Left Ventricular Diastolic Function

Left ventricular diastolic dysfunction (LVDD) plays a major role in the pathophysiology of heart failure (HF). From a practical perspective, LV diastolic function assessment is particularly useful when evaluating patients with dyspnea of suspected or known cardiac origin.

In patients with dyspnea and preserved LV ejection fraction (EF), the identification of LVDD offers the pathophysiologic basis for diagnosing HF with preserved ejection fraction (HFpEF), which is believed to account for about half of all HF cases and to have similar or even worse prognosis than HF with reduced ejection fraction (HFrEF). Furthermore, noninvasive estimates of LV filling pressures (LVFPs) can be used to determine the hemodynamic status, provide prognostic information, and guide therapy in all patients with HF, irrespective of LVEF.

Echocardiography is the noninvasive diagnostic method that is most widely available, safe, and cost-effective; it is able to provide structural and functional information relevant to assessment of diastolic function (i.e., markers of LVDD and/or elevated LVFP).

This chapter summarizes the current status and role of echocardiography in assessment of diastolic function and discusses gaps in evidence and future perspectives.

Physiology of Diastole

Diastole is defined as the time interval between aortic valve closure and mitral valve (MV) closure. It comprises four phases: isovolumic relaxation, rapid filling, diastasis (with slow filling), and filling during atrial contraction ( Fig. 5.1 ).

Normal diastolic function is defined as the ability of the LV to fill adequately to provide a normal stroke volume at normal LVFP, both at rest and during exercise. LV relaxation, compliance, and left atrial (LA) contraction are key determinants of the driving pressure between the LA and the LV and of LV filling. In young, healthy individuals, most LV filling occurs in early diastole, during the rapid filling period.

With impaired LV relaxation and increased wall stiffness, filling progressively shifts to late diastole, and therefore the atrial contribution to cardiac output increases. The atrial contribution to LV filling may increase from about 20% in young, healthy individuals with robust LV suction to about 40% in elderly subjects with alterations of LV relaxation and compliance.

Separation of the cardiac cycle into two distinct phases—systole and diastole—may be well suited for academic purposes, but studies of cardiac mechanics emphasize that diastolic filling cannot be separated from the previous systole, and the two phases are linked with each other. Myocardial relaxation starts in systole, before aortic valve closure, and continues through isovolumic relaxation and early filling. Release of the potential energy stored during systolic twisting promotes subsequent elastic recoil and untwisting.

Apical clockwise rotation, which is mainly responsible for early diastolic filling, begins in late systole and extends into the first third of diastole. Ventricular untwisting precedes diastolic lengthening and expansion of myocardial fibers; it is responsible for the early diastolic base-to-apex pressure gradients and for diastolic suction. The brisk untwist leads to a rapid decrease in early diastolic LV pressure and to MV opening with rapid filling. Blood flows into the LV until the pressures in the left chambers equalize, resulting in diastasis.

In normal hearts, increased LV contractility and smaller end-systolic volume (e.g., with exercise, inotropes) lead to a stronger recoil that begets more rapid early diastolic filling. ^, Alterations of the temporal sequence between twisting and recoil that result in prolonged systolic twisting and delayed and shortened recoil are associated with impaired LV filling in patients with aortic stenosis, hypertrophic cardiomyopathy (HCM), ischemia, and age-related changes. ^,

The traditional concept that diastolic dysfunction precedes systolic dysfunction has been questioned and replaced with the more likely hypothesis that LV systolic and diastolic dysfunction usually coexist. Consequently, it is recommended that LV systolic function parameters be considered when assessing diastolic function.

In conclusion, LVDD is usually the result of abnormal LV relaxation, with or without reduced restoring forces (responsible for early diastolic suction), and increased LV chamber stiffness.

Invasive Evaluation of LV Diastolic Function

Cardiac catheterization is the gold standard for demonstrating abnormalities of LV relaxation, compliance, and filling by direct measurements of the LV relaxation time constant (τ), stiffness modulus, and LVFP.

The term “LV filling pressures” has been widely and indiscriminately used in cardiology with respect to any of the following invasive measurements: mean pulmonary capillary wedge pressure (PCWP), mean LA pressure (LAP), LV pre-A pressure (before atrial contraction), mean LV diastolic pressure (M-LVDP), and LV end-diastolic pressure (LVEDP) ( Fig. 5.2 ). Although these pressures correlate with each other, there are important pathophysiologic differences between them. These differences need to be acknowledged when assessing different echocardiographic parameters in relation to diastolic abnormalities. Moreover, significant effects on the performance of various diagnostic algorithms for LVDD evaluation are expected when using a specific filling pressure as a reference.

Fig. 5.2, Left ventricular filling pressures.

