What is the recommended management for an adult with chronic heart failure with reduced ejection fraction?

Management of Chronic Heart Failure with Reduced Ejection Fraction (HFrEF)

All adults with HFrEF should receive simultaneous initiation of four foundational drug classes—ACE inhibitor/ARB/ARNI, beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor—started together at low doses and titrated every 2-4 weeks to target maintenance doses proven in clinical trials. 1, 2

Foundational Pharmacological Therapy (The "Four Pillars")

1. Renin-Angiotensin System Inhibition

First-line preference hierarchy: 1, 2

• ARNI (sacubitril/valsartan) is preferred over ACE inhibitors in ambulatory symptomatic HFrEF patients, as it further reduces cardiovascular death and hospitalization 1, 3
• ACE inhibitors (enalapril, lisinopril, ramipril) if ARNI not available or affordable 1
• ARBs (candesartan, valsartan) only if ACE inhibitor causes intolerable cough or angioedema 1

Critical ACE inhibitor initiation protocol: 4, 2

• Review and reduce diuretic dose 24 hours before starting to prevent excessive hypotension 4, 2
• Start with low dose (e.g., enalapril 2.5 mg twice daily) 4
• Monitor blood pressure, renal function, and electrolytes at baseline, 1-2 weeks after each dose adjustment, at 3 months, then every 6 months 1, 2
• Avoid NSAIDs and potassium-sparing diuretics during initiation 4, 2
• If switching from ACE inhibitor to sacubitril/valsartan, allow 36-hour washout period to prevent angioedema 3

2. Beta-Blockers

Use only evidence-based agents: carvedilol, metoprolol succinate (sustained-release), or bisoprolol—these specific agents reduce cardiovascular death and HF hospitalization 1, 2, 5

Start simultaneously with ACE inhibitor/ARNI, not sequentially 1, 2

• Begin with low doses and titrate every 2-4 weeks to target maintenance doses 1
• Target doses: carvedilol 25-50 mg twice daily, metoprolol succinate 200 mg daily, bisoprolol 10 mg daily 5

3. Mineralocorticoid Receptor Antagonists (MRAs)

Spironolactone or eplerenone should be used in all eligible HFrEF patients 1, 2

• Monitor potassium and renal function closely—hyperkalemia is the primary risk 1
• Contraindicated if baseline potassium >5.0 mEq/L or creatinine >2.5 mg/dL 5

4. SGLT2 Inhibitors

All HFrEF patients should receive SGLT2 inhibitors (dapagliflozin or empagliflozin) regardless of diabetes status, as they significantly reduce cardiovascular and all-cause mortality 1, 5

• This represents the most recent major advancement in HFrEF therapy 5

Symptomatic Management

Loop Diuretics

Required for all patients with signs or symptoms of fluid overload (pulmonary congestion, peripheral edema) to improve dyspnea and exercise tolerance 4, 1, 2

• Diuretics provide symptomatic relief but do not reduce mortality—they are not considered a "pillar" therapy 1
• Always combine with ACE inhibitor/ARNI 4
• Adjust dose according to volume status; avoid overdiuresis which causes hypotension 6
• Switch from thiazides to loop diuretics if eGFR <30 mL/min 2

Secondary/Additional Therapies for Persistent Symptoms

Hydralazine/Isosorbide Dinitrate

Indicated for patients intolerant to both ACE inhibitors and ARBs, particularly beneficial in self-described African American patients with NYHA class II-IV HF 1, 5

Ivabradine

Consider if heart rate remains ≥70 bpm despite maximally tolerated beta-blocker (or beta-blocker contraindicated), in patients with LVEF ≤35% in sinus rhythm 7, 5

• Reduces hospitalization for worsening HF 7
• Alternative if patient develops symptomatic hypotension preventing beta-blocker titration 6

Digoxin

May reduce HF hospitalizations in patients with persistent symptoms despite optimal therapy, though no mortality benefit 5

Vericiguat

Consider in patients with recent HF hospitalization or need for IV diuretics who remain symptomatic 5

Device Therapy Timing

Implantable Cardioverter-Defibrillator (ICD)

Indicated for primary prevention in patients with: 1, 2

• LVEF ≤35% despite ≥3 months of optimal medical therapy
• NYHA class II-III symptoms
• Expected survival >1 year with good functional status

Critical timing: Do NOT implant ICD within 40 days of myocardial infarction—it does not improve prognosis during this period 2

Cardiac Resynchronization Therapy (CRT)

Indicated for patients with: 1, 2

• Sinus rhythm with QRS ≥150 msec
• Left bundle branch block (LBBB) morphology
• LVEF ≤35% despite optimal medical therapy
• NYHA class II-IV symptoms

Critical Contraindications and Pitfalls

NEVER combine ACE inhibitor + ARB + MRA—this causes life-threatening hyperkalemia and renal dysfunction 1, 2

AVOID diltiazem and verapamil in HFrEF—they worsen heart failure and increase hospitalization risk 1, 2

Avoid excessive diuresis before initiating ACE inhibitors—volume depletion increases hypotension and acute kidney injury risk 2

Monitor for worsening renal function: If creatinine increases >30% or potassium >5.5 mEq/L, adjust doses or temporarily hold medications 4, 1

Management of Common Comorbidities

Iron Deficiency

Intravenous iron replacement recommended in patients with iron deficiency (ferritin <100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation <20%) to improve functional status and quality of life 5, 8

Diabetes Mellitus

SGLT2 inhibitors are preferred antidiabetic agents as they provide dual benefit for both diabetes and HF 4, 8

• Finerenone (non-steroidal MRA) recommended in T2DM with concomitant chronic kidney disease 4

Hypertension

Target blood pressure <130/80 mmHg if high cardiovascular risk 4

• Tight control reduces HF progression 4

Chronic Kidney Disease

Adjust medication doses based on eGFR and monitor closely 8

• SGLT2 inhibitors provide renal protection 8

Monitoring Schedule

Baseline before initiation: blood pressure, heart rate, weight, complete blood count, electrolytes (including calcium, magnesium), BUN, creatinine, fasting glucose, lipid profile, liver function tests, TSH, 12-lead ECG, chest X-ray, echocardiography 4

After each medication adjustment: blood pressure, renal function, electrolytes at 1-2 weeks 1, 2

Routine follow-up: at 3 months, then every 6 months 1, 2

Daily patient self-monitoring: weight (report gain >2-3 lbs in 1 day or >5 lbs in 1 week), symptoms of worsening dyspnea or edema 6

Non-Pharmacological Management

Patient education essentials: 4

• Explain what HF is and why symptoms occur 4
• Daily self-weighing and when to contact provider 4
• Sodium restriction (typically <2-3 g/day in severe HF) 4
• Fluid restriction (typically <2 L/day in severe HF) 4
• Avoid excessive alcohol intake 4
• Smoking cessation with nicotine replacement if needed 4

Exercise training programs recommended in stable NYHA class II-III patients to prevent muscle deconditioning 4

• Rest is NOT encouraged in stable conditions 4