What is the initial treatment approach for patients with Heart Failure with mid-range Ejection Fraction (HFmrEF)?

Initial Treatment Approach for Heart Failure with Mid-Range Ejection Fraction (HFmrEF)

The initial treatment approach for patients with Heart Failure with mid-range Ejection Fraction (HFmrEF, LVEF 40-49%) should follow the same core medication strategy as HFrEF, including SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and ACEi/ARB/ARNi. 1

Understanding HFmrEF

HFmrEF represents a distinct subgroup of heart failure patients with characteristics that are often intermediate between HFrEF and HFpEF:

• HFmrEF accounts for approximately 25-27% of all heart failure patients 2, 3
• Most HFmrEF patients (73%) represent improved HFrEF patients (prior LVEF <40%), while others are deteriorated HFpEF patients (17%) or unchanged HFmrEF (10%) 4
• HFmrEF patients have a significantly higher prevalence of ischemic heart disease and prior myocardial infarction compared to both HFrEF and HFpEF patients 2
• Prognosis is better than HFrEF but similar to HFpEF in terms of short-term mortality 3

Initial Diagnostic Evaluation

Before initiating treatment, perform a comprehensive evaluation:

• Two-dimensional echocardiography with Doppler to assess LVEF, left ventricular size, wall thickness, and valve function 5
• Complete laboratory evaluation including CBC, electrolytes, renal function, glucose, lipid profile, liver function tests, and thyroid function 5
• 12-lead ECG and chest radiograph 5
• Assessment of volume status, orthostatic blood pressure changes, and body mass index 5
• Coronary evaluation in patients with angina, significant ischemia, or known/suspected coronary artery disease 5

Core Medication Strategy

Current evidence suggests HFmrEF patients benefit from neurohormonal antagonists similar to HFrEF patients 1. Start with:

1. SGLT2 inhibitors and MRAs as first-line therapy:

   • Begin with these medications as they have minimal effect on blood pressure but provide rapid benefits 6
   • SGLT2 inhibitors are effective with moderate kidney dysfunction (eGFR ≥30 ml/min/1.73 m² for empagliflozin, ≥20 ml/min/1.73 m² for dapagliflozin) 5, 6
   • MRAs are particularly beneficial for patients with LVEF ≤35% and NYHA class II-IV symptoms 6

2. Beta-blockers:

   • Start at low dose if heart rate >70 bpm 6
   • Consider selective β₁ receptor blockers due to lesser BP-lowering effect 6
   • Carvedilol and metoprolol have demonstrated improvement in LVEF and reduction in regurgitant volume in patients with HF and secondary mitral regurgitation 5

3. ACEi/ARB or ARNi:

   • Start with low dose (25-50 mg twice daily) of sacubitril/valsartan for NYHA class II-III symptoms 6
   • If ARNi is not feasible, use ACEi or ARB 6
   • Sacubitril/valsartan has demonstrated superiority over valsartan alone in reducing functional mitral regurgitation in HF patients 5

4. Diuretics:

   • Use as needed for congestion but adjust according to volume status 6
   • Avoid overdiuresis which can lead to hypotension and impair tolerance of other HF medications 6

Implementation Strategy

For optimal implementation of the core medication strategy:

• Start all four medication classes simultaneously at low doses and titrate gradually 5, 6
• Evaluate blood pressure, heart rate, volume status, and renal function before initiating therapy 6
• For patients with adequate blood pressure, start SGLT2 inhibitor and MRA first, then add low-dose beta-blocker if heart rate >70 bpm, followed by low-dose ARNi (or ACEi/ARB) 6
• For patients with low blood pressure (SBP <100 mmHg), start with SGLT2 inhibitor and MRA as they have minimal BP-lowering effects 6
• Monitor renal function closely, especially when using ACEi/ARB/ARNi and MRAs 6
• If beta-blockers cannot be tolerated and patient is in sinus rhythm, consider ivabradine 6

Special Considerations

• Ischemic etiology: Given the high prevalence of ischemic heart disease in HFmrEF, consider coronary evaluation and appropriate revascularization when indicated 2
• Dynamic nature of HFmrEF: Recognize that many HFmrEF patients have a history of HFrEF that has improved, which may influence treatment response 4
• Avoid medications that may worsen HF: Do not use diltiazem or verapamil in HFmrEF patients as they increase the risk of HF worsening 5
• Avoid triple combination of ACEi, ARB and MRA: This combination increases risk of renal dysfunction and hyperkalemia 5

Common Pitfalls to Avoid

• Avoid the traditional step-by-step approach that delays benefits of comprehensive therapy 6
• Don't be overly cautious with dosing - even lower-than-target doses provide significant benefits 6
• Excessive diuresis can lead to hypotension and impair tolerance of other HF medications 6
• Adjust medications based on clinical response, one drug at a time to identify the source of any adverse effects 6