What is the initial management for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)?

Management of Heart Failure

The initial management for heart failure with reduced ejection fraction (HFrEF) should include four foundational medication classes: SGLT2 inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and either an angiotensin receptor-neprilysin inhibitor (ARNI), ACE inhibitor, or ARB; while management for heart failure with preserved ejection fraction (HFpEF) should focus on SGLT2 inhibitors and diuretics for symptom control. 1, 2

Management of HFrEF

First-Line Pharmacological Therapy

• ARNI (sacubitril/valsartan) is recommended as first-line therapy for patients with HFrEF and NYHA class II-III symptoms to reduce morbidity and mortality 1
• If ARNI is not feasible, an ACE inhibitor is recommended for patients with previous or current symptoms of chronic HFrEF to reduce morbidity and mortality 1
• For patients intolerant to ACE inhibitors due to cough or angioedema, an ARB is recommended when ARNI is not feasible 1
• Beta-blockers (specifically bisoprolol, carvedilol, sustained-release metoprolol succinate, or nebivolol) should be initiated for all patients with HFrEF regardless of symptom severity 1
• Mineralocorticoid receptor antagonists (spironolactone or eplerenone) are recommended for patients with NYHA class II-IV HF who can be carefully monitored for renal function and potassium levels 1, 3
• SGLT2 inhibitors should be added to the treatment regimen regardless of diabetes status 1, 2

Optimization Strategy

• These four foundation medications (ARNI/ACE-I/ARB, beta-blockers, MRAs, and SGLT2 inhibitors) should be introduced over a 4-6 week period, followed by dose up-titration over 8 weeks 4
• Start medications at low doses and titrate upward as tolerated to target doses shown to be effective in clinical trials 1
• Monitor for hypotension, hyperkalemia, and worsening renal function during initiation and titration 1

Diuretic Therapy

• Loop diuretics are indicated for patients with fluid retention and should be used at the lowest effective dose 1
• Diuretics provide symptomatic relief but have not been shown to reduce mortality 1

Additional Therapies for Specific Populations

• For self-identified African American patients with NYHA class III-IV symptoms despite optimal therapy, add hydralazine and isosorbide dinitrate 1
• For patients with persistent symptoms despite optimal medical therapy, consider device therapy such as implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) based on specific criteria 1

Patients with Improved Ejection Fraction

• Patients with previous HFrEF who improve their LVEF to >40% (HFimpEF) should continue their HFrEF treatment regimen 1

Management of HFpEF

Pharmacological Therapy

• SGLT2 inhibitors are recommended as first-line therapy for HFpEF based on evidence from recent trials showing significant reductions in heart failure hospitalizations and worsening heart failure events 1, 2
• Diuretics should be used for symptomatic relief of fluid retention, with loop diuretics being the mainstay for acute volume management 1, 2
• MRAs, particularly spironolactone, can be considered in appropriate patients to reduce heart failure hospitalizations 1, 2
• ARNIs or ARBs may be considered in selected patients, particularly those with lower ejection fraction within the preserved range or women 1, 2

Comorbidity Management

• Aggressive management of comorbidities is crucial in HFpEF, including hypertension, diabetes mellitus, obesity, atrial fibrillation, coronary artery disease, chronic kidney disease, and obstructive sleep apnea 1, 2
• Beta-blockers are not recommended as primary HFpEF therapy unless specific indications exist, such as rate control for atrial fibrillation 1, 2

Common Pitfalls and Caveats

• Failure to initiate all four foundational medications for HFrEF in a timely manner can lead to suboptimal outcomes 4
• Inadequate dose titration of medications often results in subtherapeutic dosing and reduced efficacy 1
• Excessive diuresis can lead to electrolyte abnormalities, worsening renal function, and hypotension 1
• When initiating ARNI therapy, a 36-hour washout period is required after discontinuing ACE inhibitors to avoid angioedema 5
• Monitoring of renal function and electrolytes is essential, particularly when using MRAs, as hyperkalemia is a common adverse effect 1, 3
• For HFpEF, there is a tendency to overuse medications proven only for HFrEF; treatment should focus on evidence-based therapies for HFpEF specifically 1, 2