Secondary Logo

Journal Logo

Cardiovascular Anesthesiology: Review Article

Perioperative Assessment of Diastolic Dysfunction

Matyal, Robina, MD*; Skubas, Nikolaos J., MD; Shernan, Stanton K., MD; Mahmood, Feroze, MD*

Author Information
doi: 10.1213/ANE.0b013e31822649ac
  • Free
  • SDC
  • Take the CME Test

The echocardiographic assessment of diastolic function has increasingly gained relevance as a predictor of adverse perioperative outcome.13 Before the widespread use of Doppler echocardiography, the presence of different symptoms in 2 patients with a similar degree of systolic dysfunction could not be explained,4 and invasive measurement of left ventricular (LV) end-diastolic pressure (LVEDP) was the only means to conclusively diagnose the presence of diastolic dysfunction. The use of pulse wave Doppler (PWD) to estimate LV relaxation made such an assessment clinically feasible. PWD has furthered our understanding of diastolic function and solved the mystery of discordance between symptoms and ventricular systolic function.4

Echocardiographic assessment of diastolic function has been extensively reviewed in recent American Society of Echocardiography (ASE) guidelines.5 Although not explicitly stated, these guidelines pertain to spontaneously breathing patients undergoing transthoracic echocardiography (TTE).a In this review, we provide a synopsis of the physiology of diastolic function and definitions of diastolic dysfunction, present the various Doppler modalities and how they are potentially affected by the intraoperative environment, and finally, consider how the aforementioned guidelines5 may be applicable in the perioperative setting when using transesophageal echocardiography (TEE).


It is now established that 50% of patients with congestive heart failure (CHF) have normal systolic function,6,7 and the same percentage of patients undergoing cardiac or noncardiac procedures have echocardiographically demonstrable diastolic function abnormalities.8 This may be important, because the presence of preoperative asymptomatic ventricular dysfunction (systolic and diastolic) has been associated with increased 30-day and long-term morbidity and mortality.1 The assessment of diastolic function provides incremental prognostic value over systolic function assessment5,9 and the presence of diastolic dysfunction is highly predictive of adverse events after myocardial infarction.5,10 Echocardiography has been used to diagnose perioperative diastolic dysfunction during cardiac surgery.1115 However, other than being a predictor of difficult weaning from cardiopulmonary bypass,11,12 the impact of perioperative diastolic dysfunction on short- and long-term postoperative morbidity and mortality in cardiac surgery patients is not conclusively established. Alternatively, in a retrospective review of vascular surgical patients with normal systolic function, patients with a history of CHF were found to have a longer hospital length of stay and a higher readmission rate and postoperative mortality than those without this history (Table 1).16 Although TEE has been used extensively during noncardiac surgery, its use for assessment of perioperative diastolic function is limited.17 In a prospective observational study of patients undergoing vascular surgery,2 the presence of diastolic dysfunction in hospitalized patients was a predictor of increased all-cause morbidity and mortality.1820 The presence of perioperative diastolic dysfunction, diagnosed with TEE, had a significant association with postoperative CHF and postoperative length of stay after vascular surgery (Table 1).2 Although not conclusively established, it seems that pre- and perioperative diagnosis of diastolic dysfunction may have implications for perioperative anesthetic management and, potentially, postoperative outcome.

Table 1
Table 1:
Studies Reporting Diastolic Dysfunction in Patients Undergoing Surgery


Diastole refers to the period of ventricular filling after a contraction (Fig. 1). Diastole is divided into 4 discrete parts: isovolumetric relaxation, rapid filling phase, diastasis, and atrial contraction.4 LV filling during diastole is a complex interplay regulated primarily by the pressure differences between volume and compliance of the left atrium (LA) and LV, and energy-dependent LV relaxation (Fig. 1).21 In addition to LV relaxation, extrinsic factors such as pericardial restraint, ventricular interaction, and intrinsic factors including myocardial stiffness, myocardial tone, chamber geometry, and wall thickness also have a role in LV filling.5,22 The diastolic phase of the cardiac cycle is also dependent on events that occur at the cellular, physiological, and organ level. At the cellular level, diastole begins with the hydrolyzation of adenosine triphosphate and unlinking of actin and myosin cross-linkages,23 followed by a reduction in sarcoplasmic calcium concentration and its separation from troponin (Fig. 2). Physiologically, ventricular relaxation at the onset of diastole as defined by the rate of decline of intracavitary pressure (−dP/dt) actually begins in the later portion of clinical systole, while the mitral valve is still closed (Fig. 1).4 Ventricular relaxation is an energy-dependent process, physiologically commencing during systole, continuing after mitral valve opening (clinical diastole) during rapid LV filling, lasting for the first third of this early filling phase and normally accounts for almost 70% of LV filling (Fig. 1). Hence, during the early LV diastole, in addition to the LA-LV gradient, the effectiveness of LV suction also determines the adequacy of filling. The LV continues to fill until closure of the mitral valve. The last part of the filling phase is associated with atrial contraction which normally contributes almost 30% of the LV filling. Factors that delay calcium removal impair actin-myosin cross-bridge detachment and therefore slow myocardial relaxation.22 Multiple energy-dependent enzymatic pathways maintain calcium homeostasis in the cytosol.2328

Figure 1
Figure 1:
Simultaneous display of left atrial, aortic, and left ventricular pressures during the cardiac cycle. Physiological diastole, as defined by the −Δp/Δt begins in the later part of systole with the onset of isovolumetric relaxation time (IVRT). Clinical diastole as defined by the opening of the mitral valve starts after opening of the mitral valve. (Adapted from Nishimura and Tajik.4)
Figure 2
Figure 2:
Calcium ions (Ca+) bind to sites on the actin filament. Ca+ binds to the troponin molecule causing tropomyosin to expose positions on the actin filaments for attachment of myosin heads. As a result, cross-bridges between actin filaments and myosin heads are formed. ADP = adenosine diphosphate; ATP = adenosine triphosphate; Pi = inorganic phosphate.


In the natural course of myocardial dysfunction caused by ischemia or hypertension, relaxation (early diastolic) abnormalities often precede systolic dysfunction. This results in impairment of early/rapid LV filling and a compensatory increase in late LV filling.4 The LA contribution is determined by LA preload and contractility as well as the “effective LV compliance.”4,2932 With disease progression, abnormalities of relaxation eventually progress to reduced compliance and increase of filling pressures in both the LA and LV, i.e., mean pulmonary capillary wedge pressure >12 mm Hg and LVEDP >16 mm Hg.33 The invasively measured peak negative change in LV pressure during diastole (−dP/dt) and the time constant of relaxation (τ) are considered the “gold standard” measures of LV relaxation,34,35 against which the accuracy of Doppler-derived variables of diastolic function should be established.

Although used interchangeably, diastolic dysfunction and diastolic heart failure are actually 2 different pathophysiological conditions. The use of the term “diastolic dysfunction” implies an echocardiographically demonstrated abnormality of LV filling, i.e., impaired relaxation and/or reduced compliance, which results in increased LVEDP, whereas diastolic heart failure is a clinical term, which is the symptomatic manifestation (shortness of breath and exercise intolerance) of the underlying filling abnormality, i.e., an increased LVEDP, in the presence of normal LV systolic function.36 The time course of progression from diastolic dysfunction to diastolic heart failure can be variable. For example, in patients with hypertension and LV hypertrophy, impaired relaxation may remain the predominant abnormality for a long time without any increase in LVEDP.37


Assessment of diastolic function based on Doppler findings acquired with TTE may not be entirely applicable to TEE techniques. Because of its noninvasive nature, TTE has been extensively used over the decades in epidemiological studies in subjects with normal and abnormal filling patterns. Hence, the reference values for Doppler indices of LV diastolic function are well established with this technique (Table 2).5 The invasive nature of TEE and variable intraoperative hemodynamic state has precluded similar efforts. The majority of echocardiographic studies of the assessment of diastolic function have been conducted in outpatient cardiology clinics in patients breathing spontaneously in the lateral decubitus position.30 However, the filling variables of LA and LV significantly change with alterations in posture from supine to upright and left to right lateral decubitus position.3840 In contrast, echocardiographic studies under general anesthesia (GA) are performed with TEE under varying hemodynamic states and in patients in the supine position who are receiving positive pressure ventilation and are under the effects of anesthetic drugs.

Table 2
Table 2:
Normal Values of Doppler-Derived Diastolic Function Parameters


The classification of diastolic dysfunction has evolved from the initial, transmitral flow (TMF) examination with a PWD-based explanation of LA and LV filling and its abnormalities, to the most current guidelines, which have incorporated PWD and more sophisticated techniques (Fig. 3).4,5,29,30,4146 However, such classification schemes4,29,30,44,47 for the assessment of diastolic dysfunction are suited for categorization of larger patient populations and assess response to therapy (epidemiological studies).5 For the individual patient, it is recommended to use a customized approach to answer specific mechanistic questions, e.g., diagnosis of impaired relaxation and/or a coexistent reduced compliance abnormality.5

Figure 3
Figure 3:
Doppler modalities for assessment of myocardial diastolic function. PWD = pulse wave Doppler; DT = deceleration time; Adur = A-wave duration; ME = midesophageal; LAA = left atrial appendage; LUPV = left upper pulmonary vein; CMM = color M-mode; DTI = Doppler tissue imaging; Ar = atrial reversal wave; RV = right ventricle.

