Recommendations for the Evaluation of LV Diastolic Function by Echocardiography and for HFpEF Diagnosis: An Update from the ASE (2025)

Authors, Journal, Affiliations, Type, DOI

• Sherif F. Nagueh (Chair), Danita Y. Sanborn (Co-Chair), Jae K. Oh, Bonita Anderson, Genevieve Derumeaux, Allan Klein, Konstantinos Koulogiannis, Carol Mitchell, Amil Shah, Kavita Sharma, Otto A. Smiseth, Teresa S. M. Tsang
• Affiliations: Houston Methodist, MGH, Mayo Clinic, Cleveland Clinic, Johns Hopkins, Oslo University, UBC Vancouver, and others
• Journal of the American Society of Echocardiography, Volume 38, Issue 7, July 2025
• Guideline / Expert Consensus Update (update to 2016 ASE/EACVI guideline)
• DOI: https://doi.org/10.1016/j.echo.2025.03.011

Overview

This ASE 2025 guideline updates the 2016 ASE/EACVI diastolic function assessment recommendations. It modernises the algorithm for LV diastolic dysfunction grading and LAP estimation, introduces LA reservoir strain (LARS) as a primary parameter, and provides a comprehensive stepwise algorithm for HFpEF diagnosis. It also incorporates age-specific normal ranges, diastolic exercise echocardiography guidance, AI applications, and detailed approaches for special populations (AF, valvular heart disease, HCM, restrictive cardiomyopathy, pericardial constriction, cardiac transplant, pulmonary hypertension, LBBB/pacing).

Keywords

Diastole, Echocardiography, Doppler, Heart failure, Left atrial strain, Diastolic dysfunction, HFpEF, Filling pressures

Key Takeaways

Clinical and Technical Considerations

• Guidelines apply to adults in ambulatory and acute hospital care settings; not applicable to children, normal pregnant women, or intraoperative settings
• Quality of 2D, Doppler, and STE signals must be carefully assessed before interpretation
• All indices must be interpreted in the context of clinical status and other echocardiographic parameters
• No single measurement defines diastolic function — consistency among indices is essential

Invasive Assessment of LV Diastolic Function

• LV relaxation time constant (τ): abnormally prolonged if >48 ms (load-dependent)
• LV chamber stiffness constant: elevated if >0.015
• Invasive criteria for HFpEF: rest mean PCWP >15 mmHg, rest LVEDP >16 mmHg, exercise mean PCWP ≥25 mmHg, exercise LVEDP ≥23 mmHg, PCWP/CO slope >2 mmHg/L/min
• LVEDP and LAP are not the same: elevated LVEDP can occur with normal LAP (early diastolic dysfunction)

Normal Ranges for Diastolic Measurements

• Age-specific ranges derived from fifth and 95th percentile values in subjects free of CVD/risk factors
• E wave, A wave, E/A ratio, e' (septal/lateral/average), E/e' ratio, TR velocity, LAVi, and LA strain all show significant age dependence
• Normal ranges ≠ optimal values; aging itself affects diastolic function
• E/e' ratio and LAVi show near-linear (no threshold) associations with HF incidence and death
• Age-specific normal ranges for e' (cutoffs for impaired relaxation):
  • Age 20–39: septal <7, lateral <10, average <9 cm/s
  • Age 40–65: septal <6, lateral <8, average <7 cm/s
  • Age >65: septal <6, lateral <7, average <6.5 cm/s

Definition of LV Diastolic Dysfunction

• Two-step algorithm (Figure 2):
  • Step 1: Assess e' as marker of impaired LV relaxation
    • Reduced if: septal ≤6 cm/s OR lateral ≤7 cm/s OR average ≤6.5 cm/s
  • Step 2: Assess markers of LA/LV remodeling and elevated LAP:
    • Average E/e' >14
    • LARS ≤18%
    • E/A ≤0.8 (age-adjusted) OR ≥2
    • LAVi >34 mL/m²
  • Diastolic dysfunction present if: reduced e' + ≥1 Step 2 marker, OR normal e' + ≥2 Step 2 markers
  • Additional finding consistent with diastolic dysfunction: LV mass index >95 g/m² (women) or >115 g/m² (men), excluding athletes

