Introduction

Left ventricular (LV) diastolic function is a key determinant of LV filling, stroke volume, and ultimately cardiac output. Abnormalities in LV active relaxation, elastic recoil, and chamber stiffness lead to elevated LV filling pressures (LVFP), symptoms of heart failure, and adverse prognosis, even when left ventricular ejection fraction (LVEF) is preserved.

 

Echocardiography is the primary noninvasive tool to characterize LV diastolic function, estimate LV filling pressures and evaluate the impact of diastolic dysfunction on pulmonary pressures

 

LV diastolic function is modulated by several interacting factors:

• Right ventricular–LV interaction

• LA function and pressure

• Pericardial constraint

• LV systolic performance and systolic/diastolic dyssynchrony

• Coronary blood flow and myocardial perfusion
   

A systematic approach that integrates clinical information with 2D and Doppler echocardiography is required for accurate diagnosis and grading of diastolic dysfunction.

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Importantly, normal LV filling pressures at rest (normal resting echocardiogram) does not exclude diastolic dysfunction, because diastolic abnormalities may only become evident under exercise/stress or increased preload.

 

 

 

 

 

 

 

 

 

 

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Terminology: diastolic dysfunction, diastolic heart failure, and HFpEF

Diastolic dysfunction refers to abnormalities of LV relaxation, elastic recoil, and/or stiffness documented by imaging or invasive hemodynamics. It is a physiological/imaging concept and does not automatically mean heart failure.

 

Diastolic heart failure describes a clinical syndrome in which symptoms and signs of heart failure are primarily explained by elevated LV filling pressures due to diastolic abnormalities. In diastolic heart failure there is diastolic dysfunction pattern on echo or there is other evidence of diastolic dysfunction (eg from invasive measurements or stress echo).

 

Not all patients with diastolic dysfunction have diastolic heart failure, and not all patients with heart failure with preserved ejection fraction (HFpEF) have a “diastolic dysfunction” pattern on echocardiography.

 

Heart failure with preserved ejection fraction (HFpEF) is a broader clinical syndrome defined by:

• Symptoms and/or signs of heart failure

• Preserved LVEF

• Objective evidence of cardiac structural and/or functional abnormalities and/or elevated natriuretic peptides, in the absence of an alternative explanation
   

Current ESC/AHA guidelines do not require that patients must meet formal echocardiographic “diastolic dysfunction grade” criteria to diagnose HFpEF. Structural abnormalities, biomarker elevation, or exercise hemodynamics can fulfil the objective evidence requirement. Consequently, some patients with HFpEF will have normal or indeterminate diastolic function by guideline diastolic algorithms on echocardiography.

 

Basic Physiology

Myocardial Contraction

During systole, the cardiac myocyte contracts in response to an action potential that opens L-type calcium channels in the cell membrane. The small influx of calcium triggers a much larger calcium release from the sarcoplasmic reticulum (calcium-induced calcium release). The resulting rise in cytosolic calcium allows calcium to bind to troponin C, moving tropomyosin away from the actin-binding sites and enabling actin–myosin cross-bridge cycling. This process generates force and myocyte shortening.

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Although contraction is a systolic event, its characteristics (e.g., extent of shortening, end-systolic volume) have important downstream effects on diastolic recoil and filling.  LV systolic dysfunction is almost invariably associated with abnormalities of diastolic function, and patients with reduced ejection fraction are generally considered to have coexistent diastolic dysfunction.

 

Myocardial Relaxation

Relaxation is an active, energy-dependent process. At the cellular level:

• Detachment of actin–myosin cross-bridges occurs during diastole and is associated with declining cellular tension.

• Calcium uptake into the sarcoplasmic reticulum happens primarily via the sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a).

• SERCA2a activity is modulated by phospholamban.

  • In its unphosphorylated state, phospholamban inhibits SERCA2a.

  • Phosphorylation of phospholamban by cyclic AMP–dependent protein kinase (e.g., during beta-adrenergic stimulation) relieves this inhibition, enhancing calcium uptake and producing a positive lusitropic effect (faster relaxation).
     

In heart failure, the function of SERCA2a is reduced, contributing to delayed relaxation. Because calcium handling and cross-bridge detachment require ATP, myocardial ischemia impairs relaxation.

 

Chamber-Level Relaxation and Recoil

At the chamber level, LV relaxation (and elastic recoil to some extent) is reflected by the rate at which LV pressure falls during isovolumic relaxation (IVR), the period between aortic valve closure and mitral valve opening. 