The clinical application of these guidelines has also demonstrated the limitations of such classification schemes. In one study, one of the Doppler criteria, pulmonary venous PWD profile, could not be obtained in 28% of patients undergoing elective TTE examinations,48 and in the study by Redfield et al.44 (n = >2000), in which only 2 of the 4 Doppler criteria were required for classification, 12% of patients could not be accurately classified and were termed “indeterminate patterns.” Intraoperative rigid application of the most recent ASE guidelines has also demonstrated their limitation in classifying perioperative diastolic dysfunction.3

Factors such as ventricular interdependence,49 effects of positive pressure ventilation,50,51 and even acute alterations in coronary blood flow by altering the vascular turgor (i.e., the “erectile effect”),52 are not accounted for in these classifications, but affect ventricular compliance.4,29,30,44,47 Changes in LV filling variables with induction of GA are also associated with significant changes in LA and LV diameters implying contribution of the loading conditions to these observed effects.53

The intraoperative hemodynamic state is very variable. Consequently, an isolated Doppler measurement should be considered only a “snapshot” of a continuous process. Even minor alterations in the Doppler measurements can lead to a patient being classified into a different grade/stage of diastolic dysfunction in the same clinical setting. Unlike the previous recommendations,4,29,30,44 the current ASE guidelines for echocardiographic assessment of diastolic function have acknowledged the limitations of rigid application of the conventional Doppler indices.4,30,5460 Therefore, the most recent guidelines no longer recommend the acquisition of E and A waves of the TMF with PWD as the initial step in the decision tree of grading diastolic dysfunction (Fig. 4).5

Figure 4
Figure 4:
Practical approach to diastolic function. DT = deceleration time; Avg. = average; Ar = pulmonary venous A-wave reversal wave; Adur = transmitral A-wave duration. (Adapted from Nagueh et al.5)


The techniques for acquisition and interpretation of specific Doppler abnormalities have already been extensively reviewed.5,54 In the following section, the specific steps of obtaining satisfactory Doppler profiles for diastolic function evaluation using TEE are discussed. Echocardiographic evaluation of diastolic function is best accomplished when it is incorporated within a standardized echocardiographic examination, which should also include a comprehensive evaluation of LV systolic function.56,61 Before starting the Doppler examination, it is essential to ensure the most optimal parallel Doppler alignment during interrogation to minimize the degree of underestimation of peak velocities and gradients. Alignment is usually most optimal when using the midesophageal (ME) 4-chamber and ME long-axis views for the majority of the Doppler indices. Echocardiographic evaluation of perioperative diastolic dysfunction with TEE should include a focused and precise examination using a combination of PWD (transmitral and pulmonary venous flows), transmitral color M-mode, and Doppler tissue imaging (DTI) (Fig. 3).

LV Inflow

The traditional assessment of LV filling has been based on assessment of the pattern of diastolic blood flow through the mitral valve (LV inflow) using PWD.43 Flow across the mitral valve during the relaxation phase is determined by the LA-LV pressure gradient and the effectiveness of the suction properties of the LV (Fig. 5).60,62 Kitabatake et al.,43 in 1982, described Doppler interrogation of mitral inflow during diastole as a reflection of the global LV relaxation properties.57,58,60,63,64 Abnormalities of the “active relaxation phase” of diastole are generally the earliest manifestations of diastolic dysfunction. The relaxation abnormalities present echocardiographically as changes in E wave peak velocity and deceleration time (DT) initially, and then further changes with disease progression. Based on this progression of abnormalities (impaired relaxation to reduced compliance), distinct echocardiographic patterns, including normal, impaired relaxation, pseudonormal, and restrictive patterns (Figs. 58) of LV filling, were described.41,6571 Mathematical modeling has demonstrated that LA stiffness remains constant during early LV relaxation and DT is proportional to the inverse square root of LV stiffness.31,7274 Consequently, when there is advanced diastolic dysfunction with reduced compliance, DT is shortened again in the more advanced stage of diastolic dysfunction (Fig. 8). Therefore, in addition to being prolonged during the impaired relaxation phase, DT is an important variable that reliably predicts LV compliance in the more advanced stages of diastolic dysfunction.75

Figure 5
Figure 5:
Typical transmitral pulse wave Doppler pattern. Left panel, Actual pulse wave Doppler pattern. Right panel, Graphic description of measurement of peak velocities and gradients. E wave = rapid filling phase; A wave = atrial “kick”; DT = deceleration time; Adur = duration of transmitral A wave.
Figure 6
Figure 6:
Transmitral pulse wave Doppler: impaired relaxation pattern. Left panel, Actual pulse wave Doppler pattern. Right panel, Graphic description of measurement of peak velocities and gradients. E/A <1 = prolonged deceleration time; DT = deceleration time.
Figure 7
Figure 7:
Pseudonormal pattern and Valsalva maneuver. Left panel, Typical transmitral pulse wave Doppler pseudonormal pattern. Right panel, Transmitral pulse wave Doppler during a Valsalva maneuver. Left atrial (LA) pressure reduction maneuvers to “unmask” the underlying relaxation abnormality. In a typical LA pressure reduction maneuver, a pseudonormal transmitral flow (TMF) pattern changes to an impaired relaxation pattern, with a reduction in the amplitude of the rapid filling phase (E wave) and increased amplitude and duration of the atrial “kick” (A wave) with a prolongation of the deceleration time (DT). LV = left ventricle.
Figure 8
Figure 8:
Transmitral pulse wave Doppler: restrictive pattern elevated left atrial pressure. Left panel, Actual pulse wave Doppler pattern. Right panel, Graphic description of measurement of peak velocities and gradients. E/A >1.5 = shortened deceleration time (DT).

Intraoperative Measurement

Placement of a color flow Doppler (CFD) sector on the LV inflow can be helpful in aligning the Doppler beam with the direction of the blood flow, which is generally directed toward the lateral wall.61 All measurements should be made during apnea to minimize the hemodynamic changes and movement of the PWD sample volume during controlled mechanical ventilation. For LV inflow assessment, a sample volume of 1 to 3 mm is placed between the mitral tips during diastole with the sweep speed set at 50 to 100 mm/s (Fig. 5). Measurements should include peak E and A velocity, the E/A ratio, DT, and A-wave duration (Adur). For measurement of Adur, it is best to move the cursor to the mitral annular plane with a simultaneous reduction in wall filters (Fig. 5).61 The actual measurement of volumetric flow (continuity equation) does not add any further information.30

Intraoperative Application

Transmitral PWD has been the cornerstone of classification schemes for diastolic dysfunction. Because of its load dependence, TMF is of value only when considered in combination with other Doppler variables, such as the pulmonary venous inflow (PVF), TMF propagation velocity (Vp), and DTI, which are discussed in later sections.

Pulmonary Venous Inflow

The LA acts as a conduit during early diastole, as a contractile chamber during late diastole, and as a reservoir during systole when the mitral valve is closed. During diastole, the LV, LA, and pulmonary veins remain in continuity with a shared pressure gradient.7683 Hence, the assessment of diastolic function by transmitral PWD can be further refined with incorporation of measurements from the pulmonary venous PWD spectral recording.79,80,8487 The PVF pattern has shown good correlation with LV filling pressures (LVFPs) in patients with sinus rhythm as well as heart block, but is generally less reliable in patients with significant mitral regurgitation, stenosis, or prosthetic mitral valves and annuloplasty rings.82,88

Intraoperative Measurement

To acquire a PVF PWD spectral display, a 2- to 3-mm sample volume is placed at 1 cm depth usually in the left upper pulmonary vein visualized in an ME view (Fig. 9). Wall filters must be low to optimize the acquisition of the atrial reversal (Ar) wave. Although satisfactory acquisition of the Ar wave has been reported in almost 80% of ambulatory patients, it is more difficult in critical care settings.89,90

Figure 9
Figure 9:
Pulse wave Doppler of the left upper pulmonary vein (LUPV). S1 = systolic 1 wave caused by left atrial relaxation; S2 = systolic 2 wave caused by right ventricular systole; D = diastolic wave; Ar = atrial reversal wave caused by atrial systole.

Intraoperative Application

During a PWD examination of the PVF, peak S and D waves, the S/D ratio, and Ar peak velocity and duration should be measured (Fig. 10). Technical difficulties in obtaining the PVF wave profiles, their load dependence, presence of LA wall artifacts, and the effects of arrhythmias on atrial contraction are the major limiting factors.30,91 Further extrapolation of the PVF profile includes S/D ratio calculation and comparison of the duration of the Ar wave with transmitral Adur for LVEDP estimation (Ar duration will be longer than Adur because of decreased antegrade flow caused by reduced LA compliance with LA contraction) (Fig. 10).

Figure 10
Figure 10:
A comparison of the transmitral A-wave duration, i.e., the “antegrade flow,” with the duration of the pulmonary venous inflow atrial reversal (Ar) wave, i.e., the “retrograde flow,” which occur simultaneously because of atrial contraction. Greater retrograde flow implies increased left ventricular end-diastolic pressure.

Transmitral Color M-Mode–Derived Early Propagation Velocity

Early diastolic LV filling is dependent on the development of progressively negative intraventricular pressure gradients, which create a wavefront of propagation from the LV base to the apex.9296 This wavefront can be visually appreciated with CFD interrogation of the LV cavity during diastole, when blood is seen entering along the lateral LV walls (Fig. 11). Transmitral Vp is a velocity profile derived by simultaneous use of CFD and M-mode (Fig. 11). Similar to the transmitral E wave, Vp reflects the effectiveness of the LV “suction” during early diastole. Vp is a more valid assessment of the LV relaxation properties compared with TMF, which is a point measurement at the tips of the mitral leaflets.

Figure 11
Figure 11:
Transmitral flow propagation velocity. Left panel, Midesophageal 4-chamber view with color flow Doppler sector and M-mode cursor aligned with the left ventricular (LV) inflow. Right panel, Measurement of the transmitral flow propagation velocity.

Intraoperative Measurement

A CFD sector using a Nyquist limit <40 cm/s is placed on the LV cavity, directed toward the lateral wall, to develop a flow profile. An M-mode cursor is then positioned through the center of the flow profile (Fig. 11). Multiple methods of measuring Vp have been described with varying degrees of intra- and interobserver variability.92,97,98 The method described by Garcia et al., in which the slope of the first aliasing velocity (the outermost velocity) is measured, is considered the most reliable and reproducible method.97,99 A Vp value of <0.50 m/s is consistent with impaired relaxation.5

Intraoperative Application

The feasibility of the intraoperative use of Vp for assessment of diastolic function has been demonstrated.2,12,14,90 Because Vp can be easily measured in a single step, it is an attractive option for intraoperative assessment of LV relaxation. However, sometimes in addition to the diastolic suction force, multiple other factors, e.g., changes in LV geometry, contractile dyssynchrony, and tissue viscoelastic forces also have a role in creating these LV inflow vortices.100102 However, it may not be possible to measure Vp because the slope of flow propagation is sometimes curvilinear and does not “travel” a sufficient distance (<4 cm) into the LV cavity or is difficult to appreciate.99 Additionally, an abnormal Vp merely diagnoses the presence of abnormal relaxation, and not necessarily its severity. Therefore, an abnormal Vp may not differentiate among the various stages of abnormal diastolic function, and a decreasing Vp value has not been associated with progressive worsening of diastolic function. Despite these limitations, Vp remains a valuable tool in the determination of development of intraventricular pressure gradients. However, Vp has been shown to increase with increasing preload and can be normal despite increased filling pressures in patients with a normal ejection fraction (EF) and LV volume.99

Doppler Tissue Imaging

Recent advancements in echocardiographic equipment, including the ability to record “high amplitude and low velocity” signals, have made it possible to measure tissue velocities and motion. In ultrasound systems with installed DTI presets, a 5- to 10-mm sample volume is placed in the lateral or medial mitral annulus to obtain a PWD spectral pattern (Fig. 3). A typical DTI signal consists of the following 3 main waves: early (E′) and late (A′) diastolic, and a systolic (S′) (Fig. 12).61 Similar to the TMF E wave, the E′ wave peak velocity has been associated with the relaxation constant (τ). Although both TMF E and the DTI E′ waves represent early diastolic filling, under normal conditions, the DTI E′ wave precedes the TMF E wave because myocardial relaxation precedes opening of the mitral valve and LV inflow. Similarly, the DTI A′ wave is associated with late LV inflow and atrial contraction. Myocardial motion at the atrioventricular (AV) interface has also been shown to correlate with LVFP.103106

Figure 12
Figure 12:
Spectral tissue Doppler display. E′ = rapid relaxation wave; A′ = atrial systolic wave; S′ = ventricular systolic wave.

