How to manage a low ejection fraction in the absence of Coronary Artery Disease (CAD)?

Management of Low Ejection Fraction Without Coronary Artery Disease

For patients with heart failure with reduced ejection fraction (HFrEF) without coronary artery disease, guideline-directed medical therapy (GDMT) including ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors should be initiated and optimized to target doses to reduce mortality and hospitalizations.

First-Line Therapies for HFrEF Without CAD

Foundation Medications

• ACE inhibitors or ARBs: First-line therapy for all patients with HFrEF regardless of etiology 1

  • Start at low dose and titrate to target doses
  • Monitor renal function and potassium levels 1-2 weeks after initiation or dose changes
  • Consider switching to sacubitril/valsartan in patients who remain symptomatic

• Beta-blockers: Essential disease-modifying treatment for all HFrEF patients 1, 2

  • Target maximum tolerated doses
  • Continue even if patient is asymptomatic
  • Common options: carvedilol, metoprolol succinate, bisoprolol

• Mineralocorticoid receptor antagonists (MRAs): Add when LVEF ≤35% and NYHA class II-IV symptoms persist despite ACE inhibitor/ARB and beta-blocker therapy 1

  • Spironolactone 25mg daily is typical starting dose
  • Monitor potassium and renal function closely
  • Shown to reduce mortality and hospitalization

Advanced Therapies

• Sacubitril/valsartan: Consider replacing ACE inhibitor/ARB in patients who remain symptomatic despite optimal therapy 3

  • Superior to enalapril in reducing cardiovascular death or heart failure hospitalization (HR 0.80; 95% CI, 0.73,0.87) 3
  • Improves overall survival (HR 0.84; 95% CI [0.76,0.93]) 3
  • Dosing: Start at 24/26 mg or 49/51 mg twice daily, target 97/103 mg twice daily

• SGLT2 inhibitors: Recommended as disease-modifying therapy even in non-diabetic patients 4

  • Empagliflozin 10mg daily or dapagliflozin 10mg daily
  • Reduces heart failure hospitalizations and improves quality of life

Management Algorithm Based on LVEF and Symptoms

For LVEF ≤40%:

1. Start ACE inhibitor/ARB and beta-blocker simultaneously at low doses
2. Titrate both medications to target doses over 2-3 months
3. If LVEF ≤35% and symptoms persist (NYHA II-IV), add MRA
4. Consider switching from ACE inhibitor/ARB to sacubitril/valsartan if symptoms persist
5. Add SGLT2 inhibitor regardless of diabetes status
6. Manage volume status with loop diuretics as needed (not mortality benefit but symptom relief)

For Persistent Symptoms Despite Optimal Medical Therapy:

• Device Therapy Evaluation:
  • Consider ICD if LVEF ≤35% despite ≥3 months of optimal medical therapy 1
  • Evaluate for cardiac resynchronization therapy (CRT) if QRS duration ≥130ms

Specific Non-CAD Etiologies to Consider

When managing HFrEF without CAD, investigate and treat these potential causes:

1. Hypertensive heart disease: Optimize blood pressure control
2. Valvular heart disease: Echocardiographic assessment and appropriate intervention
3. Cardiomyopathies:
   • Dilated cardiomyopathy: Consider genetic testing
   • Alcoholic cardiomyopathy: Alcohol cessation
   • Peripartum cardiomyopathy: Specialized management
4. Arrhythmia-induced cardiomyopathy: Rhythm or rate control
5. Infiltrative diseases: Specific therapies based on etiology
6. Toxic cardiomyopathy: Remove offending agent (chemotherapy, etc.)

Common Pitfalls to Avoid

1. Underdosing medications: Only a minority of patients receive target doses of GDMT in real-world practice (17% for ACE inhibitors/ARBs, 28% for beta-blockers) 1

2. Inappropriate discontinuation: High discontinuation rates (24-55%) are observed in clinical practice 1

3. Failure to optimize all medication classes: Incremental use of GDMT is associated with improved survival 1

4. Inappropriate use of calcium channel blockers: Most calcium channel blockers (except amlodipine) should be avoided in HFrEF 4

5. Ignoring comorbidities: Manage anemia, atrial fibrillation, and other conditions that can worsen heart failure 1

6. Inadequate monitoring: Regular assessment of symptoms, volume status, renal function, and electrolytes is essential 4

By systematically implementing and optimizing GDMT, most patients with HFrEF without CAD can experience significant improvements in symptoms, quality of life, and survival.