What is the management of Heart Failure with preserved Ejection Fraction (HFpEF)?

Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

Initiate SGLT2 inhibitors (dapagliflozin or empagliflozin) immediately as first-line disease-modifying therapy for all HFpEF patients, combined with loop diuretics for symptom relief. 1, 2

Diagnostic Confirmation

• Confirm HFpEF using LVEF ≥50%, elevated natriuretic peptides (NT-proBNP ≥125 ng/L in sinus rhythm or >365 ng/L in atrial fibrillation), and evidence of structural heart disease (average E/e' ≥15, LA volume index ≥40 mL/m², or LV mass index ≥95 g/m² in males or females) 3, 1
• Perform transthoracic echocardiography with LV diastolic function assessment as the key diagnostic test 3
• Rule out HFpEF mimics including cardiac amyloidosis, hypertrophic cardiomyopathy, and pericardial disease before initiating standard therapy 1

First-Line Pharmacological Management

Disease-Modifying Therapy (Priority Order)

SGLT2 Inhibitors (Class 2a Recommendation)

• Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily immediately upon diagnosis—these are the only agents with proven mortality and morbidity benefits in HFpEF 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 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 4
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 2

Symptom Management

• Use loop diuretics (furosemide 20-40 mg daily initially) at the lowest effective dose to relieve congestion and manage orthopnea/paroxysmal nocturnal dyspnea 3, 1, 2
• Titrate diuretic dose based on symptoms and volume status before adding combination diuretic strategies 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade 2

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (Class 2b Recommendation)

• Consider spironolactone 12.5-25 mg daily, 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 TOPCAT but did not reduce the primary composite outcome 2
• Monitor potassium and renal function closely to minimize hyperkalemia risk 2

Angiotensin Receptor-Neprilysin Inhibitors (Class 2b Recommendation)

• Consider sacubitril/valsartan 24/26 mg twice daily (titrate to 97/103 mg twice daily) for selected patients, especially women and those with LVEF 45-57% 2
• PARAGON-HF showed potential benefit in women (rate ratio 0.73,95% CI 0.59-0.90) and patients with LVEF below the median 2

Management of Comorbidities

Hypertension

• Achieve blood pressure target <130/80 mmHg using appropriate antihypertensive medications 3, 1
• Six major guidelines strongly recommend tight blood pressure control in HFpEF 3

Atrial Fibrillation

• Use rate control as the preferred initial strategy over rhythm control 4
• Prescribe beta-blockers as first-line agents for rate control due to favorable effects on ventricular response 4
• Consider non-dihydropyridine calcium channel blockers (diltiazem) if beta-blockers are contraindicated or ineffective 4
• Do not perform AV node ablation without first attempting pharmacological rate control 4

Diabetes

• Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits 1, 4
• Consider finerenone (a non-steroidal MRA) in patients with type 2 diabetes and concomitant chronic kidney disease 3

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs to improve functional capacity and quality of life (Class 1 recommendation) 3, 1, 2
• Recommend sodium restriction to <2-3 g/day 1
• Advise weight reduction in obese patients and smoking cessation 3

Monitoring and Follow-Up

• Monitor symptoms, vital signs, weight, renal function, and electrolytes regularly 1
• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension 1
• Consider wireless pulmonary artery pressure monitoring in patients with recurrent hospitalizations 1, 2

Common Pitfalls to Avoid

• Do not delay initiation of SGLT2 inhibitors—they have the strongest evidence for mortality and morbidity benefits and should be started immediately 1, 2
• Avoid excessive diuresis which can lead to hypotension, worsening renal function, and impaired tolerance of other medications 1, 2
• Do not treat HFpEF patients identically to those with reduced ejection fraction—response to therapies differs significantly between these populations 2, 5
• Do not overlook management of comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes 2, 4

Advanced Treatment Considerations

• Refer to an advanced heart failure specialist team for patients with advanced HFpEF refractory to standard therapies 2
• Consider cardiac transplantation in eligible patients with advanced HFpEF 2