Intraoperative Measurement

DTI should be performed in the ME 4-chamber view to obtain a parallel Doppler alignment. Most modern echocardiographic systems have manufacturer-installed presets to obtain DTI signals. During acquisition, the velocity scale should be set to <20 cm/s. Acquisition should be performed at end-expiration, and at a sweep speed of 50 to 100 mm/s. An average of >3 beats of the lateral mitral annular DTI should be measured. Because systolic function also has a role in mitral annular excursion, it is recommended that different E′ cutoff values be used for patients with a depressed EF. In cases of regional LV dysfunction and wall motion abnormalities, it is important to average velocity measurements from both septal and lateral mitral annuli.5,107

Intraoperative Application

The normal value of the E′ wave is age dependent and determined by the site of measurement (i.e., lateral versus medial mitral annulus) (Table 2).5 For diastolic function interrogation, a reduced E′ velocity for age is considered diagnostic of abnormal LV relaxation. Further measurements of the E′ wave (acceleration/deceleration rate) do not add any incremental information.108 However, calculation of the time interval between the QRS wave and onset of the E′ wave can possibly provide incremental information about diastolic function generally and relaxation abnormalities in particular.107,109 An E′/A′ ratio of >1 during a Valsalva maneuver has also been used to establish normalcy of diastolic function.105,110 As opposed to pseudonormalization of TMF, an abnormal E′/A′ ratio (<1) does not revert to normal (>1) when the LA pressure is increased.105 In addition, the average E′ velocity may not accurately represent global LV diastolic function in the presence of basal lateral and septal wall motion abnormalities, after mitral valve replacement and surgical septal myectomy.61 Furthermore, similar to Vp, the E′ wave represents only the relaxation (early) phase of diastole and does not provide any information about LV compliance.


With a primary relaxation abnormality, there is a delayed equilibration of pressure between LA and LV, which results in less filling in early diastole and more filling during atrial contraction. Therefore, in a typical impaired relaxation pattern, which is considered the initial stage of diastolic dysfunction, there is a decrease in E wave velocity, prolongation of DT, and a compensatory increase in A wave velocity, resulting in an E/A ratio <1 (DT >220 milliseconds) (Fig. 6). A typical impaired relaxation pattern is also characterized by a PVF pattern in which the S/D ratio remains <1 expressing decreased early diastolic flow, and a Vp <50 cm/s, while E′/A′ will be <1 and the onset of E′ will be delayed compared with the E wave. Persistence of relaxation abnormalities due to continued myocardial dysfunction causes LV remodeling and leads to reduced LV compliance, which manifests itself as an increase of LVEDP and an increase in LA pressure. The increased LA pressure overcomes the resistance to LV early filling because of impaired relaxation, and results in increased filling during early diastole and rapid equalization of pressure between the LA and LV because of reduced compliance characterized by an increased E velocity and shortened DT. As a result, there is limited filling during atrial contraction because of decreased LV compliance (Fig. 8). Also, PVF will show an S/D ratio >1, implying increased LA pressure and decreased flow from the pulmonary veins into an incompletely emptied LA during diastole. Vp will be <50 cm/s and DTI will reveal an E′/A′ <1 (Ar duration will be longer than Adur because of decreased antegrade flow due to reduced LA compliance with LA contraction). This is described as a restrictive filling pattern, the final stage of diastolic dysfunction (Fig. 8). An intermediate pattern can sometimes be appreciated during progression from impaired relaxation to the restrictive phase. Because it resembles the normal pattern, it is called a “pseudonormal” pattern and is difficult to appreciate, mostly because of load dependence of the Doppler variables. Because of impaired filling during early diastole, blood backs up in the LA and leads to an increase of the LA pressure. In this intermediate stage, the LA pressure, not ventricular relaxation, is the driving force for early LV filling, and compliance can be normal in this stage (Fig. 13). This indeterminate pattern often precedes the appearance of the restrictive phase. Echocardiographic representation of this stage is seen as a “recovered” E/A ratio (E/A >1) and a shortened DT (Fig. 13), which approaches a normal value. Therefore, in pseudonormalization, despite the underlying impaired relaxation, the transmitral PWD velocities change to a “normal-appearing” profile (Fig. 7).

Figure 13
Figure 13:
Effect of elevated left atrial (LA) pressure (LAP) on the transmitral filling patterns. Normal relaxation and normal LAP (E/A >1, normal deceleration time [DT]). Impaired relaxation and normal LAP (E/A <1, prolonged DT). Impaired relaxation and elevated LAP (E/A >1, normalization of DT). LV = left ventricle.

Hence, the challenge during echocardiographic evaluation is to differentiate pseudonormal (volume compensation with impaired relaxation) from a true normal filling pattern. Because the underlying relaxation abnormality coexists with a compensatory increase of LA pressure to preserve early LV filling, maneuvers that reduce LA pressure including the Valsalva maneuver have been advocated to unmask this compensation and uncover the underlying impaired relaxation. A reduction in LA pressure results in a decreased LA-LV gradient during early diastole, thus negating the effect of increased LA pressure as the main driving force for LV filling. Typically, during such a maneuver, a normal-appearing pattern reverses to an impaired relaxation pattern (E/A <1) and a prolongation of DT (Fig. 7).42,45,46 Performance of the Valsalva maneuver in a “true” normal TMF pattern would result in an equal reduction in the E and A wave magnitude with the E/A ratio remaining >1. Although frequently used, there is no standardized method of performing the Valsalva maneuver. An increase of intrathoracic pressure to 40 mm Hg for at least 10 seconds with simultaneous recording of transmitral PWD has been used in various studies.111,112 During controlled mechanical ventilation, the Valsalva maneuver can be performed by discontinuing the controlled mode and using the “pop-off” valve of the anesthesia machine to generate the required peak inspiratory pressure. The accuracy of Valsalva as well as other preload reduction maneuvers (nitroglycerin administration, which acts by reducing cardiac preload) in conclusively differentiating a normal from pseudonormal pattern of LV filling has been questioned.112 Particularly during an intraoperative TEE examination, the inability to maintain parallel Doppler alignment during the Valsalva maneuver, the associated hemodynamic instability (hypotension) and availability of Doppler indices, which are less likely to demonstrate pseudonormalization, e.g., Vp and DTI, limit the utility of information gained from routine performance of the Valsalva maneuver.


The dependence of PWD variables on loading conditions was established early on.54,57,113 Different LV filling patterns could be observed in the same patient, because of varying loading conditions, only hours apart.4,57,58,60,114116 For example, because of the curvilinear relationship of the pressure-volume relationship, sudden preload augmentation without alteration in compliance results in a higher pressure (Fig. 14). A similar and indistinguishable effect can also be observed with increased pericardial restraint associated with pericardial effusion or constrictive pericarditis (Fig. 14).4 Both of the aforementioned scenarios would lead to an increased LA pressure resulting in an increase in the peak E velocity and shortened DT,4 causing a pseudonormal pattern.

Figure 14
Figure 14:
Pressure-volume relationship in 2 different clinical conditions and their effect on pulse wave Doppler–derived transmitral flow patterns. A, A normal pressure volume. C, The pulse wave Doppler–derived transmitral flow pattern from a normal pressure-volume relationship. B1, Pressure-volume relationship of the left ventricle (LV) after preload augmentation. B2, Pressure-volume relationship of the LV after reduced compliance. D, Transmitral pulse wave Doppler resulting from situations B1 and B2, demonstrating identical effects of the 2 situations on the transmitral filling patterns. Both situations give rise to indistinguishable E and A waves on the pulse wave Doppler interrogation of the transmitral flow, i.e., increased E-wave peak velocity and reduced A-wave velocity.


It has been demonstrated in animal experiments that a moderate increase in preload does not affect relaxation.117 Although the exact mechanism is unknown, changes in sarcolemmal calcium ion metabolism with preload alterations have been demonstrated on a cellular level.118 Clinically, TMF (E and A waves and DT), PVF (S and D), and DTI E′ waves show changes with alteration of the loading conditions.4,5,29 Because patients undergoing hemodialysis undergo acute reduction in preload with dialysis, they are a unique cohort for such an assessment.119124 Such studies have, however, generated conflicting results, with some showing independence,119125 and others demonstrating dependence on preload changes.126129 It is quite possible that the conflicting results are attributable to the differences in the duration of dialysis and volume of fluid removed during dialysis in these patients.

Whether Vp is load independent has not been conclusively established.5,29,96,98,99,130133 Even though the E′ peak velocity has also shown to be preload dependent when diastolic function is normal, in the presence of diastolic dysfunction, both Vp and E′ become preload independent and remain reduced despite increasing preload.105 However, in a study in which preload was reduced during hemodialysis, DTI values consistently varied with the magnitude of preload reduction.126,134,135 However, these findings were dependent on the site of DTI measurement with the lateral mitral annular E′ velocity being more resistant to acute reduction in preload than the medial annulus E′ peak velocity.134,136 It is important to consider that a single DTI E′ value is a regional value only, and unless averaged from as many basal sites as possible, it should not be used independently in the diagnosis of diastolic dysfunction.


