LV Diastolic Function
Definition
LV diastolic function encompasses LV relaxation (the active, energy-dependent process of LV pressure decline after systole) and LV chamber stiffness (the passive property resisting filling). Diastolic dysfunction is defined echocardiographically by a combination of reduced e' velocity (impaired relaxation) and markers of elevated LV filling pressures and structural remodeling. (sources/echo-hfpef-ase-2025, rating: very high)
Key Concepts
Invasive Hemodynamic Reference Standards
- LV relaxation time constant τ >48 ms = impaired relaxation (load-dependent) (sources/echo-hfpef-ase-2025, rating: very high)
- LV chamber stiffness constant >0.015 = increased stiffness (sources/echo-hfpef-ase-2025, rating: very high)
- Invasive HFpEF thresholds: rest mean PCWP >15 mmHg, rest LVEDP >16 mmHg, exercise mean PCWP ≥25 mmHg, exercise LVEDP ≥23 mmHg (sources/echo-hfpef-ase-2025, rating: very high)
- LVEDP ≠ mean LAP: Elevated LVEDP can occur with normal LAP (early-stage diastolic dysfunction). Doppler correlates of LVEDP include mitral A velocity, pulmonary vein Ar velocity, Ar-A duration, and LA pump strain. Correlates of mean LAP include mitral E velocity, E/A ratio, E/e' ratio, and LARS. (sources/echo-hfpef-ase-2025, rating: very high)
Key Echocardiographic Parameters
- Mitral annular e' velocity: Best index of LV relaxation; reduced across all grades of dysfunction; less load-dependent than E velocity; lateral, septal, and average have different cutoffs; unreliable with significant MAC, prosthetic MV, pericardial disease, and regional dysfunction at sampled site (sources/echo-hfpef-ase-2025, rating: very high)
- E/e' ratio: Average >14 = high specificity for elevated LAP; average <8 = normal; 8–14 = grey zone/indeterminate; septal ≥15 or lateral ≥13 also abnormal thresholds (sources/echo-hfpef-ase-2025, rating: very high)
- LA Reservoir Strain (LARS): Peak positive LA strain during ventricular systole; ≤18% = high specificity for elevated LAP; correlates inversely with LAP; LA stiffness index = E/e' ÷ LARS (highest accuracy for HFpEF identification); LARS should NOT be used to assess LAP in AF, significant MR, HTX, normal EF with GLS >18%, or suspected LA stunning; age-dependent (decreases with age) (sources/echo-hfpef-ase-2025, rating: very high)
- LAVi: Marker of chronic (not acute) LAP elevation; >34 mL/m² abnormal; poor correlation with acute LAP changes; secondary marker in current algorithm (not primary); non-diastolic causes: anemia, athletic heart, AF/flutter, MV disease, high-output states (sources/echo-hfpef-ase-2025, rating: very high)
- TR velocity / PASP: Elevated PASP passively reflects elevated LAP in absence of pulmonary vascular disease; PASP ≥35 mmHg (or TR velocity ≥2.8 m/s when RAP unavailable) = elevated LAP; use intravenous agitated saline or UEA to complete incomplete TR envelopes (sources/echo-hfpef-ase-2025, rating: very high)
- PV S/D ratio: ≤0.67 (= systolic filling fraction ≤40%) indicates elevated mean LAP; most reliable with reduced LVEF; unreliable in normal EF, AF, HCM, MV disease (sources/echo-hfpef-ase-2025, rating: very high)
- IVRT: ≤70 ms = elevated LAP (high specificity); >110 ms = likely normal LAP; age-dependent and preload-dependent; particularly useful in MAC (sources/echo-hfpef-ase-2025, rating: very high)
- Ar-A duration: >30 ms = elevated LVEDP; age- and EF-independent; accurate in MR and HCM (sources/echo-hfpef-ase-2025, rating: very high)
- Valsalva maneuver: E/A decrease ≥50% = highly specific for elevated LAP; age-independent; standardize as 40 mmHg intrathoracic pressure sustained for 10 s (sources/echo-hfpef-ase-2025, rating: very high)
Age-Specific Normal Ranges
- E wave, A wave, E/A ratio, e' velocity, E/e' ratio, TR velocity, LAVi, and LARS are all significantly age-dependent
- Age-specific cutoffs for impaired LV relaxation (e' velocity):
| Age Group | Septal e' (cm/s) | Lateral e' (cm/s) | Average e' (cm/s) |
|---|---|---|---|
| 20–39 y | <7 | <10 | <9 |
| 40–65 y | <6 | <8 | <7 |
| >65 y | <6 | <7 | <6.5 |
- Normal ranges ≠ optimal values — aging itself reduces diastolic function
