What is the recommended evaluation and diagnostic approach for an older adult patient with a history of hypertension, diabetes, or obesity, presenting with shortness of breath, fatigue, and swelling, to diagnose Heart Failure with preserved Ejection Fraction (HFpEF)?

How to Diagnose HFpEF

The diagnosis of HFpEF requires three components: symptoms/signs of heart failure, preserved ejection fraction ≥50%, and either elevated natriuretic peptides OR objective evidence of congestion, followed by systematic exclusion of HFpEF mimics. 1, 2

Initial Clinical Assessment

Begin by identifying the clinical syndrome of heart failure through specific findings:

Major criteria (any 2 establish heart failure):

• Orthopnea
• Jugular venous distension
• Hepatojugular reflux
• Pulmonary rales
• S3 gallop rhythm
• Acute pulmonary edema
• Cardiomegaly 3

Minor criteria (1 major + 2 minor also establish heart failure):

• Dyspnea on exertion
• Nocturnal cough
• Ankle edema
• Tachycardia >120 bpm
• Hepatomegaly
• Pleural effusion 3

Key risk factors to identify:

• Hypertension
• Obesity (BMI >30 kg/m²)
• Diabetes mellitus
• Age >60 years
• Atrial fibrillation 4, 5

Essential Diagnostic Testing

Natriuretic Peptides (Required)

Ambulatory thresholds:

• BNP >35 pg/mL OR
• NT-proBNP >125 pg/mL 1, 2

Hospitalized thresholds:

• BNP >100 pg/mL OR
• NT-proBNP >300 pg/mL 2

Critical caveat: In obese patients, use 50% lower cutoff values, as obesity significantly suppresses natriuretic peptides despite elevated filling pressures. 4 Normal natriuretic peptides do NOT exclude HFpEF in obesity—maintain high suspicion and low threshold for further testing. 2

Echocardiography (Required)

Confirm preserved EF ≥50% 4, 1

Assess for structural/functional abnormalities:

• E/e' ratio >9 (>15 strongly suggests elevated filling pressures) 4, 1
• Left atrial volume index >34 mL/m² 4
• LV mass index >149/122 g/m² (M/F) 4
• Relative wall thickness >0.42 4
• Pulmonary artery systolic pressure >35 mmHg 4
• LV wall thickness ≥12 mm 4

Must exclude valve disease, as this is a structural abnormality that can cause heart failure regardless of EF. 1

Basic Laboratory and Imaging

• Complete blood count, comprehensive metabolic panel, liver function tests, thyroid-stimulating hormone, fasting glucose/HbA1c, lipid profile 4
• 12-lead ECG (completely normal ECG makes HF unlikely) 4, 3
• Chest X-ray (PA and lateral) 4

Diagnostic Scoring Systems

H₂FPEF Score (Practical for Initial Assessment)

Use when diagnosis uncertain after initial workup:

Component	Points
Heavy (BMI >30 kg/m²)	2
Hypertension (≥2 medications)	1
Atrial Fibrillation	3
Pulmonary hypertension (PASP >35 mmHg)	1
Elder (age >60 years)	1
Filling pressure (E/e' >9)	1

Score ≥6 points: highly diagnostic of HFpEF 4

Advantage: Does not require natriuretic peptides, useful in obesity where peptides are unreliable. 4

HFA-PEFF Algorithm (Comprehensive Approach)

Step 1 - Pretest Assessment: Clinical evaluation, natriuretic peptides, ECG, echocardiography 4, 6

Step 2 - Echocardiographic and Natriuretic Peptide Score:

• Major criteria (2 points each): Septal e' <7 cm/s or lateral e' <10 cm/s; average E/e' >15; TR velocity >2.8 m/s; LAVI >34 mL/m²
• Minor criteria (1 point each): LVMI or RWT elevated; GLS impaired; moderate natriuretic peptide elevation
• Score ≥5: definite HFpEF
• Score 2-4: proceed to Step 3
• Score ≤1: HFpEF unlikely 4, 6

Step 3 - Functional Testing (if score 2-4):

• Diastolic stress echocardiography OR
• Invasive hemodynamic exercise testing 4, 6

Practical note: Many clinicians initiate a therapeutic trial of guideline-directed medical therapy (diuretics + SGLT2 inhibitor) instead of stress testing when diagnosis is uncertain, assessing for symptomatic improvement. 4

Exclude HFpEF Mimics (Critical Step)

Do not diagnose HFpEF until these are excluded:

Cardiac Mimics

• Cardiac amyloidosis: Increased LV wall thickness, carpal tunnel syndrome, neuropathy → Technetium pyrophosphate scan, monoclonal protein screen 4
• Hypertrophic cardiomyopathy: Unexplained LV hypertrophy, family history → Cardiac MRI 4
• Valvular heart disease: Comprehensive valve assessment on echocardiography 4, 1
• Pericardial disease: Prior cardiac surgery/radiation, right-sided HF symptoms → Cardiac MRI, invasive hemodynamics 4
• Cardiac sarcoidosis: Extracardiac disease, AV block, ventricular arrhythmias → Cardiac MRI, FDG-PET 4

Non-Cardiac Causes

• Chronic kidney disease
• Liver failure/cirrhosis
• Chronic venous insufficiency
• Severe anemia
• Thyroid disease 2

Not every patient requires exhaustive testing—use clinical suspicion to guide which mimics to pursue. 4, 2

Advanced Testing (When Diagnosis Remains Uncertain)

• Cardiac MRI: Evaluate for infiltrative disease, fibrosis, pericardial abnormalities 4, 2
• Invasive hemodynamic assessment: Confirm elevated LV filling pressures (LVEDP >16 mmHg or PCWP >15 mmHg at rest, >25 mmHg with exercise) 2, 6

Common Diagnostic Pitfalls

Obesity: The most important pitfall. Obese patients have lower natriuretic peptides despite worse hemodynamics—do not attribute all dyspnea to obesity without thorough evaluation. 4, 2

Over-reliance on single parameters: HFpEF diagnosis requires integration of clinical, laboratory, and imaging findings, not just one abnormal value. 2

Assuming preserved EF excludes significant cardiac disease: Valve disease, infiltrative cardiomyopathy, and pericardial disease can all present with preserved EF. 4, 1

Elderly patients with comorbidities: Not all dyspneic elderly patients with hypertension and diabetes have HFpEF—systematic exclusion of alternatives is essential. 2, 7