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

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

Start SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately as first-line disease-modifying therapy for all patients with HFpEF, combined with loop diuretics for symptom relief in those with congestion. 1, 2, 3

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm the diagnosis using a two-step approach:

• Establish heart failure symptoms with LVEF ≥50%, elevated natriuretic peptides, and evidence of structural heart disease or elevated filling pressures 1, 3
• If uncertain after initial evaluation, proceed to stress testing to confirm diagnosis 1
• Rule out HFpEF mimics including cardiac amyloidosis, hypertrophic cardiomyopathy, pericardial disease, valvular disease, or high-output states that require specific alternative treatments 1, 3

First-Line Disease-Modifying Therapy

SGLT2 Inhibitors (Class 2a Recommendation)

SGLT2 inhibitors are the cornerstone of disease-modifying therapy and should be initiated early to maximize mortality and morbidity benefits. 1, 2, 3

• Dapagliflozin 10 mg daily reduces cardiovascular death and HF hospitalizations by 18% (HR 0.82,95% CI 0.73-0.92) based on the DELIVER trial 2, 3
• Empagliflozin 10 mg daily reduces HF hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) based on EMPEROR-PRESERVED 2, 3
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 2, 3
• Do not delay initiation of SGLT2 inhibitors as they have proven mortality benefits 1

Symptom Management with Diuretics

Loop Diuretics for Congestion

• Use loop diuretics at the lowest effective dose to relieve dyspnea, orthopnea, and edema in patients with fluid overload 1, 2, 3
• 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, initial IV dose should be at least equivalent to oral dose 2
• Titrate diuretic dose based on symptoms and volume status before considering combination diuretic strategies 1, 2
• If inadequate response despite dose increases, consider changing to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade 2

Critical Pitfall to Avoid

• Avoid excessive diuresis which can lead to hypotension, worsening renal function, and impaired tolerance of other medications 1, 2

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (Class 2b Recommendation)

• Consider spironolactone particularly in patients with LVEF in the lower range of preservation (40-50%) 1, 2
• Spironolactone reduced heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial 2
• Monitor potassium, renal function, and diuretic dosing carefully to minimize risk of hyperkalemia and worsening renal function 2

Angiotensin Receptor-Neprilysin Inhibitors (Class 2b Recommendation)

• Sacubitril/valsartan may be considered for selected patients, particularly 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) 2
• This is a Class 2b recommendation, meaning it is lower priority than SGLT2 inhibitors 2

Management of Comorbidities

Blood Pressure Control

• Target blood pressure <130/80 mmHg using appropriate antihypertensive medications 1, 2, 3
• Avoid diltiazem or verapamil as they increase risk of heart failure worsening and hospitalization 2, 3

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefits for diabetes and heart failure 1, 2, 3

Atrial Fibrillation Management

• Control rate using beta-blockers or non-dihydropyridine calcium channel blockers in HFpEF patients with atrial fibrillation 1

Non-Pharmacological Interventions

Exercise Training (Class 1 Recommendation)

• Prescribe supervised exercise training programs to improve functional capacity and quality of life 1, 2, 3
• This is a Class 1 recommendation with Level of Evidence A, making it one of the strongest recommendations in HFpEF management 2

Dietary Modifications

• Recommend sodium restriction to <2-3 g/day to reduce congestive symptoms 1, 2, 3
• Consider fluid restriction when appropriate 1

Monitoring and Follow-up

• Monitor symptoms, weight, vital signs, renal function, and electrolytes regularly 1, 2, 3
• Adjust diuretic doses based on daily weights and congestion status to avoid both under- and over-diuresis 1, 3
• Reassess volume status at each visit 3
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 1, 2

Treatment Algorithm Summary

Step 1: Confirm diagnosis and rule out mimics 1, 3

Step 2: Initiate SGLT2 inhibitor (dapagliflozin or empagliflozin) immediately 1, 2, 3

Step 3: Add loop diuretic if congestion present, titrate to lowest effective dose 1, 2, 3

Step 4: Optimize blood pressure control to <130/80 mmHg, avoiding diltiazem/verapamil 1, 2, 3

Step 5: Consider adding spironolactone if LVEF 40-50% 1, 2

Step 6: Consider sacubitril/valsartan for women or those with LVEF 45-57% 1, 2

Step 7: Prescribe supervised exercise training 1, 2, 3

Step 8: Implement sodium restriction <2-3 g/day 1, 2, 3

Key Pitfall to Avoid

Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations 2, 4