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LV diastolic function can be characterized by LV relaxation, LV early diastolic recoil, and chamber stiffness. These 3, in turn, determine LV filling pressures.

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The “gold standard” invasive measure of relaxation is the time constant of LV pressure decay (tau). A normal LV demonstrates rapid pressure decline and low minimal LV pressure during IVR. Increased LV afterload slows and delays relaxation.

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When afterload (LV wall stress during ejection) increases — for example, due to hypertension, aortic stenosis, or acute vasoconstriction — it affects relaxation in two major ways:

1. Prolonged systole: The ventricle has to generate higher pressure to overcome the elevated outflow resistance. Cross-bridge detachment is delayed; the myocardium stays “activated” longer. Relaxation starts later and is slower.
    

2. Increased residual stress and calcium load: Higher afterload → higher end-systolic wall tension → more intracellular calcium retention → delayed reuptake by the sarcoplasmic reticulum. This delays the fall of cytosolic calcium concentration, which is necessary for relaxation.

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LV elastic recoil, largely determined by systolic deformation and intrinsic myocardial properties, contributes to the early drop in LV pressure and the suction effect that promotes rapid early filling.

 

Role of Titin and LV Elastic Recoil

The cytoskeletal protein titin acts as an elastic spring within the sarcomere. It is compressed during systole and recoils during diastole, contributing to LV expansion and early diastolic suction.

 

Different titin isoforms have distinct compliance:

• N2BA: More compliant

• N2B: Stiffer, less compliant
   

The ratio of these isoforms differs between disease states. In heart failure with reduced ejection fraction (HFrEF), the N2BA/N2B ratio is increased, reflecting a higher proportion of the more compliant isoform. In heart failure with preserved ejection fraction (HFpEF), the stiffer N2B isoform is relatively more prominent, contributing to increased diastolic stiffness.

 

LV Chamber Stiffness

LV diastolic stiffness relates LV volume to pressure. With increased stiffness:

• LV late diastolic and end-diastolic pressures rise for a given volume.

• Consequently LA pressure also increases, often leading to LA enlargement over time.

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Echocardiographic Assessment of LV Diastolic Function

Diastolic function is a latent variable: it cannot be visualized directly, only inferred from its consequences. In the same way that gravity is not seen but was studied by Newton through its effects on motion, diastolic performance is evaluated through a set of indirect, surrogate measurements. There is no single parameter on echocardiography that “shows” diastolic function itself; instead, we observe how the ventricle fills, how pressures behave, and how the myocardium relaxes and recoils, and from these signals we infer the underlying diastolic physiology.

 

 

 

 

 

 

 

 

 

 

 

 

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It is critically important to recognize that the echocardiographic guideline algorithms follow two distinct pathways. One pathway applies to patients with a normal ejection fraction and no evidence of myocardial disease. The other pathway applies to patients with reduced ejection fraction or those in whom myocardial disease is known or identified.

 

The 2016 ASE/EACVI two different algorithms:

• Algorithm A – for patients with:

  • normal LVEF and

  • no evidence of underlying myocardial disease / structural heart disease.
     

• Algorithm B – for:

  • reduced LVEF or

  • myocardial disease with normal LVEF.

 

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In this latter group B, diastolic dysfunction is assumed to be present, and the focus shifts directly to grading the severity of diastolic dysfunction. In contrast, in the first part of the algorithm A the aim is to screen for diastolic dysfunction; if it is identified, the next step is to grade the degree of diastolic dysfunction.

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So in the B group you already expect LV relaxation to be abnormal, and you’re mainly asking: what are the filling pressures and grade of diastolic dysfunction?

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The guidelines use “myocardial disease” loosely. It includes, for example:

• LV hypertrophy

  • Hypertensive heart disease

  • Aortic stenosis with LVH

  • Hypertrophic cardiomyopathy
     

• Ischemic heart disease or myocardial scar

  • Prior myocardial infarction

  • Significant coronary artery disease with regional wall-motion abnormalities
     

• Primary cardiomyopathies

  • Dilated cardiomyopathy

  • Restrictive cardiomyopathy

  • Chemotherapy-induced or other toxic cardiomyopathies
     

• Infiltrative or storage disease

  • Cardiac amyloidosis

  • Sarcoidosis, Fabry disease, etc.
     

It also includes other clear structural or functional LV abnormalities, such as:

• LV dilation or remodeling

• Reduced ejection fraction (HFrEF)

• Clearly abnormal global longitudinal strain (GLS) or systolic annular S′ (subclinical systolic dysfunction)
   

Also right ventricular dysfunction is included.

