What is the management approach for a patient with low ejection fraction?

Management of Low Ejection Fraction (Heart Failure with Reduced Ejection Fraction)

All patients with heart failure and reduced ejection fraction (HFrEF, LVEF ≤40%) should be initiated on four foundational medication classes as quickly as possible: SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and renin-angiotensin system (RAS) inhibitors, with the goal of maximizing survival and reducing hospitalizations. 1, 2, 3

Initial Medication Initiation Strategy

Start with SGLT2 inhibitors and MRAs first, as these have minimal blood pressure-lowering effects while providing significant mortality benefits 1, 2:

• SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be initiated immediately, even during hospitalization for acute decompensated heart failure 2
• MRAs (spironolactone 12.5-25 mg daily or eplerenone 25 mg daily) should be started concurrently if eGFR >30 mL/min/1.73m² and potassium <5.0 mEq/L 2, 4

Next, add beta-blockers and RAS inhibitors based on heart rate and blood pressure tolerance 2:

• Beta-blockers (metoprolol succinate, carvedilol, or bisoprolol) should be initiated if heart rate >70 bpm, starting at low doses 1, 2, 3
• RAS inhibitors (ACE inhibitors, ARBs, or preferably ARNI/sacubitril-valsartan) should be started at low doses and titrated up gradually 1, 2, 3

Diuretic Management

• Loop diuretics should be used for symptom relief in patients with fluid retention, with doses adjusted based on volume status 1, 2
• Diuretic doses should be reduced when initiating ACE inhibitors to prevent excessive hypotension 2

Titration Approach

Titrate medications gradually to target doses proven effective in clinical trials, though early benefits occur even at low doses 5:

• Monitor renal function and electrolytes 1-2 weeks after each dose increment of RAS inhibitors and MRAs 2
• The proven benefits in trials were achieved with average doses below target, so some benefit occurs even if target doses cannot be reached 5
• Prioritize getting all four medication classes on board over achieving target doses of individual medications 1, 5

Managing Low Blood Pressure

Asymptomatic or mildly symptomatic low blood pressure (systolic BP 80-100 mmHg) should NOT be a reason to reduce or stop guideline-directed medical therapy (GDMT) 1:

• SGLT2 inhibitors and MRAs have minimal BP effects and may actually increase BP in some patients with low baseline pressures 1
• Only consider medication reduction if systolic BP <80 mmHg or if low BP causes significant symptoms (dizziness, syncope, organ hypoperfusion) 1

If medication adjustment is necessary due to symptomatic hypotension 1:

• First, discontinue unnecessary non-cardiac medications that lower BP (alpha-blockers for prostate, certain antidepressants) 1
• Look for reversible causes (dehydration, excessive diuresis, infection, anemia) 1
• If heart rate >70 bpm: reduce ACE inhibitor/ARB/ARNI dose first 1
• If heart rate <60 bpm: reduce beta-blocker dose first 1
• Maintain SGLT2 inhibitors and MRAs whenever possible 1
• When BP improves, always attempt to reinitiate medications that were reduced, starting with the better-tolerated agents 1

Monitoring and Follow-Up

• Close follow-up within 1-2 weeks after medication initiation or dose changes 2
• Monitor blood pressure, heart rate, symptoms, weight, renal function (creatinine, eGFR), and electrolytes (potassium) 2, 4
• Assess for signs of fluid retention or worsening heart failure at each visit 1, 2

Special Populations and Considerations

For patients with eGFR <30 mL/min/1.73m² 2:

• Reduce or avoid MRAs
• Adjust RAS inhibitor dosing
• SGLT2 inhibitors should not be initiated but may be continued if already established 2

For patients with hyperkalemia (K+ >5.0 mEq/L) 2, 4:

• Reduce MRA dose first
• Ensure adequate diuresis
• Consider potassium binders if needed to maintain GDMT

For patients with persistent hypotension preventing GDMT optimization 1:

• Refer early to heart failure specialist or advanced therapy programs
• Consider device therapies (CRT if QRS ≥130 ms with LBBB morphology) 6
• Evaluate for advanced therapies if refractory 1

Additional Therapies

For patients with NYHA class III-IV symptoms despite optimal GDMT 4:

• Spironolactone specifically reduces mortality by 30% and cardiac hospitalizations by 30% in this population 4
• Consider ivabradine if heart rate remains >70 bpm despite maximally tolerated beta-blocker dose 6, 7
• Digoxin may be used for symptom control but has no mortality benefit 7

Critical Pitfalls to Avoid

• Do not defer SGLT2 inhibitor initiation to the outpatient setting—start during hospitalization to reduce early post-discharge mortality 2
• Do not withhold or reduce GDMT for asymptomatic low BP readings—this compromises long-term survival 1
• Do not use inadequate doses without attempting titration—aim for target doses when tolerated 8, 5
• Do not fail to refer patients with persistent inability to optimize GDMT to heart failure specialists 1
• Do not use non-evidence-based beta-blockers (atenolol, propranolol)—only metoprolol succinate, carvedilol, or bisoprolol have proven mortality benefits 9