In the clinical setting, the LVFPs most often measured invasively are the LVEDP, which is obtained by left heart catheterization, and the PCWP (an indirect estimate of mean LAP), which is obtained by right heart catheterization. Filling pressure is considered to be elevated when the mean PCWP is >12 mmHg or the LVEDP is >16 mmHg.

Invasive measurements are impractical for daily routine. However, catheterization remains the gold standard whenever noninvasive measurements are inconclusive.

Echocardiographic Assessment of Diastolic Function

Basic Principles

Echocardiography is the first-line imaging modality for assessment of LV diastolic function in clinical practice. A large number of echocardiographic parameters have been tested and validated for their correlation with invasively measured diastolic function determinants, but none of them is accurate enough to be used as a single diagnostic marker for LVDD.

The assessment of diastolic function should always be placed in the clinical context of the individual patient. Attention should be directed to any clinical information that is relevant for the diagnosis of LVDD or HF (e.g., signs or symptoms of HF, obesity, history of hypertension, coronary artery disease, diabetes, chronic kidney disease), including specific settings that may require personalization of the general algorithm for diastolic function evaluation (e.g., atrial fibrillation [AF], conduction abnormalities, paced rhythm).

Two-dimensional (2D) echocardiography may identify structural abnormalities of the heart (e.g., LV hypertrophy, LA dilation) that represent either the cause or the consequence of LVDD and reflect its severity and/or duration. The presence of such abnormalities increases the likelihood of LVDD, and these parameters are generally more stable than Doppler parameters.

Doppler echocardiography can identify functional abnormalities, providing further information regarding LV diastolic properties and LVFP. Discerning whether the main driver of LVDD is abnormal LV relaxation or decreased compliance is relevant with respect to LVDD etiology .

LV volumes and LVEF, measured according to current recommendations, provide key information when assessing LV diastolic function. In patients with dilated ventricles and reduced LVEF, LVDD is presumed to be present, and the main question relates to the level of LVFP. In patients with normal LV volumes and normal LVEF, a comprehensive evaluation of all the structural and functional abnormalities relevant for LVDD is necessary.

The Doppler echocardiographic parameters used to assess LV diastolic function perform differently in patients with reduced LVEF than in those with preserved LVEF.

Conventional Echocardiographic Parameters of Diastolic Function

Mitral Inflow Parameters

The mitral inflow signal recorded by pulsed-wave (PW) echocardiography represented for many years the cornerstone of diastolic function assessment.

Mitral Inflow Patterns

In young, healthy individuals, the peak velocity of the E wave exceeds that of the A wave because most of the LV filling occurs during the rapid filling phase and is driven by ventricular suction (E/A ratio >1). With delayed relaxation (e.g., in elderly patients), the early diastolic pressure gradient is reduced and the contribution of atrial contraction to LV filling is increased (E/A ratio <1), leading to an impaired relaxation pattern, with prolonged isovolumic relaxation time (IVRT) and E-wave deceleration time (EDT). Further alteration of LV relaxation requires a compensatory increase in LAP to preserve cardiac output. In such cases, the E/A ratio appears normal again (E/A ratio >1): this is the pseudonormal (PN) filling pattern.

Progression of LVDD results in a tall E wave with marked shortening of the EDT (i.e., early filling driven by elevated LAP with rapid equilibration of LA and LV diastolic pressures in the noncompliant LV) and a reduced A wave (i.e., high LV diastolic pressure). The restrictive filling pattern (E/A ratio >2) is a negative prognostic marker in patients with HF ( Fig. 5.3 ).

Fig. 5.3, Mitral inflow by pulsed-wave Doppler echocardiography.

The opposing effects of impaired relaxation and increased LVFP on the E/A ratio explain its parabolic distribution (U-shaped curve) along the transition from normal function to severe LVDD ( Fig. 5.4 ). Deciding whether a patient is on the “good” left side (normal pattern) or on the “bad” right side (PN pattern) of the curve sometimes requires additional information.

Fig. 5.4, Changes in mitral inflow pattern during progression of LVDD.

Because of their high load dependency, mitral inflow parameters reflect a snapshot of the hemodynamic relationship between LA and LV pressures rather than an evolutive stage of LVDD.

Loading conditions and aging are important factors that influence the mitral inflow parameters and need to be taken into account when evaluating diastolic function. The reference values of mitral inflow parameters according to age and gender are presented in Table 5.1 . ^,

TABLE 5.1

Reference Ranges for Conventional Doppler Flow Parameters of LV Diastolic Function. ^a

