What is the initial management for patients with heart failure, particularly those with reduced ejection fraction?

Initial Management of Heart Failure with Reduced Ejection Fraction

Start all four foundational medication classes simultaneously in patients with HFrEF: SGLT2 inhibitors, ACE inhibitors (or ARNI/ARB), beta-blockers, and mineralocorticoid receptor antagonists, along with loop diuretics for fluid retention. 1

Immediate Medication Initiation Strategy

First-Line Therapy (Start Simultaneously)

Begin with SGLT2 inhibitor and MRA first, as these have minimal blood pressure effects and provide rapid mortality benefit 1, 2:

• SGLT2 inhibitor: Dapagliflozin 10 mg daily or empagliflozin 10 mg daily for all patients with eGFR >20-30 mL/min/1.73 m² 1, 2
• MRA: Spironolactone 12.5-25 mg daily or eplerenone 25 mg daily for patients with eGFR >30 mL/min/1.73 m² 2, 3

Sequential Addition (Within 1-2 Weeks)

Add beta-blocker next if heart rate >70 bpm, starting with low doses of bisoprolol, carvedilol, or metoprolol succinate 1:

• Start at low doses and uptitrate every 1-2 weeks 1
• Target doses proven in trials, though benefits occur even at sub-target doses 4

Then add ACE inhibitor (or ARNI/ARB) at low dose and titrate up 1, 2:

• Lisinopril starting at 2.5-5 mg daily, targeting 20-35 mg daily 5
• All symptomatic patients (Stage C) require ACE inhibitors unless contraindicated 6

Diuretic Management

Loop diuretics for all patients with fluid overload, adjusted based on volume status 6, 2:

• Avoid excessive diuresis before starting ACE inhibitors, as this precipitates hypotension 1
• Reduce diuretic dose when initiating ACE inhibitors 2

Blood Pressure-Based Approach

For Low Baseline Blood Pressure (But Adequate Perfusion)

• Start SGLT2 inhibitor and MRA first 1
• Add low-dose beta-blocker only if heart rate >70 bpm 1
• Defer or use very low-dose ACE inhibitor/ARNI initially 1

For Normal Blood Pressure

• Start SGLT2 inhibitor and MRA simultaneously 1
• Add either low-dose beta-blocker or low-dose ACE inhibitor/ARNI 1
• Uptitrate one drug at a time using small increments every 1-2 weeks 1

Critical Monitoring Parameters

Baseline Laboratory Assessment

Check complete blood count, urinalysis, fasting lipids, liver function, electrolytes, BUN, creatinine, glucose, and TSH before starting therapy 1

Post-Initiation Monitoring

Check blood pressure, heart rate, renal function, and electrolytes at 1-2 weeks after each medication increment 1, 2:

• For potassium-sparing diuretics, check potassium and creatinine after 5-7 days and recheck every 5-7 days until stable 1
• Early follow-up within 1-2 weeks of medication changes improves outcomes 1

Medication Adjustments for Complications

Hyperkalemia (K+ >5.0 mEq/L)

• Reduce MRA dose first 2
• Continue ACE inhibitor/ARB/ARNI if possible 2

Renal Dysfunction (eGFR <30 mL/min/1.73 m²)

• Reduce or avoid MRAs 2
• Adjust RAS inhibitor dosing 2
• Don't use thiazides unless combined synergistically with loop diuretics 1

Symptomatic Hypotension

Never discontinue GDMT for asymptomatic or mildly symptomatic low blood pressure 1:

• If heart rate >70 bpm: reduce ACE inhibitor/ARB/ARNI first 7
• If heart rate <60 bpm: reduce beta-blocker first 7
• Maintain SGLT2 inhibitors and MRAs as they have least effect on blood pressure 7

Additional Guideline-Directed Therapy

Class I Recommendations (Must Use)

• Digoxin for patients not adequately responsive to ACE inhibitors and diuretics, or for atrial fibrillation with rapid ventricular rates 6
• Anticoagulation for patients with atrial fibrillation or previous systemic/pulmonary embolism 6
• Beta-blockers for high-risk patients after acute myocardial infarction 6

Contraindicated Therapies

• Avoid calcium channel blockers unless coexistent angina or hypertension 6
• Avoid NSAIDs, as they interfere with ACE inhibitor efficacy and worsen renal function 1
• Don't treat asymptomatic ventricular arrhythmias 6

Timing of SGLT2 Inhibitor Initiation

Initiate SGLT2 inhibitors during hospitalization for acute decompensated heart failure 2:

• In-hospital initiation is consistent with regulatory labels and guidelines 2
• Deferring to outpatient setting exposes patients to excess risk of early post-discharge clinical worsening and death 2

Referral Criteria for Advanced Therapy

Refer to heart failure specialist when 1:

• Persistent low blood pressure with major symptoms despite optimization attempts
• Inability to uptitrate GDMT due to hemodynamic intolerance
• Refractory symptoms on optimal medical therapy

Device Therapy Considerations

Cardiac Resynchronization Therapy (CRT)

Recommended for patients in sinus rhythm with LVEF ≤35%, QRS duration ≥150 ms, and left bundle branch block morphology who remain symptomatic 1

Implantable Cardioverter-Defibrillator (ICD)

Consider for primary prevention in patients with LVEF ≤35% and ischemic heart disease 1

Non-Pharmacological Management

Encourage moderate dynamic exercise to tolerance (walking, recreational biking), but discourage intense physical exertion and isometric exercise 6:

• Physical conditioning programs increase blood flow to exercising muscles and delay anaerobic threshold 6
• Sodium restriction <2-3 g daily 7
• Daily weight monitoring 7

Refractory Heart Failure Management

For patients becoming refractory to oral therapy 6:

• Hospital admission for short periods of bed rest may produce diuresis 6
• Change from oral to intravenous diuretics 6
• Low-dose dobutamine (2-5 µg/kg/min) or intravenous milrinone for temporary improvement in cardiac output 6
• Consider heart transplantation for patients refractory to medical or surgical therapy 6