Heart Failure with Preserved Ejection Fraction (HFpEF)
Summary
Heart Failure with Preserved Ejection Fraction (HFpEF) is a clinical syndrome characterised by signs and symptoms of heart failure with a left ventricular ejection fraction (LVEF) ≥50% and evidence of diastolic dysfunction or elevated filling pressures. Accounting for approximately 50% of all heart failure cases, HFpEF is increasingly prevalent due to aging populations and rising rates of obesity, hypertension, and diabetes. Unlike HFrEF, therapeutic options for HFpEF have been limited until recent trials demonstrated benefit of SGLT2 inhibitors. Management focuses on treating underlying comorbidities, diuretics for congestion, and lifestyle modification.
Key Facts
- Definition: LVEF ≥50% with symptoms/signs of HF and evidence of elevated filling pressures
- Prevalence: 50% of all heart failure; increasing with aging population
- Typical Patient: Older, female, obese, hypertensive, diabetic
- Mortality: 5-year mortality 50-60% (similar to HFrEF)
- Pathophysiology: Diastolic dysfunction, myocardial stiffness, systemic inflammation
- Treatment Breakthrough: SGLT2 inhibitors (EMPEROR-Preserved, DELIVER trials)
- Diagnostic Challenge: Requires elevated natriuretic peptides and/or diastolic dysfunction evidence
Clinical Pearls
High-Yield Points:
- HFpEF is a diagnosis of exclusion - rule out other causes of dyspnoea
- Natriuretic peptides may be lower than in HFrEF; use appropriate thresholds
- Comorbidity management is the cornerstone of therapy
- SGLT2 inhibitors now have Class I indication (ESC 2023)
- Exercise intolerance may be out of proportion to echo findings
- AF management is crucial - rate control and anticoagulation
Why This Matters Clinically
HFpEF represents one of the greatest challenges in modern cardiology. The condition affects predominantly elderly patients with multiple comorbidities, making diagnosis and management complex. Unlike HFrEF, there was no proven mortality-reducing therapy until recent SGLT2 inhibitor trials. Understanding the phenotypic heterogeneity and comorbidity-driven nature of HFpEF is essential for optimal patient care.
Incidence and Prevalence
| Metric | Value | Notes |
|---|---|---|
| Proportion of HF | 50% | Increasing with age |
| Prevalence over 65 | 4-5% | Higher in women |
| Annual Incidence | 1-3 per 1000 | Age-dependent |
| Hospital Admissions | 50% of HF admissions | Similar to HFrEF |
Demographics
- Age: Mean age 70-80 years (older than HFrEF)
- Sex: More common in females (60-65%)
- Ethnicity: Higher rates in African Americans
- Comorbidity Burden: Average 5+ comorbidities
Risk Factors
Strongly Associated:
- Hypertension (present in 60-90%)
- Obesity (50-60%)
- Diabetes mellitus (30-50%)
- Atrial fibrillation (30-50%)
- Coronary artery disease (40-60%)
- Chronic kidney disease (30-50%)
Other Associations:
- Aging
- Female sex
- Sedentary lifestyle
- Obstructive sleep apnoea
- Anaemia
Mechanism Overview
HFpEF is now understood as a systemic disorder driven by comorbidity-induced inflammation:
Stage 1: Comorbidity Burden
- Obesity, diabetes, hypertension create pro-inflammatory state
- Endothelial dysfunction develops systemically
Stage 2: Coronary Microvascular Dysfunction
- Inflammation affects coronary microvasculature
- Reduced nitric oxide availability
- Impaired vasodilatory reserve
Stage 3: Myocardial Changes
- Cardiomyocyte stiffness (titin hypophosphorylation)
- Interstitial fibrosis (collagen deposition)
- Concentric remodeling/hypertrophy
Stage 4: Diastolic Dysfunction
- Impaired ventricular relaxation
- Reduced ventricular compliance