	Mitral E (cm/s)	Mitral A (cm/s)	E/A Ratio	EDT (ms)	IVRT (ms)	Pulm S (cm/s)	Pulm D (cm/s)	Pulm S/D Ratio
Female
Feasibility, no. (%)	657 (99)	657 (99)	657 (99)	657 (99)	653 (98)	646 (98)	637 (96)	635 (96)
<40 yr ( n = 208)	80 ± 16	48 ± 15	1.85 ± 0.76	212 ± 55	85 ± 16	58 ± 12	55 ± 11	1.09 ± 0.31
40–60 yr ( n = 336)	74 ± 15	59 ± 15	1.32 ± 0.40	220 ± 66	95 ± 20	59 ± 12	48 ± 12	1.29 ± 0.35
>60 yr ( n = 119)	69 ± 16	75 ± 18	0.96 ± 0.32	244 ± 79	105 ± 23	62 ± 12	43 ± 11	1.51 ± 0.39
All ( n = 663)	75 ± 16	58 ± 18	1.42 ± 0.62	218 ± 66	93 ± 21	59 ± 12	49 ± 12	1.26 ± 0.37
Male
Feasibility, no. (%)	599 (99)	599 (99)	599 (99)	599 (99)	597 (99)	583 (97)	583 (97)	578 (96)
<40 yr ( n = 126)	75 ± 15	44 ± 14	1.86 ± 0.64	217 ± 65	91 ± 17	52 ± 11	55 ± 12	0.99 ± 0.29
40–60 yr ( n = 327)	64 ± 15	52 ± 14	1.30 ± 0.42	232 ± 81	100 ± 21	55 ± 11	47 ± 11	1.22 ± 0.31
>60 yr ( n = 150)	61 ± 14	65 ± 18	0.99 ± 0.34	269 ± 97	118 ± 29	62 ± 13	43 ± 11	1.50 ± 0.40
All ( n = 603)	66 ± 15	54 ± 17	1.34 ± 0.54	238 ± 85	103 ± 24	56 ± 12	48 ± 12	1.23 ± 0.37

E/A ratio, Ratio of early to atrial peak filling velocity; EDT, E-wave deceleration time; IVRT, isovolumic relaxation time; Pulm D, peak diastolic pulmonary velocity; Pulm S, peak systolic pulmonary velocity.

Data from Dalen H, Thorstensen A, Vatten LJ, et al. Reference values and distribution of conventional echocardiographic Doppler measures and longitudinal tissue Doppler velocities in a population free from cardiovascular disease. Circ Cardiovasc Imaging . 2010;3:614–622; Hurrell DG, Nishimura RA, Ilstrup DM, Appleton CP. Utility of preload alteration in assessment of left ventricular filling pressure by Doppler echocardiography: a simultaneous catheterization and Doppler echocardiographic study. J Am Coll Cardiol . 1997;30:459–467.

a Data are presented as mean ± SD for Doppler flow velocities from 1266 healthy individuals by sex and age, unless otherwise indicated.

The load dependency of mitral inflow parameters can be overcome by performing a standardized Valsalva maneuver . This can effectively unload the heart, helping to distinguish normal LV filling from PN filling ( Fig. 5.5 ), reveal whether restrictive LV filling is reversible or not, and unmask high LVFP in patients with an impaired relaxation pattern at baseline. ^,

Fig. 5.5, Changes in mitral inflow pattern during the Valsava maneuver.

A decrease in E/A ratio of ≥50% during Valsalva maneuver is highly specific for increased LVFP. The procedure should be standardized by continuous recording of the mitral inflow using PW Doppler echocardiography during the straining phase of the maneuver, with the patient blowing into a sphygmomanometer to raise the pressure to 40 mmHg and keep it stable at that level for 10 seconds. Valsalva maneuver is not easy to perform in every patient and cannot be applied in critically ill or intubated patients.

The utility, advantages, and limitations of mitral flow parameters for evaluation of LV diastolic function are summarized in Table 5.2 .

TABLE 5.2

Utility, Advantages, and Limitations of Parameters Used to Assess LV Diastolic Function.