The response of myocardial relaxation to increasing afterload depends on the LV contractile reserve.137141 The magnitude, duration, and timing of increased afterload also affect diastolic function.21,142 If LV systolic function is normal, an afterload increase shortens DT, implying improved relaxation and a more rapid, compensatory pressure equilibration between the LA and LV.21 Alternatively, if systolic function is depressed, severe afterload increase in the latter third of diastole prolongs DT, implying impairment in active relaxation143 and is a decompensatory response.142 “Afterload reserve” determines the ability of the LV to respond to increases in afterload without changes in end-systolic volume. Reduced afterload reserve has been shown in the LV with systolic dysfunction143147 and increases of afterload in such a situation can cause marked deterioration of diastolic function.137,148 A decrease in the rate of LV pressure decline and incomplete relaxation during diastole eventually lead to an increase of pressure in the LA and pulmonary vasculature.149,150

Clinically, the echocardiographic changes in LV diastolic function have been investigated in patients undergoing open abdominal aortic aneurysm surgery.90,151153 In a study using intraoperative TEE and a pulmonary artery catheter, it was demonstrated that application of an aortic cross-clamp in the infrarenal position led to increased pulmonary artery occlusion pressure without a concomitant change in LV end-diastolic area. Because of the lack of Doppler availability, the authors attributed this observation to reduced compliance of the LV after cross-clamp application with a higher intracavitary pressure for the same volume and, thus, a change in diastolic filling without a concomitant change in systolic function.151 Minor changes in diastolic function with abdominal and thoracoabdominal aortic cross-clamp application were reported in TMF with PWD, probably reflecting changes with loading conditions.152,154 However, when Vp with a cutoff value of <0.45 m/s was used for a similar assessment, an abdominal aortic cross-clamp application was associated with a worsening of LV relaxation, which returned to baseline value after unclamping of the aorta.90 In this study,90 traditional PWD measures (including TMF and PVF) of diastolic function were also used for comparison with Vp but were not as conclusive.

Heart Rate

TMF variables are affected by heart rate and rhythm.5,155 Sinus tachycardia and first-degree AV block can result in fusion of E and A waves,5 making it difficult to distinguish E from A and measure DT. Similarly, in atrial flutter, there are usually no A waves.5,155 Different AV blocks (3:1, 4:1) may show multiple atrial filling waves and occasionally diastolic mitral regurgitation during the nonconducted beats.156 During atrial fibrillation, there are no A waves on the spectral PWD, but the DT correlates with the LVFP if systolic function is impaired.155,157 Similarly, peak E′ velocity can be reliably used for assessment of relaxation abnormalities in patients with atrial fibrillation using the same cutoff values as for patients with sinus rhythm.155,157

Heart rate alterations have not been shown to affect the Vp slope.100 Because direct atrial pacing does not seem to change the Vp slope, the positive correlation between Vp and heart rate observed in animal studies is attributed to the pharmacological β-adrenergic stimulation used in these studies.98,130

Myocardial Ischemia

The effects of acute ischemia on diastolic function depend on the specific mechanism.158 Myocardial ischemia due to acute or chronic reduction of blood supply leads to the onset of systolic dysfunction with diastolic function remaining relatively preserved.159,160 Alternatively, myocardial ischemia due to increased demand causes diastolic dysfunction with little or no effect on systolic function.160164 The exact cause of these different responses is unknown.160 Perioperatively, myocardial ischemia occurs because of increased demand, and hence changes of diastolic function associated with impaired relaxation are more likely to occur during such an episode. More recently, DTI has been investigated as a sensitive marker of myocardial ischemia, with E′ velocities decreasing acutely with the onset of ischemia.165,166 In an animal model of myocardial ischemia, reduction of E′ peak velocity and E′/A′ ratio occurred before the appearance of wall motion abnormalities,167,168 in proportion to the reduction in blood supply,167,168 making it a promising early echocardiographic marker of ischemia. The reduction in E′/A′ ratio is easy to appreciate visually, and does not require an absolute parallel Doppler alignment. An E′/A′ ratio <1 is usually measured in a majority of hypokinetic and akinetic segments.105


When evaluating diastolic function, measurements should be performed multiple times during periods of apnea and relative hemodynamic stability to minimize the effects of hemodynamic alterations (preload, afterload, heart rate, and contractility). In light of the recent ASE guidelines, the Doppler variables used to interrogate LV diastolic function should be used to assign a severity grade and define and diagnose the specific abnormality, e.g., abnormal relaxation and/or decreased compliance. It is important to remember that the diastolic function assessment must be performed within the context of the recommendations of the current ASE guidelines.

The changes in appearance of Doppler modalities in an impaired relaxation abnormality are determined by the rapidity of equilibration of LA and LV pressures. When this is delayed, it manifests itself as a reduced E velocity, prolonged DT, decreased E′, and reduced Vp. These changes can be masked with increased filling pressures, particularly if systolic function is intact. Because the exact effect of alterations in loading conditions on Doppler assessment of LV filling is unknown, preferably a single Doppler variable should not be used to interrogate diastolic function. The ASE guidelines recommend the assessment of relaxation abnormalities using Doppler modalities, which assess LV relaxation directly or indirectly. Of the “direct” measures of relaxation, isovolumetric relaxation time (IVRT) can be easily measured in the operating room (Fig. 15); however, as an independent measure, it has limited accuracy as a result of multiple factors. For practical application in the operating room, the modalities that assess LV relaxation indirectly are easier to measure and compute (Fig. 16). Particularly, Vp has been shown to be a more reliable index of LV relaxation in patients with depressed EF and those with dilated cardiomyopathy. Similarly, most patients with lateral E′ velocity <8.5 cm/s have impaired relaxation abnormalities.

Figure 15
Figure 15:
Measurement of isovolumetric relaxation time (IVRT). The transesophageal echocardiography probe is advanced to the deep transgastric position, and with omniplane rotation and probe manipulation, a parallel Doppler alignment is achieved and a sample volume of pulse wave Doppler (PWD) is placed between the left ventricular outflow tract (LVOT) and mitral inflow to obtain a spectral display that simultaneously displays the left ventricular outflow and mitral inflow profile. IVRT is measured as the time interval between the LVOT velocity time integral to the start of the transmitral flow. AV = aortic valve; MV = mitral valve.
Figure 16
Figure 16:
Indirect measures of left ventricular (LV) relaxation. Transmitral flow (TMF) demonstrating a typical impaired relaxation pattern E/A <1 and deceleration time (DT) >220 milliseconds. Impaired relaxation is the earliest abnormality and present in most patients with diastolic dysfunction. E′ velocity <8 cm/s is consistent with the diagnosis of diastolic dysfunction and is more sensitive than the pulse wave Doppler–derived TMF. Flow propagation velocity (Vp) correlates with the rate of myocardial relaxation. It can be normal despite impaired relaxation, particularly in patients with normal ejection fractions and LV volumes. DTI = Doppler tissue imaging.

Assessment of Compliance

Invasive calculation of the LV chamber stiffness constant (i.e., pressure-volume relationship) is considered the gold standard of LV compliance. The compliance constant can be estimated indirectly using echocardiography, but is of limited accuracy, particularly in patients with advanced diastolic dysfunction. Reduced LV compliance is associated with a faster pressure equilibration between the LA and LV, which leads to a shortened DT, an important surrogate measure of reduced compliance (Fig. 18). The transmitral A wave represents the LA-LV pressure gradient during late diastole, and is affected by the LA contractile function as well as LV compliance. Similarly, A-wave transit time, which is the time it takes for the atrial contraction wave to propagate to the LV apex, can be considered a surrogate measure of LV stiffness and has shown good correlation with simultaneously measured invasive LV pressures.169,170 However, the applicability of this particular Doppler modality for use in the operating room as a sole measure of LV compliance remains to be established.

Echocardiographic assessment of diastolic function is performed to specifically assess relaxation or compliance, but has to be performed in the context of assigning a severity grade based on the recommended guidelines (Fig. 4). According to the recommendations, it should start with DTI of the mitral annulus and then progress in a stepwise logical approach incorporating information obtained from the TMF, PVF, and, if required, subsequent performance of a Valsalva maneuver (Fig. 7). Using the ratios of various peak velocities obtained with Doppler, LVFP can be estimated and hence help in further refining the assessment of diastolic function.

Estimation of LVFP

The ASE guidelines suggest that Doppler variables can also be used for estimation of LVFP. However, the degree of systolic function should be taken into consideration when making such estimations (Figs. 17 and 18). For patients with a depressed EF, such an assessment should start with a PWD of the TMF. A peak E velocity <50 cm/s or E/A ratio <1 implies a normal LA pressure. An E/A ratio >2 or a DT <160 milliseconds is considered diagnostic of increased LA pressure (Fig. 17). For TMF, E/A patterns between the 2 extremes need further assessment using DTI (E′), PVF (S/D ratio, Adur, and Ar duration comparison), Vp, and sometimes changes in E/A ratio with the Valsalva maneuver. In the presence of systolic dysfunction, preload does not affect E′ velocity; hence, in patients with impaired relaxation, the ratio of E/E′ can be used to correct for the effect of increased preload on the E wave and prediction of filling pressures. Similarly, E/Vp ratio has also been shown to correlate with increased LA pressure, and a longer Ar duration than the Adur implies increased filling pressure. Although recommended by the ASE guidelines, LA volume cannot be calculated or measured reliably using intraoperative TEE.

Figure 17
Figure 17:
Estimation of filling pressures in patients with a depressed ejection fraction. LAP = left atrial pressure; Ar = pulmonary venous A wave; A = transmitral A wave; E = transmitral pulse wave Doppler E wave; E′ = Doppler tissue mitral annular wave; avg = average; PAS = pulmonary artery systolic pressure. (Adapted from Nagueh et al.5)
Figure 18
Figure 18:
Estimation of filling pressures in patients with a normal ejection fraction. LAP = left atrial pressure; Ar = pulmonary venous A wave; A = transmitral A wave; E = transmitral pulse wave Doppler E wave; E′ = Doppler tissue mitral annular wave; PAS = pulmonary artery systolic pressure; Val = Valsalva. (Adapted from Nagueh et al.5)

Specifically, in patients with depressed systolic function (EF <50%), E/Vp >2.5,97,107 E/E′ >15,171 and Ar-Adur >30 milliseconds (Figs. 17 and 18) are indicative of increased filling pressures.5 When LA pressure is elevated, the transmitral E wave occurs before the mitral annular E′ wave, and the time interval between the onset of E and E′ wave (TE–E′) is prolonged. An IVRT/TE–E′ ratio of <2 is dependent on τ and is a sensitive indicator of increased LV pressures.172

Estimation of LVFPs in patients with preserved systolic function is approached differently. It should be initiated with calculation of an E/E′ ratio. An E/E′ ratio >13 indicates increased LVFP (Fig. 18).103,104,107,171,173176 An E/E′ ratio of <8 implies normal LVFPs and when the ratio is between 9 and 13, other Doppler variables may be used to estimate LVFP.103 It is recommended to use the averaged mitral annulus–derived E/E′ ratio calculation for LVFPs.107,173 An Ar-Adur >30 milliseconds and an IVRT/TE–E′ ratio of <2 are also indicative of increased LVFPs.5

Because an E/E′ ratio of 9 to 13 can be associated with a normal or an increased LA pressure, it is important to integrate information from multiple Doppler modalities and clinical information. For example, pulmonary artery catheter–derived systolic pressure can be used to diagnose increased LA pressure when E/E′ is 9 to 13 in the presence of depressed or normal systolic function. The ratio E/Vp can be more reliably used to predict LVFP in patients with depressed systolic function.5

LA Size and Diastolic Dysfunction

Recently, LA size/volume measured with TTE has been found to be an indicator for the severity/chronicity of diastolic dysfunction, because during diastole the LA gets exposed to the elevated LVEDP. Clinically, LA size can be considered the “barometer” of the severity of diastolic dysfunction.177 It is recommended that the size of the LA should be measured by Simpson's biplane method and indexed to the body surface area.177179 The graded LA volume is a simple measure and can be clinically used as a predictor of adverse cardiovascular complications including myocardial infarction and stroke.180184 However, it is important to know that LA size cannot be accurately measured with TEE because of atrial foreshortening. Hence, the relevance of LA size in the perioperative assessment of diastolic dysfunction is limited to the knowledge of its preoperative size and interpretation of perioperative Doppler indices in the context of this information.


