Heart Failure with Preserved Ejection Fraction (HFpEF)
HF symptoms with LVEF ≥50% from diastolic dysfunction — now has class I medical therapy.
Also known as: HFpEF, diastolic heart failure, diastolic dysfunction
Overview
Clinical syndrome of heart failure (signs/symptoms) with LVEF ≥50% on echo. Driven by impaired LV relaxation and filling rather than reduced contractility. Accounts for ~50% of all HF cases and is now the more common phenotype.
Epidemiology
Disproportionately affects older women, often with multiple comorbidities (HTN, obesity, diabetes, CKD, AFib). Mortality approaches HFrEF.
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Risk factors
- Hypertension (most common driver — LVH from chronic pressure overload)
- Obesity
- Diabetes mellitus
- Older age, female sex
- Atrial fibrillation
- Coronary artery disease, CKD, sleep apnea
- Infiltrative: cardiac amyloidosis (consider in elderly with HFpEF + carpal tunnel, low-voltage ECG, or apical sparing on strain echo)
Pathophysiology
Impaired LV relaxation (active, ATP-dependent) and reduced compliance (passive stiffening from fibrosis, hypertrophy) elevate filling pressures at any given volume. The resulting pulmonary venous congestion produces classic HF symptoms despite normal contractility and stroke volume at rest.
Clinical presentation
Symptoms
- Indistinguishable from HFrEF clinically: DOE, orthopnea, PND, fatigue, edema
- Symptoms may be more exertion-dependent early on (preserved resting CO)
- Atrial fibrillation often unmasks symptoms (loss of atrial kick)
Signs / physical exam
- Similar to HFrEF: JVD, crackles, S4 gallop (vs S3 in HFrEF — stiff ventricle accentuates A wave)
- Hypertension on exam common
- Lower-extremity edema, weight gain
Differential diagnosis
- HFrEF / HFmrEF — Reduced EF on echo distinguishes; manage with full 4-pillar GDMT
- Cardiac amyloidosis — Elderly with HFpEF + carpal tunnel syndrome (often bilateral), low-voltage ECG despite LVH on echo, apical sparing on strain imaging; technetium pyrophosphate or biopsy
- Hypertrophic cardiomyopathy — Disproportionate LVH (often septal), LVOT obstruction with dynamic murmur, family history of sudden death; HCM management diverges from HFpEF
- Constrictive pericarditis — Pericardial thickening on CT/MRI, respirophasic interventricular dependence on echo, Kussmaul sign; surgically curable
- Restrictive cardiomyopathy (infiltrative) — Biventricular failure, low voltage, atrial enlargement out of proportion to ventricles; amyloid most common
- Pulmonary hypertension (any cause) — Right HF dominates over left HF; PA pressure elevated on echo; consider chronic thromboembolic, idiopathic, secondary causes
- Severe obesity / deconditioning — Exertional dyspnea without elevated BNP and with normal echo; address activity, weight
- Chronic kidney disease with volume overload — Elevated BUN/Cr, oliguria; volume status responds to dialysis or aggressive diuresis
Diagnostic workup
Diagnostic criteria
H2FPEF score (heavy, hypertensive, AFib, pulmonary HTN, elder, filling pressure) — ≥6 makes HFpEF likely. EF cutoff ≥50% (40-49% = HFmrEF, mid-range).
Labs
- BNP / NT-proBNP — elevated, though may be lower than in HFrEF for same severity (especially in obesity)
- CBC, BMP, TSH, A1c, lipid panel
- Cardiac amyloid screen if suspicion (SPEP/UPEP, free light chains, technetium pyrophosphate scan)
Imaging
- TTE: LVEF ≥50% with diastolic dysfunction parameters (E/e' >14, LA dilation >34 mL/m², elevated PASP, abnormal mitral inflow patterns)
- Stress echo can unmask exercise-induced diastolic dysfunction
- Cardiac MRI if amyloid or HCM suspected
Diagnostic algorithm
| Feature | HFrEF | HFpEF |
|---|---|---|
| LVEF | ≤40% | ≥50% |
| Primary defect | Reduced contractility | Impaired relaxation / stiffness |
| Gallop | S3 | S4 |
| Typical demographic | Older men, CAD | Older women, HTN, obesity, DM |
| GDMT (mortality benefit) | ARNI + BB + MRA + SGLT2i | SGLT2i (class I) |
| Beta-blocker | Class I (carvedilol, metop succ, bisop) | Use for HTN/AFib indications, not HF per se |
| AFib prevalence | ~30% | ~50%+ |
| Common phenotypes | Ischemic, dilated CM | HTN, obese, amyloid |
Treatment
First-line
- SGLT2 inhibitor — dapagliflozin or empagliflozin; class I recommendation across full EF range (EMPEROR-Preserved, DELIVER); reduces HF hospitalization
- Loop diuretic for volume overload — furosemide, torsemide, or bumetanide; titrated to symptom relief; avoid overdiuresis (preload-dependent ventricles drop CO)
- Aggressive treatment of comorbidities: HTN, AFib, CAD, sleep apnea, weight loss
- ARNI (sacubitril-valsartan) — reasonable, especially in HFmrEF and lower end of HFpEF (PARAGON-HF subgroup)
- MRA — spironolactone or eplerenone; reasonable per TOPCAT subgroup analysis, especially with elevated BNP
Second-line / adjunct
- Address phenotype-specific drivers:
- • Amyloid → tafamidis if transthyretin amyloid confirmed
- • AFib → rate control and anticoagulation per CHA2DS2-VASc; consider rhythm strategy
- • Obesity → structured weight loss; semaglutide showed symptom benefit in STEP-HFpEF
- • Hypertension → strict BP control (<130/80)
Complications
- Recurrent HF hospitalizations
- Atrial fibrillation (50%+ lifetime incidence)
- Pulmonary hypertension, right HF
- Renal dysfunction
PANCE pearls
- ACEi, ARB, and traditional beta-blockers do NOT have the same mortality benefit in HFpEF as in HFrEF. Don't extrapolate.
- Always screen elderly HFpEF patients for cardiac amyloid — undiagnosed amyloid masquerades as HFpEF in ~15% of older adults.
- Diuretics provide symptomatic relief only — don't overdiurese (pre-load dependent ventricles drop CO with volume depletion).
- AFib in HFpEF is particularly poorly tolerated; rhythm control may be more beneficial than in HFrEF.
References
- AHA/ACC/HFSA 2022 — 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (Heidenreich et al., Circulation 2022)
- EMPEROR-Preserved — Empagliflozin in Heart Failure with a Preserved Ejection Fraction (Anker et al., NEJM 2021)
- DELIVER — Dapagliflozin in Heart Failure with Mildly Reduced or Preserved EF (Solomon et al., NEJM 2022)
- PARAGON-HF — Angiotensin-Neprilysin Inhibition in HFpEF (Solomon et al., NEJM 2019)
- STEP-HFpEF — Semaglutide in Patients with Obesity-Related HFpEF (Kosiborod et al., NEJM 2023)
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