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

Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)

Start all HFpEF patients on an SGLT2 inhibitor (empagliflozin or dapagliflozin) as first-line disease-modifying therapy, regardless of diabetes status, as this is the only intervention with strong evidence for reducing heart failure hospitalizations and cardiovascular death. 1

First-Line Disease-Modifying Therapy

• SGLT2 inhibitors (empagliflozin or dapagliflozin) carry a Class 2a recommendation and should be initiated in all HFpEF patients as foundational therapy. 1, 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in the EMPEROR-PRESERVED trial. 1
• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in the DELIVER trial. 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation. 1

Symptom Management with Diuretics

• Use loop diuretics (furosemide 20-40 mg, bumetanide 0.5-1.0 mg, or torsemide 5-10 mg) at the lowest effective dose to achieve euvolemia and relieve congestion. 3, 2
• For acute decompensation with orthopnea/paroxysmal nocturnal dyspnea, start with 20-40 mg IV furosemide (or equivalent); if already on chronic diuretics, use at least the equivalent of the oral dose intravenously. 1
• Titrate diuretic dose based on daily weights and symptoms to avoid excessive diuresis, which reduces cardiac output and causes hypotension and renal dysfunction in HFpEF. 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade. 1

Second-Line Pharmacotherapy

• Consider adding spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%). 1, 2

• Spironolactone reduced heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial, though it did not significantly reduce the primary composite outcome. 1

• Monitor potassium and renal function closely when using mineralocorticoid receptor antagonists to prevent life-threatening hyperkalemia. 2

• Sacubitril/valsartan may be considered (Class 2b recommendation) for selected patients, especially women and those with LVEF 45-57%. 1, 2

• The PARAGON-HF trial showed a trend toward benefit (rate ratio 0.87,95% CI 0.75-1.01, p=0.06) overall, with stronger effects in women (rate ratio 0.73) and those with LVEF 45-57% (rate ratio 0.78). 1

Essential Comorbidity Management

• Aggressively treat hypertension to target <130/80 mmHg using appropriate antihypertensive medications. 3, 1, 2
• For patients with type 2 diabetes, prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits. 3
• For atrial fibrillation, provide rate control using beta-blockers or rate-limiting calcium channel blockers (diltiazem, verapamil), and anticoagulate based on CHA₂DS₂-VASc score. 2, 4

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation, Level of Evidence A) to improve functional capacity and quality of life. 3, 1
• The evidence for exercise training in HFpEF is strong, though most supporting data emanates from heart failure with reduced ejection fraction studies. 3
• Recommend weight reduction for obese patients, as obesity is a key comorbidity driving HFpEF pathophysiology. 5

Medications to Avoid

• Do not use nitrates or phosphodiesterase-5 inhibitors (sildenafil) as they do not improve activity or quality of life in HFpEF. 2
• Avoid thiazolidinediones and saxagliptin due to increased heart failure risk. 2
• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations. 1, 6

Treatment Algorithm

1. Start SGLT2 inhibitor (empagliflozin or dapagliflozin) immediately as foundational therapy 1, 2
2. Add loop diuretic at lowest effective dose for congestion management 3, 2
3. Optimize blood pressure to target <130/80 mmHg 3, 1
4. Consider adding mineralocorticoid receptor antagonist if LVEF is 40-50% and patient tolerates monitoring 1, 2
5. Consider sacubitril/valsartan for women or those with LVEF 45-57% 1, 2
6. Manage atrial fibrillation with rate control and anticoagulation if present 2, 4
7. Initiate supervised exercise training program 3, 1

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with mineralocorticoid receptor antagonist therapy. 1, 4
• Monitor symptoms and functional capacity using tools like the Kansas City Cardiomyopathy Questionnaire or 6-minute walk distance to guide treatment adjustments. 3
• Consider wireless pulmonary artery pressure monitoring devices in selected patients for optimizing volume status. 1

Critical Pitfalls to Avoid

• Avoid excessive diuresis, which reduces cardiac output in HFpEF and causes hypotension and renal dysfunction. 2
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes in HFpEF. 1
• Most drugs that improve exercise capacity in heart failure with reduced ejection fraction (spironolactone, sacubitril/valsartan, empagliflozin) have been disappointing for improving exercise capacity in HFpEF, with the exception of dapagliflozin in the PRESERVED-HF trial. 3