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 HFpEF patients, combined with loop diuretics at the lowest effective dose for symptom relief in those with congestion. 1, 2

Immediate Pharmacological Management

Disease-Modifying Therapy (Start First)

• Initiate SGLT2 inhibitors early as they reduce heart failure hospitalizations by 23% and cardiovascular mortality (HR 0.82,95% CI 0.73-0.92 in DELIVER trial; HR 0.79,95% CI 0.69-0.90 in EMPEROR-PRESERVED trial). 2
• Choose dapagliflozin if eGFR >30 mL/min/1.73m² or empagliflozin if eGFR >60 mL/min/1.73m². 2
• Do not delay SGLT2 inhibitor initiation while waiting for symptom control—this is a critical pitfall that reduces mortality benefits. 1, 2

Symptom Management with Diuretics

• Use loop diuretics (furosemide 20-40 mg IV for new-onset symptoms, or equivalent to current oral dose for chronic patients) to relieve congestion, orthopnea, and paroxysmal nocturnal dyspnea. 1, 2
• Titrate to the lowest effective dose based on volume status to avoid overdiuresis, which causes hypotension and impairs tolerance of other medications. 1, 2
• If inadequate response despite dose increases, switch to a different loop diuretic or add a thiazide for sequential nephron blockade before escalating further. 2

Additional Pharmacological Options (Second-Line)

Mineralocorticoid Receptor Antagonists

• Consider spironolactone specifically for patients with LVEF 40-50% (lower preserved range), where it reduces heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99). 2
• Monitor potassium and renal function closely to prevent hyperkalemia. 2
• This has Class 2b recommendation—weaker evidence than SGLT2 inhibitors. 2

ARNIs (Sacubitril/Valsartan)

• Reserve for women and patients with LVEF 45-57%, where subgroup analyses showed benefit (rate ratio 0.73 in women, 0.78 in LVEF 45-57%). 2
• This is Class 2b recommendation as the primary PARAGON-HF trial was neutral (rate ratio 0.87,95% CI 0.75-1.01, p=0.06). 2
• Do not use as first-line therapy—SGLT2 inhibitors have stronger evidence. 2

Comorbidity Management (Essential Component)

Blood Pressure Control

• Target <130/80 mmHg using appropriate antihypertensives, as hypertension is a key driver of HFpEF pathophysiology. 1, 2

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their dual heart failure and diabetes benefits. 1

Atrial Fibrillation Management

• Use beta-blockers or non-dihydropyridine calcium channel blockers for rate control. 1
• Anticoagulate based on CHA₂DS₂-VASc score. 3
• Consider catheter ablation-based rhythm control for paroxysmal or early persistent AF, as retrospective data suggest improved cardiovascular outcomes. 4

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs to improve functional capacity and quality of life. 1, 2
• Restrict sodium to <2-3g/day and fluids when appropriate. 1
• Implement multidisciplinary heart failure programs involving HF specialists, nurses, dieticians, and physiotherapists. 2

Diagnostic Confirmation Before Treatment

• Confirm HFpEF using LVEF ≥50%, elevated natriuretic peptides, and evidence of structural heart disease or elevated filling pressures. 1
• Rule out HFpEF mimics (cardiac amyloidosis, hypertrophic cardiomyopathy, pericardial disease) that require specific treatments. 1
• Proceed to stress testing if diagnosis remains uncertain. 1

Monitoring Strategy

• Assess volume status, renal function, and electrolytes regularly, especially with MRA therapy. 2, 3
• Monitor symptoms, vital signs, and weight to guide diuretic adjustments. 1
• Consider wireless pulmonary artery pressure monitoring in patients with recurrent hospitalizations. 1, 2

Critical Pitfalls to Avoid

• Never delay SGLT2 inhibitor initiation—they have proven mortality benefits that are lost with delayed treatment. 1, 2
• Avoid excessive diuresis leading to hypotension and worsening renal function, which impairs tolerance of disease-modifying therapies. 1, 2
• Do not treat HFpEF patients identically to HFrEF patients—response to therapies differs significantly between these populations. 2
• Do not overlook comorbidity management (hypertension, diabetes, obesity, atrial fibrillation), which significantly impacts outcomes. 2

Treatment Algorithm Summary

1. Confirm diagnosis and exclude mimics
2. Start SGLT2 inhibitor immediately (dapagliflozin or empagliflozin)
3. Add loop diuretic if congested (lowest effective dose)
4. Optimize blood pressure to <130/80 mmHg
5. Consider spironolactone if LVEF 40-50%
6. Consider ARNI if female or LVEF 45-57%
7. Manage all comorbidities aggressively
8. Implement exercise training and dietary sodium restriction