What are the treatment guidelines for a patient with heart failure with preserved ejection fraction (HFpEF)?

Treatment Guidelines for Heart Failure with Preserved Ejection Fraction (HFpEF)

First-Line Disease-Modifying Therapy

Start an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately in all patients with HFpEF, regardless of diabetes status. 1, 2, 3

• SGLT2 inhibitors are the cornerstone of HFpEF treatment with the strongest evidence for reducing heart failure hospitalizations and cardiovascular outcomes. 1, 3
• 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, 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED. 1, 2, 3
• These benefits occur independent of glucose-lowering effects and represent a Class 2a recommendation from the 2022 ACC/AHA/HFSA guidelines. 1, 2
• 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 at the lowest effective dose to relieve congestion, titrating based on daily weights and symptoms. 1, 2, 3

• Start furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, or torsemide 5-10 mg) and adjust based on volume status. 2, 3
• Train patients to self-adjust diuretic doses based on daily weight monitoring to maintain euvolemia. 2
• Avoid excessive diuresis, which reduces cardiac output in HFpEF and causes hypotension and renal dysfunction. 2, 3
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade. 1

Blood Pressure Management

Target blood pressure <130/80 mmHg using medications already prescribed for heart failure. 1, 2, 3

• The SGLT2 inhibitor and loop diuretic will contribute to blood pressure control. 2
• ACE inhibitors or ARBs are reasonable for additional blood pressure control if needed, though they have not shown mortality benefit in HFpEF specifically. 1, 2
• Beta-blockers may be used for blood pressure control and are reasonable in HFpEF, particularly if atrial fibrillation is present for rate control. 2, 3

Additional Pharmacological Options for Selected Patients

Consider adding spironolactone 12.5-25 mg daily (titrating to 50 mg) particularly if LVEF is in the lower preserved range (40-50%). 1, 2, 3

• Spironolactone has a Class 2b recommendation based on the TOPCAT trial showing reduction in heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but no significant mortality benefit. 1, 2
• Monitor potassium and renal function closely—check within 1 week of initiation and after dose changes, as hyperkalemia is a significant risk. 2, 3

Sacubitril/valsartan may be considered specifically for women and patients with LVEF 45-57%. 1, 2, 3

• The PARAGON-HF trial showed a trend toward benefit (rate ratio 0.87, p=0.06) overall, with greater benefit in women (rate ratio 0.73) and those with LVEF 45-57% (rate ratio 0.78). 1, 3
• This carries a Class 2b recommendation from the 2022 ACC/AHA/HFSA guidelines. 1

Management of Comorbidities

Aggressively treat hypertension, diabetes, obesity, and atrial fibrillation, as these significantly impact outcomes in HFpEF. 1, 2, 3

• For diabetes, prioritize SGLT2 inhibitors (already prescribed for HFpEF) and consider adding GLP-1 receptor agonists if additional glycemic control is needed. 2
• Avoid thiazolidinediones (pioglitazone) as they cause fluid retention and worsen heart failure. 2, 3
• For atrial fibrillation, use rate control with beta-blockers or rate-limiting calcium channel blockers (verapamil, diltiazem) and appropriate anticoagulation. 3, 4

Non-Pharmacological Interventions

Prescribe supervised exercise training programs (Class 1 recommendation) as they improve functional capacity by 12-14% and quality of life. 1, 2, 3

• Exercise programs typically involve 3 sessions per week for 1-8 months at 40-90% of exercise capacity, using walking, stationary cycling, or high-intensity interval training. 1
• Recommend dietary sodium restriction to <2-3 g/day to help control volume status and reduce congestion. 2

Critical Medications to Avoid

Do not use nondihydropyridine calcium channel blockers (diltiazem, verapamil) for HFpEF treatment, as they have negative inotropic effects and increase the risk of heart failure worsening. 1, 3

Avoid nitrates and phosphodiesterase-5 inhibitors (sildenafil) as they do not improve activity or quality of life and may cause harm. 1, 3

Do not use saxagliptin due to increased heart failure risk. 3

Monitoring and Follow-Up

At each visit, assess volume status, renal function, electrolytes (especially potassium if on MRA), and symptoms. 1, 2

• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension and renal dysfunction. 2
• Consider wireless, implantable pulmonary artery monitors in selected patients for optimizing volume status. 1

Treatment Algorithm Summary

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

Important Caveats

No medication has been definitively shown to reduce mortality in HFpEF. 1, 5, 6

• The goal of therapy is to alleviate symptoms, improve quality of life, and reduce hospitalizations. 1
• SGLT2 inhibitors provide the strongest evidence for reducing composite cardiovascular outcomes, driven primarily by reductions in heart failure hospitalizations rather than mortality alone. 1
• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly. 1, 5