LAP Estimation Algorithm (Figure 3)

• Three primary variables (sinus rhythm patients without severe MR, MS, moderate/severe MAC, AF, HTX, non-cardiac PH, pericardial constriction, LVAD):
  1. Reduced e' (septal ≤6 or lateral ≤7 or average ≤6.5 cm/s)
  2. Increased E/e' (septal ≥15, lateral ≥13, or average ≥14)
  3. Increased TR velocity ≥2.8 m/s or PASP ≥35 mmHg
• All normal → Normal LAP, Normal diastolic function
• All 3 abnormal or any 2 abnormal → Elevated LAP; Grade 2 if E/A <2, Grade 3 if E/A ≥2
• Reduced e' only, or 1 of above abnormal with E/A >0.8 → Assess supplemental: LARS, PV S/D ≤0.67, LAVi >34 mL/m², IVRT ≤70 ms
  • Grade 1 diastolic dysfunction: reduced e', normal E/e' + PASP, E/A ≤0.8
• In symptomatic patients with Grade 1 or indeterminate: refer for diastolic exercise echocardiography
• Key change from 2016: LAVi is no longer a primary variable — demoted to secondary position due to poor correlation with acute LAP changes and other causes of LA enlargement

Key Echocardiographic Parameters

• e' velocity: Best index of LV relaxation; less load-dependent than transmitral E; reduced across all grades of diastolic dysfunction; lateral/septal/average have different cutoffs
• E/e' ratio: Average >14 high specificity for elevated LAP; 8–14 is grey zone; unreliable with MAC, prosthetic MV, pericardial disease
• LA Reservoir Strain (LARS): ≤18% has high specificity for elevated LAP; highest diagnostic accuracy for HFpEF when combined with E/e' (LA stiffness index = E/e' / LARS); age-dependent (decreases with age); should NOT be used in AF, significant MR, HTX recipients, normal EF with GLS >18%, suspected LA stunning
• LAVi: Marker of chronic LAP elevation; >34 mL/m² abnormal; not a reliable acute marker; causes other than diastolic dysfunction include anemia, athletic heart, high-output states, AF, MV disease
• TR velocity ≥2.8 m/s / PASP ≥35 mmHg: Indirect marker of elevated LAP; use intravenous agitated saline or ultrasound enhancing agents to complete TR envelope
• Supplemental parameters: PR end-diastolic velocity ≥2 m/s, L-wave ≥50 cm/s, Ar-A duration >30 ms, Valsalva E/A decrease ≥50%, diastolic MR

Diastolic Exercise Echocardiography

• Indications: Symptomatic patients with Grade 1 diastolic dysfunction or indeterminate LAP at rest; up to 50% of HFpEF patients have normal resting LAP
• Contraindications for referral: completely normal diastolic function with preserved e' (unlikely to develop elevated pressures), or already elevated resting LAP (diagnosis established)
• Method: Supine bicycle preferred; treadmill also acceptable; dobutamine stress testing strongly discouraged
• Positive criteria (definite abnormal): Average E/e' ≥14 (or septal ≥15) AND peak TR velocity >3.2 m/s
• Normal: Average E/e' <10 AND TR velocity <2.8 m/s
• Likely HFpEF: E/e' >14 + TR velocity >2.8 but <3.2 m/s
• PASP >50 mmHg portends worse outcome
• 17% of patients develop elevated filling pressure with exercise; 28% show myocardial ischemia; elevated filling pressure without ischemia has worse prognosis than isolated ischemia
• Lung B-line scanning during diastolic exercise stress echo is emerging as adjunct tool

AI Applications

• Multiple AI approaches being tested: rule-based with expert measurements, multi-view ML, single-view deep learning
• 2016 guidelines used as reference → AI systems inherit the "indeterminate" problem
• Continuous diastolic function scores developed (vs categorical grading) — reduces indeterminate cases
• Electrocardiographic AI showed good accuracy for diastolic dysfunction grading with similar prognostic value to echo (study of ~100,000 paired ECG/echo)
• Validation using invasive hemodynamics and clinical outcomes in multicenter studies needed