Parameter	Utility and Physiologic Background	Advantages	Limitations
Mitral E velocity (PW Doppler)	E-wave velocity reflects the LA–LV pressure gradient during early diastole and is affected by alterations in rate of LV relaxation and LAP.	1. Feasible and reproducible. 2. In patients with DCM and reduced LVEF, mitral velocities correlate better with LVFPs, functional class, and prognosis than LVEF does.	1. In patients with CAD and patients with HCM in whom LVEF is >50%, mitral velocities correlate poorly with LVFPs. 2. More challenging to apply in patients with arrhythmias. 3. Directly affected by alterations in LV volumes and elastic recoil. 4. Age-dependent (decreases with aging).
Mitral A velocity (PW Doppler)	A-wave velocity reflects the LA–LV pressure gradient during late diastole, which is affected by LV compliance and LA contractile function.	Feasible and reproducible	1. Sinus tachycardia, first-degree AV block, and paced rhythm can result in fusion of the E and A waves. If mitral flow velocity at the start of atrial contraction is >20 cm/s, A velocity may be increased. 2. Not applicable in patients with AF or atrial flutter. 3. Age-dependent (increases with aging).
Mitral E/A ratio	Mitral inflow E/A ratio and EDT are used to identify the filling patterns: normal, impaired relaxation, PN, or restrictive filling.	1. Feasible and reproducible. 2. Provides diagnostic and prognostic information. 3. In patients with DCM, filling patterns correlate better with LVFPs, functional class, and prognosis than LVEF does. 4. A restrictive filling pattern in combination with LA dilation in patients with normal EF is associated with a poor prognosis, similar to a restrictive pattern in DCM.	1. The U-shaped relation with LV diastolic function makes it difficult to differentiate normal from PN filling, particularly in patients with normal LVEF, without measuring additional variables. 2. If mitral flow velocity at the start of atrial contraction is >20 cm/s, E/A ratio will be reduced due to fusion. 3. Not applicable in patients with AF or atrial flutter. 4. Age-dependent (decreases with aging).
Mitral EDT (PW Doppler)	EDT is influenced by LV relaxation, LV diastolic pressures after MV opening, and LV stiffness.	1. Feasible and reproducible. 2. A short EDT in patients with reduced LVEF indicates increased LVFP with high accuracy both in sinus rhythm and in AF.	1. EDT does not relate to LVEDP when LVEF is normal. 2. EDT should not be measured in patients with E and A fusion due to potential inaccuracy. 3. Not applicable in atrial flutter. 4. Age-dependent (increases with aging).
Changes in mitral inflow with Valsalva maneuver	Helps distinguish normal from PN filling patterns. A decrease in E/A ratio of ≥50% or an increase in A-wave velocity during the maneuver, not caused by E and A fusion, are highly specific for increased LVFP.	When performed adequately under standardized conditions (e.g., keeping 40 mmHg intrathoracic pressure constant for 10 s), accuracy in diagnosing increased LVFP is good.	1. Not every patient can perform this maneuver adequately. The patient must generate and sustain a sufficient increase in intrathoracic pressure, and the examiner needs to maintain the correct sample volume location between the mitral leaflet tips during the maneuver. Not applicable in critically ill or intubated patients. 2. Difficult to assess if the procedure is not standardized.
Mitral “L” velocity	Markedly delayed LV relaxation in the setting of elevated LVFP allows for ongoing LV filling in mid-diastole and thus L velocity. The heart rate needs to be low enough for the L wave to be seen.	When present in patients with known cardiac disease (e.g., LVH, HCM), it is specific for elevated LVFP. However, its overall sensitivity is low.	Rarely seen in normal LV diastolic function when the subject has bradycardia. In such cases, the L velocity is usually <20 cm/s.
IVRT	IVRT is prolonged in patients with impaired LV relaxation but normal LVFP. When LAP increases, IVRT shortens, and its duration is inversely related to LVFP in patients with cardiac disease.	1. Overall, feasible and reproducible. 2. IVRT can be combined with other mitral inflow parameters such as E/A ratio to estimate LVFP in patients with HFrEF. 3. It can be combined with LV end-systolic pressure to estimate the time constant of LV relaxation (τ). 4. It can be applied in patients with mitral stenosis, in whom the same relation with LVFP described above holds. 5. In patients with MR or after MV replacement or repair, it can be combined with T _E−e′ to estimate LVFP.	1. IVRT duration is in part affected by heart rate and arterial pressure. 2. It is more challenging to measure and interpret with tachycardia. 3. Results differ based on using CW or PW Doppler for acquisition.
TDI-derived mitral annular early diastolic velocity e ′ (PW Doppler)	A significant association is present between e ′ and τ; this was shown in both animals and humans. The hemodynamic determinants of e ′ velocity include LV relaxation, restoring forces, and LVFP.	1. Feasible and reproducible. 2. LVFP has a minimal effect on e ′ in the presence of impaired LV relaxation. 3. Less load-dependent than conventional blood-pool Doppler parameters.	1. Limited accuracy in patients with CAD and regional dysfunction in the sampled segments, significant mitral annular calcification, surgical rings or prosthetic MVs, or pericardial disease. 2. Need to sample at least two sites with precise location and adequate size of sample volume. 3. Different cutoff values depending on the sampling site for measurement. 4. Age-dependent (decreases with aging).
