The diastolic phase of the cardiac cycle is recognized as an important, independent component of cardiac performance. Quantification of the LV diastolic properties and filling pressures was initially performed via cardiac catheterization. The introduction of two-dimensional (2D) and pulsed wave Doppler (PWD) echocardiography, and later of tissue Doppler imaging (TDI), has revolutionized the assessment and understanding of diastolic function. Being less invasive, portable, and a safer technique, echocardiography has emerged as the clinical modality of choice for the evaluation of diastolic function.
Over the last several decades, echocardiography has helped delineate diastolic dysfunction as a major pathophysiologic component of several cardiac disorders including acute and chronic heart failure (HF) (1
). In addition, Doppler echocardiographic modalities have been used to predict functional class and prognosis (2
). In the perioperative arena, Flu et al. has identified that the presence of preoperative asymptomatic ventricular diastolic dysfunction is associated with increased short- and long-term morbidity and mortality (3
). In patients undergoing vascular surgery, the presence of perioperative diastolic dysfunction has been linked with postoperative HF and increased hospital length of stay (4
). Other echocardiographic studies have suggested that diastolic dysfunction may contribute to hemodynamic instability and adverse outcomes following cardiac surgery (5
). This chapter presents a practical approach to understanding the importance and utility of echocardiographic modalities in assessing ventricular filling and diastolic function.
BASICS OF DIASTOLIC PHYSIOLOGY
Diastolic performance is an energy-dependent process (7
). It involves an intricate interplay between various dynamic phenomena including myocardial wall relaxation, suction force generation by the left ventricular (LV) cavity, left atrial (LA) contribution to ventricular filling, viscoelastic forces of the myocardium, pericardial restraint, ventricular interaction, mitral valve (MV) geometry and patient hemodynamics (8
). Not surprisingly, diastolic function may be affected by a patient’s fluid status, position, ventilation, heart rate and rhythm, all factors which vary significantly during the intraoperative period. Therefore, the assessment of diastolic function performed in the perioperative arena should be regarded as a dynamic process.
Clinically the diastolic phase of the cardiac cycle is defined as the period from aortic valve closure (AVC) to mitral valve closure (MVC) (Fig. 7.1
). Diastole can be further divided into four phases: an initial isovolumic relaxation period, followed by early rapid LV inflow, diastasis, and finally, atrial systole (9
). Isovolumic relaxation
starts with the closure of the aortic valve (AV). Due to ventricular relaxation, the pressure in the LV declines rapidly to levels below left atrial pressure (LAP) thus promoting the opening of the MV. The rapid filling phase
is responsible for 70% to 80% of diastolic filling. Due to the continuous myocardial relaxation as well as to the elastic recoil properties of the myocardium during this phase, the LV pressure (LVP) continues to drop (in spite of an LV volume increase) therefore creating a suction effect and promoting forward flow from the pulmonary veins via the LA into the LV. Diastasis
is characterized by the equilibration of LAP and LVP. At this time point, filling is minimal and is based on the passive compliance of the LV. Atrial systole
results in an increase in LAP, which promotes forward flow into the LV as well as retrograde flow into the pulmonary veins. Therefore, the contribution of this phase to the total stroke volume (usually 20% to 25%) varies dependent upon ventricular compliance and atrial contractility. At this time point, any LV volume increase is coupled with an LVP increase. The increasing LVP eventually exceeds that of the LAP and promotes closure of the MV.
Physiologically, based on the load-bearing characteristics of the myocardium, diastole is characterized by a relaxation and a diastolic filling phase. The physiologic relaxation phase
is comprised sequentially by the second half of ejection, isovolumic relaxation, and the rapid filling phase. Relaxation commences immediately after maximal ejection is reached, while the LV is still in the clinical systolic phase (Fig. 7.1
). At this point, calcium from the cytosol is resequestrated in to the sarcoplasmic reticulum via a complex energydependent process. Consequently, the contractile elements are deactivated and the myofibrils return to their
original, precontraction length and force (10
). The physiologic diastolic filling phase
is comprised sequentially by the last part of the rapid filling, diastasis and atrial systole. The interdependency of systole and diastole is underscored by this physiologic process.