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It should be noted that the 2016 ASE/EACVI algorithm is optimized towards specificity: when it identifies diastolic dysfunction with elevated left atrial pressure, this is usually a true abnormality. However, its sensitivity for detecting early diastolic dysfunction is limited.

 

Echocardiography provides multiple indices that relate to LV relaxation, recoil, and stiffness. No single parameter is sufficient and the guidelines highlight consistency across parameters. If most of the available parameters are either normal or abnormal (e.g. 4/4, 3/4, 3/3, 2/3), diastolic function can be classified as normal or abnormal accordingly. If there is no clear majority (e.g. 2/4, 1 out of 2, or only a single parameter available), diastolic function should be considered indeterminate.

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Key echocardiographic diastolic parameters include:

• Mitral inflow Doppler (E and A waves, E/A ratio, deceleration time)

• Tissue Doppler imaging (TDI) of the mitral annulus (e′ velocities)

• LA size (left atrial volume index, LAVI)

• Tricuspid regurgitation (TR) velocity (estimate of pulmonary artery systolic pressure)

• Pulmonary venous flow patterns

• Additional Doppler signatures (e.g., L-wave, response to Valsalva, comparison with tricuspid inflow)
   

As noted earlier, diastolic function is determined by three main factors: LV active relaxation, elastic recoil, and chamber stiffness. Of the echocardiographic parameters listed above, almost all (E, E/A, deceleration time, TR Vmax, LAVI, TR velocity) are weighted toward measuring filling and left atrial pressures, and only e′ is primarily a marker of LV relaxation and elastic recoil. Of course, slow LV relaxation will also delay LV filling and therefore influence parameters such as the E wave.

 

Tissue Doppler e′ and LV Relaxation

Relation to Relaxation

Early diastolic mitral annular velocity (e′) measured by TDI reflects longitudinal myocardial relaxation. Studies have demonstrated a significant inverse relationship between e′ and τ (the time constant of relaxation). e′ is also influenced by LV recoil; smaller LV end-systolic volumes (better systolic emptying) are associated with faster recoil and higher e′.

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e′ is measured using Tissue Doppler Imaging (TDI) at the mitral annulus (commonly at the septal and lateral sides). It reflects the myocardial velocity at the mitral annulus and early diastolic relaxation of the myocardium, i.e., how fast the LV myocardium relaxes and lengthens after systole.  Corresponds to early diastolic filling when the mitral valve first opens and blood flows rapidly from the left atrium to the ventricle. It Occurs during early diastole and the e´ wave is a negative deflection on TDI because the annulus moves away from the apex during systole

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Preload Dependence

The relationship between e′ and preload (LA pressure) depends on the status of LV relaxation:

• Normal LV relaxation:

  • The transmitral pressure gradient directly influences e′. Higher LA pressure and transmitral gradients increase e′.

  • Thus, in a normal heart, e′ is preload-dependent and should not be used with E to estimate LV filling pressure.
     

• Impaired LV relaxation (myocardial disease):

  • LA pressure has a relatively smaller effect on e′.

  • In this setting, e′ reflects relaxation more than preload, making it useful in conjunction with E to estimate LVFP.

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e′ is the MAXIMUM velocity of early diastolic longitudinal recoil of the mitral annulus, driven by both intrinsic LV relaxation and the LA–LV pressure gradient (preload).

• Normal relaxation: LV pressure falls quickly, the LA–LV gradient appears early, and higher LA pressure → higher transmitral gradient → higher e′ as the ventricle is “pushed” open by the inflow of blood with higher pressure. So in a normal heart, e′ is preload-sensitive and rises with filling pressure.

• Impaired relaxation: LV pressure falls slowly and stays high longer. The onset of e′ is delayed to mid-diastole to a time when LV pressure is nearly equal to LA pressure, so there is no significant transmitral pressure gradient left to drive early filling velocity so raising LA pressure adds little drive to early filling. e′ stays low and becomes relatively preload-independent, reflecting intrinsic relaxation.
   

Clinically, this is why E/e′ tracks LV filling pressure mainly when relaxation is abnormal: E increases with higher filling pressure, while e′ remains low, so E/e′ rises​

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Limitations of e′
Annular e′ is not recommended as a solitary marker of diastolic dysfunction, because:

• Up to 10–20% of healthy individuals may have relatively low e′ values without any other abnormal findings or symptoms.