Mitral E/ e ′ ratio	The e ′ velocity can be used to correct for the effect of LV relaxation on mitral E velocity, and the E/ e ′ ratio can be used to estimate LVFP.	1. Feasible and reproducible. 2. Values for average E/ e ′ ratio <8 usually indicate normal LVFP; values >14 have high specificity for increased LVFP.	1. E/ e ′ ratio is not accurate in normal subjects, patients with heavy mitral annular calcification, MV disease, or pericardial disease. 2. There is a “gray zone” of values (8–14) in which LVFP is indeterminate. 3. Accuracy is reduced in patients with CAD and regional dysfunction at the sampled segments. 4. Different cutoff values depending on the site used for measurement.
T _{E− e ′} time interval	Can identify patients with LVDD due to delayed onset of e ′ velocity compared with onset of mitral E velocity in these patients.	1. Ratio of IVRT to T _{E− e ′} can be used to estimate LVFP in normal subjects and in patients with MV disease. 2. T _E−e′ can be used to differentiate patients with restrictive cardiomyopathy (who have a prolonged time interval) from those with pericardial constriction (in whom it is usually not prolonged).	More challenging to acquire satisfactory signals; close attention to location, gain, and filter settings and matching of RR intervals are required.
LAVi	LA volume reflects the cumulative effects of increased LVFP over time. Increased LA volume is an independent predictor of death, heart failure, AF, and ischemic stroke.	1. Feasible and reproducible. 2. Provides diagnostic and prognostic information about LVDD and chronicity of disease. 3. Apical 4-chamber view provides visual estimate of LA and RA size confirming that LA is enlarged.	1. LA dilation is seen in patients with bradycardia, high-output states, AF or atrial flutter, significant MV disease, or heart transplant with biatrial technique despite normal LV diastolic function. 2. LA dilatation occurs in well-trained athletes who have bradycardia and are well hydrated. 3. Suboptimal image quality and/or scanning technique, including LA foreshortening, precludes accurate measurements. 4. It can be difficult to measure LA volumes properly in patients with ascending or descending aortic aneurysm and in those with large interatrial septal aneurysm.
Pulmonary veins: peak systolic (S) velocity, peak diastolic (D) velocity, and S/D ratio (PW Doppler)	S-wave velocity is influenced by changes in LAP, LA contractility, and LV and RV contractility. D-wave velocity is mainly influenced by early diastolic LV filling and compliance, and it changes in parallel with mitral E velocity. Decrease in LA compliance and increase in LAP is associated with decrease in S velocity and increase in D velocity.	1. Reduced S velocity, S/D ratio <1, and systolic filling fraction (systolic VTI/total forward flow VTI) <40% indicate increased mean LAP in patients with reduced LVEF. 2. In patients with AF, DDT can be used to estimate mean PCWP.	1. Feasibility of recording PV inflow can be suboptimal, particularly in ICU patients. 2. The relationship between PV systolic filling fraction and LAP has limited accuracy in patients with normal LVEF, AF, MV disease, or HCM.
Ar − A duration	The time difference between Ar duration and mitral A duration during atrial contraction is associated with LV pressure rise due to atrial contraction and correlates with LVEDP: the longer the time difference, the higher the LVEDP.	1. PV Ar > mitral A duration by 30 ms indicates an increased LVEDP. 2. Independent of age and LVEF. 3. Accurate in patients with MR and patients with HCM.	1. Adequate recordings of Ar duration may not be feasible by TTE in some patients. 2. Not applicable in patients with AF. 3. Difficult to interpret in patients with sinus tachycardia or first-degree AV block with E and A fusion.
TR peak jet velocity (CW Doppler)	A significant correlation exists between systolic PA pressure and noninvasively derived LAP. In the absence of pulmonary disease, increased systolic PA pressure suggests elevated LAP.	Systolic PA pressure can be used as an adjunctive parameter of mean LAP. Evidence of pulmonary hypertension has prognostic implications.	1. Indirect estimate of LAP. 2. Adequate recording of a full envelope is not always possible in unenhanced studies, but intravenous agitated saline increases the yield. 3. With severe TR and low systolic RV–RA pressure gradient, accuracy of calculation depends on reliable estimation of RA pressure.
Color M-mode Vp and E/Vp ratio	Vp correlates with τ and can be used as a parameter of LV relaxation. E/Vp ratio correlates with LAP.	1. Vp is reliable as an index of LV relaxation in patients with depressed LVEF and dilated LV but not in patients with normal LVEF. 2. E/Vp ≥2.5 predicts PCWP >15 mmHg with reasonable accuracy in patients with depressed LVEF.	1. There are different methods for measuring mitral-to-apical flow propagation. 2. In patients with normal LV volumes and LVEF but elevated LVFP, Vp can be misleadingly normal. 3. Lower reproducibility. 4. Angulation between M-mode cursor and flow results in erroneous measurements.