Assessment in Special Populations

Valvular Heart Disease

• Mitral stenosis: IVRT, TE-e', mitral E/A velocities useful; E/e' ratio not useful; IVRT/TE-e' ratio correlates with mean PCWP
• Mitral regurgitation: Ar-A >30 ms and IVRT/TE-e' <5.6 for normal EF; E/e' only for depressed EF (not useful in primary MR with normal EF); LARS unreliable in significant MR
• MAC (moderate/severe): E/A <0.8 → normal LAP; E/A >1.8 → elevated LAP; E/A 0.8–1.8 → use IVRT (≥80 ms normal, <80 ms elevated)
• After TEER: LAP = 4V² + RAP where V is interatrial flow velocity; >1.7 m/s shunt velocity suggests elevated LAP
• Aortic stenosis: Standard algorithm applicable; assess diastolic function in all AS patients (predicts outcomes post-TAVR/SAVR)
• Aortic regurgitation: LA enlargement, avg E/e' >14, LARS <18%, TR >2.8 m/s support elevated filling pressures in chronic severe AR

Cardiac Transplantation

• E/A ≥2 common in early post-transplant period (normal donor heart phenotype, myocardial edema)
• Simplified algorithm: avg E/e' <7 = normal LAP; >14 = elevated LAP; 7–14 → use SRIVR (E/SRIVR ≤200 cm = normal; >200 cm = elevated); if SRIVR unavailable → TR velocity (≤2.8 m/s normal; >2.8 m/s elevated)

Pulmonary Hypertension

• Septal wall flattening → use lateral E/e' (not average); lateral E/e' >13 elevated LAP; <8 normal; 8–13 indeterminate
• E/A ≤0.8 → precapillary (Group I/III-V) PH; E/A ≥2 → postcapillary (Group II) PH
• LAVi >34 mL/m², lateral E/e' >13, LARS <16% favour Group II PH

LBBB / RV Pacing / CRT

• LBBB → prolonged IVRT, reduced septal e' → lateral E/e' preferred; average E/e' less reliable
• RV pacing creates LBBB-like dyssynchrony; septal e' unreliable
• If only mitral A velocity present: TR velocity >2.8 m/s as indicator of elevated LAP

HCM

• Diastolic dysfunction ubiquitous in HCM; occurs before LVH in gene-positive relatives
• Use: mitral inflow velocities, PV velocities, annular velocities, TR velocity, biplane LAVi
• Average E/e' >14, Ar-A ≥30 ms, TR >2.8 m/s, LAVi >34 mL/m² indicate elevated LAP
• Restrictive filling (E/e' elevated) associated with HF hospitalizations and SCD in HCM

Restrictive Cardiomyopathy / Cardiac Amyloidosis

• Early stage: Grade 1 dysfunction → progressive to Grade 2 → Grade 3 with disease progression
• Advanced disease: E/A >2.5, DT <150 ms, IVRT <50 ms, septal and lateral e' 3–4 cm/s
• Cardiac amyloidosis "5-5-5 sign": systolic/early diastolic/late diastolic annular velocities all <5 cm/s
• Amyloid "red flags": increased LV/RV wall thickness, biatrial enlargement, preserved EF with low stroke volume index, paradoxical low-flow/low-gradient AS, diastolic dysfunction with markedly reduced annular velocities
• Apical sparing on GLS: Ratio of apical strain to mid + basal strain >1; septal apical-to-basal ratio >2.1; EF/strain ratio >4.1 — distinguishes amyloidosis from HCM/hypertensive LVH/AS
• Grade 3 diastolic dysfunction in restrictive CM associated with poor outcome

Pericardial Constriction

• Key features: respirophasic septal shift, septal bounce, mitral inflow variation >25%, tricuspid inflow variation >40%, expiratory hepatic vein end-diastolic reversal/forward ≥0.8
• Annulus reversus: Septal e' >7 cm/s (normal or increased) while lateral e' reduced — opposite of restrictive CM
• Strain reversus: Lateral LV and RV free wall peak systolic strain diminished vs septal strain
• TE-e' interval typically NOT prolonged in pericardial constriction (vs prolonged in restrictive CM)

