What is the management for a 34-year-old male with reduced Left Ventricular Ejection Fraction (LVEF) of 45% and an otherwise normal echocardiogram?

Management of a 34-Year-Old Male with LVEF 45% and Otherwise Normal Echocardiogram

For a 34-year-old male with LVEF 45% (mildly reduced ejection fraction) and an otherwise normal echocardiogram, treatment with an SGLT2 inhibitor is strongly recommended as first-line therapy, followed by evidence-based beta-blockers, ACE inhibitors/ARBs, and mineralocorticoid receptor antagonists. 1

Classification and Significance

• This patient has heart failure with mildly reduced ejection fraction (HFmrEF), defined as LVEF 41-49% according to current guidelines 1
• HFmrEF represents a distinct category between HFrEF (LVEF ≤40%) and HFpEF (LVEF ≥50%) 1
• Patients with mildly reduced LVEF are at increased risk for disease progression, clinical deterioration, and sudden death compared to those with normal LVEF 2, 3

Treatment Recommendations

First-Line Therapy

• SGLT2 inhibitors have a Class 2a recommendation (moderate strength) for HFmrEF and should be initiated first to decrease heart failure hospitalizations and cardiovascular mortality 1
• Diuretics should be prescribed as needed for symptom management and fluid retention 1

Additional Pharmacological Therapy (Class 2b recommendations)

• Evidence-based beta-blockers (bisoprolol, carvedilol, or sustained-release metoprolol succinate) should be initiated, particularly since the patient is young and has reduced LVEF 1
• ACE inhibitors or ARBs should be added to the regimen to reduce the risk of heart failure progression 1
• Mineralocorticoid receptor antagonists (MRAs) like spironolactone should be considered, particularly for patients with LVEF on the lower end of the HFmrEF spectrum 1, 4
• Angiotensin receptor-neprilysin inhibitors (ARNi) may be considered as an alternative to ACE inhibitors/ARBs 1

Medication Titration Strategy

• Start with SGLT2 inhibitor and add other medications sequentially 1
• Target maximum tolerated doses of each medication before adding the next agent 1
• Monitor renal function, electrolytes, and blood pressure regularly during medication initiation and titration 1

Additional Considerations

Diagnostic Evaluation

• Investigate potential underlying causes of reduced LVEF, including:
  • Coronary artery disease (most common cause of HFmrEF) 1, 5
  • Hypertension 1
  • Cardiomyopathy, including genetic causes given the young age 1
  • Valvular heart disease (though noted as normal on echocardiogram) 5

Monitoring

• Regular follow-up echocardiograms are essential as LVEF in HFmrEF patients can be dynamic:
  • Patients may improve to normal LVEF or deteriorate to HFrEF 6
  • The HFmrEF category is particularly unstable, with <25% of patients remaining in this category after one year 6

Special Considerations for Young Patients

• For a 34-year-old male, aggressive medical therapy is warranted given:
  • Longer life expectancy and cumulative risk of heart failure progression 2
  • Higher likelihood of improvement with optimal medical therapy 1
  • Greater risk of sudden cardiac death with even mildly reduced LVEF 3

Potential Pitfalls and Caveats

• Do not assume stability of LVEF - patients with mildly reduced LVEF have significant variability over time and require close monitoring 6
• Avoid calcium channel blockers with negative inotropic effects (verapamil, diltiazem) as they may worsen ventricular function 1
• Be vigilant for tachyarrhythmias, particularly atrial fibrillation, which can exacerbate or cause cardiomyopathy 1
• Consider ICD therapy only if LVEF deteriorates to ≤35% despite optimal medical therapy 1

Follow-up Recommendations

• Reassess LVEF after 3-6 months of optimal medical therapy 1
• If LVEF improves to >50%, continue HFmrEF treatment as "HF with improved EF" 1
• If LVEF deteriorates to ≤40%, intensify therapy according to HFrEF guidelines 1