What is the recommended treatment for a patient with severe left ventricular systolic dysfunction and a reduced ejection fraction?

Treatment of Severe Left Ventricular Systolic Dysfunction (LVEF 25-30%)

All patients with heart failure and reduced ejection fraction (HFrEF) should be initiated on four medication classes simultaneously at low doses—ACE inhibitor (or ARB/ARNI), beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor—then uptitrated every 2-4 weeks to target doses, rather than optimizing medications sequentially. 1, 2, 3

Foundational Quadruple Therapy

ACE Inhibitor (or ARB if ACE-I intolerant)

• Start immediately in all symptomatic patients with LVEF <40%, which reduces cardiovascular death and hospitalization by 15-25% 4, 2, 3
• Before initiating, review and potentially reduce diuretic dose 24 hours prior to avoid excessive volume depletion, which increases risk of hypotension and acute kidney injury 2, 3
• Monitor blood pressure, renal function (creatinine), and electrolytes (potassium) at baseline, 1-2 weeks after initiation, 1-2 weeks after each dose increase, then every 6 months 4, 2
• Target doses proven in trials: enalapril 10-20 mg twice daily, lisinopril 20-40 mg daily, or ramipril 5-10 mg daily 4

Beta-Blocker

• Initiate simultaneously with ACE inhibitor using evidence-based agents: carvedilol, metoprolol succinate, or bisoprolol 4, 1, 3
• These agents reduce mortality by at least 20% and specifically reduce sudden cardiac death 4, 1, 3
• Start with very low doses and double every 1-2 weeks if tolerated, targeting maintenance doses from large trials 1
• Ensure patient is relatively stable without intravenous inotropic support or marked fluid retention before initiating 1
• If worsening symptoms occur during titration, increase diuretics or ACE inhibitors first before reducing beta-blocker dose 1
• For hypotension during titration, reduce vasodilators first rather than the beta-blocker 1

Mineralocorticoid Receptor Antagonist (MRA)

• Add spironolactone or eplerenone as soon as possible for patients with persistent symptoms despite ACE inhibitor and beta-blocker therapy 4, 1, 3
• Start with spironolactone 25 mg daily if serum potassium <5.0 mmol/L and creatinine <250 μmol/L 1
• Provides meaningful mortality reduction (≥20%) and reduces sudden death risk 4, 3
• Check potassium and creatinine after 4-6 days of initiation; reduce dose by 50% or stop if potassium persistently elevated 1

SGLT2 Inhibitor

• Initiate early regardless of diabetes status as the fourth pillar of therapy 1, 3
• Reduces cardiovascular death and heart failure hospitalization 1, 5

Symptomatic Management

Loop Diuretics

• Use for all patients with signs or symptoms of fluid overload (trace-mild mitral regurgitation, trace-mild tricuspid regurgitation, and bilateral atrial dilation suggest volume overload) 2, 3
• Improves symptoms and exercise capacity but does not prolong survival 2, 3
• Avoid excessive diuresis before initiating ACE inhibitors 2

Device Therapy Considerations

Implantable Cardioverter-Defibrillator (ICD)

• Recommend ICD for primary prevention when LVEF ≤35% despite ≥3 months of optimal medical therapy, NYHA Class II-III, and expected survival >1 year 2, 3
• Do not implant within 40 days of myocardial infarction as it does not improve prognosis during this period 2

Cardiac Resynchronization Therapy (CRT)

• Consider CRT if patient remains symptomatic despite optimal medical therapy with QRS ≥150 msec, LBBB morphology, and LVEF ≤35% 2

Surgical/Interventional Options

Coronary Revascularization

• CABG or percutaneous intervention is indicated for patients on guideline-directed medical therapy with angina and suitable coronary anatomy, especially for left main stenosis >50% or left main equivalent disease 4
• CABG to improve survival is reasonable in patients with mild to moderate LV systolic dysfunction and significant multivessel CAD when viable myocardium is present 4

Transcatheter Mitral Valve Repair

• May be considered in patients with severe secondary mitral regurgitation, though benefit is uncertain 4, 5

Critical Contraindications

• Never combine ACE inhibitor with ARB and MRA simultaneously—this causes life-threatening hyperkalemia and renal dysfunction 4, 2, 3
• Avoid diltiazem and verapamil in HFrEF as they worsen heart failure and increase hospitalization risk 2
• Avoid digoxin in patients with bradycardia, second- or third-degree AV block, sick sinus syndrome, and electrolyte abnormalities 1

Monitoring Protocol

• Check blood pressure, renal function, and electrolytes at baseline, 1-2 weeks after each medication adjustment, at 3 months, then every 6 months 2, 3
• Refer to specialist care for severe heart failure, bradycardia, low blood pressure, or suspected asthma/bronchial disease 1

Prognosis Context

• With this degree of severe LV systolic dysfunction (LVEF 25-30%), 5-year survival after hospitalization is approximately 25% without optimal therapy 5
• However, guideline-directed medical therapy dramatically improves outcomes, with potential for improvement in ejection fraction (HFimpEF) in a substantial proportion of patients 6
• Patients with mild to moderate LV systolic dysfunction (EF 0.25-0.50) should undergo intervention, as severely symptomatic patients (NYHA Class IV) with advanced LV dysfunction (EF <0.25) have mortality approaching 10% with valve replacement, but this is still better than medical management alone 4