- Elevated filling pressures
Stage 5: Clinical Syndrome
- Pulmonary congestion with exertion
- Exercise intolerance
- Fluid retention
Key Differences from HFrEF
| Feature | HFpEF | HFrEF |
|---|---|---|
| Primary Problem | Diastolic dysfunction | Systolic dysfunction |
| LV Size | Normal or small | Dilated |
| Wall Thickness | Often increased | Often thin |
| Neurohormonal Activation | Less pronounced | Prominent |
| Therapeutic Targets | Comorbidities, congestion | RAAS, SNS blockade |
Typical Presentation
Symptoms:
Signs:
Atypical Presentations
Red Flags
URGENT ASSESSMENT:
- Acute pulmonary oedema with severe hypertension
- New-onset rapid AF with haemodynamic compromise
- Syncope
- Signs of cardiogenic shock
Structured Approach
General: Body habitus (obesity common), peripheral oedema, respiratory distress
Cardiovascular:
- BP: Often elevated
- Heart sounds: S4 gallop (suggests diastolic dysfunction)
- JVP: May be elevated, especially with exercise
Respiratory:
- Crackles may be absent at rest
- Pleural effusions in advanced cases
Peripheral:
- Dependent oedema
- Signs of volume overload
Diagnostic Algorithm (HFA-PEFF Score)
Step 1: Pre-test Assessment
- Symptoms and signs of HF
- LVEF ≥50%
- Structural heart disease (LVH, LAE)
Step 2: HFA-PEFF Score
- Functional (E/e', TR velocity, diastolic dysfunction grade)
- Morphological (LAVi, LVMi, LV wall thickness)
- Biomarkers (NT-proBNP, BNP)
| Parameter | Major (2 points) | Minor (1 point) |
|---|---|---|
| E/e' | ≥15 | 9-14 |
| NT-proBNP | Over 220 pg/mL (SR) or over 660 (AF) | Over 125 (SR) or over 365 (AF) |
| LAVi | Over 34 mL/m² | 29-34 mL/m² |
Interpretation:
- 0-1 points: HFpEF unlikely
- 2-4 points: Consider stress testing or invasive haemodynamics
- 5-6 points: HFpEF confirmed
Key Investigations
| Investigation | Findings | Purpose |
|---|---|---|
| Echocardiography | LVEF ≥50%, diastolic dysfunction, LAE, LVH | Confirm diagnosis |
| NT-proBNP/BNP | Elevated (but often lower than HFrEF) | Diagnosis, prognosis |
| Exercise Testing | Abnormal haemodynamic response | Confirm exercise limitation |
| Invasive Haemodynamics | PCWP over 15 mmHg or over 25 with exercise | Gold standard if uncertain |
EF Classification
| Category | LVEF |
|---|---|
| HFpEF | ≥50% |
| HFmrEF | 41-49% |
| HFrEF | ≤40% |
Phenotypic Classification
Recent evidence suggests HFpEF is heterogeneous with distinct phenotypes:
- Obesity Phenotype: Central obesity, metabolic syndrome, plasma volume expansion
- Aging/Fibrosis Phenotype: Elderly, chronotropic incompetence, LA fibrosis
- Pulmonary Vascular Phenotype: Elevated pulmonary pressures, RV dysfunction
- CAD Phenotype: Ischaemic burden, microvascular dysfunction
Algorithm Overview
Step 1: Confirm Diagnosis
- Exclude alternative causes of dyspnoea
- Establish HFpEF diagnosis with HFA-PEFF algorithm
Step 2: Treat Congestion
- Loop diuretics (furosemide, bumetanide)
- Titrate to euvolaemia
- Monitor electrolytes and renal function
Step 3: Treat Comorbidities Aggressively
| Comorbidity | Target | Treatment |
|---|---|---|
| Hypertension | BP under 130/80 mmHg | ACE-I/ARB, CCB, diuretics |
| Diabetes | HbA1c under 7% | SGLT2i preferred |
| Obesity | 5-10% weight loss | Lifestyle, GLP-1 agonists considered |
| AF | Rate control, anticoagulation | Beta-blocker/digoxin, DOAC |
| CAD | Risk factor control | Revascularisation if ischaemic |
Step 4: SGLT2 Inhibitors (Class I)
- Empagliflozin 10 mg OD (EMPEROR-Preserved)
- Dapagliflozin 10 mg OD (DELIVER)
- Benefit independent of diabetes status
Step 5: Consider Additional Therapies
- MRA (spironolactone) - modest benefit
