What is the approach to diagnose heart failure with preserved ejection fraction (HFpEF)?

Diagnosing Heart Failure with Preserved Ejection Fraction (HFpEF)

The diagnosis of HFpEF requires the presence of clinical signs and symptoms of heart failure, a preserved ejection fraction (≥50%), elevated natriuretic peptides, and objective evidence of cardiac structural and functional abnormalities, with careful exclusion of alternative causes. 1

Diagnostic Criteria

HFpEF diagnosis follows a stepwise approach:

1. Clinical Assessment

   • Evaluate for symptoms and signs of heart failure 1, 2:
     • Major criteria: orthopnea, jugular venous distension, hepatojugular reflux, rales, S3 gallop rhythm, acute pulmonary edema, cardiomegaly 2
     • Minor criteria: dyspnea on exertion, nocturnal cough, ankle edema, tachycardia, hepatomegaly, pleural effusion 2
   • Assess for typical risk factors: hypertension, obesity, diabetes mellitus, advanced age, and atrial fibrillation 1, 2

2. Basic Diagnostic Tests

   • Echocardiography to confirm preserved EF (≥50%) 1
   • Natriuretic peptide measurements 1:
     • Ambulatory setting: BNP >35 pg/mL or NT-proBNP >125 pg/mL
     • Acute setting: BNP >100 pg/mL or NT-proBNP >300 pg/mL
   • ECG to identify abnormalities such as atrial fibrillation, LV hypertrophy, and repolarization abnormalities 1, 2

3. Cardiac Structural and Functional Assessment

   • Echocardiographic parameters indicating diastolic dysfunction 1:
     • Average E/e' ≥15 (major criterion) or >14 (depending on guideline)
     • Left atrial volume index ≥40 mL/m²
     • LV mass index ≥95 g/m² (both males and females)
     • Septal e' <7 cm/s (females) or <10 cm/s (males)
     • Tricuspid regurgitation velocity ≥35 mmHg

Advanced Diagnostic Approaches

When initial assessment is inconclusive (intermediate probability):

1. Functional Testing

   • Exercise stress echocardiography or invasive hemodynamic testing to unmask elevated filling pressures 1, 2, 3
   • Cardiopulmonary exercise testing (CPET) to help identify the cause of dyspnea and quantify functional capacity 1, 2

2. Additional Imaging

   • Cardiovascular magnetic resonance (CMR) if echocardiography is non-diagnostic, to assess cardiac structure and function or help determine etiology 1

3. Invasive Assessment

   • Right heart catheterization to aid diagnosis, monitor pulmonary artery pressure, or as workup for advanced treatment 1
   • Endomyocardial biopsy if a specific cause of HF is suspected that would influence therapy (e.g., myocarditis, amyloidosis) 1

Diagnostic Algorithms

Two validated scoring systems can help with diagnosis when uncertainty exists:

1. HFA-PEFF Score 3:

   • Major criteria (2 points each) and minor criteria (1 point each) based on echocardiographic parameters and natriuretic peptide levels
   • Score ≥5 points: definite HFpEF
   • Score ≤1 point: HFpEF unlikely
   • Score 2-4 points: requires functional testing

2. H2FPEF Score 4:

   • Assesses likelihood of HFpEF based on clinical and echocardiographic parameters

Exclusion of HFpEF Mimics

Critical to rule out conditions that can mimic HFpEF 1, 2:

1. Non-cardiac causes:

   • Kidney failure, liver disease, chronic venous insufficiency 1, 2

2. Cardiac mimics with preserved EF:

   • Infiltrative/restrictive cardiomyopathies (e.g., cardiac amyloidosis)
   • Hypertrophic cardiomyopathy
   • Valvular heart disease
   • Pericardial disease
   • High-output heart failure 1, 2

Common Pitfalls and Challenges

• Normal natriuretic peptide levels do not exclude HFpEF, especially in obese patients who may have lower values despite elevated filling pressures 2, 5
• Not all patients with dyspnea, preserved EF, and comorbidities have HFpEF; careful exclusion of alternative diagnoses is essential 1, 2
• Avoid over-reliance on a single parameter; diagnosis requires integration of clinical, laboratory, and imaging findings 2, 4
• The diagnosis of HFpEF remains challenging, especially in elderly patients with comorbidities and no obvious signs of fluid overload 1, 5

Special Considerations

• Women have higher EFs and more preserved LV global longitudinal strain compared to men, making them more likely to develop HFpEF than HFrEF 1
• A history of pregnancy complications, particularly pre-eclampsia, is associated with increased risk for subsequent HFpEF 1
• Genetic testing should be considered if an inherited cardiomyopathy is suspected 1

By following this systematic approach to diagnosis, clinicians can more accurately identify patients with HFpEF and distinguish them from those with alternative conditions, leading to more appropriate management strategies and improved outcomes.