Immediate Management of Tongue Swelling and Heart Failure Optimization
URGENT: Discontinue Entresto Immediately
Stop Entresto (sacubitril/valsartan) immediately due to tongue swelling, which represents angioedema—a potentially life-threatening adverse effect that is contraindicated for rechallenge. 1 The FDA label explicitly warns that sacubitril/valsartan is contraindicated in patients with a history of angioedema, and tongue swelling is a manifestation of this serious reaction. 1
Critical Safety Actions:
- Assess airway patency immediately—examine for tongue swelling progression, difficulty swallowing, stridor, or respiratory compromise requiring emergency intervention 2
- Do not rechallenge with any ARB or ACE inhibitor for at least 36 hours after Entresto discontinuation, as cross-reactivity risk exists 1, 2
- Monitor closely for 24-48 hours as angioedema can progress even after drug discontinuation 1
Diuretic Optimization for Volume Management
Increase furosemide to at least 80 mg IV twice daily (2.5× the home oral dose) to address the elevated BNP of 294, which indicates persistent congestion. 3 The American Journal of Kidney Diseases recommends starting intravenous loop diuretics at twice the daily home dose for acute heart failure, with evidence from the DOSE trial supporting higher doses (2.5× home dose) for improved fluid loss and symptom relief. 3
Diuretic Strategy:
- Switch from oral to IV furosemide during acute optimization, as intestinal edema in heart failure causes unpredictable oral absorption 3
- Target net fluid loss of 2-3 liters over 48-72 hours with daily weights and strict intake/output monitoring 4
- Monitor renal function and electrolytes daily during active diuresis—check serum creatinine, BUN, potassium, and sodium 3, 4
- Once euvolemic, transition back to oral furosemide at the effective IV dose equivalent (oral dose = 2× IV dose due to 50% bioavailability) 3
Beta-Blocker Titration
Uptitrate carvedilol from 6.25 mg BID to 12.5 mg BID after achieving euvolemia, with target dose of 25 mg BID. 3, 5, 6 The European Society of Cardiology guidelines recommend gradual beta-blocker titration over weeks to months, and carvedilol has demonstrated mortality reduction in severe heart failure when titrated to target doses. 3, 5, 6
Titration Protocol:
- Do not uptitrate beta-blocker during active decompensation—wait until patient is euvolemic and hemodynamically stable 6
- Double the dose every 2-4 weeks as tolerated, monitoring for symptomatic hypotension, bradycardia (<55 bpm), or worsening heart failure 3, 5
- Carvedilol 6.25 mg BID is subtherapeutic—the COPERNICUS trial demonstrated safety and efficacy of carvedilol 25 mg BID even in severe heart failure (EF <25%) 6
Alternative RAAS Inhibition After Angioedema
After 36-hour washout from Entresto, initiate hydralazine 37.5 mg TID plus isosorbide dinitrate 20 mg TID as alternative vasodilator therapy, as ACE inhibitors and ARBs are contraindicated after angioedema. 3, 7 The European Heart Journal recommends hydralazine/nitrate combination when ACE inhibitors and ARBs are not tolerated, though this is less effective than RAAS inhibition for mortality reduction. 3, 7
Alternative RAAS Strategy:
- Hydralazine/nitrate combination reduces mortality in heart failure patients who cannot tolerate ACE inhibitors or ARBs 3
- Titrate hydralazine to 75 mg TID and isosorbide dinitrate to 40 mg TID over 2-4 weeks as blood pressure tolerates 3
- Monitor for headache, hypotension, and drug-induced lupus (rare with hydralazine <200 mg/day) 3
Aldosterone Antagonist Addition
Add spironolactone 12.5 mg daily after confirming potassium <5.0 mEq/L and creatinine <2.5 mg/dL, with target dose of 25 mg daily. 3, 4 The European Heart Journal recommends aldosterone antagonists in NYHA class III-IV heart failure for additional mortality benefit beyond ACE inhibitors and beta-blockers. 3, 4
Aldosterone Antagonist Protocol:
- Check potassium and creatinine before initiation and recheck in 4-6 days 3
- Hold spironolactone if potassium >5.5 mEq/L or reduce dose by 50% if potassium 5.0-5.5 mEq/L 3
- Increase to 25 mg daily after 1 month if symptoms persist and potassium remains <5.0 mEq/L 3
- Elderly patients have higher hyperkalemia risk—monitor potassium weekly for first month 8, 4
Critical Monitoring Parameters
Within 24-48 Hours:
- Airway assessment for progression of tongue swelling 2
- Daily weights, intake/output during IV diuresis 4
- Serum creatinine, BUN, potassium, sodium daily during active diuresis 3, 4
Within 7-10 Days:
- Repeat BNP to assess treatment response—successful therapy should decrease BNP 4
- Orthostatic vital signs after medication changes, as elderly patients are at high risk for symptomatic hypotension 8, 4
- Recheck potassium and creatinine 4-6 days after starting spironolactone 3
Within 2-4 Weeks:
- Clinical reassessment for symptom improvement, volume status, and medication tolerance 4
- Consider beta-blocker uptitration if euvolemic and hemodynamically stable 3, 5
Common Pitfalls to Avoid
- Never rechallenge with Entresto, ACE inhibitors, or ARBs after angioedema—this is an absolute contraindication with risk of fatal airway compromise 1, 2
- Do not uptitrate beta-blockers during active decompensation—wait until euvolemic, as beta-blockade can worsen acute heart failure 6
- Avoid excessive diuresis causing prerenal azotemia—worsening renal function during hospitalization is associated with increased long-term mortality 3
- Do not use thiazide diuretics in elderly patients—loop diuretics are required due to reduced GFR 8, 4
- Monitor for hyperkalemia closely when combining spironolactone with any residual RAAS inhibition or in elderly patients with renal impairment 3, 8, 4