What are the treatment recommendations for patients with preserved Left Ventricular Ejection Fraction (LVEF)?

Treatment Recommendations for Heart Failure with Preserved LVEF

SGLT2 inhibitors should be used as first-line therapy in patients with heart failure with preserved ejection fraction (HFpEF) to decrease hospitalizations and cardiovascular mortality. 1

Pharmacological Management

First-Line Therapies

• SGLT2 inhibitors (Class 2a recommendation):
  • Empagliflozin has shown a 21% reduction in the composite endpoint of HF hospitalization or cardiovascular death, driven primarily by a 29% reduction in HF hospitalizations 1
  • Benefit is similar regardless of diabetes status
  • Particularly effective for reducing total HF hospitalizations and slowing eGFR decline

Second-Line Therapies (Class 2b recommendations)

• Mineralocorticoid Receptor Antagonists (MRAs):

  • May be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum 1
  • Requires careful monitoring of renal function and potassium levels

• Angiotensin Receptor-Neprilysin Inhibitors (ARNi):

  • May be considered to decrease hospitalizations, especially in patients with LVEF on the lower end of the preserved spectrum 1
  • More beneficial in women and patients with LVEF between 45-57% 1

• Angiotensin Receptor Blockers (ARBs):

  • May be considered to decrease hospitalizations, particularly in patients with LVEF on the lower end of the preserved spectrum 1

Management of Comorbidities

• Hypertension Control (Class 1 recommendation):

  • Blood pressure should be aggressively controlled according to clinical practice guidelines 1
  • Target blood pressure should be lower than for uncomplicated hypertension (e.g., <130/80 mmHg) 1
  • Thiazide or thiazide-like diuretics can be useful for BP control and to reverse mild volume overload 1

• Atrial Fibrillation Management (Class 2a recommendation):

  • Management of AF is useful to improve symptoms in HFpEF patients 1
  • In patients with HFpEF and preserved LVEF, a non-dihydropyridine calcium channel antagonist (alone or with digoxin) should be considered to control heart rate at rest and during exercise 1

Treatments to Avoid

• Nitrates and Phosphodiesterase-5 Inhibitors (Class 3: No Benefit):

  • Routine use of these medications to increase activity or quality of life is ineffective 1
  • The NEAT-HFpEF trial showed no beneficial effects on activity levels, QOL, exercise tolerance, or NT-proBNP levels 1

• Calcium Channel Blockers with Negative Inotropic Effects:

  • Not recommended in patients with EF less than 40% after MI 1
  • However, non-dihydropyridine calcium channel blockers may be considered for rate control in HFpEF patients with atrial fibrillation 1

Lifestyle Modifications

• Exercise Training:

  • Regular physical activity (at least 30 minutes per day, most days of the week) is recommended 2

• Dietary Recommendations:

  • DASH diet to promote weight loss and blood pressure reduction 2
  • Sodium restriction for patients with fluid retention 1
  • Increased consumption of fruits, vegetables, and low-fat dairy products 2

• Weight Management:

  • Weight reduction for overweight or obese patients 2

Monitoring and Follow-up

• Regular blood pressure monitoring, including home monitoring
• Echocardiographic follow-up every 6-12 months to assess:
  • LV hypertrophy regression
  • Mitral regurgitation progression
  • Left atrial size
  • LVEF changes
• Laboratory monitoring of electrolytes, renal function, and natriuretic peptide levels

Clinical Pitfalls to Avoid

1. Misclassification of HF phenotype: Recognize that LVEF exists on a continuum, and patients with values at the lower end of the preserved range (50-55%) may benefit more from therapies typically used for reduced EF 3

2. Undertreating hypertension: Hypertension exerts a deleterious effect on ventricular function by causing both structural and functional changes in the heart 1

3. Overlooking atrial fibrillation: Patients with HFpEF may be particularly sensitive to loss of atrial kick, which supports a potential benefit for restoration of sinus rhythm in patients with atrial fibrillation 1

4. Inappropriate use of negative inotropic agents: Calcium channel blockers with negative inotropic effects should be avoided in patients with EF less than 40% 1

5. Delaying treatment: Early intervention is crucial to prevent progression of left ventricular hypertrophy and development of heart failure symptoms 2