What are the clinical manifestations and diagnostic criteria for heart failure with preserved ejection fraction (HFpEF)?

Heart Failure with Preserved Ejection Fraction: Clinical Manifestations and Diagnosis

HFpEF should be diagnosed when patients present with dyspnea, exertional intolerance, or edema AND have an ejection fraction ≥50%, elevated natriuretic peptides (BNP >35 pg/mL or NT-proBNP >125 pg/mL in ambulatory settings), plus objective evidence of structural/functional cardiac abnormalities or elevated filling pressures. 1

Clinical Manifestations

Primary Symptoms

The cardinal symptom is exertional dyspnea accompanied by exercise intolerance 1. Patients may also present with:

Major criteria (Framingham):

• Orthopnea
• Jugular venous distension
• Hepatojugular reflux
• Pulmonary rales
• S3 gallop rhythm
• Acute pulmonary edema
• Cardiomegaly 1

Minor criteria:

• Dyspnea on exertion
• Nocturnal cough
• Ankle edema
• Tachycardia (>120 bpm)
• Hepatomegaly
• Pleural effusion 1

Important Clinical Context

HFpEF patients typically present with higher BMI and have lower natriuretic peptide levels relative to HFrEF for the same degree of elevated left ventricular end-diastolic pressure 1. This is a critical pitfall—don't be falsely reassured by "normal-ish" natriuretic peptides in an obese patient with dyspnea.

Diagnostic Algorithm

Step 1: Initial Assessment (Primary Care Level)

When evaluating dyspnea, exertional intolerance, or edema 1:

1. Measure natriuretic peptides:

   • Ambulatory: BNP >35 pg/mL or NT-proBNP >125 pg/mL
   • Hospitalized: BNP >100 pg/mL or NT-proBNP >300 pg/mL 1

2. Order echocardiogram to:

   • Confirm EF ≥50% 2
   • Assess for structural/functional cardiac abnormalities 1
   • Exclude significant valvular disease or ischemia 2

3. Apply Framingham criteria: Diagnosis requires 2 major criteria OR 1 major + 2 minor criteria 1

Step 2: Echocardiographic Confirmation (Cardiology Level)

The Universal Definition of HF requires symptoms/signs PLUS at least one of 1:

• Elevated natriuretic peptides (as above), OR
• Objective evidence of cardiogenic pulmonary/systemic congestion

Key echocardiographic parameters indicating elevated filling pressures 2:

• E/e' ratio ≥15 (major criterion)
• E/e' ratio >9 (minor criterion)
• Left atrial volume index elevation
• LV mass index elevation
• Pulmonary artery systolic pressure >35 mmHg
• LV global longitudinal strain abnormalities

Step 3: H2FPEF Score for Diagnostic Uncertainty

When diagnosis remains uncertain, apply the H2FPEF score (0-9 points) 2:

• Heavy (obesity): 2 points
• Hypertension (≥2 antihypertensive medications): 1 point
• Atrial Fibrillation (paroxysmal/persistent): 3 points
• Pulmonary hypertension (echo PA systolic pressure >35 mmHg): 1 point
• Elder (age >60 years): 1 point
• Filling pressure (E/e' >9): 1 point

Interpretation:

• Score ≥6: High likelihood of HFpEF
• Score 2-5: Intermediate—proceed to exercise testing
• Score <2: Low likelihood—consider alternative diagnoses

The H2FPEF score has excellent discrimination (c-statistic 0.841) and helps distinguish HFpEF from noncardiac dyspnea 2.

Step 4: Exercise Testing (When Score 2-5 or Persistent Uncertainty)

For intermediate probability cases 2:

• Exercise echocardiography with diastolic parameter assessment, OR
• Invasive hemodynamics (rest or exercise) measuring:
  • Pulmonary capillary wedge pressure
  • LV end-diastolic pressure
  • PA pressures
  • Stroke volume and cardiac output

Elevated filling pressures with exercise confirm HFpEF diagnosis 2.

Critical Diagnostic Pitfalls

Natriuretic Peptide Interpretation

Obesity blunts natriuretic peptide levels 1. A "borderline" BNP of 40-50 pg/mL in an obese patient with dyspnea and structural abnormalities may still represent HFpEF. Don't dismiss the diagnosis based solely on modestly elevated peptides in high BMI patients.

Alternative Diagnoses Must Be Excluded

Before confirming HFpEF, systematically exclude 1:

• Pulmonary causes: COPD, interstitial lung disease, pulmonary hypertension
• Cardiac mimics: Significant valvular disease, ischemia, pericardial disease
• Noncardiac edema: Venous insufficiency, liver disease, nephrotic syndrome
• Deconditioning: Pure physical deconditioning without cardiac pathology

When to Refer

Cardiology referral when 1:

• Diagnostic uncertainty after initial workup
• Need to exclude alternative diagnoses
• Optimization of guideline-directed medical therapy

Heart failure specialist referral when 1:

• Diagnostic dilemma persists after cardiology evaluation
• Special/unusual cardiomyopathies suspected
• Advanced testing needed (invasive hemodynamics)
• Clinical trial eligibility assessment

Practical Clinical Approach

For primary care clinicians: Maintain high suspicion for HFpEF in patients presenting with dyspnea, exertional intolerance, or edema—particularly those with obesity, hypertension, diabetes, elderly age, or atrial fibrillation 1. Order natriuretic peptides and echocardiogram early. Don't wait for florid congestion; many HFpEF patients lack overt volume overload at rest 3.

For cardiologists: Use comprehensive echocardiography to assess diastolic function systematically. Apply the H2FPEF score to guide need for exercise testing. Remember that HFpEF diagnosis requires both symptoms/signs AND objective cardiac abnormalities—not just an EF ≥50% with dyspnea 2.

The diagnosis is challenging because symptoms are nonspecific and traditional signs of congestion may be absent at rest 3. A structured, stepwise approach integrating clinical assessment, natriuretic peptides, and echocardiographic evaluation of filling pressures is essential for accurate diagnosis 4, 5.