What is the primary management approach for Heart Failure with Preserved Ejection Fraction (HFpEF)?

Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

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

First-Line Pharmacological Management

Disease-Modifying Therapy

• Start SGLT2 inhibitors immediately as they reduce heart failure hospitalizations and cardiovascular death by 18-21% based on the DELIVER and EMPEROR-PRESERVED trials 1, 2
• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death (HR: 0.82; 95% CI: 0.73-0.92) and decreased heart failure hospitalizations by 23% (HR: 0.77; 95% CI: 0.67-0.89) 1
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 1

Symptom Management with Diuretics

• Use loop diuretics at the lowest effective dose to relieve congestion and manage fluid retention 3, 1
• For new-onset HFpEF with orthopnea/paroxysmal nocturnal dyspnea, start with 20-40 mg IV furosemide (or equivalent) 1
• Titrate diuretic dose based on symptoms and volume status before adding combination diuretic strategies 1
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade 1, 4

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (MRAs)

• Consider spironolactone (Class 2b recommendation) 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 the TOPCAT trial, though it did not significantly reduce the primary composite outcome 1
• Monitor potassium, renal function, and diuretic dosing carefully to minimize hyperkalemia and worsening renal function 1

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Sacubitril/valsartan may be considered (Class 2b recommendation) for selected patients, especially women and those with LVEF 45-57% 1, 2
• The PARAGON-HF trial showed potential benefit in patients with LVEF below the median (45%-57%) (rate ratio 0.78; 95% CI 0.64-0.95) and in women (rate ratio 0.73; 95% CI 0.59-0.90) 1
• This is a lower priority than SGLT2 inhibitors given the Class 2b recommendation versus Class 2a for SGLT2 inhibitors 1

Management of Comorbidities

• Optimize blood pressure control to target <130/80 mmHg using appropriate antihypertensive medications 1, 4
• Manage diabetes with preference for SGLT2 inhibitors given their additional heart failure benefits 1, 4
• For atrial fibrillation, prescribe anticoagulation based on CHA₂DS₂-VASc score and control rate using beta-blockers or non-dihydropyridine calcium channel blockers 5, 4
• Avoid diltiazem or verapamil as they increase the risk of heart failure worsening and hospitalization 4

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life 1, 4
• Recommend sodium restriction to <2-3 g/day to reduce congestive symptoms 4
• Offer multidisciplinary heart failure programs to all patients 1

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with MRA therapy 1, 4
• Monitor symptoms, vital signs, weight, and functional capacity to guide treatment adjustments 1, 4
• Adjust diuretic doses based on congestion status to avoid overdiuresis which can lead to hypotension 4
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 4

Critical Pitfalls to Avoid

• Do not delay initiation of SGLT2 inhibitors which have proven mortality and morbidity benefits 4
• Avoid treating HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations 1
• Do not use excessive diuresis which may lead to hypotension and worsening renal function 1, 4
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes 1
• Do not assume all heart failure medications work in HFpEF, as most traditional heart failure therapies have not shown efficacy in this population 4

Advanced Treatment Options

• Consider referral to an advanced heart failure specialist team for patients with advanced HFpEF refractory to standard therapies 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 1