Atrial Fibrillation

• No single parameter has strong enough association with LAP to be a stand-alone marker
• Multiparametric algorithm (Figure 8): Use average values from multiple representative cycles
  • 4 primary variables: E velocity ≥100 cm/s, Septal E/e' >11, TR velocity >2.8 m/s or PASP >35 mmHg, DT ≤160 ms
  • 0–1 abnormal: normal LAP (unless LARS <18% or PV S/D <1 or BMI >30)
  • 2 abnormal: indeterminate
  • ≥3 abnormal: elevated LAP
• Less beat-to-beat transmitral inflow variability in AF usually indicates elevated LAP

HFpEF Diagnosis

• Clinical Diagnosis: HF symptoms ± signs + LVEF ≥50% + exclusion of other cardiac/non-cardiac causes
• HFpEF Stepwise Algorithm (Figure 9):
  1. History, physical, CXR, labs, natriuretic peptides → exclude non-cardiac dyspnea
  2. Comprehensive echocardiogram → exclude: significant MS/primary MR/AS/AR/TR, significant CAD, non-cardiac PH, cardiac amyloidosis, HCM, pericardial constriction
  3. Apply LAP estimation algorithm (Figure 3)
  4. If LAP elevated → HFpEF confirmed
  5. If LAP normal → diastolic exercise echo (or RHC with/without exercise)
  6. If exercise echo positive → HFpEF confirmed; if negative → non-cardiac dyspnea
• ACC/AHA definition: LVEF ≥50% + symptoms/signs + diastolic dysfunction
• ESC definition: LVEF ≥50% + symptoms/signs + elevated NP + at least one of: structural (LAVi >34 mL/m² or LVMi ≥115/95 g/m²) or functional (E/e' ≥13 or mean e' <9 cm/s) abnormality
• Natriuretic peptides: up to 30% of HFpEF can have normal NP levels (particularly obese patients); normal NP does not exclude HFpEF
• HFpEF Prediction Scores:
  • H2FPEF (Reddy 2019): Heavy (BMI >30, 2 pts) + Hypertensive (≥2 antihypertensives, 1 pt) + AF (3 pts) + PH/PASP >35 (1 pt) + Elder >60y (1 pt) + Filling pressure E/e' >9 (1 pt); 0–2 = low; 2–5 = intermediate (40–80% HFpEF likelihood); >5 = high
  • HFA-PEFF algorithm (ESC): Stepwise pretest probability → comprehensive echo + NP score → exercise/invasive testing if intermediate
• ATTR-CA prevalence in HFpEF: 5–13% estimated (based on limited autopsy/nuclear scan screening data)
• RHC gold standard: PCWP >15 mmHg rest or ≥25 mmHg exercise (end-expiration) confirms HFpEF

Limitations of the Document

• Age-specific prognostic thresholds only validated in subjects >65 years (ARIC study); younger age data insufficient
• LA strain not validated in AF, significant MR, HTX, normal EF with GLS >18%, or LA stunning
• No standardization of Valsalva maneuver technique across all centres
• ATTR-CA prevalence estimates in HFpEF are from selected/referral populations — community burden unclear
• AI models validated against 2016 guidelines (which inherited indeterminate cases); need validation against invasive hemodynamics

Key Concepts Mentioned

• concepts/LV-Diastolic-Function — primary focus of guideline
• concepts/HFpEF — diagnosis algorithm and scoring systems
• concepts/Valvular-Heart-Disease — modifications for valvular populations

Key Entities Mentioned

• entities/ATTR-Amyloidosis — restrictive CM echo findings, apical sparing, 5-5-5 sign
• entities/Heart-Failure — HFpEF diagnosis criteria, natriuretic peptides
• entities/HCM — diastolic assessment in HCM
• entities/Atrial-Fibrillation — LAP estimation in AF
• entities/Pulmonary-Hypertension — LAP estimation algorithm modifications in PH

Wiki Pages Updated

• Created: wiki/sources/echo-hfpef-ase-2025.md
• Created: wiki/concepts/LV-Diastolic-Function.md
• Updated: wiki/concepts/HFpEF.md
• Updated: wiki/entities/ATTR-Amyloidosis.md
• Updated: wiki/wikiindex.md
• Updated: wiki/sourceindex.md