What is the prognosis for a patient with heart failure and a left ventricular ejection fraction (LVEF) of 35%?

Prognosis for Heart Failure with Ejection Fraction of 35%

A patient with heart failure and LVEF of 35% faces substantial mortality risk, with approximately 75% mortality at 5 years, though prognosis can be significantly improved with optimal medical therapy including ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors. 1, 2

Baseline Mortality Risk

• Five-year mortality for HFrEF (LVEF ≤40%) is approximately 75%, which is markedly elevated compared to the general population across all age groups 1
• Median survival after hospitalization for HFrEF is only 2.1 years overall, with post-hospitalization 5-year survival as low as 25% 1, 2
• At an LVEF of 35%, mortality risk falls in the intermediate range within the HFrEF spectrum—lower than patients with LVEF ≤15% (51.7% mortality) but higher than those with LVEF 36-45% (25.6% mortality) 3
• Mortality decreases in near-linear fashion as LVEF increases from 15% up to 45%, but improvements above 45% do not confer additional survival benefit 3

Impact of Optimal Medical Therapy

Guideline-directed medical therapy dramatically alters the natural history of HFrEF and must be implemented aggressively:

Foundational Pharmacotherapy (Class I Recommendations)

• ACE inhibitor (or ARB if ACE-I intolerant) plus beta-blocker are mandatory first-line agents that reduce both HF hospitalization and death 4
• Mineralocorticoid receptor antagonist (MRA) should be added for patients remaining symptomatic despite ACE-I and beta-blocker to further reduce hospitalization and mortality 4
• Sacubitril/valsartan should replace ACE-I in ambulatory patients with persistent symptoms despite optimal therapy with ACE-I, beta-blocker, and MRA to further reduce HF hospitalization and death 4
• SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality irrespective of diabetes status and represent a major recent breakthrough 2

Device Therapy Considerations

For patients with LVEF ≤35% who remain symptomatic (NYHA Class II-III) despite ≥3 months of optimal medical therapy:

• ICD implantation is Class I-A recommendation for ischemic cardiomyopathy (unless MI occurred within prior 40 days) to reduce sudden death and all-cause mortality 4
• ICD is Class I-B recommendation for dilated cardiomyopathy patients meeting the same criteria 4
• Cardiac resynchronization therapy (CRT) is Class I-A recommendation for patients in sinus rhythm with QRS ≥150 msec and LBBB morphology to improve symptoms and reduce morbidity and mortality 4
• CRT is Class I-B for QRS 130-149 msec with LBBB morphology 4

Potential for LVEF Recovery

• Approximately 24.5% of HFrEF patients demonstrate LVEF recovery (defined as second LVEF >40% with ≥10% absolute improvement) 5
• HFrEF patients with recovered ejection fraction (HFrecEF) have significantly better outcomes: 8.1% mortality versus 18.8% in persistent HFrEF, and 26.8% rehospitalization versus 48.6% 5
• Recovery confers lower mortality risk at 12 and 24 months, with hazard ratio of 2.30 for persistent HFrEF versus HFrecEF 5
• Greater degrees of LVEF improvement (≥20% versus 10-20%) correlate with better outcomes 5

Modes of Death

Leading causes of death occur across all LVEF ranges but vary in absolute risk:

• Patients with lower LVEF face increased absolute risk of arrhythmic death and death from worsening heart failure 3
• However, arrhythmia and progressive HF remain leading causes of death even at higher LVEF values within the HFrEF spectrum 3
• This underscores the importance of both ICD therapy for sudden death prevention and optimal medical therapy for HF progression 4, 3

Critical Pitfalls to Avoid

• Do not delay ICD implantation within 40 days of MI—this timing does not improve prognosis and is contraindicated (Class III-A) 4
• Avoid diltiazem or verapamil (Class III-C)—these increase risk of HF worsening and hospitalization 4
• Avoid NSAIDs/COX-2 inhibitors (Class III-B) and thiazolidinediones (Class III-A)—both increase HF worsening and hospitalization risk 4, 6
• Do not add ARB to combination of ACE-I plus MRA (Class III-C) due to increased risk of renal dysfunction and hyperkalemia 4
• Right ventricular pacing alone worsens outcomes in patients with systolic dysfunction—use CRT instead when pacing is needed 4

Monitoring Strategy

• Serial natriuretic peptide measurements (BNP/NT-proBNP) guide therapy optimization and assess treatment response 4, 7
• Regular cardiac rhythm monitoring is essential as atrial fibrillation risk increases with HFrEF and certain therapies 4
• Repeat echocardiography at appropriate intervals to assess for LVEF recovery and ventricular remodeling 7, 5