Since the early pioneering work performed by Pagel et al.49,160,185191 to assess the effects of anesthetic drugs on LV diastolic function, there has been little or no effort by anesthesiologists to use Doppler to investigate the same effects (Table 3). Incorporation of Doppler interrogation of ventricular filling characteristics has the potential to transform the currently performed “anatomical” intraoperative TEE examination to an “anatomical and physiological” examination. In the following section, a synopsis of the available literature on the effects of anesthetic drugs on LV diastolic characteristics (echocardiographic and invasively measured) is presented.

Table 3
Table 3:
Studies Assessing the Effects of Anesthetic Drugs on Left Ventricular Diastolic Function

Inhaled Anesthetics

The effect of anesthetic drugs on LV relaxation is not well known. Animal studies with invasive manometric catheters in the 1990s have demonstrated that halothane, isoflurane, enflurane, and desflurane prolong the IVRT,187,192,193 leading to impaired early LV filling.188,190 Echocardiographic studies in rats have demonstrated significant changes in TMF of LV filling during induction of GA with inhaled drugs.194 Among the inhaled anesthetics, only halothane has been shown to reduce LV compliance in an animal model.187,195 Impaired LV relaxation caused by inhaled anesthetics is possibly mediated by altered sarcoplasmic calcium metabolism because it is possible to reverse it with exogenous calcium administration in animal experiments.186,188 In the aforementioned studies, LV and aortic pressures were measured invasively with micromanometric catheters.187,192,193,196198 Whether inhaled drugs have similar effects on patients with preexisting diastolic dysfunction is unknown. Interestingly, desflurane and isoflurane have been shown to preserve regional systolic function and improve diastolic function in ischemic dogs, an effect possibly mediated by a reduced LV preload.185

More recently, investigators using Doppler echocardiography and a standardized GA protocol in patients without any preexisting cardiac disease demonstrated that halothane and sevoflurane did not cause prolongation of the IVRT199 and the impairment of relaxation was not considered of significant magnitude to be clinically relevant.199 In patients with preexisting diastolic dysfunction, however, administration of sevoflurane caused a slight improvement in early LV relaxation assessed with E′ velocity.200 The results seem to contradict the earlier reported adverse effects of inhaled anesthetics on LV relaxation.187,192,193,196198 Differences in study population (animals versus humans), medication doses, and methodology (Doppler versus invasive pressure measurements) could possibly explain these contradictory results.199,200 Similar effects were also observed in one human study in which isoflurane did not exacerbate preexistent diastolic dysfunction201 and had no lusitropic effects, i.e., improving relaxation in an animal study using invasive means.202 In 2 separate animal studies, the addition of nitrous oxide and desflurane was shown to increase chamber and myocardial stiffness.203,204 Inhaled anesthetic drugs also exert profound effects on the contractile, reservoir, and conduit function of the LA and also significantly impact LV filling as assessed by TMF with E and A waves.189,205 This loss of LA contractile function was also observed in human atrial tissue in an in vitro study.206

IV Drugs

There are only a few studies that have investigated the effects of IV drugs on perioperative diastolic function. Barbiturates and ketamine exert similar effects by inhibition of sarcolemmal transport of calcium ions, and ketamine has also been additionally shown to reduce chamber compliance.191,207212 In animal studies, propofol does not seem to affect myocardial relaxation or compliance.191 One study in humans using echocardiography has demonstrated that propofol prolongs the IVRT in patients with no history of cardiac disease,199 but does not cause worsening of preexisting diastolic dysfunction.200,213 The impact of etomidate on LV diastolic function has not been studied, but in vitro experiments have shown that it has minimal effects on intracellular calcium metabolism; therefore, it is unlikely that it would affect LV diastolic function.214


The ASE guidelines for assessment of diastolic function recommend a very comprehensive grading algorithm.5 However, the guidelines also recommend a simplified and reproducible approach for individual patients. In the perioperative arena during variable hemodynamics, an approach that rigorously requires the presence of all of the measured variables may be particularly difficult to apply. In one such study, the rigorous application of ASE guidelines for grading diastolic dysfunction during cardiac surgery led to only 20% of the 905 patients being graded as having diastolic dysfunction with no association with postoperative outcome.3 Conversely, when a simplified algorithm (lateral annulus E′ velocity) was used in the same patient group, almost 99% of patients were diagnosed with diastolic dysfunction and demonstrated a significant association with postoperative outcome.3 However, this study is limited by its retrospective nature, the possibility of selection bias, and lack of availability of any hemodynamic data. Validation of such an approach would require prospective application of simplified algorithms, which are modifications of the ASE guidelines.

In anesthetized patients, the ranges of normal values of the Doppler indices of LV filling have not yet been established. Currently, perioperative assessment of diastolic function is based on extrapolation of data obtained during awake-state hemodynamics. According to the ASE guidelines,5 An E′ velocity >8 cm/s essentially excludes the presence of diastolic dysfunction. However, because of the aforementioned factors, TMF and PVF should also be recorded for a comprehensive assessment and interrogation and severity grade assignment (Fig. 4). It is usually not difficult to distinguish an impaired relaxation abnormality (E/A <1, prolonged DT, and S/D >1) from a typical restrictive pattern (E/A >2, short DT, and S/D <1). These findings should be considered in the context of the underlying systolic function and E′ velocity to assign a grade of severity. Systolic function is often within normal limits in most patients with impaired relaxation compared with those with a restrictive pattern. The following caveats should be kept in mind: rhythm other than sinus makes interpretation of E/A and S/D difficult or impossible, “accessory” LV filling with aortic insufficiency, for example, will affect both E/A and S/D, and impaired relaxation will revert to a pseudonormal pattern with increased preload and vice versa. A brief “Valsalva” should be executed; reverse Trendelenburg or a lung recruitment maneuver with a prolonged inspiratory hold will probably unmask preload compensation because increased intrathoracic pressure will decrease blood return to the chest and eventually decrease LA preload. If a normal E/A ratio changes to impaired relaxation, the true underlying diastolic abnormality is most likely a pseudonormal state. A DTI E′/A′ <1 or a Vp <45 cm/s suggests the presence of diastolic impairment; however, the ratio will be decreased once relaxation is impaired.

Regarding estimation of LVFPs, systolic function should be evaluated as the first step. If normal, longer forward flow during atrial systole (A-Ar >0) generally means that the LVFP is normal. The same holds true if the change in E/A ratio with a Valsalva maneuver is <0.5. Retrograde flow for a longer duration during atrial contraction (A-Ar <30 milliseconds) or E/A change >0.5 with Valsalva is associated with increased LVFP. Interestingly, echocardiographic assessment of diastolic function is more reliable if there is concomitant systolic dysfunction because there is less preload effect on E′, Vp and it is easier to apply indices such as E/E′, E/Vp to estimate LVFP. In depressed LVEF, the S/D and E/Vp ratios also provide a clear separation between normal or elevated LVFP, in addition to the aforementioned E/A and A-Ar cutoffs mentioned above. Irrespective of the underlying LVEF, E/E′ <8 and >13 to 15 distinguish normal from elevated LVFP.


The established cutoff values for the various Doppler indices have been derived from TTE studies in awake patients, and may not be entirely applicable to patients examined with TEE under GA. However, in the absence of such normal values, a modified strategy based on the TTE-derived standards should be attempted. Hence, the perioperative approach described in this review, although different, is based on the same principles, avoiding cutoff values of any single Doppler variable. There is no single Doppler index that can diagnose with absolute certainty the presence or absence of diastolic dysfunction. A comprehensive approach should use multiple Doppler modalities with realization of their strengths and weaknesses. Future studies will be needed to establish the standards of LV filling characteristics of patients under GA.

Assessment of systolic function is based on a 2-dimensional examination, whereas diastolic function assessment is performed with Doppler, creating the impression that somehow these 2 exist separately.177 The use of Doppler has allowed us to define events during the cardiac cycle with precision, and to appreciate global myocardial function or performance (combined systolic and diastolic function).154 Newer techniques such as strain, speckle tracking, and velocity vector imaging may allow us to better define the LV filling dynamics and more accurately classify diastolic function. It is now important for anesthesiologists to incorporate Doppler examination of LV filling as part of a “comprehensive” intraoperative echocardiographic examination. In the absence of a specific therapy to improve diastolic function, the impact of routine intraoperative echocardiographic assessment of diastolic function on postoperative outcome is unclear. However, recent evidence suggests that the presence of preoperative asymptomatic LV systolic and diastolic dysfunction is associated with adverse outcome. Anesthesiologists involved in the perioperative care of patients with cardiovascular disorders routinely manage these patients appropriately, perhaps without realizing the stages of diastolic dysfunction. The appreciation of the severity stage of diastolic dysfunction can possibly be used to modify/refine clinical care. For example, during the impaired relaxation phase, augmentation of LA pressure and heart rate control can optimize LV filling by increasing the LA-LV pressure gradient and increasing filling time. However, in the more advanced stage of diastolic dysfunction, fluid restriction and judicious use of diuretics would be the logical therapeutic choices. Future studies will be needed to accurately assess the therapeutic impact of such a strategy.


Name: Robina Matyal, MD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Robina Matyal approved the final manuscript.

Conflicts of Interest: Robina Matyal reported no conflicts of interest.

Name: Nikolaos J. Skubas, MD.

Contribution: This author helped write the manuscript.

Attestation: Nikolaos J. Skubas approved the final manuscript.

Conflicts of Interest: Nikolaos J. Skubas reported no conflicts of interest.

Name: Stanton K. Shernan, MD.

Contribution: This author helped write the manuscript.

Attestation: Stanton K. Shernan approved the final manuscript.

Conflicts of Interest: Stanton K. Shernan reported a conflict of interest with Philips Healthcare and reported a conflict of interest with E-Echocardiography.

