What is the initial approach to managing air hunger and anxiety in a patient with chronic systolic heart failure and reduced ejection fraction?

Managing Air Hunger and Anxiety in Chronic Systolic Heart Failure with Reduced Ejection Fraction (EF 32%)

Immediately optimize guideline-directed medical therapy with quadruple therapy (SGLT2 inhibitor, ARNI/ACE inhibitor, beta-blocker, and mineralocorticoid receptor antagonist) using aggressive forced-titration protocols, as this addresses the underlying pathophysiology causing dyspnea and provides 73% mortality reduction over 2 years, while adding loop diuretics only if clinical fluid overload is present. 1, 2

Immediate Assessment and Diuretic Management

First, determine if fluid overload is present by examining for:

• Pulmonary congestion (rales, orthopnea, paroxysmal nocturnal dyspnea)
• Peripheral edema
• Elevated jugular venous pressure
• Rapid weight gain 3

If fluid overload is present:

• Start loop diuretics immediately for rapid symptom relief, as they produce rapid improvement in dyspnea and increased exercise tolerance 3
• Always combine diuretics with ACE inhibitors or ARNI 3
• If inadequate response, increase diuretic dose, combine loop diuretics with thiazides, or administer loop diuretics twice daily 3
• Avoid thiazides if GFR <30 mL/min unless used synergistically with loop diuretics 3, 2

If no fluid overload is present:

• Air hunger likely reflects inadequate cardiac output and neurohormonal activation rather than volume overload
• Proceed directly to optimizing guideline-directed medical therapy without diuretics 2

Foundation: Quadruple Guideline-Directed Medical Therapy

The core strategy is simultaneous initiation of all four medication classes, not sequential addition. This approach provides the most rapid mortality benefit and symptom relief. 2

Initiation Strategy for Standard Blood Pressure Patients:

Week 1:

• Start SGLT2 inhibitor (dapagliflozin 10mg daily or empagliflozin 10mg daily) - provides rapid mortality benefit with minimal blood pressure effects 2
• Start mineralocorticoid receptor antagonist (spironolactone 12.5-25mg daily) - does not lower blood pressure 2
• Check potassium and creatinine after 5-7 days 3

Week 2:

• Add low-dose ACE inhibitor (enalapril 2.5mg twice daily) OR preferably ARNI (sacubitril/valsartan 24/26mg or 49/51mg twice daily) 2, 4
• ARNI provides at least 20% mortality reduction versus 5-16% for ACE inhibitors/ARBs 1
• Allow 36-hour washout if switching from ACE inhibitor to ARNI 4

Week 3-4:

• Add low-dose beta-blocker (carvedilol 3.125mg twice daily, bisoprolol 1.25mg daily, or metoprolol succinate 12.5-25mg daily) 3, 2
• Beta-blockers provide at least 20% mortality reduction 1

Aggressive Uptitration Protocol:

Uptitrate every 1-2 weeks using forced-titration strategy as used in landmark trials 1, 2:

• ARNI target: 97/103mg twice daily 4
• Beta-blocker targets: Carvedilol 25-50mg twice daily, bisoprolol 10mg daily, or metoprolol succinate 200mg daily 3
• MRA target: Spironolactone 25-50mg daily 3
• SGLT2 inhibitor: Already at target dose 2

Monitor at each uptitration:

• Blood pressure, heart rate, renal function, electrolytes at 1-2 weeks after each increment 3, 2
• Recheck potassium and creatinine every 5-7 days until stable when adjusting MRA 3

Critical Management Principles for Air Hunger

Do not discontinue or reduce medications for asymptomatic hypotension - this is the most common error that compromises long-term outcomes 2:

• Asymptomatic low blood pressure should not prevent uptitration 1
• Systolic BP 80-90 mmHg is acceptable if patient has adequate perfusion (warm extremities, normal mentation, adequate urine output) 5

Accept modest creatinine increases:

• Up to 30% increase above baseline is acceptable and should not prompt discontinuation 1
• Only stop ACE inhibitor/ARNI if renal function deteriorates substantially 3

For patients with baseline low blood pressure but adequate perfusion:

• Start SGLT2 inhibitor and MRA first (neither lowers blood pressure significantly) 2
• Add low-dose beta-blocker if heart rate >70 bpm 2
• Add ARNI/ACE inhibitor last, at lowest dose 2

Addressing Anxiety Component

The anxiety associated with air hunger typically improves as cardiac output and neurohormonal activation are optimized through GDMT 3:

• Counsel patient and family that dyspnea and anxiety will improve with medication optimization 3
• Explain that initial low doses are temporary and rapid uptitration is essential 3
• Self-monitoring with daily weights helps patients recognize improvement 3

Avoid benzodiazepines or sedatives as they can worsen respiratory drive and mask worsening heart failure symptoms.

Medications to Avoid

Absolutely avoid:

• NSAIDs - interfere with ACE inhibitor efficacy and worsen renal function 3, 2
• Excessive diuresis before starting ACE inhibitors/ARNI - can precipitate hypotension 3, 2
• Potassium-sparing diuretics during ACE inhibitor/ARNI initiation (wait until after initiation) 3

Timeline and Follow-up

Achieve optimal therapy within 2 months in most patients 6:

• Early follow-up within 7-14 days after medication adjustments 1, 2
• Continue uptitration every 1-2 weeks until target doses achieved 1
• Combined quadruple therapy at target doses potentially extends life expectancy by 6 years compared to traditional dual therapy 1

Common Pitfalls

Never discontinue GDMT even if ejection fraction improves - discontinuation leads to clinical deterioration 2:

• Continue all four medication classes indefinitely 2
• Air hunger improvement is a sign of effective therapy, not a reason to reduce medications

In real-world practice, only 1% of eligible patients receive target doses of all recommended drugs 3, 2:

• This represents a major treatment gap
• Aggressive forced-titration protocols are essential to overcome clinical inertia 1

When Symptoms Persist Despite Optimal Therapy

If air hunger and anxiety persist after achieving target doses of quadruple therapy:

• Consider cardiac resynchronization therapy if QRS ≥150ms with left bundle branch block 2
• Refer for advanced heart failure evaluation 2
• Evaluate for other causes of dyspnea (pulmonary disease, anemia, deconditioning) 3