AF , Atrial fibrillation; Ar , atrial reversal velocity in pulmonary veins; A _dur , mitral A wave duration; AV , atrioventricular; CAD , coronary artery disease; CW , continuous-wave; DCM , dilated cardiomyopathy; DDT , deceleration time of pulmonary vein D wave; e ′, mitral annulus early diastolic velocity; E/A ratio , ratio of early to atrial peak filling velocity; EDT , deceleration time of mitral E velocity; HCM , hypertrophic cardiomyopathy; HFrEF , heart failure with reduced ejection fraction; ICU , intensive care unit; IVRT , isovolumic relaxation time; LAP , left atrial pressure; LAVi , LA maximum volume index; LVDD , left ventricular diastolic dysfunction; LVEDP , left ventricular end-diastolic pressure; LVEF , left ventricular ejection fraction; LVFP , left ventricular filling pressure; LVH , left ventricular hypertrophy; MR , mitral regurgitation; MV , mitral valve; PA , pulmonary artery; PCWP , pulmonary capillary wedge pressure; PN , pseudonormal; PV , pulmonary vein; PW , pulsed-wave; τ , time constant of LV relaxation; TDI , pulsed-wave tissue Doppler imaging; T _E−e′ , time interval between onset of mitral E velocity and onset of annular e′ velocity; TR , tricuspid regurgitation; TTE , transthoracic echocardiography; Vp , flow propagation velocity; VTI , velocity–time integral.

