What is the recommended management for a patient with chronic heart failure with preserved ejection fraction (HFpEF)?

Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis in all HFpEF patients, regardless of diabetes status, as this is the only disease-modifying therapy proven to reduce heart failure hospitalizations and composite cardiovascular outcomes. 1, 2

First-Line Disease-Modifying Pharmacotherapy

SGLT2 inhibitors are the cornerstone of HFpEF treatment and should be initiated before or alongside other therapies:

• Dapagliflozin 10 mg daily (if eGFR >30 mL/min/1.73 m²) reduced 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, 3

• Empagliflozin 10 mg daily (if eGFR >60 mL/min/1.73 m²) reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 1, 2

• These benefits occur within weeks of initiation, are independent of diabetes status, and require no dose titration 1

• Critical point: No pharmacologic agent has demonstrated standalone mortality reduction in HFpEF; the benefit of SGLT2 inhibitors is driven primarily by reduction in heart failure hospitalizations 1

Symptom Management with Diuretics

Use loop diuretics at the lowest effective dose to relieve congestion, orthopnea, and paroxysmal nocturnal dyspnea:

• Start with furosemide 20-40 mg daily (or equivalent) and titrate based on volume status 1, 2

• Loop diuretics are the only antihypertensive agents that reliably address fluid retention in heart failure 1

• If inadequate response despite dose escalation, add a thiazide diuretic (e.g., hydrochlorothiazide) for sequential nephron blockade 1

• Avoid excessive diuresis, which precipitates hypotension and worsening renal function, compromising tolerance of other therapies 1, 2

Additional Pharmacological Options for Selected Patients

After initiating SGLT2 inhibitors and optimizing diuretics, consider adding:

Mineralocorticoid Receptor Antagonists (Class 2b)

• Spironolactone 12.5-25 mg daily may be added, particularly in patients with LVEF in the lower preserved range (40-50%) 1, 2
• TOPCAT trial showed reduction in heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but no mortality benefit 1
• Monitor potassium and renal function closely to prevent hyperkalemia 1, 4

Angiotensin Receptor-Neprilysin Inhibitors (Class 2b)

• Sacubitril/valsartan may be considered specifically for women and patients with LVEF 45-57%, as these subgroups showed benefit in PARAGON-HF post-hoc analyses 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

Blood Pressure Management

Target blood pressure <130/80 mmHg using medications that provide heart failure benefits:

• After volume optimization with diuretics, use ACE inhibitors or ARBs as first-line antihypertensive agents 1, 2
• These agents effectively lower blood pressure and modestly reduce heart failure hospitalizations, though they lack the mortality benefit seen in HFrEF 1
• Nebivolol reduced the combined endpoint of mortality or cardiovascular hospitalization by approximately 19% in HFpEF patients and can be used when additional blood pressure control is needed 1

Critical Medications to Avoid

Do not prescribe the following in HFpEF patients:

• Nondihydropyridine calcium channel blockers (diltiazem, verapamil) increase risk of heart failure worsening and hospitalization due to negative inotropic effects 1, 4
• Nitrates are associated with a signal of harm in HFpEF 1
• Routine beta-blockers (unless indicated for atrial fibrillation rate control or other specific indications) have not shown benefit in HFpEF 1, 4

Management of Key Comorbidities

Systematic comorbidity management is essential, as these factors markedly influence outcomes:

Diabetes Mellitus

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefit on glucose and heart failure outcomes 1, 2

Atrial Fibrillation

• Use beta-blockers for rate control, monitoring exercise tolerance due to potential chronotropic incompetence 1
• Anticoagulate based on CHA₂DS₂-VASc score per standard atrial fibrillation guidelines 1

Hypertension

• Present in 60-89% of HFpEF patients and represents the most important modifiable risk factor 1
• Target <130/80 mmHg using ACE inhibitors, ARBs, or nebivolol 1, 2

Chronic Kidney Disease

• Monitor renal function and electrolytes regularly, particularly with MRAs or diuretics 1, 2
• Ensure eGFR thresholds are met before starting SGLT2 inhibitors (>30 mL/min/1.73 m² for dapagliflozin, >60 mL/min/1.73 m² for empagliflozin) 1

Non-Pharmacological Interventions

Prescribe supervised exercise training programs (Class 1 recommendation):

• Three sessions per week for 1-8 months at 40-90% of maximal exercise capacity 1, 2
• Improves aerobic exercise capacity by 12-14% and quality of life with clinically meaningful benefits 1
• Use walking, stationary cycling, or high-intensity interval training 1

Dietary modifications:

• Sodium restriction to <2-3 g/day to lessen congestive symptoms and support diuretic effectiveness 1, 2
• Weight reduction in obese patients 2

Monitoring and Follow-Up

Regular assessment should include:

• Symptoms, vital signs, and daily weight 2
• Volume status to guide diuretic titration 1, 2
• Renal function and electrolytes, especially with MRA therapy 1, 2
• Functional capacity to guide treatment adjustments 1

Consider advanced monitoring:

• Wireless, implantable pulmonary artery pressure monitors in selected patients with prior decompensated heart failure admissions to optimize volume status 1

Advanced Therapies for Refractory Disease

For patients with recurrent hospitalizations despite optimal therapy:

• Ultrafiltration may be employed as a last-resort strategy for persistent congestion despite maximal diuretic therapy 1
• Referral to an advanced heart failure specialist team is advised for HFpEF refractory to standard therapies 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 1

Common Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with HFrEF, as response to therapies differs significantly between these populations 1
• Do not overlook comorbidity management, which significantly impacts outcomes in HFpEF 1, 5
• Avoid inadequate dose titration of medications, which results in subtherapeutic dosing and reduced efficacy 4
• Do not use medications proven only for HFrEF without HFpEF-specific evidence 4