What is the next step for a patient with Heart Failure with preserved Ejection Fraction (HFpEF) who is not responding to 40mg of furosemide (Lasix) daily for edema?

Management of Refractory Edema in HFpEF on Furosemide 40mg Daily

For a patient with HFpEF whose edema is not responding to furosemide 40mg daily, the next step should be to increase the furosemide dose or add a thiazide diuretic for sequential nephron blockade.

Diuretic Dose Optimization

• Increase the furosemide dose to 80mg daily (either as a single dose or divided twice daily) as the current 40mg dose is at the lower end of the therapeutic range 1
• The maximum daily dose of furosemide can be increased up to 600mg if needed for resistant edema 1
• Consider switching to a more bioavailable loop diuretic such as torsemide (10-20mg once daily) or bumetanide (1-2mg daily) if the patient continues to have poor response 1

Sequential Nephron Blockade

• If increasing the loop diuretic dose is ineffective, add a thiazide diuretic for sequential nephron blockade 1
• Options include:
  • Metolazone 2.5-10mg once daily plus the loop diuretic 1
  • Hydrochlorothiazide 25-100mg once or twice daily plus the loop diuretic 1
  • Chlorthalidone 12.5-25mg once daily (longer acting than hydrochlorothiazide) 1

Monitoring During Diuretic Adjustment

• Monitor electrolytes closely, especially potassium and magnesium, as diuretic combinations significantly increase the risk of electrolyte depletion 1
• Monitor renal function, as aggressive diuresis can cause azotemia 1
• Track daily weights to assess response to therapy 1
• Assess for signs of intravascular volume depletion (hypotension, dizziness) while maintaining diuresis of peripheral edema 1

Additional Management Considerations

• Ensure sodium restriction is being followed (typically <2-3g daily) 1, 2
• Consider adding spironolactone 12.5-25mg daily, which can help with diuresis while preserving potassium 1
• For patients with HFpEF, consider adding an SGLT2 inhibitor (dapagliflozin or empagliflozin) which has shown benefit in reducing HF hospitalizations 3
• Evaluate for and treat precipitating factors of fluid retention such as uncontrolled hypertension, atrial fibrillation, or dietary indiscretion 2

Special Considerations for Diuretic Resistance

• For true diuretic resistance, twice-daily dosing of loop diuretics may be more effective than once-daily dosing 1
• Consider a brief course of intravenous furosemide if oral therapy continues to be ineffective 4
• High-dose furosemide (≥500mg daily) has been used successfully in refractory cases with appropriate monitoring 5
• Avoid NSAIDs and other medications that may interfere with diuretic efficacy 1

Common Pitfalls to Avoid

• Using inappropriately low doses of diuretics will result in persistent fluid retention 1
• Using excessively high doses can lead to volume contraction, hypotension, and renal insufficiency 1
• Failing to monitor electrolytes when using combination diuretic therapy 1
• Not reassessing diuretic requirements periodically - some patients may eventually require less diuretic therapy while others may need more 1

Remember that diuretics should not be used in isolation but combined with other guideline-directed medical therapy for heart failure 1, 3.