What is the recommended management for a patient with severe left‑ventricular dysfunction (ejection fraction ≤35%)?

Management of Severe Left Ventricular Dysfunction (LVEF ≤35%)

For patients with LVEF ≤35%, you must immediately initiate quadruple guideline-directed medical therapy (GDMT) and simultaneously evaluate for device therapy—these interventions run in parallel, not sequentially. 1, 2

Immediate Pharmacologic Therapy (Start All Four Classes)

First-Line Neurohormonal Blockade

• ACE inhibitors (or ARNi if tolerated) must be started immediately and titrated to target doses with monitoring of renal function and potassium every 1-2 weeks during uptitration 2, 3

  • Lisinopril demonstrated mortality benefit in post-MI patients with LV dysfunction, with target dosing of 10-20 mg daily 4
  • ARNi (sacubitril/valsartan) is preferred over ACE inhibitors when tolerated, as it provides superior outcomes 5

• Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) reduce mortality by approximately 35% and must be initiated regardless of symptom severity 2, 3

  • Carvedilol showed 23% mortality reduction (HR 0.77,95% CI 0.60-0.98) in post-MI patients with LVEF ≤40% in the CAPRICORN trial 6
  • Target dose: carvedilol 25 mg twice daily, metoprolol succinate 200 mg daily, or bisoprolol 10 mg daily 1

• Mineralocorticoid receptor antagonists (spironolactone or eplerenone) should be added as second-line therapy for patients who remain symptomatic despite ACE inhibitor and beta-blocker 2, 3

  • Monitor potassium and creatinine closely; avoid if K+ >5.0 mEq/L or eGFR <30 mL/min 3

• SGLT2 inhibitors (dapagliflozin or empagliflozin) reduce cardiovascular mortality independent of diabetes status and should be started in all patients 3, 5

  • This represents the most recent advancement in HFrEF therapy with significant mortality benefit 5

Common Pitfalls in Medical Therapy

• Do not delay device evaluation while attempting to optimize medical therapy—these must proceed in parallel 2
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) entirely in patients with LVEF ≤35% due to negative inotropic effects 3
• Clinical inertia is a major barrier: up to 50% of patients do not reach target doses for unknown reasons, suggesting both provider and patient hesitancy 7
• Hypotension, bradycardia, renal dysfunction, and hyperkalemia are the main physiologic barriers to uptitration, but these should be managed aggressively rather than accepting suboptimal dosing 7

Device Therapy Evaluation (Initiate Within 90 Days)

ICD for Primary Prevention of Sudden Cardiac Death

ICD therapy is Class I recommendation (highest level) for patients with LVEF ≤35% who meet specific criteria 1, 2:

• For NYHA Class II or III symptoms: ICD is indicated if patient has reasonable expectation of meaningful survival >1 year and is at least 40 days post-MI (for ischemic cardiomyopathy) 1
• For NYHA Class I symptoms: ICD is indicated if LVEF ≤30% (note the lower threshold) and patient is at least 40 days post-MI 1
• Economic value is highest when risk of arrhythmic death is high and risk of non-arrhythmic death is low based on comorbidity burden 1

Timing of ICD Decision

• The conventional 3-month window for ICD decision-making remains appropriate even with modern GDMT including ARNI and SGLT2 inhibitors 8
• In a 2025 prospective study, 58% of patients achieved LVEF >35% by 3 months with intensive GDMT, but among those who remained ≤35% at 3 months, only 18% recovered by 12 months 8
• This means: if LVEF remains ≤35% after 3 months of optimal GDMT, proceed with ICD implantation without further delay 8

Cardiac Resynchronization Therapy (CRT)

CRT is Class I recommendation for patients with LVEF ≤35%, sinus rhythm, LBBB with QRS ≥150 ms, and NYHA Class II-IV symptoms 1, 3:

• CRT reduces total mortality, hospitalizations, and improves symptoms and quality of life 1
• CRT provides high economic value (Class I, Level B-NR) in this population 1
• For non-LBBB patterns with QRS ≥150 ms, CRT is Class IIa (reasonable) 1
• For QRS 120-149 ms with LBBB, CRT is Class IIa; for non-LBBB patterns at this QRS duration, CRT is Class IIb (may be considered) 1

CRT in Atrial Fibrillation

• CRT can be useful in AF patients with LVEF ≤35% if you ensure near 100% biventricular pacing (Class IIa) 1, 3
• This requires either pharmacologic rate control achieving >90-95% biventricular pacing OR AV nodal ablation 3
• AF with rapid ventricular response is the leading cause of inadequate biventricular pacing and will negate CRT benefit 3
• Plan for AV nodal ablation upfront if pharmacologic rate control is unlikely to achieve adequate pacing percentage 3

Device Therapy Contraindications

• Do not implant ICD or CRT if life expectancy <1 year due to comorbidities or frailty 1
• Do not implant CRT if QRS duration <120 ms (Class III, harm) 1
• For NYHA Class I-II with non-LBBB pattern and QRS <150 ms, CRT is not recommended 1

Revascularization Considerations

When to Consider Revascularization

For patients with ischemic cardiomyopathy and LVEF ≤35%, a Heart Team should evaluate for revascularization 1, 3:

• CABG is Class IIa (reasonable) to improve morbidity and mortality in patients with severe LV dysfunction (EF <35%) and significant multivessel CAD 1
• CABG provides greater benefit than medical therapy alone when viable myocardium is present in the territory of intended revascularization 1, 3
• Consider CABG even without proven viability if operable coronary anatomy exists (Class IIb) 1

Revascularization Decision Algorithm

1. Confirm presence of significant CAD (≥70% stenosis in major vessels or ≥50% left main) 1
2. Assess for viable myocardium using stress imaging or PET 3
3. Evaluate surgical risk and comorbidities via Heart Team discussion 3
4. If left main stenosis or multivessel disease with viable myocardium: proceed with CABG 1, 3
5. Use FFR/iFR to guide lesion selection in multivessel disease 3

Risk Stratification and Special Populations

Age Considerations

• In patients ≥75 years, primary prevention ICD still shows 24% mortality reduction, though absolute benefit may be lower due to competing comorbidities 2
• Age alone should not exclude device therapy if functional status and comorbidities permit meaningful survival >1 year 2

Comorbidity Impact

• Patients with CKD, COPD, or diabetes still derive survival benefit from ICD therapy (HR 0.72), though end-stage renal disease patients have less clear benefit 2
• Increasing age, higher baseline EF (within the ≤35% range), atrial fibrillation, COPD, prior stroke, and dementia are associated with decreased GDMT use in real-world practice 9

Post-Sepsis LV Dysfunction

• Sepsis survivors with LVSD benefit from standard GDMT, with 89% (8/9 patients) demonstrating LV recovery (mean LVEF improvement 16±11%) after 6 months of therapy 10
• Treat post-sepsis LVSD identically to other forms of HFrEF with full GDMT 10

Monitoring and Follow-Up

Echocardiographic Reassessment

• Repeat echocardiography at 3 months after initiating GDMT to reassess LVEF and guide ICD decision 8
• If LVEF improves to >35%, defer ICD but continue GDMT and monitor closely 8
• If LVEF remains ≤35% at 3 months, proceed with ICD implantation as further improvement by 12 months is unlikely (only 18% recovery rate) 8

Laboratory Monitoring During Uptitration

• Check renal function and electrolytes every 1-2 weeks during ACE inhibitor/ARNi and MRA uptitration 2
• Monitor for hypotension (target SBP >90 mmHg), bradycardia (target HR >50 bpm), hyperkalemia (K+ <5.0 mEq/L), and worsening renal function (Cr increase <0.3 mg/dL acceptable) 4, 7

Device Follow-Up

• For CRT patients, check biventricular pacing percentage at every follow-up with target ≥90-95% 3
• If pacing percentage is inadequate, optimize AV/VV intervals, consider rate control intensification, or proceed with AV nodal ablation 3