What is the treatment for Heart Failure with preserved Ejection Fraction (HFpEF)?

Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors (dapagliflozin or empagliflozin) should be the first-line disease-modifying therapy for HFpEF to reduce hospitalizations and cardiovascular mortality, followed by mineralocorticoid receptor antagonists and ARNI therapy as appropriate. 1

Comprehensive Management Approach

The management of HFpEF requires a structured approach focusing on three key areas:

1. Risk stratification and comorbidity management
2. Non-pharmacological interventions
3. Pharmacological therapy

First-Line Pharmacological Therapy

SGLT2 Inhibitors

• First choice: Dapagliflozin or empagliflozin
• Both demonstrated significant reduction in the primary composite outcome of worsening HF and cardiovascular death (HR: 0.82 and 0.79 respectively) 1
• Particularly effective at reducing HF hospitalizations (HR: 0.77 for dapagliflozin, 0.71 for empagliflozin) 1
• Dapagliflozin also improved quality of life and 6-minute walk distance in the PRESERVED-HF trial 1

Diuretics

• Use loop diuretics judiciously to manage congestion and improve symptoms 1
• Titrate to maintain euvolemia while avoiding excessive diuresis 2

Second-Line Pharmacological Options

Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone showed benefit in North American patients in TOPCAT trial (HR: 0.82) 1
• Consider in patients with persistent symptoms despite SGLT2i therapy
• Monitor for hyperkalemia, especially in patients with renal dysfunction

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Sacubitril/valsartan may be beneficial in selected patients 1
• Consider especially in women and those with LVEF below the median (≤57%) 1

Angiotensin Receptor Blockers (ARBs)

• Candesartan showed borderline benefit in CHARM-Preserved trial (HR: 0.86) 1
• Consider in patients who cannot tolerate other therapies

Management of Comorbidities

Hypertension

• Aggressive BP control is essential for HFpEF management 1
• Target BP according to current hypertension guidelines 1
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) 1

Atrial Fibrillation

• Common comorbidity requiring specific management 3
• Rate control with beta-blockers (if indicated for other reasons)
• Consider rhythm control strategies, particularly catheter ablation in appropriate candidates 3

Diabetes Mellitus

• SGLT2 inhibitors provide dual benefit for diabetes and HFpEF 1
• Optimize glycemic control

Obesity

• Weight reduction in overweight/obese patients 1
• Consider referral to structured weight management programs

Non-Pharmacological Interventions

Exercise Training

• Class I recommendation (Level of Evidence A) for patients with HF 1
• Supervised exercise training improves exercise capacity and quality of life 1, 4
• Improves peak oxygen consumption and functional capacity 1
• Consider cardiac rehabilitation referral when available

Sodium and Fluid Restriction

• Moderate sodium restriction (2-3g/day)
• Fluid restriction as needed based on symptoms 2

Pulmonary Artery Pressure Monitoring

• Wireless implantable monitors may reduce hospitalizations in selected patients 1

Treatment Algorithm

1. Initial Assessment:

   • Confirm HFpEF diagnosis (LVEF >40%, symptoms of HF, evidence of diastolic dysfunction)
   • Evaluate for specific etiologies (e.g., amyloidosis, hemochromatosis)
   • Assess comorbidities

2. First-Line Therapy:

   • Start SGLT2 inhibitor (dapagliflozin or empagliflozin)
   • Add diuretics as needed for congestion

3. Second-Line Therapy (if symptoms persist):

   • Add MRA (spironolactone)
   • Consider ARNI (sacubitril/valsartan), particularly in women or those with LVEF ≤57%

4. Comorbidity Management:

   • Treat hypertension aggressively
   • Manage atrial fibrillation
   • Address obesity, diabetes, sleep apnea

5. Non-Pharmacological Interventions:

   • Prescribe supervised exercise training
   • Recommend sodium restriction
   • Consider pulmonary artery pressure monitoring in selected cases

Common Pitfalls and Caveats

1. Misdiagnosis: Ensure proper diagnosis of HFpEF before initiating therapy, as treatment differs from HFrEF

2. Overdiuresis: Excessive diuresis can lead to hypotension and worsening renal function; titrate carefully

3. Beta-Blockers: Unlike in HFrEF, beta-blockers have not shown mortality benefit in HFpEF and should be used only for specific indications (prior MI, angina, AF) 1

4. Neglecting Exercise: Exercise training is often overlooked but provides significant benefits for symptoms and quality of life 1, 4

5. Focusing Only on Medications: A comprehensive approach including lifestyle modifications and comorbidity management is essential for optimal outcomes

6. Inappropriate Calcium Channel Blocker Use: Non-dihydropyridine calcium channel blockers should be avoided due to negative inotropic effects 1