What is the treatment for a patient with a left ventricular ejection fraction (LVEF) of 40%?

Treatment for Left Ventricular Ejection Fraction of 40%

A patient with an LVEF of 40% has heart failure with reduced ejection fraction (HFrEF) and should be treated with comprehensive quadruple guideline-directed medical therapy (GDMT) consisting of: (1) ACE inhibitor/ARB or ARNI, (2) evidence-based beta-blocker, (3) mineralocorticoid receptor antagonist (MRA), and (4) SGLT2 inhibitor, plus diuretics as needed for volume management. 1, 2

Classification and Rationale

• An LVEF of exactly 40% falls into the HFrEF category (defined as LVEF ≤40%), which has the strongest evidence base for mortality and morbidity reduction with GDMT 1
• This classification is critical because patients with HFrEF have proven survival benefit from the four-pillar medication regimen, unlike those with higher ejection fractions 1, 2

Core Pharmacological Therapy (The Four Pillars)

1. RAAS Inhibition: ACE Inhibitor/ARB or ARNI

• Start with an ACE inhibitor (such as lisinopril) as first-line therapy for all HFrEF patients unless contraindicated 3, 2, 4
• ACE inhibitors reduce cardiovascular mortality, heart failure hospitalizations, and improve symptoms in patients with LVEF <40-45% 3, 4
• Consider switching to ARNI (sacubitril/valsartan) after stabilization on ACE inhibitor, as ARNI provides superior outcomes compared to ACE inhibitors alone 1, 5
• If ACE inhibitor is not tolerated (typically due to cough), use an ARB as alternative 2, 5
• Monitor renal function closely, especially when initiating or increasing doses, and when adding other medications affecting kidney function 3

2. Evidence-Based Beta-Blockers

• Initiate beta-blocker therapy (carvedilol, metoprolol succinate, or bisoprolol) for all patients with LVEF ≤40% 1, 2, 5
• Beta-blockers reduce heart failure hospitalizations, cardiovascular mortality, and all-cause mortality 2, 5
• These should be started even in patients who are asymptomatic (NYHA Class I) 2

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone or eplerenone for patients with LVEF ≤35% and NYHA class II-IV symptoms despite ACE inhibitor and beta-blocker therapy 2, 6
• The landmark RALES trial demonstrated a 30% reduction in all-cause mortality with spironolactone in patients with LVEF ≤35% and NYHA class III-IV symptoms 6
• Critical exclusion criteria: baseline serum creatinine >2.5 mg/dL or baseline potassium >5.0 mEq/L 6
• Requires close monitoring of potassium and renal function every 4 weeks initially, then every 3 months 6

4. SGLT2 Inhibitors

• Add an SGLT2 inhibitor (dapagliflozin or empagliflozin) regardless of diabetes status 1, 2, 5
• SGLT2 inhibitors are now a Class 1 recommendation in the 2022 AHA/ACC/HFSA guidelines for HFrEF 1
• These medications decrease heart failure hospitalizations and cardiovascular mortality 2, 5

Diuretic Therapy for Volume Management

• Use loop diuretics (furosemide, bumetanide, or torsemide) for symptom relief when volume overload is present 1, 5
• Diuretics do not improve mortality but are essential for managing congestion and improving quality of life 5

Device Therapy Considerations

Implantable Cardioverter-Defibrillator (ICD)

• ICD is indicated for primary prevention of sudden cardiac death in patients with LVEF ≤35% who are at least 40 days post-MI, have NYHA class II-III symptoms on GDMT, and expected survival >1 year 1, 2
• For patients with LVEF ≤30% and NYHA class I symptoms (at least 40 days post-MI), ICD is also recommended 1
• At LVEF of exactly 40%, ICD is generally not indicated unless there are documented sustained ventricular arrhythmias 1

Cardiac Resynchronization Therapy (CRT)

• CRT is indicated for patients with LVEF ≤35%, sinus rhythm, LBBB with QRS ≥150 ms, and NYHA class II-IV symptoms 1, 2
• Not applicable at LVEF of 40% unless EF subsequently decreases 1

Medications to Avoid

• Avoid calcium channel blockers (verapamil, diltiazem, short-acting dihydropyridines) due to negative inotropic effects 3
• Avoid Class I antiarrhythmic agents as they can worsen heart failure 3
• Avoid NSAIDs and COX-2 inhibitors due to sodium and water retention 3
• Use caution with corticosteroids (fluid retention), tricyclic antidepressants (cardiac effects), and lithium 3

Lifestyle Modifications

• Sodium restriction is important, particularly as heart failure advances 3
• Fluid restriction of 1.5-2 L/day for advanced heart failure 3
• Moderate alcohol intake (one beer or 1-2 glasses of wine daily) is generally acceptable unless cardiomyopathy is alcohol-related 3
• Encourage regular exercise tailored to avoid inducing symptoms; formal cardiac rehabilitation programs are beneficial for NYHA class II-III patients 3

Critical Implementation Strategy

Initiation sequence: Start all four medication classes as soon as possible, even before hospital discharge if presenting with acute decompensated heart failure 5, 7

Titration approach: Uptitrate each medication class to target or maximally tolerated doses over weeks to months, monitoring blood pressure, heart rate, renal function, and potassium 5, 7

Common pitfalls to avoid:

• Do not delay GDMT initiation waiting for "stability" - early initiation improves outcomes 5
• Do not discontinue GDMT if EF improves above 40% (this becomes "HF with improved EF" and requires continued therapy to prevent relapse) 1, 2
• Do not withhold therapy due to mild hypotension, bradycardia, or small increases in creatinine unless severe - adjust doses rather than discontinue 7
• Address hyperkalemia or worsening renal function with management strategies rather than stopping life-saving medications 7

Special Monitoring Requirements

• Renal function and electrolytes: Check at baseline, with each dose adjustment, and regularly during maintenance (every 4 weeks initially, then every 3 months) 6
• Blood pressure and heart rate: Monitor at each visit to guide titration 5
• Symptoms and functional status: Assess NYHA class regularly to guide therapy intensity 1