Heart Failure with Preserved Ejection Fraction (HFpEF)

1. Definition (Guideline-Based)

According to:

• European Society of Cardiology (ESC 2021)
• American College of Cardiology / American Heart Association (ACC/AHA 2022)

HFpEF is defined as:

• Symptoms ± signs of heart failure
• LVEF ≥50%
• Evidence of cardiac structural and/or functional abnormality
• Elevated natriuretic peptides

2.  Pathophysiology 

A. Central Concept

HFpEF is primarily a diastolic dysfunction syndrome, but modern understanding = systemic disease with multi-organ involvement

B. Mechanisms

1. Diastolic Dysfunction

• Impaired LV relaxation (lusitropy ↓)
• Increased LV stiffness → ↑ LVEDP
• Normal EF but ↓ stroke volume reserve

2. Myocardial Remodeling

• Concentric LV hypertrophy
• Interstitial fibrosis
• Increased collagen deposition

3. Endothelial Dysfunction & Inflammation

• Chronic systemic inflammation (obesity, DM, CKD)
• ↓ nitric oxide → ↓ cGMP → ↑ stiffness

4. Microvascular Dysfunction

• Coronary microcirculation impairment
• ↓ myocardial perfusion reserve

5. Chronotropic Incompetence

• Blunted HR response → ↓ exercise capacity

6. Ventricular–Vascular Coupling Abnormality

• Arterial stiffness + LV stiffness → ↑ afterload

7. Pulmonary Hypertension

• Post-capillary → may progress to combined PH

3. Risk Factors & Epidemiology

Classic HFpEF Patient

• Elderly
• Female
• Multiple comorbidities

Major Risk Factors

• Hypertension (MOST IMPORTANT)
• Obesity
• Type 2 DM
• CKD
• Atrial fibrillation
• CAD

4. Clinical Features

Symptoms

• Dyspnea (exertional → rest)
• Orthopnea, PND
• Exercise intolerance
• Fatigue

Signs

• Raised JVP
• S4 gallop (common)
• Pulmonary crepitations
• Peripheral edema

5. Diagnosis 

A. Natriuretic Peptides

• BNP >35 pg/mL
• NT-proBNP >125 pg/mL

 Lower levels possible in obesity

B. Echocardiography (Cornerstone)

• LVEF ≥50%
• E/e′ >14 → ↑ filling pressure
• LA enlargement
• LVH
• TR velocity >2.8 m/s

C.ECG is supportive, not diagnostic,

1. Left Ventricular Hypertrophy (LVH)

• Due to chronic HTN
• High voltage QRS

 Sokolow-Lyon criteria:

• S in V1 + R in V5/V6 >35 mm

2. Left Atrial Enlargement (LAE)

• Broad, notched P wave (P mitrale)
• Seen in:
• Lead II (wide P wave)
• V1 (biphasic P)

3. Atrial Fibrillation (VERY COMMON)

• Strong clue toward HFpEF
• Loss of atrial kick → worsens symptoms

4. Non-specific ST-T Changes

• Due to LVH strain or ischemia

D. Scoring Systems 

1. H2FPEF Score

2. HFA-PEFF Algorithm (ESC)

3 domains:

• Functional (E/e′, TR velocity)
• Structural (LA size, LV mass)
• Biomarkers (BNP)

E. Gold Standard

• Invasive hemodynamics:
• ↑ LVEDP or PCWP ≥15 mmHg

6. Differential Diagnosis

• Constrictive pericarditis
• Restrictive cardiomyopathy
• Pulmonary disease
• Deconditioning

7. Management 

A. Core Principles

Unlike HFrEF:
– No strong mortality benefit drugs (except recent advances)
– Focus = symptom relief + comorbidity control

B. Drug Therapy (ACCORDING TO ACC/AHA 2022 & ESC 2021)

1. SGLT2 Inhibitors (FIRST-LINE NOW)

• Empagliflozin
• Dapagliflozin

✔ Reduce HF hospitalization
✔ Recommended regardless of diabetes

2. Diuretics (Symptom Control)

• Loop diuretics (e.g., Furosemide)

✔ Relieve congestion
 No mortality benefit

3. Mineralocorticoid Receptor Antagonists (MRA)

• Spironolactone

✔ Selected patients (TOPCAT trial subgroup benefit)

4. ARBs / ARNIs

• Valsartan
• Sacubitril/valsartan

✔ May reduce hospitalizations
✔ Benefit in EF 50–57% subgroup

5. Beta-blockers

• For:
• Rate control in AF
• Hypertension
• Ischemic heart disease

6. Rate/Rhythm Control in AF

• Anticoagulation (CHA₂DS₂-VASc)
• Rhythm control improves symptoms

C. Non-Pharmacological Management 

1. Lifestyle

• Salt restriction (<5 g/day)
• Weight loss (critical in obesity-related HFpEF)
• Exercise training (improves peak VO₂)

2. Comorbidity Management

3. Device Therapy

• Limited role
• Consider in:
• AF (ablation)
• Pulmonary HTN trials

8. Prognosis

• Mortality ≈ HFrEF (similar long-term)
• Hospitalization rate high
• Quality of life impaired

9. Phenotypes of HFpEF 

10. Key Trials