FIGURE 7.1 Division of the cardiac cycle from a clinical and physiologic point of view. After mitral valve closure (MVC), isovolumic contraction (IVC) leads to a significant increase in left ventricular (LV) pressure while the LV volume remains fairly constant. Eventually the LV pressure increases above the aortic pressure and promotes the aortic valve opening (AVO). With continuation of LV contraction, LV pressure continues to increase and blood is ejected in the aorta leading to an LV volume decrease. At the point of maximal ejection the LV begins to relax which, coupled with the continued ejection of blood, leads to LV pressure decrease and aortic valve closure (AVC). During isovolumic relaxation (IVR) (1), LV pressure falls rapidly. When LV pressure decreases below left atrial (LA) pressure, the mitral valve opens (MVO) initiating early, rapid LV filling (RF) (2). Equilibration of LV and LA pressures results in diminished transmitral flow during diastasis (3) until atrial contraction (AC) (4) which normally contributes <20% of the total LV end-diastolic volume. Diastole terminates with MV closure (MVC) prior to isovolumic contraction and the AV opening (AVO) which permits LV ejection. (Reproduced with permission from Plotnick GD. Changes in diastolic function-difficult to measure, harder to interpret. Am Heart J 1989;118:637-641.)
Intrinsic Myocardial Factors Affecting Diastolic Performance
Diastolic function is dependent on both intrinsic and extrinsic factors. The intrinsic myocardial factors are ventricular relaxation and chamber compliance. They are the result of alterations in calcium homeostasis and modifications of the extracellular matrix and cytoskeleton. Ventricular relaxation
is gauged by the rate and duration of LVP decline. The traditional method of LV relaxation assessment consists of measuring the LVP rate of decay during isovolumic relaxation. This assessment is performed using high-fidelity, intraventricular, micromanometer catheters which measure diastolic parameters such as peak instantaneous rate of LVP decline (-d
t), and the time constant on LV relaxation (tau) (11
). Measuring tau is a clinically and experimentally acceptable technique for assessing isovolumic relaxation, although limitations have been described (10
). A prolongation of tau is usually consistent with impaired relaxation. LV chamber compliance
is determined from the exponential relationship between the change in volume and the change in pressure during diastolic filling (d
P). Chamber compliance is dependent upon the passive properties of the ventricle (11
). The stiffness modulus
, which can be measured during cardiac catheterization, is an index of LV compliance.
Extrinsic Nonmyocardial Factors Affecting Diastolic Performance
Extrinsic nonmyocardial factors significantly impact diastolic function. Tamponade, pleural effusions, mediastinal masses, and pericardial diseases may directly compress the LV and impede its adequate filling. Hemodynamic alterations such as tachycardia, rhythm disturbances, acute hypo- and hypertension, all impact filling of the LV. Right ventricular (RV) enlargement may lead to a leftward septal shift, thereby increasing LVP and impeding LV filling. Preload and LA contributions to LV end-diastolic volume (LVEDV) are important determinants of ventricular filling.
PATHOPHYSIOLOGY OF DIASTOLIC DYSFUNCTION AND PROGRESSION OF DISEASE
Diastolic dysfunction is often defined clinically as an impaired capacity of the ventricle to fill at low pressure and usually involves an abnormality in ventricular relaxation and/or chamber compliance. The first manifestation of diastolic pathophysiology consists of impaired relaxation exceeding that expected with aging alone. It usually occurs with myocardial ischemia/infarction, LV hypertrophy (LVH), hypertrophic cardiomyopathy, and in the early stages of infiltrative disorders (12
). Impaired LV relaxation implies that the LV requires a longer time to fully relax. Therefore, the isovolumic relaxation time (IVRT, the time from cessation of systolic ventricular outflow to the onset LV inflow) is prolonged and the pressure gradient between the LA and the LV (transmitral pressure gradient [TMPG]) is decreased. With progression of disease, a decreased compliance (increased stiffness) of the LV ensues, hallmarked by increases in LVP and a further reduction in the pressure gradient between the LA and the LV. As a compensatory mechanism, aimed at restoring a normal TMPG and promoting LV filling, the LAP increases. Ultimately, with further progression of disease, the LV becomes extremely stiff leading to a markedly decreased compliance and LVP and LAP significantly increase. In these advanced stages of diastolic dysfunction, ventricular filling is profoundly affected, and little forward flow occurs.
