An LVEF of 35-40% Indicates Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF), Now Classified as Heart Failure with Nonreduced Ejection Fraction (HFnrEF)
Yes, an echocardiographic LVEF of 35-40% indicates heart failure if accompanied by signs and symptoms of HF, and this patient should be treated with guideline-directed medical therapy for heart failure with nonreduced ejection fraction.
Understanding the Classification
The most recent 2025 Canadian guidelines have consolidated terminology to simplify clinical decision-making 1. Your patient with LVEF 35-40% falls into what was previously called "heart failure with mildly reduced ejection fraction" (HFmrEF), but is now unified under the term "heart failure with nonreduced ejection fraction" (HFnrEF) - defined as LVEF >40% 1.
However, there's an important nuance here: the 2022 ACC/AHA guidelines define HFrEF as LVEF ≤40% 2, 3, which means a patient with LVEF of 35-40% technically straddles the boundary between HFrEF and HFmrEF depending on which guideline you follow. The ESC 2016 guidelines similarly define HFrEF as LVEF ≤35% for device therapy considerations 4.
Diagnostic Requirements Beyond LVEF
LVEF alone is insufficient for diagnosis - you must also document:
- Signs and symptoms of heart failure (dyspnea, fatigue, edema, orthopnea, paroxysmal nocturnal dyspnea)
- Elevated natriuretic peptides (BNP or NT-proBNP) above age-specific thresholds 2, 3
- Structural or functional cardiac abnormalities on echocardiography (left atrial enlargement, increased LV mass, diastolic dysfunction) 5
The ESC specifically requires these additional objective measures beyond just symptoms and LVEF 4, 5.
Treatment Implications
For LVEF 35-40%, Initiate Foundational Therapies:
Tier 1 (Start immediately, in parallel if possible):
- SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10-25 mg daily) 1
- ACE inhibitor/ARB or ARNI (sacubitril-valsartan 24/26 mg twice daily, titrate to 97/103 mg twice daily) 1
- Beta-blocker (bisoprolol, metoprolol succinate, carvedilol, or nebivolol) 6
- Mineralocorticoid receptor antagonist (spironolactone 12.5-25 mg daily, target 25-50 mg daily) 1
The 2025 Canadian guidelines emphasize that contemporary evidence shows patients across the LVEF >40% spectrum respond consistently to these key pharmacotherapies 1. This represents a major shift - rather than treating LVEF 35-40% differently from LVEF 45%, we now recognize therapeutic consistency across this range.
Device Therapy Considerations:
For LVEF ≤35%, your patient qualifies for:
- ICD for primary prevention if symptomatic (NYHA Class II-III) after ≥3 months of optimal medical therapy, with expected survival >1 year 4, 6
- Cardiac resynchronization therapy (CRT) if QRS ≥150 ms with LBBB morphology (Class I recommendation) or QRS 130-149 ms with LBBB (also Class I) 4
Critical pitfall: Do not implant ICD within 40 days of MI - it does not improve prognosis during this period 4.
Monitoring and Trajectory
Reassess LVEF 3 months after completing medication titration 7. This is crucial because:
- Approximately 25% of patients with initial LVEF <40% will improve to >40% with optimal therapy - these patients have excellent prognosis 7
- If LVEF improves to >40%, the patient is reclassified as "HF with improved EF" (HFimpEF) but must continue all HFrEF medications to prevent relapse 2, 3
- Conversely, 25% of patients initially >40% may deteriorate to <40% 7
Common Pitfalls to Avoid
- Don't rely on a single LVEF measurement - the trajectory over time matters more than one absolute value 8, 9
- Don't delay SGLT2 inhibitors - they reduce cardiovascular mortality regardless of diabetes status and should be started early 10, 11
- Don't switch from ACE inhibitor to ARB for minor side effects - ACE inhibitors have stronger evidence; only switch if adverse effects are intolerable 6
- Don't forget to monitor potassium and renal function when adding MRA or ARB 6
- Don't assume normal natriuretic peptides exclude HF - they support diagnosis but normal levels don't rule it out, especially in obesity 2
The Bottom Line
A patient with LVEF 35-40% and symptoms/signs of heart failure definitively has heart failure and requires aggressive guideline-directed medical therapy. The exact classification (HFrEF vs HFmrEF vs HFnrEF) matters less than ensuring rapid initiation and uptitration of the four foundational drug classes that reduce mortality and hospitalization 1, 11.