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

Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)

SGLT2 inhibitors (dapagliflozin or empagliflozin) are recommended as first-line disease-modifying therapy for HFpEF to reduce hospitalizations and improve quality of life, regardless of diabetes status. 1

Pharmacological Management Algorithm

First-line Therapies:

1. Disease-modifying therapy:

   • SGLT2 inhibitors (dapagliflozin or empagliflozin) - shown to significantly reduce HF hospitalizations (HR: 0.77 for dapagliflozin, 0.71 for empagliflozin) and improve quality of life 1

2. Symptom management:

   • Diuretics (primarily loop diuretics) - for patients with volume overload symptoms, titrated to the lowest effective dose to achieve euvolemia 1
   • Use the long-acting azosemide over furosemide when available due to reduced neurohormonal impact 2

Additional Pharmacological Options:

• For patients with hypertension:

  • ACE inhibitors or ARBs - target SBP <130 mmHg 1

• For patients with LVEF 50-60% (lower range of preservation):

  • Consider Mineralocorticoid Receptor Antagonists (MRAs) with careful monitoring of potassium and renal function 1

• For selected patients:

  • Sacubitril/valsartan - potentially beneficial in women and those with LVEF ≤57% 1
  • Candesartan - showed borderline benefit in CHARM-Preserved trial (HR: 0.86) 1

• For refractory fluid overload:

  • Consider adding thiazide diuretics to loop diuretics for sequential nephron blockade 2, 1

Medications to Avoid:

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) 1
• Routine use of nitrates or phosphodiesterase-5 inhibitors 1

Management of Comorbidities

1. Obesity management:

   • Weight reduction program for overweight/obese patients 1
   • Consider GLP-1 Receptor Agonists (semaglutide 2.4mg weekly) for patients with BMI ≥30 1

2. Hypertension:

   • Target BP according to current hypertension guidelines (SBP <130 mmHg) 1
   • Patients with HFpEF often have exaggerated hypertensive response to exercise 1

3. Sleep apnea:

   • Screen and treat appropriately 1

4. Diabetes:

   • Optimize glycemic control 1

Non-Pharmacological Interventions

1. Exercise training:

   • Supervised exercise program to improve exercise capacity and quality of life (Class I recommendation, Level of Evidence A) 1

2. Dietary modifications:

   • Moderate sodium restriction (2-3g/day) 1
   • Fluid restriction as needed based on symptoms 1

Monitoring and Follow-up

• Regular assessment of symptoms, volume status, renal function, and electrolytes 1
• Adjust diuretic doses based on symptoms and weight measurements 1
• Repeat echocardiography with significant changes in clinical status 1

Emerging Approaches

Recent research indicates that certain device-based therapies may benefit specific HFpEF phenotypes, including inter-atrial shunt, greater splanchnic nerve ablation, implantable heart failure monitors, and other interventions 3. However, these are not yet part of standard guidelines.

Cautions and Pitfalls

• Avoid excessive diuresis: Can lead to hypotension and renal dysfunction, potentially preventing use of disease-modifying therapies 1
• Recognize heterogeneity: HFpEF is increasingly understood as a heterogeneous syndrome with varying pathophysiologic abnormalities among patients 4
• Consider phenotype-guided approach: Treatment may be tailored to identifiable patient clusters distinguished by predominant symptoms and/or comorbidity profiles 4

By following this evidence-based approach to HFpEF management, clinicians can optimize outcomes for this challenging patient population that has historically had limited treatment options.