What is the best approach to treating a patient with heart failure with preserved ejection fraction (HFpEF)?

Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis as first-line disease-modifying therapy for all HFpEF patients. 1

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors (First-Line)

• Dapagliflozin or empagliflozin represent the strongest evidence-based therapy for HFpEF, with Class 2a recommendations from the American College of Cardiology and American Heart Association. 1, 2
• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) and heart failure hospitalizations by 23% (HR 0.77,95% CI 0.67-0.89) 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
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation. 1

Mineralocorticoid Receptor Antagonists (Second-Line)

• Add spironolactone (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, renal function, and diuretic dosing carefully to minimize hyperkalemia and worsening renal function. 1

Angiotensin Receptor-Neprilysin Inhibitors (Selected Patients)

• Consider sacubitril/valsartan (Class 2b recommendation) specifically for women and patients with LVEF 45-57%. 1, 2
• Prespecified subgroup analyses from PARAGON-HF showed benefit in patients with LVEF below the median (45%-57%) (rate ratio 0.78,95% CI 0.64-0.95) and in women (rate ratio 0.73,95% CI 0.59-0.90). 1
• The overall PARAGON-HF trial did not achieve statistical significance for the primary endpoint (rate ratio 0.87,95% CI 0.75-1.01, p=0.06). 1

Symptom Management with Diuretics

• Use loop diuretics at the lowest effective dose to relieve congestion, orthopnea, and paroxysmal nocturnal dyspnea. 1, 2
• For new-onset HFpEF with orthopnea/PND, start with 20-40 mg IV furosemide (or equivalent); for those on chronic diuretic therapy, initial IV dose should be at least equivalent to oral dose. 1
• Titrate diuretic dose based on symptoms and volume status before considering combination diuretic strategies. 1
• If inadequate response despite dose increases, consider changing to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade. 1
• Avoid excessive diuresis which may lead to hypotension and worsening renal function. 1

Comorbidity Management

Hypertension

• Target blood pressure <130/80 mmHg using appropriate antihypertensive medications. 1, 2
• Avoid diltiazem or verapamil in HFpEF patients, as they increase the risk of heart failure worsening and hospitalization. 1

Diabetes

• Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits. 1, 2

Atrial Fibrillation

• Prescribe anticoagulation based on CHA₂DS₂-VASc score to prevent thromboembolic events. 3
• Use beta-blockers for rate control cautiously in patients with COPD, with preference for cardioselective agents. 3

Obesity

• Recommend weight reduction in obese patients. 2

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life. 1, 2
• Recommend sodium restriction to <2-3 g/day. 2
• Offer multidisciplinary heart failure programs to all patients. 1

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with MRA therapy. 1, 3, 2
• Monitor symptoms, vital signs, weight, and functional capacity to guide treatment adjustments. 1, 2
• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension. 2
• Consider wireless, implantable pulmonary artery monitors in selected patients for optimizing volume status. 1

Critical Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations. 1
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes in HFpEF. 1
• Avoid diltiazem or verapamil, which increase the risk of heart failure worsening and hospitalization. 1

Advanced Treatment Options

• Refer to an advanced heart failure specialist team for patients with advanced HFpEF refractory to standard therapies. 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF. 1

Special Populations: Women

• Women have higher EFs and more preserved LV global longitudinal strain compared with men, making diagnosis more challenging. 4
• Women showed greater benefit from sacubitril/valsartan in PARAGON-HF subgroup analyses. 1
• A history of pre-eclampsia is associated with increased risk for subsequent HFpEF hospitalization. 4