Heart Failure with Preserved Ejection Fraction (HFpEF)
Heart Failure with Preserved Ejection Fraction (HFpEF)
Definition
HFpEF is a clinical syndrome of heart failure symptoms and signs with:
- LVEF ≥ 50%
- Objective evidence of elevated LV filling pressures, at rest or with exercise
- Structural heart disease and/or diastolic dysfunction
HFpEF is not “diastolic HF alone” — it is a systemic, inflammatory, cardiometabolic syndrome.
Epidemiology
- Accounts for ~50% of all HF
- Increasing prevalence due to:
- Aging population
- Obesity
- Diabetes
- Hypertension
- Higher prevalence in women and elderly
Pathophysiology (Core Concept)
HFpEF is driven by multiorgan dysfunction, not isolated LV relaxation abnormality.
Central Mechanistic Pathway
Comorbidities → Systemic inflammation → Coronary microvascular endothelial dysfunction → ↓ NO–cGMP–PKG signaling → Myocardial stiffness
Key Contributors
- LV concentric remodeling / hypertrophy
- Increased myocardial fibrosis
- Impaired relaxation
- Increased arterial stiffness
- Chronotropic incompetence
- Pulmonary hypertension (post-capillary ± pre-capillary)
- RV dysfunction
- Renal dysfunction
Common Comorbidities (Hallmark of HFpEF)
- Hypertension
- Obesity
- Type 2 diabetes mellitus
- Atrial fibrillation
- Chronic kidney disease
- Obstructive sleep apnea
- COPD
- Iron deficiency
Clinical Features
- Exertional dyspnea (early and predominant)
- Fatigue
- Orthopnea / PND
- Peripheral edema
- Exercise intolerance (disproportionate to resting echo findings)
Diagnostic Approach
Step 1: Clinical Suspicion
HF symptoms + preserved EF
Step 2: Objective Evidence of Elevated Filling Pressure
Echocardiography (Key Parameters)
- E/e′ > 14
- Septal e′ < 7 cm/s or lateral e′ < 10 cm/s
- LA volume index > 34 mL/m²
- TR velocity > 2.8 m/s
- LV concentric remodeling / hypertrophy
Step 3: Natriuretic Peptides
- BNP / NT-proBNP:
- Often lower than HFrEF
- May be normal in obese patients
- Still prognostic
Scoring Systems (High-Yield)
H₂FPEF Score
| Variable | Points |
|---|---|
| Heavy (BMI > 30) | 2 |
| Hypertension (≥2 drugs) | 1 |
| Atrial fibrillation | 3 |
| Pulmonary hypertension | 1 |
| Elder (>60 yr) | 1 |
| Filling pressure (E/e′ > 9) | 1 |
- 0–1: Low probability
- 2–5: Intermediate
- 6–9: High probability
HFA-PEFF Algorithm (ESC)
Domains:
- Functional
- Morphological
- Biomarkers
Score:
- ≥5 → HFpEF confirmed
- 2–4 → Stress testing / invasive hemodynamics
- ≤1 → HFpEF unlikely
Role of Exercise Testing
- Diastolic stress echo
- Invasive CPET (gold standard in equivocal cases)
- PAWP ≥ 25 mmHg during exercise = HFpEF
Management Principles
1. Treat Congestion
- Loop diuretics (symptom relief only)
- Avoid over-diuresis
2. Disease-Modifying Therapies (Evidence-Based)
SGLT2 Inhibitors (Cornerstone)
- Empagliflozin (EMPEROR-Preserved)
- Dapagliflozin (DELIVER)
Benefits:
- ↓ HF hospitalization
- Benefit across EF spectrum
- Independent of diabetes status
Class I recommendation (current guidelines)
RAAS Inhibition
- ACEI / ARB / ARNI:
- No robust mortality benefit
- Useful for:
- Hypertension
- Proteinuric CKD
- Post-MI
- Sacubitril–valsartan: modest benefit (PARAGON-HF, subgroup EF 45–57%)
Mineralocorticoid Receptor Antagonists
- Spironolactone (TOPCAT)
- Reduces HF hospitalization
- Regional variability; best in:
- Elevated BNP
- Prior HF admission
3. Rate & Rhythm Control
- Aggressive management of AF
- Rhythm control often improves symptoms
- Avoid excessive beta-blockade (chronotropic incompetence)
4. Comorbidity-Focused Therapy (Most Important)
- Strict BP control (<130/80)
- Weight loss (very high yield)
- Glycemic control
- Treat sleep apnea
- Manage iron deficiency
- Pulmonary hypertension evaluation if disproportionate
Therapies with No Proven Benefit
- Routine beta-blockers (unless other indication)
- Digoxin
- Nitrates (NEAT-HFpEF negative)
- PDE-5 inhibitors
Prognosis
- Mortality similar to HFrEF
- Major cause of hospitalization
- Outcome driven largely by:
- Comorbidity burden
- Pulmonary hypertension
- RV dysfunction
Key Exam Pearls
- HFpEF = systemic inflammatory cardiometabolic disease
- Normal BNP does not exclude HFpEF
- Obesity masks HFpEF biomarkers
- SGLT2 inhibitors are the only class with consistent outcome benefit
- Exercise hemodynamics are decisive in borderline cases