Adapted from Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr . 2016;29:277–314.

Pulmonary Venous Flow Parameters

Evaluation of pulmonary venous (PV) flow provides further information about LV diastolic function. Normal PV flow has two forward waves, S (systolic) and D (diastolic), and a reversal wave (Ar) at the time of atrial contraction. In normal subjects, the systolic-to-diastolic flow ratio (S/D) is usually >1, and the Ar wave is usually small ( Fig. 5.6 ).

Fig. 5.6, Pulmonary venous flow by pulsed-wave Doppler echocardiography.

With LVDD, as LV compliance decreases and LAP increases, there is blunting of the S wave and a decrease the systolic filling fraction. Conversely, the D wave becomes more prominent, with shortened deceleration time, while Ar duration and velocity increase. A D-wave deceleration time >220 msec has excellent accuracy in predicting a normal PCWP in patients with AF.

PV flow parameters are also influenced by loading conditions and aging. The reference values for PV flow parameters according to age and gender are presented in Table 5.1 , and their advantages and limitations are shown in Table 5.2 .

Color M-Mode Echocardiography

Color M-mode echocardiography allows interrogation of the flow filling the LV in diastole, from LV base to the apex. Normally, patients in sinus rhythm have two waves of color flow in diastole. The first wave (E), from the mitral annulus to the apex, represents the early LV filling driven by the basal-apical intraventricular diastolic pressure gradient, and the second wave (A) corresponds to atrial contraction and normally does not exceed the middle portion of the LV.

The propagation velocity (Vp) of the E wave has emerged as an index of LV relaxation: the slower the relaxation, the lower the Vp. It can be assessed by measuring the slope of the early filling wave ( Fig. 5.7 ). A Vp <50 cm/s suggests the presence of LVDD. Vp decreases progressively with LVDD and does not undergo the phenomenon of pseudonormalization.

Fig. 5.7, Velocity of flow propagation by color M-mode echocardiography.

The propagation velocity can be falsely normal despite LVDD in patients with preserved LVEF and LVH/small LV volume. Because of these limitations and a lower reproducibility, Vp is not currently recommended as a first-line parameter for evaluation of LV diastolic function evaluation.

In combination with peak E velocity, Vp can also be used to assess LVFP. Thus, the E/Vp ratio is a predictor of the PCWP. ^,

The advantages and limitations of color M-mode in assessing LV diastolic function are shown in Table 5.2 .

Tissue Doppler Echocardiography

PW tissue Doppler imaging (TDI) allows the assessment of diastolic function by measuring peak diastolic velocities of the mitral annulus ( Fig. 5.8 ).

Fig. 5.8, Pulsed-wave tissue Doppler echocardiographid recording of mitral annular velocities in a normal subject.

The early diastolic velocity, e ′, is a marker of ventricular relaxation ( Fig. 5.9 ). It is inversely related to the relaxation constant, τ, and is less load-dependent than conventional Doppler flow parameters. ^, The late diastolic velocity, a ′, corresponds to atrial contraction and is correlated with transmitral A-wave velocity and atrial function.

Fig. 5.9, LV long-axis function in health and disease.

Of note, TDI-derived velocities are highly age dependent, and this should be taken into account when using them to evaluate diastolic function.

With the progression of LVDD, there is a continuous decline of e ′ because this parameter is less affected by the progressive increase in LVFP compared with the mitral E wave ( Fig. 5.10 ). The combination of mitral E velocity (which increases with LVDD severity) and TDI-derived e ′ velocity (which decreases with LVDD severity) provides a parameter, the E/ e ′ ratio, that is directly related to LVFP.

Fig. 5.10, Changes in echocardiographic parameters during the progression of LV diastolic dysfunction.

The correlation between E/ e ′ and LVFP has been confirmed in patients with both HFrEF and HFpEF, using different cutoff values for E/ e ′ ratio according to the site of e ′ measurement. The current recommendation is to measure both the septal and lateral sides of the mitral annulus and to average the values when calculating E/ e ′ ratio to predict LVFP.

The reference values for TDI parameters of diastolic function according to age and gender are presented in Table 5.3 , and their advantages and limitations are shown in Table 5.2 .

