How does ejection fraction relate to heart failure treatment?

EPSS and Ejection Fraction: Clinical Relationship

EPSS (E-point septal separation) is an M-mode echocardiographic measurement that inversely correlates with left ventricular ejection fraction—as EPSS increases, ejection fraction decreases—making it a useful screening tool for identifying reduced ejection fraction, though ejection fraction itself is the primary determinant of heart failure classification and treatment strategy.

Understanding the Relationship

EPSS as a Marker of Systolic Function

• EPSS measures the distance between the anterior mitral valve leaflet at peak opening (E-point) and the interventricular septum during early diastole 1
• An EPSS >7mm typically indicates reduced ejection fraction (<50%), while EPSS >10mm strongly suggests severe systolic dysfunction (EF <30%) 1
• The inverse relationship exists because reduced contractility causes the left ventricle to remain dilated, preventing the mitral valve from approaching the septum during diastolic filling 1

Clinical Significance of Ejection Fraction Classification

Heart failure is fundamentally classified by ejection fraction, which directly determines treatment approach 1:

• HFrEF (Heart Failure with Reduced EF): LVEF ≤40% 1
• HFmrEF (Heart Failure with Mid-Range EF): LVEF 40-49% 2
• HFpEF (Heart Failure with Preserved EF): LVEF ≥50% 1

Treatment Implications Based on Ejection Fraction

For HFrEF (Where EPSS Would Be Elevated)

Quadruple guideline-directed medical therapy provides 73% mortality reduction over 2 years and should be initiated simultaneously 3:

1. SGLT2 inhibitors (minimal BP effect, maintain even with hypotension) 4, 3
2. ARNI (sacubitril/valsartan) or ACE inhibitor (target ARNI 97/103mg twice daily) 3, 5
3. Beta-blockers (carvedilol 25-50mg twice daily or equivalent) 3
4. Mineralocorticoid receptor antagonists (spironolactone 25-50mg daily) 3

Uptitrate every 1-2 weeks using forced-titration strategy to achieve optimal therapy within 2 months 3.

For HFpEF (Where EPSS Would Be Normal)

Management focuses on SGLT2 inhibitors for mortality benefit, symptom control with diuretics, and aggressive comorbidity management 1:

• SGLT2 inhibitors reduce cardiovascular death and HF hospitalizations in HFpEF 1
• No other disease-modifying therapies have proven effective 1
• Treatment of hypertension, diabetes, and obesity is essential 1

Critical Limitations of EPSS and Ejection Fraction

EPSS Limitations

• EPSS can be falsely normal in patients with mitral stenosis, severe mitral regurgitation, or regional wall motion abnormalities 1
• EPSS should not replace formal ejection fraction measurement for treatment decisions 1

Ejection Fraction Limitations

Left ventricular ejection fraction is increasingly recognized as a poor predictor of prognosis and insensitive to subtle changes of early disease 1:

• LVEF fails to risk stratify patients with HFpEF adequately 1
• LVEF is a variable measure requiring clinical judgment in treatment decisions 5
• Myocardial strain and strain rate are more sensitive markers of myocardial dysfunction 1

Sex-Based Differences

Women are far more likely to develop HFpEF (normal EPSS) while men more commonly have HFrEF (elevated EPSS) 1:

• HFrEF is more prevalent in men, typically from ischemic cardiomyopathy 1
• Women develop HFpEF more often due to hypertensive or valvular disease 1
• Women may have higher response rates to cardiac resynchronization therapy in HFrEF 1

Common Pitfalls to Avoid

Never discontinue guideline-directed medical therapy for asymptomatic or mildly symptomatic low blood pressure, as this compromises long-term outcomes 1, 4, 3:

• Treatment with GDMT weakens the association between low BP and worse prognosis in HFrEF 1
• Accept modest creatinine increases (up to 30% above baseline) during GDMT optimization 3
• SGLT2 inhibitors and MRAs have minimal BP effects and should be maintained 4, 3

Never discontinue GDMT even if ejection fraction improves to normal, as discontinuation leads to clinical deterioration 3, 6:

• HFimpEF (improved ejection fraction) patients who stop therapy experience recrudescence of systolic dysfunction 6
• Improvement in LVEF decreases mortality but requires continued treatment 6

Monitoring Strategy

Close follow-up within 1-2 weeks after medication adjustments with monitoring of BP, heart rate, renal function, and electrolytes 4, 3:

• Serial echocardiography and biomarkers (BNP, troponin) help identify early dysfunction 1
• Consider advanced imaging with strain analysis for subtle changes not detected by LVEF 1