Name: Feroze Mahmood, MD.

Contribution: This author helped design the study, conduct the study, and analyze the data.

Attestation: Feroze Mahmood approved the final manuscript.

Conflicts of Interest: Feroze Mahmood reported no conflicts of interest.

a Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. Available at: Accessed May 12, 2011.
Cited Here


1. Flu WJ, van Kuijk JP, Hoeks SE, Kuiper R, Schouten O, Goei D, Elhendy A, Verhagen HJ, Thomson IR, Bax JJ, Fleisher LA, Poldermans D. Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery. Anesthesiology 2010;112:1316–24
2. Matyal R, Hess PE, Subramaniam B, Mitchell J, Panzica PJ, Pomposelli F, Mahmood F. Perioperative diastolic dysfunction during vascular surgery and its association with postoperative outcome. J Vasc Surg 2009;50:70–6
3. Swaminathan M, Nicoara A, Phillips-Bute B, Aeschlimann N, Milano CA, Mackensen BB, Podgoreanu MV, Velazquez EJ, Stafford-Smith M, Mathew JP; Cardiothoracic Anesthesia Research Endeavors (CARE) Group. Utility of a simple algorithm to grade diastolic dysfunction and predict outcome after coronary artery bypass graft surgery. Ann Thorac Surg 2011;91:1844–50
4. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician's Rosetta Stone. J Am Coll Cardiol 1997;30:8–18
5. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22:107–33
6. Soufer R, Wohlgelernter D, Vita NA, Amuchestegui M, Sostman HD, Berger HJ, Zaret BL. Intact systolic left ventricular function in clinical congestive heart failure. Am J Cardiol 1985;55:1032–6
7. Topol EJ, Traill TA, Fortuin NJ. Hypertensive hypertrophic cardiomyopathy of the elderly. N Engl J Med 1985;312:277–83
8. Phillip B, Pastor D, Bellows W, Leung JM. The prevalence of preoperative diastolic filling abnormalities in geriatric surgical patients. Anesth Analg 2003;97:1214–21
9. Somaratne JB, Whalley GA, Gamble GD, Doughty RN. Restrictive filling pattern is a powerful predictor of heart failure events postacute myocardial infarction and in established heart failure: a literature-based meta-analysis. J Card Fail 2007;13:346–52
10. Troughton RW, Prior DL, Frampton CM, Nash PJ, Pereira JJ, Martin M, Fogarty A, Morehead AJ, Starling RC, Young JB, Thomas JD, Lauer MS, Klein AL. Usefulness of tissue Doppler and color M-mode indexes of left ventricular diastolic function in predicting outcomes in systolic left ventricular heart failure (from the ADEPT study). Am J Cardiol 2005;96:257–62
11. Bernard F, Denault A, Babin D, Goyer C, Couture P, Couturier A, Buithieu J. Diastolic dysfunction is predictive of difficult weaning from cardiopulmonary bypass. Anesth Analg 2001;92:291–8
12. Denault AY, Couture P, Buithieu J, Haddad F, Carrier M, Babin D, Levesque S, Tardif JC. Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass. Can J Anaesth 2006;53:1020–9
13. Diller GP, Wasan BS, Kyriacou A, Patel N, Casula RP, Athanasiou T, Francis DP, Mayet J. Effect of coronary artery bypass surgery on myocardial function as assessed by tissue Doppler echocardiography. Eur J Cardiothorac Surg 2008;34:995–9
14. Djaiani GN, McCreath BJ, Ti LK, Mackensen BG, Podgoreanu M, Phillips-Bute B, Mathew JP. Mitral flow propagation velocity identifies patients with abnormal diastolic function during coronary artery bypass graft surgery. Anesth Analg 2002;95:524–30
15. Salem R, Denault AY, Couture P, Belisle S, Fortier A, Guertin MC, Carrier M, Martineau R. Left ventricular end-diastolic pressure is a predictor of mortality in cardiac surgery independently of left ventricular ejection fraction. Br J Anaesth 2006;97:292–7
16. Xu-Cai YO, Brotman DJ, Phillips CO, Michota FA, Tang WH, Whinney CM, Panneerselvam A, Hixson ED, Garcia M, Francis GS, Jaffer AK. Outcomes of patients with stable heart failure undergoing elective noncardiac surgery. Mayo Clin Proc 2008;83:280–8
17. Mahmood F, Christie A, Matyal R. Transesophageal echocardiography and noncardiac surgery. Semin Cardiothorac Vasc Anesth 2008;12:265–89
18. Achong N, Wahi S, Marwick TH. Evolution and outcome of diastolic dysfunction. Heart 2009;95:813–8
19. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure. Part II. Causal mechanisms and treatment. Circulation 2002;105:1503–8
20. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure. Part I. Diagnosis, prognosis, and measurements of diastolic function. Circulation 2002; 105:1387–93
21. Leite-Moreira AF. Current perspectives in diastolic dysfunction and diastolic heart failure. Heart 2006;92:712–8
22. Kass DA, Bronzwaer JG, Paulus WJ. What mechanisms underlie diastolic dysfunction in heart failure? Circ Res 2004;94:1533–42
23. Groban L. Diastolic dysfunction in the older heart. J Cardiothorac Vasc Anesth 2005;19:228–36
24. Besse S, Assayag P, Delcayre C, Carre F, Cheav SL, Lecarpentier Y, Swynghedauw B. Normal and hypertrophied senescent rat heart: mechanical and molecular characteristics. Am J Physiol 1993;265:H183–90
25. Cain BS, Meldrum DR, Joo KS, Wang JF, Meng X, Cleveland JC Jr, Banerjee A, Harken AH. Human SERCA2a levels correlate inversely with age in senescent human myocardium. J Am Coll Cardiol 1998;32:458–67
26. Cain BS, Meldrum DR, Meng X, Shames BD, Banerjee A, Harken AH. Calcium preconditioning in human myocardium. Ann Thorac Surg 1998;65:1065–70
27. Schmidt U, del Monte F, Miyamoto MI, Matsui T, Gwathmey JK, Rosenzweig A, Hajjar RJ. Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circulation 2000;101:790–6
28. Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD. Age-related changes in normal human hearts during the first 10 decades of life. Part II (maturity). A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc 1988;63:137–46
29. Khouri SJ, Maly GT, Suh DD, Walsh TE. A practical approach to the echocardiographic evaluation of diastolic function. J Am Soc Echocardiogr 2004;17:290–7
30. Rakowski H, Appleton C, Chan KL, Dumesnil JG, Honos G, Jue J, Koilpillai C, Lepage S, Martin RP, Mercier LA, O'Kelly B, Prieur T, Sanfilippo A, Sasson Z, Alvarez N, Pruitt R, Thompson C, Tomlinson C. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: from the Investigators of Consensus on Diastolic Dysfunction by Echocardiography. J Am Soc Echocardiogr 1996;9:736–60
31. Little WC, Ohno M, Kitzman DW, Thomas JD, Cheng CP. Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling. Circulation 1995;92:1933–9
32. Ohno M, Cheng CP, Little WC. Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure. Circulation 1994;89:2241–50
33. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539–50
34. Mirsky I. Assessment of diastolic function: suggested methods and future considerations. Circulation 1984;69:836–41
35. Mirsky I, Pasipoularides A. Clinical assessment of diastolic function. Prog Cardiovasc Dis 1990;32:291–318
36. Vasan RS, Levy D. Defining diastolic heart failure: a call for standardized diagnostic criteria. Circulation 2000;101:2118–21
37. Hatle L. How to diagnose diastolic heart failure: a consensus statement. Eur Heart J 2007;28:2421–3
38. Baldi JC, Lalande S, Carrick-Ranson G, Johnson BD. Postural differences in hemodynamics and diastolic function in healthy older men. Eur J Appl Physiol 2007;99:651–7
39. Berensztein CS, Pineiro D, Luis JF, Iavicoli O, Lerman J. Effect of left and right lateral decubitus positions on Doppler mitral flow patterns in patients with severe congestive heart failure. J Am Soc Echocardiogr 1996;9:86–90
40. Izumi C, Iga K, Himura Y, Gen H, Konishi T. Influence of gravity on pulmonary venous flow velocity patterns: analysis of left and right pulmonary venous flow velocities in left and right decubitus positions. Am Heart J 1999;137:419–26
41. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12: 426–40
42. Dumesnil JG, Gaudreault G, Honos GN, Kingma JG Jr. Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. Am J Cardiol 1991;68:515–9
43. Kitabatake A, Inoue M, Asao M, Tanouchi J, Masuyama T, Abe H, Morita H, Senda S, Matsuo H. Transmitral blood flow reflecting diastolic behavior of the left ventricle in health and disease: a study by pulsed Doppler technique. Jpn Circ J 1982;46:92–102
44. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289:194–202
45. 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;30:459–67
46. Nishimura RA, Tajik AJ. The Valsalva maneuver: 3 centuries later. Mayo Clin Proc 2004;79:577–8
47. Carson P, Massie BM, McKelvie R, McMurray J, Komajda M, Zile M, Ptaszynska A, Frangin G. The irbesartan in heart failure with preserved systolic function (I-PRESERVE) trial: rationale and design. J Card Fail 2005;11:576–85
48. Yamada H, Goh PP, Sun JP, Odabashian J, Garcia MJ, Thomas JD, Klein AL. Prevalence of left ventricular diastolic dysfunction by Doppler echocardiography: clinical application of the Canadian consensus guidelines. J Am Soc Echocardiogr 2002;15:1238–44
49. Pagel PS, Grossman W, Haering JM, Warltier DC. Left ventricular diastolic function in the normal and diseased heart: perspectives for the anesthesiologist (1). Anesthesiology 1993;79:836–54
50. Santamore WP, Bove AA, Heckman JL. Right and left ventricular pressure-volume response to positive end-expiratory pressure. Am J Physiol 1984;246:H114–9
51. Santamore WP, Heckman JL, Bove AA. Right and left ventricular pressure-volume response to respiratory maneuvers. J Appl Physiol 1984;57:1520–7
52. Gaasch WH, Bing OH, Franklin A, Rhodes D, Bernard SA, Weintraub RM. The influence of acute alterations in coronary blood flow on left ventricular diastolic compliance and wall thickness. Eur J Cardiol 1978;7:147–61
53. Couture P, Denault AY, Shi Y, Deschamps A, Cossette M, Pellerin M, Tardif JC. Effects of anesthetic induction in patients with diastolic dysfunction. Can J Anaesth 2009;56:357–65