- E/e' ratio and LAVi show near-linear (no threshold) associations with HF incidence/death in older adults (sources/echo-hfpef-ase-2025, rating: very high)
Two-Step Algorithm for Diagnosing Diastolic Dysfunction
Step 1: Assess e' as marker of impaired LV relaxation
- Reduced e': septal ≤6 cm/s OR lateral ≤7 cm/s OR average ≤6.5 cm/s (age-adjusted cutoffs can also be used)
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 (excluding athletes, anemia, AF, flutter, MV disease)
Diastolic dysfunction present if:
- Reduced e' + ≥1 marker from Step 2, OR
- Normal e' + ≥2 markers from Step 2
Additional finding: LV mass index >115 g/m² (men) or >95 g/m² (women) after excluding athletes (sources/echo-hfpef-ase-2025, rating: very high)
LAP Estimation Algorithm (Sinus Rhythm)
Three primary variables (apply to all sinus rhythm patients except: severe primary MR, any MS, moderate/severe MAC, AF, HTX, non-cardiac PH, pericardial constriction, LVAD):
- Reduced e' (septal ≤6 or lateral ≤7 or average ≤6.5 cm/s)
- Elevated E/e' (septal ≥15, lateral ≥13, or average ≥14)
- Elevated TR velocity ≥2.8 m/s (when RAP unknown) or PASP ≥35 mmHg
Algorithm outcomes:
- All 3 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
- Only e' reduced + E/A ≤0.8 → Grade 1 diastolic dysfunction (impaired relaxation, normal LAP)
- Any 1 or 2 abnormal with E/A >0.8 → Assess supplemental: LARS ≤18%, PV S/D ≤0.67, LAVi >34 mL/m², IVRT ≤70 ms
- If ≥1 supplemental positive → Elevated LAP
- If all supplemental normal → Normal LAP (consider exercise echo if symptomatic)
Key change from 2016 guidelines: LAVi no longer a primary variable (demoted to supplemental due to poor tracking of acute LAP changes and non-diastolic causes of enlargement) (sources/echo-hfpef-ase-2025, rating: very high)
Grading Diastolic Dysfunction
- Grade 1 (Mild): Reduced e', normal E/e' + PASP, E/A ≤0.8 — impaired LV relaxation with normal LAP
- Grade 2 (Mild to Moderate): Elevated LAP, E/A >0.8 but <2
- Grade 3 (Severe/Marked): Elevated LAP, E/A ≥2 (restrictive filling)
Diastolic Exercise Echocardiography
- Indications: Symptomatic patients with Grade 1 diastolic dysfunction or indeterminate resting LAP; up to 50% of HFpEF patients have normal resting LAP
- Not indicated if: Normal diastolic function at rest with preserved e' (unlikely to develop elevated pressures), or already elevated resting filling pressures (diagnosis established)
- Performance: Supine bicycle preferred; treadmill acceptable; dobutamine stress strongly discouraged
- Positive (definite): Average E/e' ≥14 (or septal ≥15) AND peak TR velocity >3.2 m/s during exercise
- Normal: Average E/e' <10 AND TR velocity <2.8 m/s during exercise
- Likely HFpEF: E/e' >14 + TR velocity >2.8 but <3.2 m/s
- PASP >50 mmHg portends worse prognosis
- 17% of patients develop elevated filling pressures with exercise; elevated filling pressure without ischemia has worse prognosis than isolated ischemia (sources/echo-hfpef-ase-2025, rating: very high)
Special Population Modifications
Atrial Fibrillation
- No single parameter has strong enough association to stand alone
- Algorithm (Figure 8): 4 primary variables (E velocity ≥100 cm/s, septal E/e' >11, TR >2.8 m/s or PASP >35 mmHg, DT ≤160 ms)
- 0–1 abnormal: normal LAP (unless LARS <18%, PV S/D <1, or BMI >30)
- 2 abnormal: indeterminate; ≥3 abnormal: elevated LAP
- Less beat-to-beat transmitral inflow variability with varying cycle length = elevated LAP (sources/echo-hfpef-ase-2025, rating: very high)
Mitral Regurgitation
- Primary MR with normal EF: E/e' ratio not reliable; use Ar-A duration >30 ms and IVRT/TE-e' <5.6
- MR with depressed EF: E/e' >14 has direct relation to LAP and predicts hospitalizations/mortality
- LARS has no significant relationship with LAP in significant MR (sources/echo-hfpef-ase-2025, rating: very high)
MAC (Moderate/Severe)
- E/A <0.8 → normal LAP; E/A >1.8 → elevated LAP
- E/A 0.8–1.8 → measure IVRT: ≥80 ms = normal, <80 ms = elevated (sources/echo-hfpef-ase-2025, rating: very high)
Pulmonary Hypertension
- Septal flattening → lateral E/e' preferred (not average); lateral E/e' >13 = elevated LAP; <8 = normal; 8–13 = indeterminate