ECHOCARDIOGRAPHIC EVALUATION OF LEFT VENTRICULAR DIASTOLIC FUNCTION
While echocardiography is unable to directly measure catheter-derived diastolic function parameters, it offers a more practical approach to a comprehensive evaluation of LV diastolic function. However, the perioperative echocardiographer assessing diastolic function must understand that most diastolic indices have been validated in studies with patients breathing spontaneously and undergoing transthoracic echocardiography, in left lateral decubitus position during cardiology visits. The extrapolation of these results to intubated patients undergoing transesophageal echocardiography (TEE) may lead to errors (13
). PWD indices are particularly impacted by positive pressure ventilation, preoperative fasting, and intraoperative
). Additionally, the perioperative echocardiographers must be cognizant of altered hemodynamic loading conditions, common in the perioperative setting, which have an impact on a patient’s diastolic assessment. Therefore, in the perioperative arena, assessment of intrinsic diastolic function should include different modalities, with an emphasis placed on those indices which are considered to be less load dependent (TDI). Moreover, intraoperative evaluation of diastolic function at several time points and under various loading conditions offers the perioperative echocardiographer a more robust understanding of the patient’s intrinsic diastolic pathology (presence of impaired relaxation versus presence of both impaired relaxation and decreased ventricular compliance). This information can be utilized to devise a targeted hemodynamic strategy tailored to the patient’s specific diastolic pathology.
Indirect evidence of diastolic dysfunction can be obtained during a comprehensive 2D echocardiographic examination of the heart. As diastolic function is dependent upon multiple factors, a complete assessment should include evaluation of LV wall thickness, cavity size and function, LA size as well as MV structure and function. Abnormalities of these structures are often indicators of chronic diastolic dysfunction.
Assessment of the LV
Echocardiographic evidence of LVH often indicates a chronic state of elevated LV filling pressures. Additionally, in a symptomatic patient, the presence of LVH without LV dilatation and with normal systolic function indicates the presence of diastolic heart failure (DHF).
Assessment of the LA
The LA serves as a blood reservoir during systole, as a conduit during early diastole and as a blood pump during late diastole (15
). The LA contribution to LV diastolic filling is usually <25% in young healthy patients, yet may approach 50% in patients with decreased LV filling associated with early diastolic dysfunction. The increased LAP which is the result of chronically elevated LVP, leads to LA remodeling and increase in size. The LA volume has been described as the “HbA1c” for assessing the chronicity of diastolic dysfunction (16
). To account for variations in LA size with respect to race and gender, the Left Atrial Volume Index (LAVI) can be utilized. This index represents the LA volume normalized for body surface area. A LAVI >34 mL/m2
in the absence of significant MV disease is an important indicator of diastolic dysfunction (13
). However, due to the close proximity of the LA to the esophagus, the entire LA is difficult to enclose in a single imaging plane when using TEE (17
). As such, the LA volume obtained by TEE underestimates the corresponding volume measured by TTE and LA linear dimension of >4 cm is substituted as a marker of dysfunction (18
Assessment of MV Structure and Function
Mitral regurgitation (MR) and/or stenosis can lead to an increase in LA size in the absence of diastolic dysfunction. Similarly, these pathologies also affect transmitral and pulmonary venous flow velocities making the assessment of diastolic function challenging. Mitral annular calcification (MAC) can complicate measurement of mitral annular tissue velocities. The evaluation of diastolic function in these scenarios is discussed in a later section.