• Age-specific cutoffs improve accuracy but are more complex to apply and still require integration with other parameters.
   

The E/e′ Ratio and Estimation of Filling Pressure

Mitral inflow E velocity is influenced by:

• LA pressure (direct relation)

• LV relaxation (inverse relation via τ)
   

Given:

• E is directly related to LA pressure and inversely related to τ

• e′ is inversely related to τ

• e′ is relatively insensitive to LA pressure in the presence of myocardial disease

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When LA pressure (preload) rises, the flow velocity across mitral valve increases and E velocity goes up.

Slow relaxation (high τ) means LV pressure remains high longer → smaller or delayed transmitral gradient → lower E.

So, when τ increases (slower relaxation), E decreases — if LA pressure is held constant.

When relaxation is slow (τ large), the annular recoil velocity (e′) is small.
in a diseased or stiff LV, relaxation is delayed and slow. 

In diseased or stiff LV, by the time the myocardium actually starts to recoil (producing e′), LA–LV pressure gradient has dissipated — LV pressure is already nearly equal to LA pressure. Therefore, e′ is no longer influenced much by preload.
It reflects intrinsic relaxation properties rather than LA pressure.

 

Because E rises with LA pressure but falls with slower relaxation, while e′ reflects only relaxation (not LA pressure in disease), dividing E by e′ removes the relaxation effect and leaves a ratio proportional to LA pressure — allowing E/e′ to estimate LV filling pressure.

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The ratio E/e′ (using septal, lateral, or average e′) becomes a dimensionless index that correlates with mean LA pressure and LVFP in patients with myocardial disease.

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Commonly used thresholds (average E/e′):

• < 8 – usually consistent with normal LV filling pressures

• > 14 – usually consistent with elevated LV filling pressures
   

Studies have shown that E/e′ can track changes in pulmonary capillary wedge pressure in ambulatory heart failure patients and in acute decompensated heart failure. However, the accuracy of E/e′ varies among different patient populations, and results are not uniform across all studies.

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Situations Where E/e′ Is Unreliable

E/e′ should not be used as a standalone estimator of LVFP when e′ is heavily influenced by non-relaxation factors, such as:

• Pericardial constriction

• Moderate to severe mitral annular calcification

• Significant mitral stenosis

• Severe mitral regurgitation with normal LVEF
   

In patients with left bundle branch block or paced rhythms, E/e′ shows weaker correlations with LVFP. In these scenarios, E/e′ must be interpreted alongside other variables such as LA volume and pulmonary artery systolic pressure.

 

Use of Mitral Inflow to Estimate LV Filling Pressures

Once myocardial disease or diastolic dysfunction has been established, mitral inflow can be used more directly to estimate LVFP:

• E/A ≥ 2:

  • Usually indicates elevated LVFP (restrictive filling pattern).
     

• E/A ≤ 0.8 and E ≤ 50 cm/s:

  • Usually indicates normal LVFP (impaired relaxation with normal filling pressures).
     

• Intermediate patterns (E > 50 cm/s or  0.8 < E/A < 2):

  • Require integration with other variables:

    • Average E/e′ ratio

    • LA maximum volume index

    • Peak TR velocity

    • Pulmonary venous S/D ratio (in depressed EF)
       

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Concordance among these variables is sought. If one out of two, or two out of four parameters are discordant, LVFP may be labeled as indeterminate.

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The rate of indeterminate studies can be reduced by:

• Multiple measurements from different views for TR velocity, careful pulmonary venous Doppler

• Considering additional Doppler signs that individually support elevated LVFP, including:

  • Increased pulmonary vein Ar-wave velocity and Ar–A duration difference (Ar–A ≥ 35 ms consistent with elevated LV end-diastolic pressure)

  • Significant change in mitral inflow pattern with Valsalva maneuver

  • L-wave velocity ≥ 50 cm/s

  • Comparison of mitral and tricuspid inflow patterns (which typically trackl each other unless one atrial pressure is selectively elevated)

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Guideline-Based Integrated Assessment (ASE/EACVI 2016)

The 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations emphasize:

• Recognition of myocardial disease

• Patients with normal EF and no clear myocardial disease

  • In patients with preserved EF and no obvious myocardial disease on clinical and imaging assessment, the guidelines recommend relying on four key parameters:

    • Annular e′ (septal and/or lateral)

    • Average E/e′ ratio

    • Peak TR velocity (peak TR velocity may be unmeasurable in roughly 30–50% of patients)

    • LA maximum volume index

• Interpretation is based on the majority of available parameters:

  • If most (e.g., 3 of 3, 3 of 4, or 4 of 4) are normal or abnormal → classify diastolic function as normal or abnormal.

