What are the treatment recommendations for a patient with Heart Failure with Reduced Ejection Fraction (HFrEF) of 20%?

Treatment Recommendations for HFrEF with EF 20%

Patients with HFrEF of 20% should receive quadruple therapy with an ARNI (sacubitril/valsartan), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor as soon as possible after diagnosis to reduce mortality and hospitalization risk. 1, 2, 3

First-Line Medication Therapy

Renin-Angiotensin System Inhibition

• Angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan is preferred over ACE inhibitors or ARBs for patients with NYHA class II-III symptoms to reduce morbidity and mortality 1, 4
• If transitioning from an ACE inhibitor to sacubitril/valsartan, a 36-hour washout period is mandatory to prevent angioedema 4
• The recommended starting dose of sacubitril/valsartan is 49/51 mg twice daily, with uptitration to 97/103 mg twice daily after 2-4 weeks as tolerated 4
• Discontinuation of sacubitril/valsartan leads to deterioration of left ventricular ejection fraction and worsening of functional class, even when replaced with ACE inhibitors or ARBs 5

Beta-Blockers

• Evidence-based beta-blockers should be initiated in all clinically stable HFrEF patients at a low dose and gradually uptitrated to maximum tolerated dose 1, 6
• Beta-blockers reduce mortality and hospitalization risk and should be part of foundational therapy even with severely reduced EF of 20% 1, 3

Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone or eplerenone should be added for all symptomatic HFrEF patients with LVEF ≤35% to reduce mortality and HF hospitalization 1
• Regular monitoring of renal function and serum potassium is mandatory when using MRAs 1

SGLT2 Inhibitors

• SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality regardless of diabetes status and should be part of quadruple therapy 2, 3, 7
• These agents provide incremental benefits beyond traditional neurohormonal therapies 2

Device Therapy Considerations

Implantable Cardioverter-Defibrillator (ICD)

• An ICD is strongly recommended for primary prevention in patients with symptomatic HF and LVEF ≤35%, which includes patients with EF of 20% 1
• This is particularly important for patients with ischemic etiology 2

Cardiac Resynchronization Therapy (CRT)

• CRT should be considered for symptomatic patients with HFrEF and a broad QRS complex with left bundle branch block (LBBB) morphology 1
• Class I indication exists if QRS ≥130 msec with LBBB in sinus rhythm 1

Advanced Heart Failure Management

• With an EF of 20%, the patient may be approaching advanced heart failure and should be referred to a specialized HF team for evaluation 1
• Mechanical circulatory support should be considered for eligible patients with very low EF who continue to deteriorate despite optimal medical therapy 1

Practical Implementation Tips

• Early initiation of low-dose combination therapy is generally tolerated by most patients 3
• Hemodynamics, frailty, and laboratory values need consideration for maximum tolerated therapy 3
• Initiation of therapy during heart failure hospitalization represents an important opportunity to improve GDMT utilization 3
• Despite compelling evidence of benefit, guideline-directed medical therapy is vastly underutilized in real-world practice 7

Common Pitfalls and Caveats

• Avoid combining ACE inhibitors with ARBs or renin inhibitors due to increased risk of renal dysfunction and hyperkalemia 8
• When transitioning from ACE inhibitors to sacubitril/valsartan, failure to observe the 36-hour washout period can lead to angioedema 4
• Despite initial symptom improvement with diuretics, they do not modify disease progression and should be used alongside disease-modifying therapies 2, 7
• Prognosis remains poor with a 5-year survival rate of 25% after hospitalization for HFrEF, emphasizing the importance of aggressive, comprehensive therapy 2