Doppler Echocardiographic Evaluation of LV Filling
Transmitral Doppler Flow
The utilization of Doppler echocardiography to measure TMDF velocities provides valuable information toward the assessment of diastolic function. The PWD recording of TMDF velocities is obtained by placing the sample volume at the MV leaflet tips in a midesophageal (ME) four-chamber view (Fig. 7.2
). It is important to ensure that the direction of the ultrasound beam is parallel to the direction of transmitral flow. In cases where this is not feasible, a ME aortic long-axis view can be utilized to align the Doppler probe parallel to the transmitral flow. A typical TMDF velocity profile has a biphasic pattern. An initial peak flow velocity (E wave) occurs during early diastolic filling and a later peak flow velocity (A wave) occurs during atrial systole. Blood flow during the interposed period of diastasis is usually minimal, since little LV filling occurs during this phase. Other than the peak flow velocities (E and A waves), several additional indices of diastolic
function have been derived from the TMDF profile and correlated with more classic measures of diastolic function including angiography, radionucleotide techniques, and direct measures of intraventricular pressures (Table 7.1
). The deceleration time (DT, the interval from the peak E-wave velocity to the zero baseline) generally reflects the mean LAP and LV compliance (20
). The IVRT correlates with the timing of MV opening and is dependent upon both LV relaxation and LAP.
FIGURE 7.2 A: Transmitral Doppler flow velocity (TMDF) profile using transesophageal echocardiography. The TMDF profile is obtained by placing a pulsed wave Doppler sample volume (1 to 2 mm) at the tips of the mitral valve (MV). The initial rapid phase of early left ventricular (LV) filling (E) is followed by a variable period of minimal flow (diastasis) and finally late diastolic filling during atrial contraction (A). B: Schematic of TMDF profile depicting relevant indices of diastolic function. Several indices of LV diastolic function can be obtained from the TMDF profile including the E- and A-wave peak velocities and ratio, the E-wave deceleration time (DT, the time interval from the peak E-wave velocity to the zero baseline), and the isovolumic relaxation time (IVRT, the time from cessation of systolic ventricular outflow to the onset of transmitral LV inflow).
TMDF velocities reflect the TMPG which is dependent upon several variables including heart rate and rhythm, early filling loads, atrial contractility, MV disease, ventricular septal interactions, the intrinsic LV lusitropic state, and ventricular compliance (21
). An efficient LV relaxation and elastic recoil observed in young adults is associated with predominant early LV filling corresponding with a greater initial TMPG, and a smaller contribution (10% to 15%) from atrial contraction.
LV relaxation is delayed with aging, resulting in a lower initial TMPG at any given LV pressure and proportionally less early filling (lower peak E-wave velocity) and a greater, compensatory late filling (higher peak A-wave velocity) accounting for 35% to 40% of LV diastolic inflow. Similar changes are seen in patients with impaired relaxation.
TABLE 7.1 Left and Right Ventricular Doppler Echocardiographic Indices of Diastolic Function Filling Dynamics in Normal Subjects
Age 21-49 y
Age ≥50 y
Left ventricular inflow
Peak E (cm/s)
Peak A (cm/s)
Peak S (cm/s)
Peak D (cm/s)
Peak A (cm/s)
Right ventricular inflow
Peak E (cm/s)
Peak A (cm/s)
Superior vena cava
Peak S (cm/s)
Peak D (cm/s)
Peak A (cm/s)
Normal reference values for Doppler echocardiographic indices of ventricular diastolic function in two age groups of normal subjects. Data presented are mean values (confidence interval). A, late diastolic atrial flow velocity associated with atrial contraction; D, diastolic flow velocity; DT, deceleration time; E, early diastolic flow velocity; IVRT, isovolumic relaxation time; S, systolic flow velocity.
Reproduced with permission from Cohen GI, Pietrolungo JF, Thomas JD, et al. A practical guide to assessment of ventricular diastolic function using Doppler echocardiography. J Am Coll Cardiol 1996;27:1753-1760.
TMDF in Diastolic Disease: Changes in LV relaxation and compliance contribute to the spectrum of Doppler LV filling patterns that are observed with progressive diastolic dysfunction.
