What is the treatment for Heart Failure with preserved Ejection Fraction (HFpEF)?

Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis, as this is the only therapy with proven mortality and morbidity benefits in HFpEF. 1, 2

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors (First-Line)

• Dapagliflozin or empagliflozin should be initiated as first-line disease-modifying therapy for all HFpEF patients (Class 2a recommendation). 3, 1, 4
• Dapagliflozin reduced the composite endpoint of 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. 2, 4
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED. 3, 2
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation. 4

Mineralocorticoid Receptor Antagonists (Second-Line)

• Consider adding spironolactone (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%). 3, 1, 4
• 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. 4
• Monitor potassium and renal function closely when prescribing spironolactone to minimize hyperkalemia risk. 4

Angiotensin Receptor-Neprilysin Inhibitors (Selective Use)

• Sacubitril/valsartan may be considered (Class 2b recommendation) for selected patients, particularly women and those with LVEF 45-57%. 3, 4
• The PARAGON-HF trial showed potential benefit in women (rate ratio 0.73; 95% CI 0.59-0.90) and patients with LVEF below the median of 45-57% (rate ratio 0.78; 95% CI 0.64-0.95). 4
• FDA approved sacubitril/valsartan for selected HFpEF patients in February 2021 based on post-hoc analyses. 3, 4

Symptom Management

Diuretic Therapy

• Use loop diuretics at the lowest effective dose to relieve congestion and manage orthopnea/paroxysmal nocturnal dyspnea. 1, 2, 4
• For acute decompensation, initial IV furosemide dose should be 20-40 mg (or at least equivalent to chronic oral dose if already on diuretics). 4
• Titrate diuretic dose based on congestion status to maintain euvolemia while avoiding excessive diuresis that leads to hypotension and renal dysfunction. 1, 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade. 4

Comorbidity Management

Blood Pressure Control

• Achieve blood pressure target <130/80 mmHg using appropriate antihypertensive medications. 3, 1, 2, 4
• Six guidelines strongly recommended tight control of hypertension as a prevention strategy. 3

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits. 2
• Five guidelines recommended initiation of SGLT2 inhibitors in patients with type 2 diabetes mellitus and high risk/presence of cardiovascular disease. 3

Atrial Fibrillation Management

• For patients with atrial fibrillation, achieve rate control using beta-blockers or non-dihydropyridine calcium channel blockers. 1

Non-Pharmacological Interventions

Exercise Training

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life. 3, 1, 2, 4
• Exercise training has demonstrated large, clinically meaningful improvements in symptoms and objectively determined exercise capacity in HFpEF. 3
• Current guidelines include a Class 1 recommendation (Level of Evidence A) for exercise training in patients with heart failure. 3

Lifestyle Modifications

• Recommend sodium restriction to <2-3 g/day and weight reduction in obese patients. 2
• All guidelines focused on control of reversible cardiovascular risk factors through lifestyle modification. 3

Monitoring and Follow-Up

• Regularly assess volume status, symptoms, vital signs, weight, renal function, and electrolytes. 1, 2, 4
• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension. 2
• Consider wireless pulmonary artery pressure monitoring devices in selected patients for optimizing volume status, as they reduced hospitalizations in HFpEF subgroup analysis. 3, 4

Critical Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly. 4, 5
• Avoid excessive diuresis which may lead to hypotension and worsening renal function. 4
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes in HFpEF. 4
• Diltiazem or verapamil are not recommended in HFpEF patients, as they increase the risk of heart failure worsening and hospitalization. 3

Advanced Treatment Considerations

• Refer to an advanced heart failure specialist team for patients with advanced HFpEF refractory to standard therapies. 4
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF. 4