  • If there is no clear majority (e.g., 2 of 4, 1 of 2, or only a single parameter available) → classify as indeterminate diastolic function and consider invasive measurements or stress echo.

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This conservative approach is designed to maintain high specificity and avoid overdiagnosis of diastolic dysfunction.

 

Exercise and Dynamic Assessment

A subset of patients with HFpEF have normal LVFP at rest but develop marked increases in LVFP with exercise. These patients may present with exertional dyspnea despite apparently normal resting echocardiography.

 

In symptomatic patients with normal resting LV filling pressures, invasive measurements or stress echocardiography with diastolic assessment during exercise can be valuable to:

• Unmask exercise-induced elevation in LVFP

• Support a diagnosis of HFpEF in otherwise inconclusive cases

 

Special Populations

The general diastolic function algorithm does not apply uniformly across all clinical settings. Certain patient groups require tailored interpretation, and specific Doppler signals may be more informative, such as:

• Significant valvular heart disease (e.g., mitral stenosis or regurgitation)

• Pericardial disease (constriction, effusion with tamponade physiology)

• Infiltrative cardiomyopathies and restrictive physiology

• Conduction abnormalities and paced rhythms
   

In these settings, guideline documents provide population-specific recommendations for the assessment of LVFP and diastolic function, often placing greater emphasis on selected parameters and pattern recognition.

 

Clinical Importance

Assessment of LV diastolic function has diagnostic, therapeutic, and prognostic implications.

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Cardiac dyspnea is mostly produced by elevated filling pressures at rest or with exercise, resulting from abnormal diastolic function.

 

Elevated LVFP is a major cause of dyspnea in:

• HFrEF

• HFpEF

• Significant valvular disease

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Noncardiac causes of dyspnea (e.g., anemia, pulmonary parenchymal disease, pulmonary vascular disease) must be distinguished, and echocardiography helps clarify the contribution of cardiac factors.
 

Biomarkers such as natriuretic peptides reflect LV wall stress but are influenced by age, sex, right ventricular function, pulmonary disease, and renal function. In contrast, echocardiography:

• Directly assesses LV and right ventricular systolic and diastolic function

• Estimates LVFP and right atrial pressure

• Evaluates valvular function, pericardial disease, and pulmonary pressures in a single examination
   

Head-to-head comparisons have shown that Doppler-derived estimates of LVFP (including E/e′) often correlate more closely with invasive wedge pressures than natriuretic peptide levels and can track dynamic changes in filling pressure over time.

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Atrial fibrillation in diastolic dysfunction

In atrial fibrillation, loss of the atrial kick causes dyspnea not because the ventricle is “underfilled,” but because achieving the same adequate filling of a stiff ventricle without atrial kick requires a much higher mean atrial pressure. Atrial contraction of course transiently increases atrial pressure, but in sinus rhythm the average atrial pressure is lower than in a patient with atrial fibrillation and diastolic dysfunction. For this reason, many patients with diastolic dysfunction decompensate or feel markedly worse during episodes of atrial fibrillation.

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When NOT to use the generic diastolic algorithm

From ASE (2016 + 2025) and European/BSE guidance, you should avoid or heavily modify the general diastolic function algorithm in:

1. Children
    

2. Perioperative patients
    

3. Atrial fibrillation and significant rhythm disturbance (fast AF, sinus tachycardia with fusion, AV block, pacing, CRT, LBBB)
    

4. Significant mitral valve disease

   • Any degree of mitral stenosis

   • severe mitral regurgitation

   • Moderate/severe mitral annular calcification

   • Mitral valve repair/replacement or transcatheter edge-to-edge repair
      

5. Other major valvular disease, especially severe aortic stenosis or aortic regurgitation (and severe tricuspid regurgitation when considering AF algorithms)
    

6. Hypertrophic cardiomyopathy
    

7. Restrictive cardiomyopathy / infiltrative diseases (e.g. amyloid)
    

8. Pulmonary hypertension (post- vs pre-capillary differentiation)
    

9. LV assist device (LVAD)
    

10. Heart transplant recipients
     

11. Complex congenital heart disease
     

12. End-stage liver disease
     

These are the “tailored interpretation” groups explicitly called out in the ASE 2016 diastolic guideline, the ASE 2025 update, and European/BSE/EACVI diastology guidance.

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