TMDF with impaired relaxation pattern:
In patients with impaired relaxation, the MV opening, although delayed, tends to occur before relaxation is complete resulting in a reduced TMPG. Consequently, the TMDF profile associated with impaired relaxation
is typically characterized by a decreased peak E-wave velocity relative to the peak A-wave velocity (E/A < 0.8) and a prolonged IVRT (>110 ms) (22
). In addition, as the LA-LV pressure gradient takes longer to equilibrate a prolonged DT is noted (8
). There is a subsequent, compensatory flow increase during atrial contraction accounting for the increased peak A-wave velocity. Due to the relatively high atrial preload, the A-wave duration is prolonged. By convention the A-wave duration is measured by placing the Doppler sample volume at the level of the MV annulus (as opposed to the MV leaflet tips used for TMDF) (13
). In summary, the TMDF velocity profile with impaired relaxation is characterized by “E/A reversal” (E/A < 0.8), prolonged IVRT, and prolonged DT.
TMDF with restrictive filling pattern:
Diastolic dysfunction associated with markedly decreased LV compliance and severely increased LAP is often described as a “restrictive” LV filling disorder (12
). The TMDF profile associated with a restrictive pattern
of LV diastolic dysfunction is characterized by an elevated peak E-wave velocity relative to the A-wave velocity due to the elevated LAP (22
). Even though impaired relaxation coexists with decreased compliance when diastolic dysfunction has progressed, the consequential increase in LV end-diastolic pressure (LVEDP) results in a markedly elevated LAP and an elevated peak E-wave velocity, consistent with very rapid filling during early diastole. The IVRT is
shortened (<60 ms) as the MV opens prematurely due to the elevated LAP. The DT is also abnormally short (<140 ms), as early transmitral flow into the poorly compliant LV results in rapid equilibration of LA and LV pressures. This phenomenon can be associated with diastolic MR (12
). Finally, the peak A-wave velocity and duration tend to be compromised by poor atrial contractility and the rapid increase in LV pressure, which can prematurely terminate late mitral inflow. In summary, a restrictive TMDF velocity profile is characterized by an elevated peak E-wave velocity and decreased peak A-wave velocity (E/A ratio >2) along with a shortened IVRT and DT.
FIGURE 7.3 Parabolic distribution of transmitral E/A velocity ratios associated with progressive diastolic dysfunction.
TMDF in pseudonormal pattern:
Typically, diastolic dysfunction progresses over time from impaired relaxation to restrictive pathophysiology. During this transition, the TMDF profile may assume an intermediate pseudonormalized pattern
that resembles normal LV filling (22
). The pseudonormalized filling pattern represents a moderate stage of diastolic dysfunction where a “normal” TMPG is generated as gradually increasing LAP from decreased LV compliance balances the lower TMPG from compromised LV relaxation. In summary, the pseudonormalized stage of diastolic dysfunction is thereby characterized by normal values for peak E- and A-wave velocities, IVRT, and DT. Provocative maneuvers can be used to differentiate between a patient with normal versus pseudonormal pattern. Reducing preload by utilizing reverse Trendelenburg positioning, partial cardiopulmonary bypass (CPB), a Valsalva maneuver (23
), or by administering nitroglycerin in a patient with a pseudonormalized transmitral inflow, will reveal the underlying impaired LV relaxation (24
). In contrast, normal individuals usually respond to preload reduction with a proportional decrease in both E- and A-wave velocities (12
). Similarly, preload reduction in patients with a restrictive diastolic dysfunction may result in a pseudonormal pattern on the TMDF (9
In summary, E/A velocity ratios observed in the progression of diastolic dysfunction resemble a parabolic shape beginning with high ratios seen with a vigorous LV relaxation pattern of young adults, evolving to a reduction of the ratio with early disease, and terminating with high E/A ratios consistent with the restrictive pattern of severe diastolic dysfunction (Fig. 7.3
Pulmonary Venous Doppler Flow
The evaluation of LA filling can provide important insight into the assessment of LV diastolic function especially when combined with data obtained from the TMDF. A typical pulmonary venous Doppler flow (PVDF) profile consists of an antegrade systolic velocity which may appear monophasic, or biphasic especially in the presence of low LAP probably owing to temporal dissociation of atrial relaxation and mitral annular motion (Fig. 7.4
). The first systolic component, PVS1
, is dependent upon LA relaxation and the subsequent decrease in pressure. The later peaking PVS2
reflects the LA compliance, the effects of early ventricular systole on LAP, any concomitant MR, and the RV stroke volume. An additional, large antegrade velocity occurs during diastole (PVD
) following early transmitral inflow while the LA serves as an open conduit between the PV and the LV. The late diastolic retrograde velocity, also known as pulmonary venous atrial flow reversal (PVAR
), occurs during LA systole and is dependent upon LA contractility, heart rate, and compliance of the LA, PV, and LV (21
FIGURE 7.4 A: Pulmonary venous Doppler flow velocity (PVDF) profile. LA filling can be assessed by placing a PWD sample volume (2 to 4 mm) approximately 1 cm into a pulmonary vein (PV) orifice where it joins the left atrium (LA). B: Schematic of PVDF profile depicting relevant indices of diastolic function. Indices of left ventricular (LV) diastolic function obtained from the PVDF include the peak S/D velocity ratio, as well as the peak A-wave reversal velocity and duration. PVAR, late diastolic retrograde velocity; PVAR dur, PVAR–wave duration; PVS1, first systolic component; PVS2, second systolic component; PVD, diastolic component; SV, sample volume; LPV, left pulmonary vein.
