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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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
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
HFrEF vs HFpEF — clinical and management differences. The 4-pillar GDMT framework applies fully to HFrEF; only SGLT2i carries class I in HFpEF.
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
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