What is the step‑by‑step approach to diagnosing heart failure with preserved ejection fraction in a typical patient – an older adult (≥65 years), often female, with hypertension, obesity, diabetes mellitus, atrial fibrillation, or chronic kidney disease?

Diagnosis of Heart Failure with Preserved Ejection Fraction (HFpEF)

In an older adult with typical risk factors (hypertension, obesity, diabetes, atrial fibrillation, or chronic kidney disease), diagnose HFpEF by confirming three mandatory elements: (1) heart failure symptoms/signs, (2) left ventricular ejection fraction ≥50%, and (3) either elevated natriuretic peptides OR objective evidence of elevated filling pressures, while systematically excluding cardiac and noncardiac mimics. 1, 2

Step 1: Confirm Heart Failure Symptoms and Signs

Assess for major criteria that strongly indicate heart failure 2:

• Orthopnea (inability to lie flat due to breathlessness) 2
• Jugular venous distension at 45 degrees 2
• Hepatojugular reflux (increased JVD with abdominal pressure) 2
• Pulmonary rales/crackles on auscultation 2
• S3 gallop rhythm on cardiac examination 2
• Acute pulmonary edema on chest imaging 2
• Cardiomegaly on chest radiograph 2

Assess for minor criteria that support the diagnosis 2:

• Dyspnea on exertion (most common presenting symptom) 1, 3
• Nocturnal cough 2
• Bilateral ankle edema 2
• Tachycardia (heart rate >100 bpm) 2
• Hepatomegaly 2
• Pleural effusion 2

Common pitfall: Approximately 35% of HFpEF patients present with "unexplained" dyspnea on exertion without overt congestion at rest, requiring provocative testing to unmask elevated filling pressures with exercise. 3

Step 2: Measure Natriuretic Peptides

Obtain BNP or NT-proBNP levels as the first objective test 1, 2:

• Ambulatory/outpatient 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
• Atrial fibrillation thresholds (higher cutoffs required): NT-proBNP >365 pg/mL OR BNP >105 pg/mL 1

Critical caveat for obesity: Natriuretic peptide levels are significantly lower in obese patients despite elevated filling pressures, potentially resulting in false-negative results below diagnostic thresholds. 1, 2 Consider reducing cutoff values by 50% in obese patients or proceed directly to advanced testing if clinical suspicion remains high despite normal peptides. 1

Step 3: Perform Echocardiography to Confirm Preserved EF and Assess Structure

Measure left ventricular ejection fraction 1, 2:

• LVEF ≥50% is required for HFpEF diagnosis 1, 2
• LVEF 41-49% indicates HFmrEF (mildly reduced EF), not HFpEF 1
• LVEF <40% indicates HFrEF (reduced EF), excluding HFpEF 4

Assess for structural cardiac abnormalities that support HFpEF diagnosis 1, 4:

• Left ventricular hypertrophy (wall thickness ≥12 mm, LV mass index >115 g/m² in men or >95 g/m² in women) 1, 4
• Left atrial enlargement (left atrial volume index >34 mL/m²) 1
• Mitral annular calcification 1
• Aortic sclerosis 1

Evaluate diastolic dysfunction parameters 1, 4:

• E/e' ratio >15 indicates elevated filling pressures (major criterion) 1
• E/e' ratio 9-15 is intermediate and requires additional supporting evidence 1, 4
• Estimated pulmonary artery systolic pressure >35 mm Hg 1

Critical warning: Do not diagnose HFpEF based solely on echocardiographic diastolic dysfunction without concurrent heart failure symptoms and elevated natriuretic peptides—this represents "diastolic dysfunction without heart failure" and requires only risk factor modification, not HFpEF-directed therapy. 4

Step 4: Apply Clinical Diagnostic Scores When Diagnosis Remains Uncertain

Use the H₂FPEF score (range 0-9) to estimate probability of HFpEF 1, 3:

• Heavy (BMI >30 kg/m²): 2 points 1
• Hypertension (≥2 antihypertensive medications): 1 point 1
• Atrial Fibrillation (paroxysmal or persistent): 3 points 1
• Pulmonary hypertension (PA systolic pressure >35 mm Hg on echo): 1 point 1
• Elder (age >60 years): 1 point 1
• Filling pressure (E/e' >9 on echo): 1 point 1

Interpretation 1, 3:

• Score ≥6: High likelihood of HFpEF (>95% probability) 1, 3
• Score 2-5: Intermediate probability, proceed to functional testing 1
• Score <2: Low likelihood of HFpEF 1

Advantage of H₂FPEF score: Does not include natriuretic peptides, making it particularly useful in obese patients where peptides may be falsely low. 1

Step 5: Exclude Cardiac Mimics That Require Different Treatment

Systematically rule out specific cardiomyopathies before finalizing HFpEF diagnosis 1, 2:

Infiltrative cardiomyopathies (especially cardiac amyloidosis in patients with carpal tunnel syndrome, lumbar spinal stenosis, or unexplained neuropathy) 1, 2:

