF workup

Imaging

• Echocardiography: key investigation
  • LVEF ≥50%
  • Diastolic dysfunction: E/e' ratio ≥13, e' velocity <9 cm/s (septal) or <13 cm/s (lateral)
  • LA enlargement (LA volume index >34 mL/m²)
  • LV mass index elevated (LVH)
  • Elevated TR velocity >2.8 m/s
• Cardiac MRI: myocardial characterisation (fibrosis, infiltration, amyloid)
• DPD/PYP scan: if cardiac amyloidosis (ATTR type) suspected

Special Tests

• Exercise stress echocardiography/diastolic stress test: unmask diastolic dysfunction during exercise
• Right heart catheterisation: gold standard for elevated filling pressures (PCWP >15 mmHg at rest or >25 mmHg with exercise)
• H2FPEF score: clinical prediction tool (Heavy, Hypertensive, AF, Pulmonary hypertension, Elder, Filling pressure)
• Endomyocardial biopsy: if infiltrative disease suspected

Non-pharmacological

• Weight loss if obese (significant symptom improvement)
• Exercise training: supervised aerobic and resistance exercise
• Salt and fluid restriction
• Treat comorbidities: hypertension, AF, diabetes, OSA, anaemia

Pharmacological

Evidence-based therapies:

• SGLT2 inhibitor: empagliflozin 10mg OD (EMPEROR-Preserved) or dapagliflozin 10mg OD (DELIVER)
  • First drugs to show benefit in HFpEF: reduced HF hospitalisation
• Diuretics: for congestion symptom relief (furosemide, bumetanide)

Comorbidity management:

• Hypertension: target <130/80 mmHg; ACEi/ARB, CCB, diuretics
• AF: rate/rhythm control; anticoagulation per CHA₂DS₂-VASc
• Diabetes: SGLT2 inhibitor preferred; GLP-1 RA for weight loss
• Iron deficiency: IV iron if ferritin <100 or TSAT <20%
• Obesity: weight management programme; consider GLP-1 RA

Drugs NOT shown to help in HFpEF:

• ACEi/ARB: no mortality benefit (CHARM-Preserved, PEP-CHF, I-PRESERVE)
• Beta-blockers: no benefit (and may worsen exercise capacity)
• MRA: no mortality benefit but may reduce hospitalisations (TOPCAT — regional variation)

Surgical/Interventional

• AF ablation: may improve symptoms and outcomes in HFpEF with AF
• Interatrial shunt devices: investigational (REDUCE LAP-HF trials)
• Specific treatment for underlying aetiology (e.g., tafamidis for ATTR amyloidosis, enzyme replacement for Fabry)

Referral Criteria

• All patients with suspected HFpEF: cardiology referral for echocardiography
• Consider referral to specialist HFpEF clinic
• If cardiac amyloidosis or Fabry disease suspected: specialist centre

• 5-year mortality: ~40-50% (similar to HFrEF, slightly better)
• Annual mortality: ~5-8%
• Hospitalisations as frequent as HFrEF
• Prognosis driven by comorbidities (diabetes, CKD, obesity, AF)
• No drug until SGLT2 inhibitors had demonstrated benefit
• Quality of life significantly impaired
• Worse prognosis if cardiac amyloidosis is the underlying cause

Comparison: HFrEF vs HFmrEF vs HFpEF

H2FPEF Score Components