HFpEF Diagnostic Criteria 2025 — Medical Education Handout

Current Diagnostic Framework (2022 AHA/ACC/HFSA)

HFpEF diagnosis requires four essential components:

Heart failure symptoms: Exertional dyspnea, fatigue, exercise intolerance, and evidence of congestion
LVEF ≥50% on echocardiography
Evidence of elevated LV filling pressures: Elevated natriuretic peptides, E/e' ≥15, or invasive hemodynamics
Structural heart disease evidence: Increased LA volume index or LV mass index

Clinical Pearl

Women with HFpEF typically exhibit higher EFs due to smaller LV chamber size and more concentric remodeling. An EF of 50–55% may represent abnormal systolic function in women, potentially leading to underdiagnosis with sex-neutral thresholds.

HFimpEF: Patients with previously reduced EF that improved to >40% should continue receiving HFrEF-directed therapy regardless of current EF.

Echocardiographic Diagnostic Criteria

E Wave: Transmitral Early Diastolic Flow Velocity

Peak velocity of early diastolic transmitral flow, measured using pulsed-wave Doppler at mitral valve leaflet tips. Reflects the pressure gradient between LA and LV after mitral valve opening. Normal: 60–100 cm/s in healthy adults (age-dependent).

e' (e-prime): Tissue Doppler Early Diastolic Velocity

Peak early diastolic velocity of the mitral annulus via tissue Doppler. Reflects intrinsic myocardial relaxation properties and is relatively independent of loading conditions.

Septal e': Normal >8 cm/s; impaired <7 cm/s
Lateral e': Normal >10 cm/s; impaired <10 cm/s

E/e' Ratio: The Integrative Measurement

E/e' Value	Interpretation
<8	Normal filling pressures — argues against HFpEF
8–15	Intermediate — requires integration with LAVI, TR velocity, natriuretic peptides
≥15	Elevated filling pressures — strongly supports HFpEF

Additional Parameters

LA Volume Index: Normal ≤34 mL/m²; >40 mL/m² strongly suggests chronic diastolic dysfunction
LA Reservoir Strain: <23% indicates impaired LA function
Global Longitudinal Strain: Less negative than −18% suggests subclinical systolic dysfunction despite preserved EF
PASP: >35 mmHg suggests pulmonary hypertension

Diagnostic Scoring Systems

HFA-PEFF Algorithm

Four-step approach: Pre-test assessment → Echo + NP scoring → Functional testing → Etiology.

Step 2: Major Criteria (2 points each)

Septal e' <7 cm/s or lateral e' <10 cm/s
TR velocity >2.8 m/s
LAVI >40 mL/m²
LV mass index ≥149 g/m² (M) or ≥122 g/m² (F)
Elevated natriuretic peptides

Score ≥5: High likelihood of HFpEF. Score ≤1: HFpEF very unlikely. Score 2–4: Proceed to stress testing.

H2FPEF Score

Component	Criteria	Points
Heavy (BMI)	>30 kg/m²	2
2 antihypertensives	≥2 BP medications	1
Fibrillation	Atrial fibrillation	3
Pulmonary hypertension	PASP >35 mmHg	1
Elder	Age >60	1
Filling pressure	E/e' >9	1

≥6: High probability. <2: Low probability. 2–5: Additional evaluation needed. AUC 0.84 in validation studies.

Approximately 35–45% of patients fall into intermediate probability categories with either scoring system, highlighting continued need for additional testing.

Diastolic Dysfunction vs. HFpEF

Component	Diastolic Dysfunction	HFpEF
Symptoms	Not required; may be asymptomatic	Mandatory
LVEF	≥50%	≥50%
Echo Evidence	Abnormal diastolic parameters sufficient	Requires elevated filling pressures (E/e' ≥15 or additional evidence)
Natriuretic Peptides	Not required; may be normal	Elevated levels support diagnosis
Structural Disease	May be present but not required	Required (LAVI >40 or LVH)
Grading	Grade I (impaired relaxation), II (pseudonormal), III (restrictive)	HFA-PEFF or H2FPEF scoring
Therapy	CV risk factor modification	GDMT: SGLT2i, ARNi/ARB, MRA
Progression	3–5% annual progression to HFpEF	Established diagnosis requiring HF management

HFpEF as a Renal Disease: Emerging Paradigm

CKD prevalence in HFpEF patients approaches 40–50%, significantly higher than age-matched controls. CKD in HFpEF is one of the strongest independent predictors of adverse outcomes.

Pathophysiological Mechanisms

Renal venous congestion: Elevated CVP impairs renal perfusion through increased renal venous pressure and decreased arteriovenous gradient (“kidney tamponade”)
Intra-abdominal pressure: Volume overload causes direct compression of renal parenchyma
Inflammatory pathways: TNF-alpha, IL-6, and CRP directly impair renal endothelial function and promote fibrosis
Metabolic syndrome: Prevalence exceeds 70% in HFpEF; AGEs, oxidative stress, and altered sodium handling contribute
Endothelial dysfunction: Unifying mechanism — reduced NO bioavailability impairs both cardiac relaxation and renal autoregulation