• Obtain serum and urine protein electrophoresis with immunofixation 1
• Perform technetium pyrophosphate (PYP) scan if clinical suspicion exists 1
• Consider cardiac MRI to assess for late gadolinium enhancement pattern 2

Hypertrophic cardiomyopathy (asymmetric septal hypertrophy >15 mm, systolic anterior motion of mitral valve) 1, 2:

• Echocardiography typically reveals the diagnosis 2
• Consider genetic testing in appropriate cases 2

Valvular heart disease (must be excluded) 1, 4, 2:

• Aortic stenosis (mean gradient >40 mm Hg or valve area <1.0 cm²) 1
• Severe mitral regurgitation 1, 4

Pericardial constriction (respiratory variation in mitral inflow, septal bounce, dilated IVC) 1, 2:

• Cardiac MRI or CT to assess pericardial thickness 2
• Invasive hemodynamics showing equalization of diastolic pressures 2

High-output heart failure (anemia, thyrotoxicosis, arteriovenous fistulas) 1:

• Check hemoglobin, thyroid function tests 2
• Assess for hyperdynamic circulation on examination 1

Step 6: Exclude Noncardiac Mimics of Dyspnea and Edema

Rule out primary noncardiovascular causes of symptoms 1, 2:

• Kidney disease: Urinalysis for proteinuria, assess eGFR and creatinine 1
• Liver disease/cirrhosis: Abdominal ultrasound, liver function tests, assess for ascites 1
• Chronic venous insufficiency: Examine for varicose veins, venous stasis changes 1
• Primary pulmonary disease: Chest imaging, spirometry, arterial blood gas 1
• Pulmonary hypertension from pulmonary vascular disease: Right heart catheterization if suspected 1
• Severe obesity alone causing dyspnea: BMI consideration, but maintain high suspicion for coexisting HFpEF 1

Critical distinction: If a primary noncardiovascular entity fully explains symptoms, the patient has "congestion primarily from" that condition rather than HFpEF. 1

Step 7: Perform Functional Testing When Diagnosis Remains Uncertain

Proceed to exercise stress testing when resting evaluation is inconclusive (H₂FPEF score 2-5, intermediate E/e' ratio, or unexplained dyspnea without overt congestion) 1, 2:

Exercise stress echocardiography 1, 2:

• Measure E/e' ratio during or immediately after exercise 1
• E/e' >15 with exercise confirms elevated filling pressures 1
• Assess for development of pulmonary hypertension with exercise 1

Invasive hemodynamic exercise testing (gold standard when noninvasive testing inconclusive) 1, 2:

• Right heart catheterization with exercise 1, 2
• Pulmonary capillary wedge pressure >25 mm Hg with exercise confirms HFpEF 1
• Pulmonary capillary wedge pressure >15 mm Hg at rest confirms HFpEF 1

Step 8: Confirm Typical Risk Factor Profile

Verify presence of characteristic comorbidities that increase HFpEF likelihood 1:

• Hypertension: Present in the vast majority of HFpEF patients, most common risk factor 1, 4
• Obesity: Present in >80% of HFpEF patients, BMI >30 kg/m² 1, 3
• Diabetes mellitus: Affects 25-50% of HFpEF patients 1, 3
• Atrial fibrillation: Common comorbidity that worsens diastolic filling 1
• Chronic kidney disease: Frequently coexists with HFpEF 1, 3
• Advanced age (≥65 years): Aging has greater impact on diastolic function than systolic function 1
• Female sex: HFpEF is more prevalent in elderly women than men 1

Pathophysiologic rationale: Aging decreases elastic properties of the heart and great vessels, leading to increased systolic blood pressure and myocardial stiffness; chronic hypertension induces concentric left ventricular hypertrophy; fibrotic remodeling and impaired relaxation decrease ventricular filling rates. 1, 4

Common Diagnostic Pitfalls to Avoid

Do not rely on E/e' ratio alone: Its correlation with invasively measured filling pressures is modest in HFpEF populations and must be integrated with other echocardiographic and clinical data. 4

Do not overlook HFpEF in obese patients with normal natriuretic peptides: Obesity significantly lowers natriuretic peptide levels despite elevated filling pressures; maintain high suspicion and proceed to functional testing. 1, 2

Do not diagnose HFpEF in patients with complete heart block or severe bradycardia: Obtain 12-lead ECG immediately to exclude high-degree AV block, which mimics HFpEF but requires pacemaker implantation rather than HFpEF-directed therapy. 5

Do not assume all elderly patients with dyspnea and comorbidities have HFpEF: Carefully exclude alternative diagnoses, as overdiagnosis is common in this population. 6, 7

Do not miss cardiac amyloidosis: In patients with carpal tunnel syndrome, lumbar spinal stenosis, or unexplained neuropathy plus HFpEF features, obtain monoclonal protein screen and technetium pyrophosphate scan. 1