How to diagnose heart failure with preserved ejection fraction (HFpEF) in an older adult, particularly a woman, with a history of hypertension, diabetes, and obesity, presenting with symptoms such as shortness of breath, fatigue, and swelling in the legs?

Diagnosing Heart Failure with Preserved Ejection Fraction (HFpEF)

In an older woman with hypertension, diabetes, and obesity presenting with dyspnea, fatigue, and leg swelling, diagnose HFpEF by confirming LVEF ≥50%, elevated natriuretic peptides (NT-proBNP >125 pg/mL or BNP >35 pg/mL), and applying the H2FPEF score to establish diagnostic probability, while systematically excluding cardiac and noncardiac mimics. 1, 2

Step 1: Apply the Universal Definition of Heart Failure

Confirm the presence of heart failure by documenting:

• Symptoms and signs of HF: Look specifically for orthopnea, jugular venous distension, hepatojugular reflux, pulmonary rales, S3 gallop, dyspnea on exertion, nocturnal cough, ankle edema, tachycardia, hepatomegaly, or pleural effusion 2
• Structural/functional cardiac abnormalities on echocardiography or other imaging 1, 2
• At least one of the following: (1) elevated natriuretic peptides (NT-proBNP >125 pg/mL or BNP >35 pg/mL in ambulatory setting; NT-proBNP >300 pg/mL or BNP >100 pg/mL if hospitalized) OR (2) objective evidence of cardiogenic pulmonary or systemic congestion 1, 2

Step 2: Confirm Preserved Ejection Fraction

Obtain echocardiography to document LVEF ≥50%, which definitively categorizes this as HFpEF rather than HFrEF (LVEF <40%) or HFmrEF (LVEF 41-49%) 1

Step 3: Calculate the H2FPEF Score for Diagnostic Probability

The H2FPEF score is the preferred clinical tool given its greater accuracy with fewer variables compared to HFA-PEFF. 1 Calculate the score (range 0-9) using these weighted variables:

• Heavy (obesity): BMI >30 kg/m² = 2 points 1
• Hypertension: ≥2 antihypertensive medications = 1 point 1
• Atrial Fibrillation: Present = 3 points 1
• Pulmonary hypertension: Echocardiographic PA systolic pressure >35 mm Hg = 1 point 1
• Elder: Age >60 years = 1 point 1
• Filling pressure: Echocardiographic E/e' ratio >9 = 1 point 1

Score interpretation:

• Score ≥6: High likelihood of HFpEF (>95% probability); diagnosis established 1, 3
• Score 2-5: Intermediate probability; proceed to Step 5 for additional testing 1
• Score <2: Low likelihood, but do not use this to exclude HFpEF if clinical suspicion remains high based on symptoms and risk factors 1

Your patient likely scores 5-7 points (obesity=2, hypertension with multiple medications=1, age>60=1, plus potential points for atrial fibrillation, elevated E/e', or elevated PA pressure on echo), placing her in the intermediate-to-high probability range. 1

Step 4: Assess Echocardiographic Structural and Functional Abnormalities

Beyond confirming LVEF ≥50%, evaluate for:

• Left atrial enlargement: LA volume index >34 mL/m² (or LAViH² >35.5 ml/m² in sinus rhythm, >38.6 ml/m² in atrial fibrillation) 1, 2, 4
• LV hypertrophy: Increased LV mass index 1, 2
• Diastolic dysfunction parameters: E/e' ratio, deceleration time, tissue Doppler velocities 1, 2
• Elevated PA systolic pressure >35 mm Hg 1

Women with HFpEF characteristically show more concentric LV remodeling and more impaired diastolic relaxation than men, which may underestimate LV dysfunction if sex-neutral EF thresholds are applied. 1

Step 5: Exclude Noncardiac Mimics

Before finalizing the HFpEF diagnosis, systematically rule out noncardiac causes of dyspnea and edema:

• Kidney disease: Check urinalysis for proteinuria (nephrotic syndrome), assess renal function 1, 2
• Liver disease/cirrhosis: Perform abdominal ultrasound if clinical suspicion exists 1, 2
• Severe obesity with peripheral edema alone (without cardiac dysfunction) 1
• Chronic lung disease: Obtain pulmonary function tests (spirometry), chest imaging, arterial blood gas if indicated 1, 2
• Chronic venous insufficiency 2

Step 6: Exclude Cardiac Mimics (HFpEF Phenocopies)

This is critical, especially for intermediate H2FPEF scores (2-5), as specific disease-directed therapies exist for these conditions:

• Infiltrative cardiomyopathies: Consider cardiac amyloidosis (technetium pyrophosphate scan, serum/urine protein electrophoresis), sarcoidosis, hemochromatosis 1, 2, 5
• Hypertrophic cardiomyopathy: Look for asymmetric septal hypertrophy, systolic anterior motion on echo 2, 5
• Valvular heart disease: Exclude significant aortic stenosis, mitral regurgitation 2, 5
• Pericardial disease: Constrictive pericarditis or effusion 2, 5
• High-output heart failure: Assess for thyrotoxicosis, severe anemia, arteriovenous fistulas 2

Referral to a cardiovascular or HF specialist is appropriate for intermediate H2FPEF scores to facilitate this evaluation. 1

Step 7: Advanced Diagnostic Testing (If Diagnosis Remains Uncertain)

If the diagnosis remains unclear after Steps 1-6:

• Exercise stress echocardiography: Assess for elevated filling pressures (E/e' ratio) or elevated PA pressures with exercise to unmask HFpEF 1, 2
• Invasive hemodynamic testing: Right heart catheterization at rest or with exercise to measure pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure, PA pressures, stroke volume, and cardiac output 1, 2
• Cardiac MRI: Evaluate for infiltrative disease, myocardial fibrosis, or pericardial abnormalities 2

However, in routine clinical practice where advanced testing is not readily available, initiating a therapeutic trial of guideline-directed medical therapy (diuretics and SGLT2 inhibitors) and assessing for symptomatic improvement is a reasonable alternative to establishing the diagnosis. 1

Critical Pitfalls and Caveats

• Do not exclude HFpEF based on normal natriuretic peptides alone, particularly in obese patients who may have falsely low values despite elevated filling pressures 2
• A low H2FPEF score should not be used to exclude HFpEF if clinical context strongly suggests it; pretest probability based on age, sex, and comorbidities guides diagnostic utility 1
• Women with HFpEF have greater attributable risk from hypertension, diabetes, and obesity, plus unique risk factors including history of pre-eclampsia and central/visceral adiposity 1
• Women present with more dyspnea and worse health status than men, despite similar physical examination findings 1
• Not all patients with dyspnea, preserved EF, and multiple comorbidities have HFpEF; the diagnosis requires integration of clinical, laboratory, and imaging findings, not reliance on a single parameter 2
• HFpEF is often a diagnosis of exclusion after ruling out specific cardiac and noncardiac causes; exhaustive testing should be guided by clinical suspicion rather than applied universally 2

Simplified First-Step Approach (Alternative)

Recent evidence suggests a simplified first-step approach using LA enlargement and natriuretic peptides can identify 60-80% of HFpEF patients with high specificity (88-97% positive predictive value):

• LA volume indexed for height² (LAViH²) >35.5 ml/m² in sinus rhythm or >38.6 ml/m² in atrial fibrillation PLUS
• Elevated natriuretic peptides (NT-proBNP >125 pg/mL or BNP >35 pg/mL)

If both criteria are met, HFpEF is highly likely and reduces the need for additional diagnostics by 21-57%. 4 If this first step is negative, then proceed with H2FPEF or HFA-PEFF scoring algorithms. 4