- Exercise rehabilitation - improves functional capacity
- GLP-1 receptor agonists for obesity
What Doesn't Work
Unlike HFrEF, the following have NOT shown mortality benefit in HFpEF:
- ACE-I/ARB (symptom benefit only)
- Beta-blockers (unless for AF rate control)
- ARNI (borderline benefit in HFmrEF/lower HFpEF)
Acute Complications
| Complication | Risk Factors | Management |
|---|---|---|
| Flash Pulmonary Oedema | Hypertensive crisis, AF | IV diuretics, BP control, NIV |
| Rapid AF | Common comorbidity | Rate control, anticoagulation |
| AKI | Over-diuresis, contrast | Careful volume management |
Chronic Complications
- Atrial fibrillation (develops in 30-50%)
- Pulmonary hypertension and RV failure
- Recurrent hospitalisations
- Functional decline and frailty
- Depression and reduced quality of life
Mortality
- 5-year mortality: 50-60% (similar to HFrEF)
- 1-year mortality: 20-25%
- Most deaths: Non-cardiovascular (cancer, infection, renal failure)
Prognostic Factors
Poor Prognosis:
- Older age
- Male sex
- Renal dysfunction
- Higher NT-proBNP
- AF
- Pulmonary hypertension
- Frailty
Quality of Life
- Often significantly impaired
- Exercise intolerance major limitation
- High symptom burden despite treatment
Key Trials
EMPEROR-Preserved (2021)
- Empagliflozin reduced HF hospitalisations by 21%
- First positive mortality/morbidity trial in HFpEF
- Led to SGLT2i Class I recommendation
DELIVER (2022)
- Dapagliflozin reduced CV death and worsening HF
- Confirmed SGLT2i benefit across EF spectrum
PARAGON-HF (2019)
- Sacubitril/Valsartan borderline benefit
- Suggested benefit in lower EF range (HFmrEF)
Current Guidelines
| Guideline | Organisation | Year | Key Recommendations |
|---|---|---|---|
| ESC HF Guidelines | ESC | 2021 (2023 update) | SGLT2i Class I, diuretics, comorbidity treatment |
| AHA/ACC/HFSA | AHA | 2022 | Similar emphasis on SGLT2i |
| NICE | UK | 2018 | Comorbidity focus |
What is HFpEF?
Heart failure with preserved ejection fraction means your heart pumps out a normal amount of blood with each beat, but the heart muscle has become stiff and doesn't relax properly. This makes it harder for the heart to fill with blood, especially during exercise.
What causes it?
The main causes are:
- High blood pressure over many years
- Being overweight
- Diabetes
- Getting older
- Irregular heartbeat (atrial fibrillation)
What are the symptoms?
- Breathlessness, especially when exercising or lying flat
- Tiredness and low energy
- Swollen ankles and legs
- Difficulty exercising like you used to
How is it treated?
Treatment focuses on:
- Water tablets (diuretics) to reduce fluid buildup
- Controlling blood pressure
- Managing diabetes
- Losing weight if overweight
- A newer medication called an SGLT2 inhibitor
- Staying as active as possible
When to seek help
Contact your doctor or go to A&E if you experience:
- Sudden severe breathlessness
- Chest pain
- Fainting
- Rapid irregular heartbeat
Primary Sources
-
Anker SD, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction (EMPEROR-Preserved). N Engl J Med. 2021;385(16):1451-1461. PMID: 34449189
-
Solomon SD, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER). N Engl J Med. 2022;387(12):1089-1098. PMID: 36027570
-
Pieske B, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm. Eur Heart J. 2019;40(40):3297-3317. PMID: 31504452
-
McDonagh TA, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599-3726. PMID: 34447992
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. It does not replace professional medical judgement. Always verify critical information and consider individual patient factors.