54. Appleton CP. Influence of incremental changes in heart rate on mitral flow velocity: assessment in lightly sedated, conscious dogs. J Am Coll Cardiol 1991;17:227–36
55. Appleton CP. Hemodynamic determinants of Doppler pulmonary venous flow velocity components: new insights from studies in lightly sedated normal dogs. J Am Coll Cardiol 1997;30:1562–74
56. Appleton CP, Jensen JL, Hatle LK, Oh JK. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. J Am Soc Echocardiogr 1997;10:271–92
57. Choong CY, Abascal VM, Thomas JD, Guerrero JL, McGlew S, Weyman AE. Combined influence of ventricular loading and relaxation on the transmitral flow velocity profile in dogs measured by Doppler echocardiography. Circulation 1988;78:672–83
58. Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am Coll Cardiol 1987;10:800–8
59. Cohen GI, Pietrolungo JF, Thomas JD, Klein AL. A practical guide to assessment of ventricular diastolic function using Doppler echocardiography. J Am Coll Cardiol 1996;27:1753–60
60. Courtois M, Vered Z, Barzilai B, Ricciotti NA, Perez JE, Ludbrook PA. The transmitral pressure-flow velocity relation: effect of abrupt preload reduction. Circulation 1988;78: 1459–68
61. Gilman G, Nelson TA, Hansen WH, Khandheria BK, Ommen SR. Diastolic function: a sonographer's approach to the essential echocardiographic measurements of left ventricular diastolic function. J Am Soc Echocardiogr 2007;20:199–209
62. Ishida Y, Meisner JS, Tsujioka K, Gallo JI, Yoran C, Frater RW, Yellin EL. Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure. Circulation 1986;74:187–96
63. Courtois M, Kovacs SJ Jr, Ludbrook PA. Transmitral pressure-flow velocity relation: importance of regional pressure gradients in the left ventricle during diastole. Circulation 1988;78: 661–71
64. Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of left ventricular diastolic function: physics and physiology. Circulation 1991;84:977–90
65. Klein AL, Hatle LK, Burstow DJ, Taliercio CP, Seward JB, Kyle RA, Bailey KR, Gertz MA, Tajik AJ. Comprehensive Doppler assessment of right ventricular diastolic function in cardiac amyloidosis. J Am Coll Cardiol 1990;15:99–108
66. Oh JK, Ding ZP, Gersh BJ, Bailey KR, Tajik AJ. Restrictive left ventricular diastolic filling identifies patients with heart failure after acute myocardial infarction. J Am Soc Echocardiogr 1992;5:497–503
67. Pinamonti B, Di Lenarda A, Sinagra G, Camerini F. Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic correlations and prognostic implications. Heart Muscle Disease Study Group. J Am Coll Cardiol 1993;22:808–15
68. Vanoverschelde JL, Raphael DA, Robert AR, Cosyns JR. Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics. J Am Coll Cardiol 1990;15:1288–95
69. Xie GY, Berk MR, Smith MD, Gurley JC, DeMaria AN. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol 1994;24:132–9
70. Appleton CP, Firstenberg MS, Garcia MJ, Thomas JD. The echo-Doppler evaluation of left ventricular diastolic function: a current perspective. Cardiol Clin 2000;18:513–46
71. DeMaria AN, Blanchard D. 50th anniversary historical article: the hemodynamic basis of diastology. J Am Coll Cardiol 1999;34:1659–62
72. Garcia MJ, Firstenberg MS, Greenberg NL, Smedira N, Rodriguez L, Prior D, Thomas JD. Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans. Am J Physiol Heart Circ Physiol 2001;280:H554–61
73. Marino P, Faggian G, Bertolini P, Mazzucco A, Little WC. Early mitral deceleration and left atrial stiffness. Am J Physiol Heart Circ Physiol 2004;287:H1172–8
74. Marino P, Little WC, Rossi A, Barbieri E, Anselmi M, Destro G, Prioli A, Lanzoni L, Zardini P. Can left ventricular diastolic stiffness be measured noninvasively? J Am Soc Echocardiogr 2002;15:935–43
75. Thomas JD, Newell JB, Choong CY, Weyman AE. Physical and physiological determinants of transmitral velocity: numerical analysis. Am J Physiol 1991;260:H1718–31
76. Appleton CP, Galloway JM, Gonzalez MS, Gaballa M, Basnight MA. Estimation of left ventricular filling pressures using two-dimensional and Doppler echocardiography in adult patients with cardiac disease: additional value of analyzing left atrial size, left atrial ejection fraction and the difference in duration of pulmonary venous and mitral flow velocity at atrial contraction. J Am Coll Cardiol 1993;22:1972–82
77. Basnight MA, Gonzalez MS, Kershenovich SC, Appleton CP. Pulmonary venous flow velocity: relation to hemodynamics, mitral flow velocity and left atrial volume, and ejection fraction. J Am Soc Echocardiogr 1991;4:547–58
78. Castello R, Pearson AC, Lenzen P, Labovitz AJ. Evaluation of pulmonary venous flow by transesophageal echocardiography in subjects with a normal heart: comparison with transthoracic echocardiography. J Am Coll Cardiol 1991;18:65–71
79. Keren G, Sherez J, Megidish R, Levitt B, Laniado S. Pulmonary venous flow pattern: its relationship to cardiac dynamics—a pulsed Doppler echocardiographic study. Circulation 1985;71:1105–12
80. Klein AL, Tajik AJ. Doppler assessment of pulmonary venous flow in healthy subjects and in patients with heart disease. J Am Soc Echocardiogr 1991;4:379–92
81. Masuyama T, Lee JM, Tamai M, Tanouchi J, Kitabatake A, Kamada T. Pulmonary venous flow velocity pattern as assessed with transthoracic pulsed Doppler echocardiography in subjects without cardiac disease. Am J Cardiol 1991;67: 1396–404
82. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol 1993;21: 1687–96
83. Smallhorn JF, Freedom RM, Olley PM. Pulsed Doppler echocardiographic assessment of extraparenchymal pulmonary vein flow. J Am Coll Cardiol 1987;9:573–9
84. Klein AL, Obarski TP, Stewart WJ, Casale PN, Pearce GL, Husbands K, Cosgrove DM, Salcedo EE. Transesophageal Doppler echocardiography of pulmonary venous flow: a new marker of mitral regurgitation severity. J Am Coll Cardiol 1991;18:518–26
85. Kuecherer HF, Muhiudeen IA, Kusumoto FM, Lee E, Moulinier LE, Cahalan MK, Schiller NB. Estimation of mean left atrial pressure from transesophageal pulsed Doppler echocardiography of pulmonary venous flow. Circulation 1990;82:1127–39
86. Kuecherer HF, Kusumoto F, Muhiudeen IA, Cahalan MK, Schiller NB. Pulmonary venous flow patterns by transesophageal pulsed Doppler echocardiography: relation to parameters of left ventricular systolic and diastolic function. Am Heart J 1991;122:1683–93
87. Nishimura RA, Abel MD, Hatle LK, Tajik AJ. Relation of pulmonary vein to mitral flow velocities by transesophageal Doppler echocardiography: effect of different loading conditions. Circulation 1990;81:1488–97
88. Torrecilla EG, Garcia Fernandez MA, Bueno H, Moreno M, Delcan JL. Pulmonary venous flow in hypertrophic cardiomyopathy as assessed by the transoesophageal approach: the additive value of pulmonary venous flow and left atrial size variables in estimating the mitral inflow pattern in hypertrophic cardiomyopathy. Eur Heart J 1999;20:293–302
89. Jensen JL, Williams FE, Beilby BJ, Johnson BL, Miller LK, Ginter TL, Tomaselli-Martin G, Appleton CP. Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr 1997;10:60–6
90. Mahmood F, Matyal R, Subramaniam B, Mitchell J, Pomposelli F, Lerner AB, Maslow A, Hess PM. Transmitral flow propagation velocity and assessment of diastolic function during abdominal aortic aneurysm repair. J Cardiothorac Vasc Anesth 2007;21:486–91
91. Yamada H, Oki T, Mishiro Y, Tabata T, Abe M, Onose Y, Wakatsuki T, Ito S. Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects. J Am Soc Echocardiogr 1999;12:574–81
92. Brun P, Tribouilloy C, Duval AM, Iserin L, Meguira A, Pelle G, Dubois-Rande JL. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20:420–32
93. Stugaard M, Brodahl U, Torp H, Ihlen H. Abnormalities of left ventricular filling in patients with coronary artery disease: assessment by colour M-mode Doppler technique. Eur Heart J 1994;15:318–27
94. Stugaard M, Risoe C, Ihlen H, Smiseth OA. Intracavitary filling pattern in the failing left ventricle assessed by color M-mode Doppler echocardiography. J Am Coll Cardiol 1994;24:663–70
95. Stugaard M, Steen T, Lundervold A, Smiseth OA, Ihlen H. Visual assessment of intra ventricular flow from colour M-mode Doppler images. Int J Card Imaging 1994;10:279–87
96. Takatsuji H, Mikami T, Urasawa K, Teranishi J, Onozuka H, Takagi C, Makita Y, Matsuo H, Kusuoka H, Kitabatake A. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol 1996;27:365–71
97. Garcia MJ, Ares MA, Asher C, Rodriguez L, Vandervoort P, Thomas JD. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol 1997;29:448–54
98. Stugaard M, Smiseth OA, Risoe C, Ihlen H. Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color M-mode Doppler echocardiography. Circulation 1993;88:2705–13
99. De Boeck BW, Oh JK, Vandervoort PM, Vierendeels JA, van der Aa RP, Cramer MJ. Colour M-mode velocity propagation: a glance at intra-ventricular pressure gradients and early diastolic ventricular performance. Eur J Heart Fail 2005; 7:19–28
100. Ohte N, Narita H, Akita S, Kurokawa K, Hayano J, Kimura G. Striking effect of left ventricular systolic performance on propagation velocity of left ventricular early diastolic filling flow. J Am Soc Echocardiogr 2001;14:1070–4
101. Rovner A, de las Fuentes L, Waggoner AD, Memon N, Chohan R, Davila-Roman VG. Characterization of left ventricular diastolic function in hypertension by use of Doppler tissue imaging and color M-mode techniques. J Am Soc Echocardiogr 2006;19:872–9
102. Yotti R, Bermejo J, Antoranz JC, Desco MM, Cortina C, Rojo-Alvarez JL, Allue C, Martin L, Moreno M, Serrano JA, Munoz R, Garcia-Fernandez MA. A noninvasive method for assessing impaired diastolic suction in patients with dilated cardiomyopathy. Circulation 2005;112:2921–9
103. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788–94
