What is the diagnosis and management for a patient with a left ventricular ejection fraction (LVEF) of 46% and septal and inferior wall hypokinesis?

Diagnosis and Management of LVEF 46% with Septal and Inferior Wall Hypokinesis

This patient has heart failure with mildly reduced ejection fraction (HFmrEF) with regional wall motion abnormalities suggestive of coronary artery disease, requiring comprehensive evaluation for ischemic etiology and initiation of guideline-directed medical therapy.

Diagnostic Classification

• LVEF of 46% classifies this patient as HFmrEF (LVEF 41-49%), which represents an intermediate category between HFrEF and HFpEF 1
• The presence of septal and inferior wall hypokinesis strongly suggests an ischemic etiology, as these regional wall motion abnormalities correspond to specific coronary territories (inferior wall typically reflects right coronary artery distribution; septal involvement suggests left anterior descending artery territory) 2, 3

Essential Diagnostic Workup

Immediate Evaluation Required

• 12-lead ECG and chest radiograph to assess for acute ischemic changes, prior infarction (Q waves), and pulmonary congestion 1
• Complete laboratory panel including CBC, comprehensive metabolic panel (electrolytes, calcium, magnesium, BUN, creatinine), fasting glucose/HbA1c, lipid profile, liver function tests, and thyroid-stimulating hormone 1
• Natriuretic peptides (BNP or NT-proBNP) to confirm heart failure diagnosis and establish baseline 1

Critical Assessment for Coronary Artery Disease

Coronary angiography is reasonable and should be strongly considered in this patient given the regional wall motion abnormalities suggesting ischemic cardiomyopathy, even in the absence of angina 1. The guidelines specifically state:

• Coronary arteriography is reasonable for patients with HF who have known or suspected coronary artery disease but do not have angina unless the patient is not eligible for revascularization 1
• The inferior and septal hypokinesis pattern is highly suggestive of prior myocardial infarction or chronic ischemia 2, 4
• Revascularization (particularly PCI including chronic total occlusion) has been shown to be a significant determinant of LVEF improvement in HFrEF patients, with similar principles applying to HFmrEF 2

Alternatively, noninvasive imaging to detect myocardial ischemia and viability (stress testing with imaging or cardiac MRI) is reasonable if coronary anatomy is unknown 1.

Guideline-Directed Medical Therapy

Foundational Pharmacotherapy

While evidence is strongest for HFrEF (LVEF ≤40%), the 2022 ACC/AHA/HFSA guidelines suggest weaker recommendations (Class 2b) for neurohormonal blockade in HFmrEF, but these medications should still be considered given the patient's reduced ejection fraction and regional dysfunction 1:

1. ACE inhibitor or ARB (or ARNI if symptoms persist)

   • Particularly important if the patient has diabetes, chronic kidney disease, or hypertension 1
   • Reduces cardiovascular mortality and morbidity 1

2. Beta-blocker

   • Especially indicated given the likely ischemic etiology 1
   • Reduces mortality in patients with systolic dysfunction 1

3. Mineralocorticoid receptor antagonist (MRA)

   • Consider if symptoms persist despite ACE inhibitor/ARB and beta-blocker 1
   • Monitor potassium and renal function closely 1

4. SGLT2 inhibitor

   • Has a Class 2a recommendation in HFmrEF per the 2022 guidelines 1
   • May be considered even in patients without diabetes 1

Lipid Management (If Ischemic Etiology Confirmed)

• High-intensity statin therapy with goal LDL-C <55 mg/dL (<1.4 mmol/L) or >50% reduction from baseline 1
• Add ezetimibe if LDL goal not achieved after 4-6 weeks of maximally tolerated statin 1
• Consider PCSK9 inhibitor if goals still not met despite statin plus ezetimibe 1

Device Therapy Considerations

• This patient does NOT currently meet criteria for ICD or cardiac resynchronization therapy with LVEF of 46% (threshold is ≤35% for primary prevention) 1, 5
• However, if LVEF remains ≤35% after ≥3 months of optimal medical therapy, reassess for ICD candidacy 1, 5
• If recent MI is identified, wearable cardioverter-defibrillator may be considered during the first 40 days when permanent ICD is not yet indicated 5

Common Pitfalls to Avoid

• Do not assume non-ischemic cardiomyopathy without ruling out coronary disease—the regional wall motion pattern strongly suggests ischemia 2
• Do not delay coronary evaluation waiting for symptoms; many patients with significant CAD and HF do not have angina 1
• Do not withhold neurohormonal therapy in HFmrEF despite weaker evidence; these patients often progress and benefit from early intervention 1
• Reassess LVEF after 3-6 months of optimal medical therapy, as improvement to >40% would reclassify the patient as HFimpEF (heart failure with improved ejection fraction), but therapy should be continued 1