What is the recommended initial management for a patient with heart failure with preserved ejection fraction (LVEF ≥ 50%) presenting with dyspnea or fatigue?

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

For a patient with HFpEF (LVEF ≥50%) presenting with dyspnea or fatigue, initiate an SGLT2 inhibitor (empagliflozin or dapagliflozin) immediately after confirming the diagnosis, optimize diuretics to the lowest dose that relieves congestion, and aggressively manage blood pressure to <130/80 mmHg using ACE inhibitors or ARBs as first-line agents. 1, 2, 3

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis requires:

• Symptoms/signs of heart failure (dyspnea, orthopnea, jugular venous distension, rales, peripheral edema) 1
• LVEF ≥50% on echocardiography 1
• Elevated natriuretic peptides: BNP >35 pg/mL (ambulatory) or >100 pg/mL (hospitalized); NT-proBNP >125 pg/mL (ambulatory) or >300 pg/mL (hospitalized) 1
• Evidence of structural/functional cardiac abnormality: E/e' ≥15, left atrial enlargement, increased LV mass, or invasive hemodynamic confirmation 1

Critical pitfall: Natriuretic peptides may be lower in HFpEF than HFrEF for the same degree of elevated filling pressure, and obesity further suppresses levels—do not exclude HFpEF based solely on borderline natriuretic peptides. 1

First-Line Pharmacological Management

SGLT2 Inhibitors (Highest Priority)

Start empagliflozin 10 mg daily or dapagliflozin 10 mg daily regardless of diabetes status. 2, 3

• These agents reduce HF hospitalizations (HR 0.77-0.82) based on DELIVER and EMPEROR-PRESERVED trials 2
• This is the only medication class with robust evidence for reducing morbidity in HFpEF 1, 2
• Continue indefinitely unless contraindicated 2

Diuretic Optimization

Titrate loop diuretics to the lowest effective dose that maintains euvolemia. 2, 3

• Use for symptomatic relief of congestion only—diuretics do not improve prognosis 2
• Monitor closely for volume depletion, electrolyte disturbances (especially hypokalemia), and worsening renal function 2
• Check serum electrolytes, BUN, and creatinine within 1-2 weeks of dose adjustments 2

Common pitfall: Excessive diuresis causes hypotension and prerenal azotemia, which limits use of other guideline-directed therapies and worsens outcomes. 2

Blood Pressure Control

Target systolic BP <130/80 mmHg (or <140/90 mmHg if age ≥65 years). 2

Use ACE inhibitors or ARBs as first-line antihypertensive agents:

• Start lisinopril 10 mg daily or losartan 50 mg daily 2
• Titrate upward until BP target achieved 2
• These agents effectively control BP but do not provide the mortality benefit seen in HFrEF 2

If additional BP control needed:

• Increase metoprolol succinate from 100 mg to 200 mg daily for additional BP and heart rate control 2
• Important caveat: Beta-blockers alone are insufficient for HFpEF management—mortality benefit is weak compared to HFrEF 2

Mineralocorticoid Receptor Antagonist Consideration

Add spironolactone 12.5-25 mg daily in selected patients if: 2

• Serum potassium <5.0 mmol/L
• Creatinine <2.5 mg/dL
• eGFR >30 mL/min/1.73m²

The TOPCAT trial showed modest reduction in HF hospitalizations (HR 0.83) but no mortality benefit. 2 Close monitoring of potassium and renal function is mandatory when combined with ACE inhibitors/ARBs. 2

Comorbidity Management

Aggressively treat comorbidities as they directly impact HFpEF outcomes: 1

• Atrial fibrillation: Control ventricular rate; consider rhythm control strategy 1
• Obesity: Recommend supervised weight reduction program 3
• Diabetes: SGLT2 inhibitors serve dual purpose for glycemic control and HF management 2
• Coronary artery disease: Systematically evaluate and revascularize if indicated 4

Monitoring Strategy

Check within 1-2 weeks of initiating/adjusting therapy: 2

• Serum potassium (especially with RAAS inhibitors + MRA)
• BUN and creatinine
• Orthostatic blood pressures
• Volume status assessment

When to Refer to Cardiology

Refer to general cardiologist if: 1

• Diagnostic uncertainty remains after initial workup
• Need to exclude HFpEF mimics (infiltrative cardiomyopathy, hypertrophic cardiomyopathy, valvular disease, pericardial disease, high-output HF) 1
• Suboptimal response to initial GDMT

Refer to HF specialist if: 1

• Advanced diagnostic testing needed (exercise echocardiography, invasive hemodynamics)
• Unusual or complex cardiomyopathy suspected
• Clinical trial eligibility consideration
• Refractory symptoms despite optimized therapy

What NOT to Do

Do not rely on beta-blockers as primary HFpEF therapy—evidence for mortality benefit is limited and they should be used primarily for BP/rate control or other indications (post-MI, atrial fibrillation). 2

Do not continue aggressive diuresis once euvolemia achieved—this causes electrolyte abnormalities and renal dysfunction that prevent optimization of other therapies. 2

Do not withhold ACE inhibitors/ARBs or beta-blockers for mild hyponatremia—their benefits outweigh concerns unless severe hemodynamic instability present. 5