HFrEF vs HFpEF: Key Differences and Management
HFrEF is defined by LVEF ≤40% and has robust evidence-based therapies that reduce mortality, while HFpEF is defined by LVEF ≥50% with evidence of elevated filling pressures and has limited mortality-reducing treatments, requiring a focus on symptom management and comorbidity control. 1
Diagnostic Definitions
LVEF-Based Classification
- HFrEF: LVEF ≤40%
- HFmrEF (mildly reduced): LVEF 41-49%
- HFpEF: LVEF ≥50%
- HFimpEF (improved): Previous LVEF ≤40% that improved to >40% 1
Critical Diagnostic Requirement for HFpEF/HFmrEF
HFpEF and HFmrEF diagnoses require more than just preserved EF—you must document evidence of elevated LV filling pressures through:
- Elevated natriuretic peptides (BNP/NT-proBNP)
- Echocardiographic diastolic dysfunction (E/e' ≥15)
- Invasive hemodynamic measurements at rest or exercise
- Structural heart disease (increased left atrial volume index or LV mass index) 1
Common Pitfall: Do not diagnose HFpEF based solely on symptoms plus normal EF—this leads to misdiagnosis. The H₂FPEF score can help: obesity, atrial fibrillation, age >60 years, ≥2 antihypertensives, E/e' >9, and PA systolic pressure >35 mmHg. Scores ≥6 indicate high likelihood of HFpEF 1.
Patient Demographics and Comorbidities
HFpEF Patients Are:
- Older (median age ~73.5 vs 69.5 years for HFrEF) 2
- More often female (56-59% vs 26% in HFrEF) 2, 3
- Higher prevalence of:
HFrEF Patients Are:
- More likely to have:
Laboratory Differences
NT-proBNP, troponin, and CRP levels are significantly higher in HFrEF compared to HFpEF, though both groups have elevated natriuretic peptides 2.
Management Approaches
HFrEF Management: Evidence-Based Mortality Reduction
Continue all HFrEF therapies even if EF improves to >40% (HFimpEF), as EF can decrease after medication withdrawal 1.
The robust GDMT for HFrEF includes:
- ACE inhibitors/ARBs/ARNIs
- Beta-blockers
- Mineralocorticoid receptor antagonists
- SGLT2 inhibitors
- These therapies have proven survival benefit in multiple RCTs 1
HFpEF Management: Symptom Control and Emerging Therapies
No therapies have definitively proven mortality reduction in HFpEF until recently 5, 6. Current approach:
First-Line Therapy
SGLT2 inhibitors (empagliflozin, dapagliflozin) are now the cornerstone of HFpEF treatment, reducing cardiovascular death and heart failure hospitalization in EMPEROR-Preserved and DELIVER trials 7, 8, 9.
Additional Therapies
- Diuretics: For fluid retention and symptom relief (no mortality benefit proven) 6
- Aggressive comorbidity management: Hypertension control, diabetes management, weight loss 5, 6
- Finerenone (nonsteroidal MRA): Emerging evidence as adjunct therapy 7, 9
- GLP-1 receptor agonists (semaglutide): Promising for obesity-related HFpEF, improving functional capacity 8, 9
- ARNIs: Under investigation, some promise in selected populations 6, 9
What NOT to Expect
Traditional HFrEF medications (ACE inhibitors, ARBs, beta-blockers) have not shown mortality benefit in large HFpEF trials 5, 6. Use them for comorbidity management (hypertension, CAD) but not as primary HFpEF therapy.
Outcomes
Despite different pathophysiology, 30-day mortality (7.8-10.2%) and readmission rates (22-25%) are similar between HFrEF and HFpEF 3. Both carry substantial morbidity and mortality burden, but HFpEF lacks the proven mortality-reducing therapies available for HFrEF.
Key Clinical Pearls
For women: Higher lifetime risk of HFpEF, history of pre-eclampsia increases risk, and sex-specific differences in presentation warrant careful evaluation 10.
Trajectory matters: LVEF can change over time. Serial measurements are essential, particularly in HFmrEF (41-49%), which represents a dynamic state between HFrEF and HFpEF 1.
Pathophysiology divergence: HFpEF involves systemic inflammation, endothelial dysfunction, and myocardial fibrosis—fundamentally different from the neurohormonal activation predominant in HFrEF 4, 9. This explains why HFrEF therapies fail in HFpEF.