Is an ejection fraction (EF) of 35% concerning?

Is an Ejection Fraction of 35% Concerning?

Yes, an ejection fraction (EF) of 35% is concerning and represents significant left ventricular systolic dysfunction that requires comprehensive heart failure management and consideration for advanced therapies including implantable cardioverter-defibrillator (ICD) therapy. 1

Clinical Significance of EF 35%

An EF of 35% places patients at a critical threshold where multiple guideline-based interventions become indicated:

• This represents heart failure with reduced ejection fraction (HFrEF), defined as LVEF ≤40%, and specifically sits at the cutoff used in major clinical trials for device therapy eligibility 1
• Mortality risk increases substantially below 45% EF, with a 39% increase in hazard ratio for all-cause mortality for every 10% reduction in ejection fraction below this threshold 2
• The relationship between EF and mortality is strongest in the range below 45%, after which risk plateaus, making 35% a particularly high-risk value 2

Immediate Management Priorities

Pharmacologic Therapy

Guideline-directed medical therapy (GDMT) must be optimized immediately:

• ACE inhibitors or ARBs should be initiated and titrated to target doses, with close monitoring of renal function and potassium 1, 3, 4
• Evidence-based beta-blockers (bisoprolol, metoprolol succinate, carvedilol, or nebivolol) are essential and reduce mortality in this population 1, 3
• Aldosterone antagonists should be added as second-line therapy for patients who remain symptomatic despite first-line treatment 1

Device Therapy Evaluation

At EF ≤35%, patients meet criteria for consideration of life-saving device therapies:

• ICD therapy for primary prevention is indicated in patients with EF ≤35% who have coronary artery disease or other structural heart disease, as this threshold was used as an inclusion criterion in major randomized trials demonstrating mortality benefit 1
• The benefit of ICD implantation increases as ejection fraction decreases below 35%, with patients having EF <30% showing larger mortality reductions (HR 0.72) compared to those with EF 30-35% (HR 0.83) 1
• Cardiac resynchronization therapy (CRT) should be evaluated if QRS duration is ≥120 ms, particularly if ≥150 ms or if mechanical dyssynchrony is present on echocardiography 1

Risk Stratification Considerations

Several factors modify the significance of EF 35%:

• Age matters: In patients ≥75 years, primary prevention ICD still shows a 24% reduction in mortality hazard ratio, though absolute benefit may be lower due to competing comorbidities 1
• Comorbidities influence outcomes: Patients with chronic kidney disease, COPD, or diabetes still derive survival benefit from ICD therapy (HR 0.72), though end-stage renal disease patients have less clear benefit 1
• Etiology is relevant: The vast majority (81%) of evidence for device therapy comes from patients with coronary artery disease, though benefits extend to other etiologies 1

Prognostic Implications

The absolute risk at EF 35% is substantial:

• Three-year mortality in patients with EF ≤20% approaches 74%, and while EF 35% carries lower risk, it remains in the high-risk category requiring aggressive intervention 5
• Once EF falls below 20%, further reductions in EF lose predictive value, but at 35%, EF remains a powerful predictor of outcomes 5, 2
• Sudden cardiac death risk is particularly elevated, with absolute rates declining significantly as EF improves above 35% 2

Monitoring and Reassessment

Serial assessment is critical because EF trajectory matters:

• Improvement in EF above 35% after one year of therapy (particularly with CRT) predicts excellent long-term survival and very low risk of sudden cardiac death 6
• Patients whose EF improves to >35% with treatment have significantly better freedom from all-cause mortality (92% vs 81%), cardiovascular mortality, and sudden death compared to those remaining ≤35% 6
• Serial echocardiography should be performed to monitor ventricular function and remodeling, as changes in LVEF may not be unidirectional 7

Common Pitfalls to Avoid

Critical errors in managing patients with EF 35%:

• Do not delay device therapy evaluation while attempting to optimize medical therapy alone—these interventions should proceed in parallel for eligible patients 1
• Avoid nondihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with EF ≤35%, as they have negative inotropic effects and may worsen outcomes 7
• Do not assume patients with EF near 35% are "borderline"—this is a validated threshold for high-risk interventions based on robust trial data 1
• Recognize that pregnant patients with EF <35% are particularly heart rate-dependent for augmenting cardiac output and require close monitoring if heart rate-lowering therapies are used 8