What are the recommended diagnostic and therapeutic approaches for heart failure with reduced ejection fraction (EF < 40%) versus heart failure with preserved ejection fraction (EF ≥ 50%)?

HFrEF vs. HFpEF: Diagnostic and Therapeutic Approaches

Diagnostic Classification

HFrEF is defined as heart failure with LVEF ≤40%, while HFpEF is defined as heart failure with LVEF ≥50%, with HFmrEF (LVEF 41-49%) representing an intermediate category that likely behaves more like HFrEF. 1, 2

Key Diagnostic Thresholds

• HFrEF: LVEF ≤40% 2
• HFmrEF: LVEF 41-49% 3, 2
• HFpEF: LVEF ≥50% 1, 2

Universal Diagnostic Criteria (Both Types)

Both HFrEF and HFpEF require symptoms/signs of heart failure PLUS at least one of the following: 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)
• Objective evidence of cardiogenic pulmonary or systemic congestion

Critical caveat: In HFpEF, natriuretic peptide levels are typically lower than HFrEF for the same degree of left ventricular end-diastolic pressure elevation, and higher BMI (prevalent in HFpEF) further suppresses these levels. 1

Clinical Features That Distinguish HFpEF from HFrEF

HFpEF patients are more likely to be:

• Female 4
• Older (>70 years) 5
• Have atrial fibrillation 4
• Have hypertension with concentric remodeling 6

HFrEF patients are more likely to have:

• Coronary heart disease 4
• Higher heart rate 4
• Left bundle branch block 4
• Ischemic ECG changes 4

HFpEF-Specific Diagnostic Considerations

Echocardiographic findings supporting HFpEF include: 6

• E/E' ratio >15 (elevated filling pressures)
• Increased relative wall thickness (RWT >0.42)
• Left atrial enlargement (>4.0 cm)
• Short mitral deceleration time (<120 ms)

Must exclude HFpEF mimics before finalizing diagnosis: 6

• Infiltrative cardiomyopathies (amyloidosis, sarcoidosis)
• Hypertrophic cardiomyopathy
• Valvular heart disease
• Pericardial disease

Therapeutic Approaches

HFrEF: Guideline-Directed Medical Therapy (GDMT)

The cornerstone of HFrEF management is quadruple therapy with proven mortality benefit, though specific evidence is not provided in these documents for HFrEF treatment details. The focus here is on the distinct HFpEF approach.

HFpEF: First-Line Therapy

Initiate SGLT2 inhibitors (dapagliflozin or empagliflozin) as first-line therapy for all HFpEF patients, as they reduce heart failure hospitalization or cardiovascular death by approximately 20%. 6

Loop diuretics (furosemide 20-40 mg daily, titrated to symptoms) should be prescribed to manage congestion. 6

HFpEF: Additional Pharmacological Options

Mineralocorticoid receptor antagonists (spironolactone 25 mg daily) may be considered in selected patients, particularly women and those with lower ejection fractions within the HFpEF range, with monitoring of potassium and renal function. 6

ARNI (sacubitril/valsartan) may be considered in patients who remain symptomatic despite first-line therapy, with potential benefit in women and those with LVEF below the normal range. 6

Critical Medication Differences

Beta-blockers should only be used in HFpEF if there are specific indications (prior MI, angina, or atrial fibrillation requiring rate control), unlike HFrEF where they are foundational therapy. 6

Avoid NSAIDs in HFpEF as they may worsen the condition. 6

Non-Pharmacological Management (Both Types, Emphasized in HFpEF)

Exercise training should be recommended to improve functional capacity and quality of life, with supervised cardiac rehabilitation if available. 6

Target 5-10% weight reduction in patients with obesity, and implement daily weight monitoring to detect early fluid retention. 6

Comorbidity Management (Particularly Important in HFpEF)

Aggressively manage hypertension with target BP <130/80 mmHg, as HFpEF patients frequently have concentric remodeling from chronic pressure overload. 6

Screen for and treat sleep apnea with sleep study if clinically indicated. 6

Women with HFpEF require special attention to pregnancy history, as pre-eclampsia increases risk for subsequent HFpEF hospitalization. 1

HFmrEF: Treatment Approach

HFmrEF should be treated more like HFrEF than HFpEF, given the high prevalence of coronary artery disease and similar response to HF therapies. 7

Serial EF measurements are necessary in HFmrEF patients, as they typically exist on a dynamic trajectory—either improving from HFrEF or deteriorating toward HFrEF. 3

Monitoring and Follow-up

Regular clinical assessment for symptoms and signs of congestion, with echocardiographic follow-up to assess response to therapy and natriuretic peptide levels to monitor disease activity. 6

Consider pulmonary artery pressure monitoring (CardioMEMS) in patients with recurrent hospitalizations. 6

Device Therapy Considerations

For HFrEF patients with LVEF ≤35% despite >3 months of optimal medical therapy, permanent ICD is recommended for primary prevention. 2

Wearable cardioverter-defibrillators may be considered as bridge therapy for recent MI patients with LVEF ≤35% during the 40-day waiting period before permanent ICD eligibility. 2

Key Clinical Pitfalls

Do not assume all dyspnea in patients with preserved EF is HFpEF—systematically exclude pulmonary, renal, and other cardiac causes. 1

Do not rely on a single EF measurement for HFmrEF diagnosis, as these patients are on a dynamic trajectory. 3

Do not apply HFrEF mortality-reducing therapies indiscriminately to HFpEF—only SGLT2 inhibitors have proven benefit across the spectrum. 6, 8