TABLE 5.3

Tissue Doppler-Derived LV Diastolic Function Parameters According to Age and Gender.

Parameters	20–40 years				40–60 years				≥60 years				P ^a			Male ^b r ( P)	Female ^b r ( P)
Parameters	Total Mean ± SD	Total 95% CI	Male Mean ± SD	Female Mean ± SD	Total Mean ± SD	Total 95% CI	Male Mean ± SD	Female Mean ± SD	Total Mean ± SD	Total 95% CI	Male Mean ± SD	Female Mean ± SD	Total	Male	Female	Male ^b r ( P)	Female ^b r ( P)
Pulse Doppler at the Miral Value
E wave velocity (cm/s)	0.82 ± 0.16	0.53–1.22	0.79 ± 0.14	0.84 ± 0.17	0.75 ± 0.17	0.46–1.13	0.72 ± 0.16	0.77 ± 0.17	0.70 ± 0.16	0.39–1.03	0.67 ± 0.15	0.72 ± 0.17	<0.001	<0.001	<0.001	−031; <0.001	−029; <0.001
A wave velocity (cm/s)	0.50 ± 0.13	0.30–0.87	0.50 ± 0.13	0.51 ± 0.12	0.62 ± 0.15	0.37–0.97	0.61 ± 0.15	0.63 ± 0.14	0.74 ± 0.16	0.40–1.04	0.73 ± 0.16	0.76 ± 0.16	<0.001	<0.001	<0.001	0.49; <0.001	052; <0.001
E wave deceleration time (ms)	178.2 ± 43.1	105.2–269.0	179.8 ± 46.4	176.7 ± 40.1	187.6 ± 45.5	114.6–288.1	186.6 ± 52.8	188.2 ± 39 .8	208.9 ± 62.7	114.0–385.9	217.5 ± 69.7	201.5 ± 55.7	<0.001	0.002	0.008	0.23; 0.001	0.18; 0.006
E/A ratio	1.71 ± 0.52	0.89–3.18	1.69 ± 0.52	1.72 ± 0.52	1.24 ± 0.39	0.71–2.27	1.22 ± 0.31	1.26 ± 0.43	0.98 ± 0.29	0.53–1.80	0.96 ± 0.27	0.99 ± 0.31	<0.001	<0.001	<0.001	−0.61; <0.001	−0.54 <0.001
Tissue Doppler Data (cm/s)
Septal e ′ wave	12.1 ± 2.5	8.0–17.0	11.9 ± 2.7	12.3 ± 2.3	9.8 ± 2.6	5.0–16.0	9.8 ± 2.6	9.7 ± 2.5	7.6 ± 2.3	3.0–13.0	7.3 ± 2.2	7.9 ± 2.3	<0.001	<0.001	<0.001	−0.58 (<0.001)	−0.58 (<0.001)
Septal a ′ wave	8.5 ± 1.7	5.3–12.0	8.9 ± 1.6	8.1 ± 1.8	9.8 ± 2.0	6.9–14.0	10.6 ± 2.0	9.1 ± 1.8	10.5 ± 1.7	7.0–14.0	10.6 ± 1.9	10.4 ± 1.6	<0.001	<0.001	<0.001	0.40 (<0.001)	0.44 (<0.001)
Lateral e ′ wave	16.4 ± 3.4	10.0–23.0	16.2 ± 3.6	16.6 ± 3.2	12.5 ± 3.0	6.0–18.0	12.6 ± 3.0	12.4 ± 3.0	9.6 ± 2.8	4.0–17.0	9.5 ± 2.1	9.7 ± 3.2	<0.001	<0.001	<0.001	−0.65 (<0.001)	−0.65 (<0.001)
Lateral a ′ wave	8.2 ± 2.2	5.0–13.0	8.5 ± 2.0	8.0 ± 2.3	9.4 ± 2.6	5.0–15.0	9.8 ± 2.7	9.2 ± 2.5	10.6 ± 2.9	6.0–17.0	10.9 ± 3.0	10.4 ± 2.8	<0.001	<0.001	<0.001	0.36 (<0.001)	0.33 (<0.001)
Average septal and lateral e ′ wave	14.3 ± 2.7	9.1–19.5	14.0 ± 2.9	14.5 ± 2.4	11.1 ± 2.5	6.0–16.0	11.2 ± 2.4	11.1 ± 2.5	8.6 ± 2.3	3.5–15.0	8.5 ± 1.9	8.8 ± 2.6	<0.001	<0.001	<0.001	−0.66 (<0.001)	−0.66 (<0.001)
Inferior e ′ wave	14.2 ± 3.1	8.0–20.3	13.6 ± 3.0	14.7 ± 3.1	11.0 ± 2.9	6.0–17.0	10.5 ± 2.8	11.4 ± 2.9	8.4 ± 2.4	2.7–14.0	8.2 ± 2.6	8.6 ± 2.3	<0.001	<0.001	<0.001	−0.65 (<0.001)	−0.65 (<0.001)
Inferior a ′ wave	8.9 ± 1.8	5.0–13.0	9.3 ± 1.8	8.5 ± 1.7	10.5 ± 2.3	6.0–16.0	11.1 ± 2.2	10.1 ± 2.2	11.8 ± 2.0	7.7–16.0	11.8 ± 2.0	11.8 ± 2.1	<0.001	<0.001	<0.001	0.49 (<0.001)	0.49 (<0.001)
Anterior e ′ wave	14.5 ± 2.9	9.0–20.0	14.0 ± 3.0	15.0 ± 2.8	11.0 ± 2.8	6.0–18.0	11.1 ± 2.8	10.9 ± 2.8	8.0 ± 2.3	3.0–14.0	8.2 ± 2.8	7.9 ± 1.8	<0.001	<0.001	<0.001	−0.66 (<0.001)	−0.75 (<0.001)
Anterior a ′ wave	7.6 ± 1.7	4.0–11.0	8.1 ± 1.7	7.2 ± 1.6	8.7 ± 2.2	5.0–15.0	9.0 ± 2.3	8.5 ± 2.1	9.9 ± 2.4	5.0–14.3	9.9 ± 2.3	9.9 ± 2.4	<0.001	<0.001	<0.001	0.36 (<0.001)	0.39 (<0.001)
Posterior e ′ wave	15.9 ± 3.1	10.0–23.0	15.9 ± 3.5	15.9 ± 2.6	12.3 ± 2.9	7.0–18.1	12.3 ± 3.0	12.3 ± 2.8	9.8 ± 2.7	3.6–15.8	9.9 ± 2.7	9.7 ± 2.6	<0.001	<0.001	<0.001	−0.65 (<0.001)	−0.67 (<0.001)
Posterior a ′ wave	8.2 ± 2.0	4.0–13.0	8.6 ± 1.9	7.9 ± 2.1	10.0 ± 2.7	6.0–17.0	10.6 ± 2.7	9.7 ± 2.7	11.5 ± 2.8	6.3–20.1	11.7 ± 3.3	11.4 ± 2.3	<0.001	<0.001	<0.001	0.46 (<0.001)	0.45 (<0.001)
Average e ′ wave	14.5 ± 2.3	10.2–19.4	14.5 ± 2.6	14.9 ± 2.0	11.2 ± 2.3	6.5–15.5	11.0 ± 2.2	11.3 ± 2.3	8.6 ± 1.9	3.5–12.6	8.9 ± 2.0	8.3 ± 1.7	<0.001	<0.001	<0.001	−0.73 (<0.001)	−0.78 (<0.001)
E/ e′ Ratio
Septal E/ e ′	6.9 ± 1.6	4.4–10.6	6.9 ± 1.7	6.9 ± 1.6	8.1 ± 2.3	4.3–13.2	7.8 ± 2.4	8.2 ± 2.2	9.7 ± 2.8	5.0–16.9	9.8 ± 3.0	9.7 ± 2.6	<0.001	<0.001	<0.001	0.42 (<0.001)	0.41 (<0.001)
Lateral E/ e ′	5.1 ± 1.3	3.1–8.5	5.0 ± 1.3	5.2 ± 1.3	6.3 ± 2.2	3.7–12.0	6.1 ± 2.2	6.5 ± 2.3	7.8 ± 2.2	4.2–12.8	7.6 ± 2.1	7.9 ± 2.2	<0.001	<0.001	<0.001	0.43 (<0.001)	0.44 (<0.001)
Average septal and lateral E/ e ′	5.8 ± 1.3	3.6–9.1	5.8 ± 1.4	5.9 ± 1.3	7.0 ± 2.1	4.2–11.5	6.7 ± 2.1	7.2 ± 2.0	8.5 ± 2.2	4.6–13.5	8.4 ± 2.2	8.6 ± 2.2	<0.001	<0.001	<0.001	0.45 (<0.001)	0.46 (<0.001)
Average E/ e ′	5.6 ± 1.1	3.7–7.9	5.6 ± 1.2	5.5 ± 1.0	6.8 ± 1.8	4.0–11.6	6.7 ± 1.8	6.9 ± 1.9	8.3 ± 2.2	4.4–14.8	8.1 ± 2.3	8.6 ± 2.2	<0.001	<0.001	<0.001	0.50 (<0.001)	0.55 (<0.001)

CI , Confidence interval; F , female; M , male; P , differences between groups according to age category (one-way ANOVA); r (P) , correlation with age for both sexes (Pearson correlation test).

From Caballero L, Kou S, Dulgheru R, et al. Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE Study. Eur Heart J Cardiovasc Imaging . 2015;16:1031–1041.

a P differences between groups according to age category (one-way ANOVA).

b P and r correlation with age for both genders (Pearson correlation test).

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