What are the current guidelines for treating Heart Failure with Reduced Ejection Fraction (HFrEF)?

Current Guidelines for Heart Failure with Reduced Ejection Fraction (HFrEF)

Guideline-directed medical therapy (GDMT) for HFrEF now includes four foundational medication classes that should be initiated as soon as possible after diagnosis to reduce mortality and morbidity. 1

First-Line Medications (The Four Pillars)

• Renin-Angiotensin System Inhibitors: Either an angiotensin receptor-neprilysin inhibitor (ARNI), angiotensin-converting enzyme inhibitor (ACEi), or angiotensin receptor blocker (ARB) 1

  • ARNI (sacubitril/valsartan) is recommended as first-line therapy for NYHA class II-III symptoms to reduce morbidity and mortality 1
  • ACEi should be used when ARNI is not feasible 1, 2
  • ARB should be used when patients are intolerant to ACEi (due to cough or angioedema) and ARNI is not feasible 1

• Beta-blockers: Recommended for all patients with current or previous symptoms of chronic HFrEF to reduce mortality and hospitalizations 1

  • Should be initiated in clinically stable patients at a low dose and gradually up-titrated to maximum tolerated dose 1
  • Should be cautiously initiated in hospital for patients admitted with acute HF, once stabilized 1

• Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone are recommended for all symptomatic patients with HFrEF and LVEF ≤35% 1

  • Reduce mortality and HF hospitalization 1
  • Require monitoring of renal function and serum potassium levels 1, 3
  • Eplerenone is specifically indicated to improve survival in stable patients with symptomatic HFrEF after an acute myocardial infarction 3

• Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i): Now considered a fundamental component of HFrEF therapy 1, 4

  • Added as the fourth pillar in the most recent guidelines 1
  • Reduce hospitalization and cardiovascular mortality 4

Treatment Algorithm

1. Initiation Strategy: The 2022 AHA/ACC/HFSA guidelines recommend that all four medication classes can be started simultaneously at initial low doses rather than waiting for sequential titration 1, 5

   • Alternatively, medications may be started sequentially, with sequence guided by clinical factors 1
   • Early benefits are obtained even with low doses of most foundational therapies 5

2. Dose Titration: Medication doses should be increased to target as tolerated 1

   • The "target dose" in clinical trials was often not reached, with benefits demonstrated at average doses lower than target 5
   • Regular monitoring of renal function, blood pressure, and electrolytes is essential during titration 1, 3

3. Special Considerations:

   • For patients with atrial fibrillation, beta-blockers should be considered for rate control 1, 4
   • In patients with symptomatic hypotension, kidney disease, or hyperkalemia, therapy should be modified rather than discontinued 4
   • For patients who remain symptomatic despite optimal medical therapy, device therapy should be considered 6

Device Therapy

• Cardiac Resynchronization Therapy (CRT): Class I indication for symptomatic patients with HFrEF and a broad QRS complex with left bundle branch block (LBBB) morphology 1, 6

  • Recommended if QRS ≥130 msec and LBBB in sinus rhythm 1
  • May be considered if QRS ≥130 msec with non-LBBB in sinus rhythm 1

• Implantable Cardioverter-Defibrillator (ICD): For primary prevention in patients with symptomatic HF and LVEF ≤35% 1

• Alternative Electrical Therapies: For patients not eligible for CRT (narrow QRS or non-LBBB morphology) 6

  • Baroreflex activation therapy (BAT)
  • Cardiac contractility modulation (CCM)

Advanced Heart Failure Management

• Referral to HF Specialist: Patients with advanced HF who wish to prolong survival should be referred to a team specializing in HF 1, 7

• Mechanical Circulatory Support: For eligible patients with advanced HF 1

Common Pitfalls and Challenges

• Underprescription and Underdosing: In real-world practice, many patients do not receive target doses due to hypotension, bradycardia, renal dysfunction, or hyperkalemia 7

  • Up to half of patients may be undertreated for unknown reasons, suggesting clinical inertia 7

• Medication Intolerance: Strategies to manage common side effects include:

  • For hypotension: Adjust diuretic dose, administer medications at different times of day 4
  • For hyperkalemia with MRAs: Careful monitoring, dietary potassium restriction 1, 3
  • For worsening renal function: Temporary dose reduction rather than discontinuation 4

• Comorbidities: Tailoring therapy for patients with kidney disease, diabetes, or atrial fibrillation requires careful consideration but should not lead to unnecessary reduction of life-saving treatment 4, 7

The evidence strongly supports that even partial implementation of these guideline-directed therapies significantly improves outcomes in HFrEF patients, with treatment benefits observed even at lower-than-target doses 5, 8, 7.