Normally, the PV systolic peak velocity is equal to or slightly greater than the corresponding PVD
velocity (Table 7.1
). In addition, the normal PVAR
duration (≈90 to 115 ms) is the same or less than the transmitral A-wave duration (≈120 to 140 ms) (20
). In a normally compliant LV, LA contraction should result in a greater net forward blood flow compared with any retrograde flow in the PV. A PVAR
velocity that exceeds the mitral A-wave by >35 cm/s or PVAR
duration longer than the transmitral A-wave duration by 30 ms usually indicates diastolic dysfunction with increased LVEDP (26
The analysis of PVDF compliments the assessment of TMDF in the evaluation of various stages of diastolic dysfunction.
PVDF with impaired relaxation pattern: The PVDF profile consistent with impaired LV relaxation is characterized by a reduced PVD velocity that parallels the mitral E-wave velocity, and a compensatory increase in the PVS velocity, resulting in a pattern of systolic predominance (PVS significantly greater than PVD).
PVDF with restrictive pattern:
Conversely, when the LV filling is restrictive, due to the elevated LAP and decreased LV compliance, the systolic antegrade velocity is reduced and a greater proportion of antegrade flow occurs during diastole, resulting in a pattern of systolic blunting
lower than PVD
). Additionally, the PVAR
velocity and duration may be increased in the presence of restrictive pathophysiology. However, in patients with severe restrictive filling, the PVAR
velocity may be diminished due to atrial mechanical failure (27
PVDF in pseudonormal pattern:
The pseudonormalized PV Doppler flow velocity profile is often characterized by a pattern of relative systolic blunting and a increased PVAR
duration and velocity. In this scenario, the PVDF pattern may be helpful in distinguishing a pseudonormal from normal TMDF profile. It must be emphasized however, that in normal young adults and athletes, who do not rely on a significant LA contribution for LV filling, the LA behaves more like a “passive conduit,” and PVS
blunting may be commonly observed (27
Influence of Physiologic Variables on Doppler Flow Profiles
The TMDF and PVDF profiles are considered useful for evaluating LV diastolic function in both nonsurgical and surgical patient populations. The utility of these echocardiographic parameters throughout the perioperative period is limited, however, by the unavoidable effects of changes in preload, afterload, heart rate, and rhythm on peak velocities and proportions of early and late filling (28
). Increases in preload
will often be associated with a more proportionate increase in the transmitral peak E-wave velocity, a shortened IVRT, and steeper DT. Decreases in preload
will result in opposite changes. MR
may produce a TMDF velocity profile with an increased E-wave velocity due to the elevated LAP and increased volume flow rate across the MV. Tachycardia
causes fusion of the transmitral E- and A-wave velocities and a pseudo-increase in the A-wave velocity and duration (21
). Dysrhythmias and pacing
may also be associated with unique alterations in the TMDF and PVDF profiles. For example, atrial flutter may present with “flutter waves” in the TMDF profile. Isolated LV systolic dysfunction
may also be associated with an increased transmitral peak E-wave velocity and reduced A-wave since diastolic filling occurs at a steeper portion of the LV pressure-volume curve (29
Only gold members can continue reading. Log In