- E/A ≤0.8 favours precapillary PH; E/A ≥2 favours postcapillary (Group II) PH
- Combine with LAVi >34 mL/m² and LARS <16% to identify Group II PH (sources/echo-hfpef-ase-2025, rating: very high)
Cardiac Transplantation
- Avg E/e' <7 = normal LAP; >14 = elevated LAP; 7–14 → SRIVR (E/SRIVR ratio ≤200 cm = normal; >200 cm = elevated); if SRIVR unavailable → TR velocity (≤2.8 m/s normal; >2.8 m/s elevated) (sources/echo-hfpef-ase-2025, rating: very high)
LBBB / RV Pacing / CRT
- Septal e' reduced by dyssynchrony → lateral E/e' preferred; average and septal E/e' less reliable
- If E+A fusion (complete): rely on TR velocity and LAVi/LARS for filling pressure estimation (sources/echo-hfpef-ase-2025, rating: very high)
Restrictive Cardiomyopathy / Cardiac Amyloidosis
- Advanced disease: E/A >2.5, DT <150 ms, IVRT <50 ms, e' 3–4 cm/s; Grade 3 = poor prognosis
- Cardiac amyloidosis "5-5-5 sign": systolic/e'/a' annular velocities all <5 cm/s
- Amyloidosis apical sparing: apical/mid+basal strain ratio >1; septal apical-to-basal ratio >2.1; EF/strain ratio >4.1 — differentiates from HCM, hypertensive LVH, AS (sources/echo-hfpef-ase-2025, rating: very high)
Pericardial Constriction
- Key features distinguishing from restrictive CM:
- Respirophasic septal shift (>25% mitral / >40% tricuspid inflow variation)
- Normal or elevated medial annular e' (>7 cm/s) — annulus reversus
- Expiratory hepatic vein reversal/forward ≥0.8
- Lateral and RV free wall strain diminished vs septum — strain reversus
- TE-e' interval typically NOT prolonged (prolonged in restrictive CM) (sources/echo-hfpef-ase-2025, rating: very high)
AI Applications
- Multiple approaches: rule-based, multi-view ML, single-view deep learning (from apical 4-chamber)
- Continuous diastolic function score (reduces "indeterminate" labelling)
- Electrocardiographic AI models showed good accuracy for diastolic dysfunction grades with similar prognostic value to echo (n~100,000 paired ECG/echo)
- All current AI models trained on 2016 guidelines — validation against invasive hemodynamics and outcomes needed (sources/echo-hfpef-ase-2025, rating: very high)
Contradictions / Open Questions
- LAVi as a primary vs supplemental variable: The 2016 ASE guidelines included LAVi as a primary parameter. The 2025 update demoted it to secondary/supplemental due to its weak and indirect correlation with acute LAP changes and multiple non-diastolic causes of LA enlargement. However, LAVi retains prognostic value (independent predictor of death, HF, AF, stroke) creating a tension between its prognostic and diagnostic roles. (sources/echo-hfpef-ase-2025, rating: very high)
- LARS age-dependence and EF-dependence: LARS has highest LAP estimation accuracy in patients with reduced LVEF; in normal EF patients it can be normal despite elevated LAP (especially if GLS >18%). This means LARS is most useful precisely in the patients where clinical diagnosis of HFpEF is already clearest, and least useful in the more ambiguous preserved EF group. (sources/echo-hfpef-ase-2025, rating: very high)
- E/e' grey zone (8–14) remains unresolved: Despite replacing the 2016 4-variable algorithm, a substantial grey zone persists for E/e' ratio between 8–14 where LAP is indeterminate. The 2025 update adds LARS and supplemental parameters to resolve this but accuracy in the grey zone remains moderate. (sources/echo-hfpef-ase-2025, rating: very high)
- Age-specific prognostic thresholds only validated for >65 years: The ARIC study data providing prognostically relevant diastolic measurements covers only adults >65 years. For younger patients, the 2025 guidelines use normal range cutoffs rather than outcomes-based thresholds, creating potential misclassification in younger individuals. (sources/echo-hfpef-ase-2025, rating: very high)
Connections
- Related to concepts/HFpEF
- Related to entities/Heart-Failure
- Related to entities/HCM
- Related to entities/ATTR-Amyloidosis
- Related to entities/Atrial-Fibrillation
- Related to entities/Pulmonary-Hypertension
- Related to concepts/Valvular-Heart-Disease
- Related to sources/echo-hfpef-ase-2025