What does an ejection fraction of 42% and fractional shortening of 21% on an echocardiogram indicate, and what is the optimal management?

EF 42% and FS 21%: Heart Failure with Mildly Reduced Ejection Fraction

Your patient has heart failure with mildly reduced ejection fraction (HFmrEF), and should be started on an SGLT2 inhibitor immediately, followed by consideration of additional guideline-directed medical therapy including ACE inhibitors/ARBs/ARNi, beta-blockers, and mineralocorticoid receptor antagonists.

What These Numbers Mean

An ejection fraction (EF) of 42% with fractional shortening (FS) of 21% indicates:

• Reduced left ventricular systolic function - EF of 42% falls into the HFmrEF category (LVEF 41-49%) 1
• The FS of 21% is at the lower limit of normal (normal typically >25%), which correlates with the mildly reduced EF 2
• This patient sits on the lower end of the HFmrEF spectrum, meaning they will likely respond similarly to patients with HFrEF (EF <40%) 1

The 2025 Canadian guidelines now recommend using the unified term "heart failure with nonreduced ejection fraction (HFnrEF)" for all patients with LVEF >40%, as they respond consistently to the same therapies 3.

Optimal Management Algorithm

First-Line Therapy (Start Immediately)

SGLT2 Inhibitor (empagliflozin or dapagliflozin)

• This is a Class 2a recommendation with the strongest evidence for HFmrEF 1, 3
• The EMPEROR-Preserved trial showed 21% reduction in HF hospitalization/cardiovascular death in patients with LVEF >40%, with greatest benefit at lower EF ranges 1
• Benefits include: reduced HF hospitalizations, slowed kidney function decline, and improved quality of life
• Works regardless of diabetes status

Second-Line Therapies (Add Sequentially)

Because your patient's EF of 42% is on the lower end of the HFmrEF spectrum, strongly consider adding:

1. ACE inhibitor, ARB, or ARNi (Class 2b) 1, 3

   • ARNi (sacubitril/valsartan) may be preferred if tolerated
   • Reduces HF hospitalization and cardiovascular mortality

2. Evidence-based beta-blocker (Class 2b) 1

   • Carvedilol, metoprolol succinate, or bisoprolol
   • Meta-analysis showed mortality benefit in patients with LVEF 40-49% 1
   • Higher doses correlate with better outcomes 4

3. Mineralocorticoid receptor antagonist (spironolactone or eplerenone) (Class 2b) 1, 3

   • Reduces HF hospitalization risk

Critical Management Points

Diuretics as needed for volume management (Class 1) 1

Repeat echocardiography at 6-12 months to assess LVEF trajectory 1, 4:

• LVEF improvement >10% (HFimpEF) predicts better outcomes
• Benefits emerge as early as 6 months 4
• If EF drops further into HFrEF range (<40%), intensify GDMT more aggressively

Important Caveats

• Don't wait for symptoms to worsen - the evidence supports treating HFmrEF proactively, especially at EF 42% 1
• Dose matters more than drug count - achieving higher doses of RAS inhibitors and beta-blockers is more important than simply checking boxes 4
• This is NOT preserved EF - while some older literature grouped EF 40-50% with HFpEF, current evidence shows these patients benefit from HFrEF-type therapies 1, 3
• The FS of 21% may underestimate myocardial dysfunction compared to EF due to geometric factors, particularly if there's any LV hypertrophy 5

The key is starting SGLT2i immediately and building a comprehensive GDMT regimen, with particular attention to adequate dosing rather than just drug selection.