What is the initial management approach for patients with Heart Failure with preserved Ejection Fraction (HFpEF)?

Initial Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin or empagliflozin) immediately as first-line disease-modifying therapy, combined with loop diuretics titrated to the lowest effective dose for symptom relief if the patient has congestion. 1, 2

Immediate Pharmacological Interventions

Disease-Modifying Therapy (Start First)

Initiate SGLT2 inhibitors early as they provide mortality and morbidity benefits with strong evidence from major trials:

• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR: 0.82; 95% CI: 0.73-0.92) in the DELIVER trial and decreased heart failure hospitalizations by 23% (HR: 0.77; 95% CI: 0.67-0.89) 2
• Empagliflozin reduced hospitalization for heart failure and cardiovascular death by 21% (HR: 0.79; 95% CI: 0.69-0.90) in the EMPEROR-PRESERVED trial 2
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 2
• SGLT2 inhibitors carry a Class 2a recommendation (Level of Evidence: B-R), indicating they "can be beneficial in decreasing HF hospitalizations and cardiovascular mortality" 2

Symptom Management with Diuretics

Use loop diuretics at the lowest effective dose to manage fluid retention and relieve congestion:

• For new-onset HFpEF with orthopnea/paroxysmal nocturnal dyspnea, start with 20-40 mg IV furosemide (or equivalent) 2
• For patients already on chronic diuretic therapy, the initial IV dose should be at least equivalent to their oral dose 2
• Titrate diuretic dose based on symptoms and volume status before considering combination diuretic strategies 2
• If inadequate response despite dose increases, consider changing to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade 2

Additional Pharmacological Options (Second-Line)

Mineralocorticoid Receptor Antagonists (MRAs)

Consider spironolactone particularly in patients with LVEF in the lower range of preservation (40-50%):

• Spironolactone has a Class 2b recommendation (Level of Evidence: B-R), indicating it "may be considered to decrease hospitalizations, particularly among patients with LVEF on the lower end of this spectrum" 2
• The TOPCAT trial showed spironolactone reduced heart failure hospitalizations (HR: 0.83; 95% CI: 0.69-0.99) though it did not significantly reduce the primary composite outcome 2
• Monitor potassium, renal function, and diuretic dosing carefully to minimize hyperkalemia risk 2

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

Sacubitril/valsartan may be considered for selected patients, especially women and those with LVEF 45-57%:

• The PARAGON-HF trial did not achieve a significant reduction in the primary composite endpoint (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06) 2
• Prespecified subgroup analyses showed potential benefit in patients with LVEF 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) 2
• Carries a Class 2b recommendation, indicating it "may be considered" for selected patients 2

Management of Comorbidities (Essential Component)

Hypertension Control

Target blood pressure <130/80 mmHg using appropriate antihypertensive medications 2, 3

Diabetes Management

Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits 2, 3

Atrial Fibrillation Management

• Prescribe anticoagulation based on CHA₂DS₂-VASc score to prevent thromboembolic events 1
• Control rate using beta-blockers (cardioselective agents preferred if COPD present) or non-dihydropyridine calcium channel blockers 1, 3

Non-Pharmacological Interventions

Prescribe supervised exercise training programs to improve functional capacity and quality of life 2, 3

Implement sodium restriction to <2-3 g/day to reduce congestive symptoms 3

Consider fluid restriction when appropriate based on congestion status 3

Monitoring and Follow-Up Strategy

Regularly assess the following parameters to guide treatment adjustments:

• Volume status, symptoms, vital signs, and weight 2, 3
• Renal function and electrolytes, especially with MRA therapy 1, 2
• Functional capacity to guide treatment optimization 2
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 2, 3

Critical Pitfalls to Avoid

Do not delay initiation of SGLT2 inhibitors, which have proven mortality and morbidity benefits 3

Avoid excessive diuresis, which can lead to hypotension, worsening renal function, and impaired tolerance of other medications 2, 3

Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations 2

Do not overlook comorbidity management, including hypertension, diabetes, obesity, and atrial fibrillation, which significantly impact outcomes 2, 3

Avoid assuming all traditional heart failure medications work in HFpEF, as most have not shown efficacy in this population 3