What are the treatment approaches for different classes of heart failure, including Heart Failure with reduced Ejection Fraction (HFrEF) and Heart Failure with preserved Ejection Fraction (HFpEF)?

Treatment Approaches for Different Classes of Heart Failure

The cornerstone of heart failure management should be guided by the specific heart failure classification, with SGLT2 inhibitors now recommended for all types of heart failure regardless of ejection fraction. 1

Heart Failure with Reduced Ejection Fraction (HFrEF) - LVEF ≤40%

First-Line Therapies (Quadruple Therapy)

• Beta-blockers: Evidence-based beta-blockers (carvedilol, metoprolol succinate, bisoprolol) 1, 2
• Renin-Angiotensin System Inhibitors: Preferably ARNI (sacubitril/valsartan) or ACE inhibitors (if ARNI not feasible) or ARBs (if ACE inhibitor not tolerated) 1
• Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone for NYHA class II-IV with LVEF ≤35% 1, 3
• SGLT2 Inhibitors: Dapagliflozin or empagliflozin regardless of diabetes status 1, 4

Additional Therapies Based on Specific Indications

• Ivabradine: For patients with persistent symptoms, sinus rhythm, LVEF ≤35%, and heart rate ≥70 bpm despite maximally tolerated beta-blocker dose 1, 5
• Hydralazine/Isosorbide Dinitrate: Particularly beneficial in self-identified African American patients with NYHA class III-IV symptoms 1
• Diuretics: For symptom relief of congestion, not for mortality benefit 1

Device Therapy

• ICD: For primary prevention in patients with LVEF ≤35%, NYHA class II-III on GDMT or NYHA class II with LVEF ≤30% on GDMT 1
• CRT: For NYHA class II-IV, LVEF ≤35%, LBBB with QRS ≥150 ms 1

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF) - LVEF 41-49%

Recommended Therapies

• SGLT2 Inhibitors: Strong recommendation (Class 2a) for decreasing HF hospitalizations and cardiovascular mortality 1
• Beta-blockers, ARNI, ACEi, ARB, and MRAs: Weaker recommendation (Class 2b), particularly beneficial for patients with LVEF closer to 40% 1
• Diuretics: For symptom relief as needed 1

Heart Failure with Preserved Ejection Fraction (HFpEF) - LVEF ≥50%

Recommended Therapies

• SGLT2 Inhibitors: Strongest recommendation (Class 2a) for decreasing HF hospitalizations and cardiovascular mortality 1, 6
• Diuretics: First-line therapy for symptom management in patients with volume overload 6
• MRAs: May be considered (Class 2b) to decrease hospitalizations, particularly in patients with LVEF closer to 50% 1, 6
• ARNI: May be considered (Class 2b) to decrease hospitalizations, particularly in patients with LVEF closer to 50% and in women 1, 6
• ARBs: May be considered (Class 2b) for patients with hypertension and HFpEF 1, 6

Comorbidity Management

• Hypertension: Aggressive treatment with target SBP <130 mmHg 6, 7
• Atrial Fibrillation: Rate or rhythm control as appropriate 6
• Obesity: Weight reduction for BMI ≥30 6, 7
• Sleep Apnea: Screening and appropriate treatment 6

Treatments to Avoid in HFpEF

• Nitrates or Phosphodiesterase-5 Inhibitors: Not recommended (Class 3: No Benefit) 1, 6
• Combining verapamil/diltiazem with beta-blockers in atrial fibrillation 6

Heart Failure with Improved Ejection Fraction (HFimpEF)

Patients who improve their LVEF from ≤40% to >40% should continue their HFrEF treatment regimen to prevent relapse, even if they become asymptomatic. 1

Advanced Heart Failure (Stage D)

For patients with refractory symptoms despite optimal medical therapy:

• Advanced care measures: Heart transplantation evaluation 1
• Mechanical circulatory support: For carefully selected patients 1
• Chronic inotropes: For palliative management 1
• Palliative care and hospice: When appropriate 1

Important Clinical Considerations

• Medication Titration: Start at low doses and gradually titrate to target doses as tolerated, monitoring for side effects 2
• Higher BMI: Associated with achieving upper-range doses of ACE-I/ARBs 8
• Diabetes: Associated with achieving upper-range doses of beta-blockers 8
• Women: May have more difficulty achieving target beta-blocker doses 8
• Monitoring: Regular assessment of symptoms, volume status, renal function, and electrolytes is essential 6
• Exercise Training: Recommended to improve exercise capacity and quality of life 6

Clinical Pearls

• HFpEF patients typically have more non-cardiac comorbidities than HFrEF patients 7, 9
• CHD is more strongly associated with HFrEF, while atrial fibrillation and female sex are more associated with HFpEF 9
• The economic value of SGLT2 inhibitors is considered intermediate, while ARNIs, ACEIs, ARBs, beta-blockers, MRAs, ICDs, and CRT are considered high economic value 1

By following these evidence-based treatment approaches tailored to the specific heart failure classification, clinicians can optimize outcomes and improve quality of life for patients with heart failure.