What is the primary treatment goal and management strategy for patients with Heart Failure with preserved Ejection Fraction (HFpEF)?

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 titrated to the lowest effective dose for symptom relief. 1, 2

Initial Pharmacological Approach

Disease-Modifying Therapy (Start First)

• Initiate SGLT2 inhibitors as the cornerstone of HFpEF treatment, with dapagliflozin (Class 2a recommendation) showing a 23% reduction in heart failure hospitalizations (HR: 0.77; 95% CI: 0.67-0.89) and an 18% reduction in the composite endpoint of worsening heart failure and cardiovascular death (HR: 0.82; 95% CI: 0.73-0.92) in the DELIVER trial. 1, 2

• Empagliflozin demonstrated similar benefits in EMPEROR-PRESERVED with a 21% reduction in hospitalization for heart failure and cardiovascular death (HR: 0.79; 95% CI: 0.69-0.90). 1

• Verify eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before starting therapy. 1

Symptom Management with Diuretics

• Use loop diuretics (furosemide 20-40 mg daily initially) titrated to relieve congestion while avoiding excessive diuresis that can cause hypotension and worsening renal function. 3, 1, 2

• For acute decompensation with orthopnea/paroxysmal nocturnal dyspnea, start with 20-40 mg IV furosemide (or equivalent); if already on chronic diuretics, use at least the equivalent of their oral dose intravenously. 1

• If inadequate response despite dose escalation, switch to a different loop diuretic (bumetanide 0.5-1.0 mg or torasemide 5-10 mg) or add a thiazide diuretic for sequential nephron blockade. 3, 1

Secondary Pharmacological Options

Mineralocorticoid Receptor Antagonists

• Consider spironolactone (12.5-25 mg daily, up to 50 mg) specifically for patients with LVEF in the lower preserved range (40-50%), as it carries a Class 2b recommendation based on the TOPCAT trial showing a 17% reduction in heart failure hospitalizations (HR: 0.83; 95% CI: 0.69-0.99) despite not meeting the primary composite endpoint. 1, 2

• Monitor potassium levels closely (target <5.0 mEq/L) and renal function every 1-2 weeks after initiation and dose changes, then monthly once stable. 1, 2

Angiotensin Receptor-Neprilysin Inhibitors

• Consider sacubitril/valsartan (starting 24/26 mg twice daily, target 97/103 mg twice daily) for women and patients with LVEF 45-57%, based on PARAGON-HF subgroup analyses showing benefit in these populations (rate ratio 0.73; 95% CI 0.59-0.90 for women). 1, 2

• This carries a Class 2b recommendation and should be considered after SGLT2 inhibitors are established. 1

Angiotensin Receptor Blockers

• Candesartan may be considered as an alternative if ARNIs are not tolerated, based on CHARM-Preserved showing reduction in investigator-reported heart failure admissions, though this is a weaker recommendation. 3, 2

Comorbidity Management (Critical Component)

Blood Pressure Control

• Target blood pressure <130/80 mmHg using the medications above that also treat HFpEF (SGLT2 inhibitors, ARNIs, ARBs, or MRAs), avoiding the need for additional antihypertensives when possible. 1, 2

Diabetes Management

• Preferentially use SGLT2 inhibitors for diabetes control in HFpEF patients, providing dual benefit for both conditions. 1, 2

Atrial Fibrillation Management

• Prescribe anticoagulation based on CHA₂DS₂-VASc score (anticoagulate if score ≥2 in men or ≥3 in women). 4

• Use cardioselective beta-blockers (metoprolol, bisoprolol) for rate control, particularly in patients with concurrent COPD, avoiding non-selective agents. 4

Coronary Artery Disease

• Treat myocardial ischemia aggressively with revascularization when appropriate, as ischemia significantly worsens HFpEF outcomes. 3, 2

Non-Pharmacological Interventions

Exercise Training

• Prescribe supervised exercise training programs showing large, clinically meaningful improvements in exercise capacity and quality of life, with effect sizes comparable to or larger than those seen in HFrEF. 3

• Exercise training addresses the peripheral vascular, skeletal muscle, and cardiovascular abnormalities that contribute to exercise intolerance in HFpEF through pleiotropic effects. 3

Weight Management and Lifestyle

• Implement sodium restriction (<2-3 grams daily) and fluid restriction (1.5-2 liters daily) for volume management. 2, 5

• Encourage weight loss in obese patients, as obesity is a major contributor to HFpEF pathophysiology. 2, 6

Monitoring Strategy

• Assess volume status, renal function (creatinine, eGFR), and electrolytes (potassium, sodium) every 1-2 weeks after medication changes, then every 3 months once stable. 1, 2

• Monitor natriuretic peptide levels (BNP or NT-proBNP) to assess disease severity and guide therapy adjustments. 2

• Track functional capacity using 6-minute walk distance or cardiopulmonary exercise testing to objectively measure treatment response. 3

• Consider wireless implantable pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations to optimize volume status. 1, 2

Critical Pitfalls to Avoid

• Do not treat HFpEF patients identically to HFrEF patients—many HFrEF therapies (high-dose beta-blockers without specific indication, digoxin in sinus rhythm) lack evidence in HFpEF and may worsen outcomes. 1, 5

• Avoid excessive diuresis leading to hypotension, prerenal azotemia, and worsening fatigue, which paradoxically reduces functional capacity. 1

• Do not overlook comorbidity management, as hypertension, diabetes, obesity, atrial fibrillation, and coronary disease significantly impact HFpEF outcomes and must be aggressively treated. 1, 2

• Avoid using beta-blockers as primary HFpEF therapy unless specific indications exist (recent MI, angina, atrial fibrillation requiring rate control), as they lack mortality benefit in HFpEF and may worsen chronotropic incompetence. 2

Referral Indications

• Refer to a heart failure specialist when patients remain symptomatic (NYHA Class III-IV) despite optimal medical therapy, have recurrent hospitalizations, or require advanced therapies. 3, 2

• Consider referral for cardiac transplantation evaluation in eligible patients with advanced, refractory HFpEF. 1