What should a family medicine resident know about heart failure with preserved ejection fraction (HFpEF)?

What Family Medicine Residents Must Know About HFpEF

Family medicine residents should recognize HFpEF as a diagnosis of exclusion requiring systematic evaluation to rule out cardiac mimics (infiltrative cardiomyopathy, hypertrophic cardiomyopathy, valvular disease, pericardial disease) and noncardiac mimics (kidney disease, liver disease, chronic venous insufficiency) before establishing the diagnosis, followed by initiation of SGLT2 inhibitors as foundational therapy. 1, 2

Diagnostic Framework

Step 1: Establish Heart Failure Diagnosis

You need all four of these criteria 2:

• Symptoms/signs of heart failure (dyspnea, edema, fatigue)
• LVEF ≥50% on echocardiogram
• Elevated natriuretic peptides (BNP or NT-proBNP)
• Objective cardiac abnormality: left atrial enlargement, LV hypertrophy, diastolic dysfunction (E/e' >16), or elevated filling pressures

Step 2: Rule Out Mimics Before Diagnosing HFpEF

This is critical and often missed. HFpEF is a diagnosis of exclusion 1. You must systematically evaluate for:

Cardiac Mimics ("HF attributed to"):

• Infiltrative cardiomyopathy (especially cardiac amyloidosis—look for LV wall thickness >1.5 cm, low voltage ECG despite thick walls, monoclonal protein screen, technetium pyrophosphate scan)
• Hypertrophic cardiomyopathy
• Valvular heart disease
• Pericardial disease (constrictive pericarditis)
• High-output heart failure

Noncardiac Mimics ("Congestion primarily from"):

• Kidney disease
• Liver disease with ascites
• Chronic venous insufficiency

Clinical Red Flags Requiring Further Workup

Look for these clues suggesting a specific mimic rather than true HFpEF 1:

• LV wall thickness ≥1.5 cm (consider amyloidosis, especially if age >60, neuropathy, carpal tunnel syndrome)
• Disproportionate symptoms to comorbidity burden
• Rapid progression
• Lack of typical HFpEF risk factors (hypertension, obesity, diabetes, atrial fibrillation, older age)

Risk Factor Recognition

High-risk patients you should screen 3, 4:

• Older adults with unexplained exertional dyspnea
• Obesity (especially BMI >30)
• Diabetes mellitus
• Hypertension
• Atrial fibrillation
• Chronic kidney disease

Use HFpEF screening scores in primary care 4:

• HFpEF-ABA score or BREATH2 score help estimate pre-test probability
• Patients with intermediate-to-high probability warrant cardiology referral

Management Algorithm

Immediate Actions for Confirmed HFpEF

1. Initiate SGLT2 Inhibitor (Class 1 Recommendation) 2, 5, 6

• Empagliflozin or dapagliflozin are first-line pharmacotherapy
• These reduce heart failure hospitalizations and cardiovascular death
• Start regardless of diabetes status
• This is the strongest evidence-based therapy available

2. Diuretics for Congestion 5

• Use loop diuretics to relieve symptoms
• Titrate to euvolemia, then maintain lowest effective dose
• Monitor renal function and electrolytes

3. Aggressive Comorbidity Management 1, 6

• Hypertension: Target <130/80 mmHg
• Diabetes: Optimize glycemic control; GLP-1 receptor agonists (semaglutide) show additional benefit in obesity-related HFpEF 6, 7
• Obesity: Weight reduction improves outcomes 5
• Atrial fibrillation: Rate/rhythm control, anticoagulation
• Coronary artery disease: Standard guideline-directed therapy

4. Supervised Exercise Training 5

• Recommended to improve functional capacity and quality of life
• Structured cardiac rehabilitation programs when available

Additional Pharmacologic Considerations

ARNIs (Angiotensin Receptor-Neprilysin Inhibitors) 6:

• May be considered in selected patients
• Evidence less robust than SGLT2 inhibitors

Mineralocorticoid Receptor Antagonists 6:

• Finerenone shows promise in ongoing trials
• Traditional MRAs (spironolactone) have mixed evidence

Common Pitfalls to Avoid

1. Assuming all dyspnea + preserved EF = HFpEF 1

• Always exclude mimics first
• Missing cardiac amyloidosis is particularly problematic as it requires specific therapy

2. Underdiagnosing in obese patients 4

• Natriuretic peptides may be falsely low in obesity
• Lower threshold for stress testing or invasive hemodynamics

3. Failing to initiate SGLT2 inhibitors 2, 5

• These are not just "diabetes drugs"
• They are foundational HFpEF therapy regardless of diabetes status

4. Treating symptoms without addressing comorbidities 1, 6

• HFpEF is a systemic syndrome
• Hypertension, diabetes, obesity, and AF management are integral to treatment

When to Refer to Cardiology

• Diagnostic uncertainty after initial workup 4
• Suspected cardiac mimics requiring advanced imaging (CMR) or invasive testing
• Refractory symptoms despite optimal medical therapy
• Need for stress echocardiography or invasive hemodynamic testing
• Consideration of device therapy or advanced heart failure interventions

Key Pathophysiology Concepts

HFpEF involves 3:

• Diastolic dysfunction and ventricular stiffness
• Left atrial myopathy
• Pulmonary hypertension and right ventricular dysfunction
• Chronotropic incompetence
• Systemic inflammation and endothelial dysfunction
• Multi-organ involvement (skeletal muscle, kidneys, brain)

Understanding this helps explain why comorbidity management is as important as cardiac-specific therapy 6.