How should I manage a patient with heart‑failure with preserved ejection fraction (EF 50‑55%) and progressive lower‑extremity lymphedema?

Management of HFpEF with Progressive Lower-Extremity Lymphedema

Immediate Diagnostic Clarification

Your patient with EF 50-55% has heart failure with preserved ejection fraction (HFpEF), as the American College of Cardiology defines HFpEF as LVEF ≥50%. 1 However, this EF range (50-55%) represents a critical threshold where 11% of patients may progress to mildly reduced EF (HFmrEF) over time, particularly those with ischemic etiology. 2

Critical First Step: Exclude HFpEF Mimics and Lymphedema Causes

Before attributing all symptoms to HFpEF, you must systematically exclude:

Cardiac Mimics Requiring Different Treatment

• Infiltrative cardiomyopathy (especially cardiac amyloidosis—look for carpal tunnel syndrome, lumbar spinal stenosis, increased wall thickness >1.2 cm) 1, 3
• Hypertrophic cardiomyopathy (asymmetric septal hypertrophy on echo) 1
• Valvular heart disease (perform comprehensive valve assessment) 1
• Pericardial disease (assess for constrictive physiology) 1

Noncardiac Causes of Edema

• Chronic venous insufficiency (venous duplex ultrasound to assess for venous obstruction/reflux) 1, 3
• Nephrotic syndrome (urinalysis for proteinuria, 24-hour urine protein) 1
• Liver disease/cirrhosis (abdominal ultrasound, liver function tests) 1
• Primary lymphedema (lymphoscintigraphy if indicated) 3

The progressive nature of the lymphedema suggests this may NOT be simple HFpEF-related edema, which typically responds to diuretics and fluctuates with volume status. 3

First-Line Pharmacologic Management

Initiate SGLT2 Inhibitor Immediately

Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily as first-line disease-modifying therapy. 3, 4, 5 These agents:

• Reduce HF hospitalization or cardiovascular death by 18-21% in HFpEF 3, 4
• Are particularly beneficial as they do not worsen peripheral edema 3
• Work independently of volume status 4

Optimize Diuretic Therapy for Congestion

Prescribe loop diuretics (furosemide 20-40 mg daily or torsemide) titrated to achieve euvolemia. 3, 5 However, recognize that:

• Progressive lymphedema may not respond adequately to diuretics alone 3
• If inadequate response, escalate by: increasing loop diuretic dose, switching furosemide to bumetanide/torsemide, adding thiazide/metolazone, or administering loop diuretic twice daily 3
• Monitor weight daily to detect early fluid retention 3, 6

Consider Mineralocorticoid Receptor Antagonist

Add spironolactone 25 mg daily if patient remains symptomatic, particularly if female or EF trending toward lower end of preserved range. 3, 6 Monitor potassium and renal function closely. 3

Aggressive Comorbidity Management

Blood Pressure Control

Target BP <130/80 mmHg using appropriate antihypertensive medications. 3, 6 This is critical as hypertension drives HFpEF pathophysiology and your patient's EF of 50-55% suggests possible chronic pressure overload. 3, 6

Address Obesity if Present

If BMI >30 kg/m², target 5-10% weight reduction through diet and exercise. 3, 6 Obesity is present in >80% of HFpEF patients and excess intra-abdominal fat plays a pivotal role in the obese/metabolic HFpEF phenotype. 3

Optimize Diabetes Management

If diabetic, the SGLT2 inhibitor serves dual purpose for both HFpEF and glycemic control. 3

Specific Management of Progressive Lymphedema

The progressive nature of lower-extremity lymphedema in this context requires:

• Referral to vascular surgery or lymphedema specialist to evaluate for chronic venous insufficiency, lymphatic obstruction, or primary lymphatic dysfunction 1, 3
• Complete Doppler ultrasound of lower extremities to exclude venous obstruction/deep venous thrombosis 1
• Consider compression therapy (graduated compression stockings 20-30 mmHg) if venous insufficiency confirmed, but only after excluding arterial disease 3
• Manual lymphatic drainage and complete decongestive therapy if primary or secondary lymphedema diagnosed 3

Non-Pharmacologic Interventions

Exercise Training

Prescribe supervised cardiac rehabilitation or structured exercise program. 3, 6, 5 Exercise training produces large, clinically meaningful improvements in exercise capacity and quality of life in HFpEF. 6, 5

Sodium Restriction

Restrict sodium to <2-3 g/day to reduce fluid retention. 6

HF Self-Care Education

Educate on medication adherence, dietary restrictions, daily weight monitoring, and symptom recognition. 5

Monitoring Strategy

Assess at each visit:

• Volume status through weight measurement, orthostatic BP changes, and physical examination 3
• Renal function and electrolytes, especially with diuretic and MRA therapy 3
• Natriuretic peptides (BNP >35 pg/mL ambulatory or NT-proBNP >125 pg/mL) to monitor disease activity, though levels are lower in HFpEF than HFrEF 1, 3, 6

When to Refer to Cardiology/HF Specialist

Refer if:

• Diagnostic uncertainty regarding HFpEF vs. specific cardiomyopathy (especially given EF 50-55% threshold) 1, 2
• Progressive symptoms despite optimal medical therapy 1
• Need for advanced testing (invasive hemodynamics, cardiac MRI, endomyocardial biopsy) 1
• Consideration for clinical trial enrollment 1

Critical Pitfalls to Avoid

• Do not assume all lower-extremity edema is cardiac in origin—progressive lymphedema suggests alternative or additional pathology requiring specific evaluation 1, 3
• Do not delay SGLT2 inhibitor initiation—this is the only proven disease-modifying therapy for HFpEF 3, 5
• Do not use beta-blockers unless specific indication (prior MI, angina, or atrial fibrillation requiring rate control) 3, 6
• Avoid NSAIDs as they worsen HFpEF 3, 6
• Recognize that EF 50-55% carries 90.9% sensitivity for future progression to HFmrEF, particularly with ischemic etiology—monitor EF longitudinally 2