What is the initial management for patients with heart failure with preserved ejection fraction (HFpEF)?

Initial Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start SGLT2 inhibitors (dapagliflozin or empagliflozin) immediately as first-line disease-modifying therapy for all patients with HFpEF, combined with loop diuretics for symptom relief in those with congestion. 1, 2, 3

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis using a two-step approach:

• Establish HF symptoms with LVEF ≥50%, elevated natriuretic peptides (BNP or NT-proBNP), and evidence of structural heart disease or elevated filling pressures 2
• Rule out HFpEF mimics including cardiac amyloidosis, hypertrophic cardiomyopathy, pericardial disease, valvular disease, or high-output states that require specific alternative treatments 1, 2
• If diagnostic uncertainty persists after initial evaluation, proceed to stress testing or invasive hemodynamic assessment 2

First-Line Pharmacological Management

Disease-Modifying Therapy (Start Immediately)

SGLT2 inhibitors are the cornerstone of HFpEF treatment and should be initiated early:

• Dapagliflozin 10 mg daily (Class 2a recommendation) reduces cardiovascular death and HF hospitalizations by 18% (HR 0.82,95% CI 0.73-0.92) based on the DELIVER trial 2, 3
• Empagliflozin 10 mg daily (Class 2a recommendation) reduces HF hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) based on EMPEROR-PRESERVED 3, 4
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 3
• Do not delay SGLT2 inhibitor initiation—these agents have proven mortality and morbidity benefits 2, 3

Symptom Management with Diuretics

Loop diuretics are essential for congestion relief:

• Use loop diuretics at the lowest effective dose to relieve dyspnea, orthopnea, and edema 2, 3
• Start with furosemide 20-40 mg daily (or equivalent bumetanide/torsemide) and titrate based on volume status 3
• Increase the loop diuretic dose before adding combination therapy if initial response is inadequate 2
• If refractory to loop diuretics alone, add a thiazide diuretic (e.g., metolazone 2.5-5 mg) for sequential nephron blockade 2, 3
• Avoid excessive diuresis which leads to hypotension, worsening renal function, and impaired tolerance of other medications 2, 3

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (MRAs)

• Consider spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%) 2, 3
• Spironolactone reduced HF hospitalizations by 17% (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial 3
• Monitor potassium and renal function closely to minimize hyperkalemia risk 3

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Sacubitril/valsartan 24/26 mg twice daily, titrated to 97/103 mg twice daily may be considered (Class 2b recommendation) for selected patients 3
• Prioritize for women and patients with LVEF 45-57% who showed greater benefit in PARAGON-HF subgroup analyses 3
• The overall PARAGON-HF trial narrowly missed statistical significance (rate ratio 0.87,95% CI 0.75-1.01, p=0.06) 3

Management of Comorbidities (Critical Component)

Comorbidity management significantly impacts outcomes in HFpEF:

Hypertension

• Target blood pressure <130/80 mmHg using appropriate antihypertensive medications 2, 3
• Avoid diltiazem or verapamil as they increase risk of HF worsening and hospitalization 3

Atrial Fibrillation

• Use rate control strategy with beta-blockers as first-line for ventricular rate control 2, 4
• Target resting heart rate <80 bpm and <110 bpm during moderate exercise 4
• Non-dihydropyridine calcium channel blockers (diltiazem) can be used for rate control when combined with digoxin, but avoid as monotherapy 4
• Ensure appropriate anticoagulation based on CHA₂DS₂-VASc score 4

Diabetes

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefits for diabetes and heart failure 2, 3

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life 2, 3
• Recommend sodium restriction to <2-3 g/day to reduce congestive symptoms 2, 3
• Fluid restriction may be appropriate in selected patients with severe congestion 2

Monitoring and Follow-up

• Monitor symptoms, weight, vital signs, renal function (creatinine, eGFR), and electrolytes (potassium, sodium) regularly 2, 3
• Adjust diuretic doses based on daily weights and congestion status 2
• Reassess volume status at each visit to avoid both under- and over-diuresis 3
• Consider wireless pulmonary artery pressure monitoring in patients with recurrent hospitalizations 2, 3

Critical Pitfalls to Avoid

• Do not treat HFpEF patients identically to those with reduced ejection fraction—response to traditional HF therapies differs significantly 3
• Do not delay SGLT2 inhibitor initiation while waiting for symptom control with diuretics 2, 3
• Do not use excessive diuresis which causes hypotension and limits tolerance of disease-modifying therapies 2, 3
• Do not overlook comorbidity management as it significantly impacts outcomes 3
• Do not use diltiazem or verapamil as monotherapy due to increased HF worsening risk 3

When to Refer to HF Specialist

• Diagnostic uncertainty despite initial workup 1
• Refractory symptoms despite optimal medical therapy 3
• Need for advanced diagnostic testing (exercise hemodynamics, cardiac catheterization) 1
• Consideration of advanced therapies or clinical trial enrollment 1, 3