104. Sohn DW, Song JM, Zo JH, Chai IH, Kim HS, Chun HG, Kim HC. Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation. J Am Soc Echocardiogr 1999;12:927–31
105. Skubas N. Intraoperative Doppler tissue imaging is a valuable addition to cardiac anesthesiologists' armamentarium: a core review. Anesth Analg 2009;108:48–66
106. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474–80
107. Rivas-Gotz C, Manolios M, Thohan V, Nagueh SF. Impact of left ventricular ejection fraction on estimation of left ventricular filling pressures using tissue Doppler and flow propagation velocity. Am J Cardiol 2003;91:780–4
108. Ruan Q, Rao L, Middleton KJ, Khoury DS, Nagueh SF. Assessment of left ventricular diastolic function by early diastolic mitral annulus peak acceleration rate: experimental studies and clinical application. J Appl Physiol 2006;100: 679–84
109. Nagueh SF, Sun H, Kopelen HA, Middleton KJ, Khoury DS. Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler. J Am Coll Cardiol 2001;37: 278–85
110. Dumesnil JG, Paulin C, Pibarot P, Coulombe D, Arsenault M. Mitral annulus velocities by Doppler tissue imaging: practical implications with regard to preload alterations, sample position, and normal values. J Am Soc Echocardiogr 2002;15: 1226–31
111. Nishimura RA, Tajik AJ. The Valsalva maneuver and response revisited. Mayo Clin Proc 1986;61:211–7
112. Wijbenga AA, Mosterd A, Kasprzak JD, Ligthart JM, Vletter WB, Balk AH, Roelandt JR. Potentials and limitations of the Valsalva maneuver as a method of differentiating between normal and pseudonormal left ventricular filling patterns. Am J Cardiol 1999;84:76–81
113. Nishimura RA, Housmans PR, Hatle LK, Tajik AJ. Assessment of diastolic function of the heart: background and current applications of Doppler echocardiography. Part I. Physiologic and pathophysiologic features. Mayo Clin Proc 1989;64:71–81
114. Nishimura RA, Abel MD, Housmans PR, Warnes CA, Tajik AJ. Mitral flow velocity curves as a function of different loading conditions: evaluation by intraoperative transesophageal Doppler echocardiography. J Am Soc Echocardiogr 1989;2:79–87
115. Takahashi T, Iizuka M, Sato H, Serizawa T, Momomura S, Mochizuki T, Kohmoto O, Aoyagi T, Matsui H, Ikenouchi H, Sakamoto T, Sugimoto T. Doppler echocardiographic-determined changes in left ventricular diastolic filling flow velocity during the lower body positive and negative pressure method. Am J Cardiol 1990;65:237–41
116. Triulzi MO, Castini D, Ornaghi M, Vitolo E. Effects of preload reduction on mitral flow velocity pattern in normal subjects. Am J Cardiol 1990;66:995–1001
117. Gaasch WH, Carroll JD, Blaustein AS, Bing OH. Myocardial relaxation: effects of preload on the time course of isovolumetric relaxation. Circulation 1986;73:1037–41
118. Gillebert TC, Raes DF. Preload, length-tension relation, and isometric relaxation in cardiac muscle. Am J Physiol 1994;267:H1872–9
119. Barberato SH, Mantilla DE, Misocami MA, Goncalves SM, Bignelli AT, Riella MC, Pecoits-Filho R. Effect of preload reduction by hemodialysis on left atrial volume and echocardiographic Doppler parameters in patients with end-stage renal disease. Am J Cardiol 2004;94:1208–10
120. Chakko S, Girgis I, Contreras G, Perez G, Kessler KM, Myerburg RJ. Effects of hemodialysis on left ventricular diastolic filling. Am J Cardiol 1997;79:106–8
121. Hayashi SY, Brodin LA, Alvestrand A, Lind B, Stenvinkel P, Mazza do Nascimento M, Qureshi AR, Saha S, Lindholm B, Seeberger A. Improvement of cardiac function after haemodialysis: quantitative evaluation by colour tissue velocity imaging. Nephrol Dial Transplant 2004;19:1497–506
122. Rozich JD, Smith B, Thomas JD, Zile MR, Kaiser J, Mann DL. Dialysis-induced alterations in left ventricular filling: mechanisms and clinical significance. Am J Kidney Dis 1991;17: 277–85
123. Suliman ME, Stenvinkel P, Qureshi AR, Barany P, Heimburger O, Anderstam B, Alvestrand A, Lindholm B. Hyperhomocysteinemia in relation to plasma free amino acids, biomarkers of inflammation and mortality in patients with chronic kidney disease starting dialysis therapy. Am J Kidney Dis 2004;44:455–65
124. Sztajzel J, Ruedin P, Stoermann C, Monin C, Schifferli J, Leski M, Rutishauser W, Lerch R. Effects of dialysate composition during hemodialysis on left ventricular function. Kidney Int Suppl 1993;41:S60–6
125. Chamoun AJ, Xie T, Trough M, Esquivel-Avila J, Carson R, DeFilippi C, Ahmad M. Color M-mode flow propagation velocity versus conventional Doppler indices in the assessment of diastolic left ventricular function in patients on chronic hemodialysis. Echocardiography 2002;19:467–74
126. Agmon Y, Oh JK, McCarthy JT, Khandheria BK, Bailey KR, Seward JB. Effect of volume reduction on mitral annular diastolic velocities in hemodialysis patients. Am J Cardiol 2000;85:665–8
127. Dincer I, Kumbasar D, Nergisoglu G, Atmaca Y, Kutlay S, Akyurek O, Sayin T, Erol C, Oral D. Assessment of left ventricular diastolic function with Doppler tissue imaging: effects of preload and place of measurements. Int J Cardiovasc Imaging 2002;18:155–60
128. Drighil A, Perron JM, Lafitte S, Rakotoarison P, Bader H, Zabsonre P, Chraibi N, Roudaut R. Study of variations in preload on the new echocardiography parameters of diastolic function in health subjects [in French]. Arch Mal Coeur Vaiss 2002;95:573–80
129. Galetta F, Cupisti A, Franzoni F, Carpi A, Barsotti G, Santoro G. Acute effects of hemodialysis on left ventricular function evaluated by tissue Doppler imaging. Biomed Pharmacother 2006;60:66–70
130. Garcia MJ, Smedira NG, Greenberg NL, Main M, Firstenberg MS, Odabashian J, Thomas JD. Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation. J Am Coll Cardiol 2000;35:201–8
131. Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, Zuckerman J, Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol 2000;36:1664–9
132. Garcia MJ, Palac RT, Malenka DJ, Terrell P, Plehn JF. Color M-mode Doppler flow propagation velocity is a relatively preload-independent index of left ventricular filling. J Am Soc Echocardiogr 1999;12:129–37
133. Moller JE, Poulsen SH, Sondergaard E, Egstrup K. Preload dependence of color M-mode Doppler flow propagation velocity in controls and in patients with left ventricular dysfunction. J Am Soc Echocardiogr 2000;13:902–9
134. Drighil A, Madias JE, Mathewson JW, El Mosalami H, El Badaoui N, Ramdani B, Bennis A. Haemodialysis: effects of acute decrease in preload on tissue Doppler imaging indices of systolic and diastolic function of the left and right ventricles. Eur J Echocardiogr 2008;9:530–5
135. Hung KC, Huang HL, Chu CM, Yeh KH, Fang JT, Lin FC. Effects of altered volume loading on left ventricular hemodynamics and diastolic filling during hemodialysis. Ren Fail 2004;26:141–7
136. Vignon P, Allot V, Lesage J, Martaille JF, Aldigier JC, Francois B, Gastinne H. Diagnosis of left ventricular diastolic dysfunction in the setting of acute changes in loading conditions. Crit Care 2007;11:R43
137. Pirracchio R, Cholley B, De Hert S, Solal AC, Mebazaa A. Diastolic heart failure in anaesthesia and critical care. Br J Anaesth 2007;98:707–21
138. Gillebert TC, Leite-Moreira AF, De Hert SG. Relaxation-systolic pressure relation: a load-independent assessment of left ventricular contractility. Circulation 1997;95:745–52
139. Gillebert TC, Leite-Moreira AF, De Hert SG. The hemodynamic manifestation of normal myocardial relaxation: a framework for experimental and clinical evaluation. Acta Cardiol 1997;52:223–46
140. Leite-Moreira AF, Gillebert TC. Nonuniform course of left ventricular pressure fall and its regulation by load and contractile state. Circulation 1994;90:2481–91
141. Gillebert TC, Leite-Moreira AF, De Hert SG. Load dependent diastolic dysfunction in heart failure. Heart Fail Rev 2000;5:345–55
142. Leite-Moreira AF, Gillebert TC. The physiology of left ventricular pressure fall. Rev Port Cardiol 2000;19:1015–21
143. Eichhorn EJ, Willard JE, Alvarez L, Kim AS, Glamann DB, Risser RC, Grayburn PA. Are contraction and relaxation coupled in patients with and without congestive heart failure? Circulation 1992;85:2132–9
144. De Hert SG, Gillebert TC, Ten Broecke PW, Mertens E, Rodrigus IE, Moulijn AC. Contraction-relaxation coupling and impaired left ventricular performance in coronary surgery patients. Anesthesiology 1999;90:748–57
145. De Hert SG, Gillebert TC, Ten Broecke PW, Moulijn AC. Length-dependent regulation of left ventricular function in coronary surgery patients. Anesthesiology 1999;91:379–87
146. De Hert SG, ten Broecke PW, Rodrigus IE, Mertens E, Stockman BA, Vermeyen KM. The effects of the pericardium on length-dependent regulation of left ventricular function in coronary artery surgery patients. J Cardiothorac Vasc Anesth 2001;15:300–5
147. De Hert SG, Vander Linden PJ, ten Broecke PW, De Mulder PA, Rodrigus IE, Adriaensen HF. Assessment of length-dependent regulation of myocardial function in coronary surgery patients using transmitral flow velocity patterns. Anesthesiology 2000;93:374–81
148. Chemla D, Coirault C, Hebert JL, Lecarpentier Y. Mechanics of relaxation of the human heart. News Physiol Sci 2000;15:78–83
149. Gandhi SK, Powers JC, Nomeir AM, Fowle K, Kitzman DW, Rankin KM, Little WC. The pathogenesis of acute pulmonary edema associated with hypertension. N Engl J Med 2001;344:17–22
150. Leite-Moreira AF, Correia-Pinto J. Load as an acute determinant of end-diastolic pressure-volume relation. Am J Physiol Heart Circ Physiol 2001;280:H51–9
151. Gillespie DL, Connelly GP, Arkoff HM, Dempsey AL, Hilkert RJ, Menzoian JO. Left ventricular dysfunction during infrarenal abdominal aortic aneurysm repair. Am J Surg 1994;168:144–7
152. Meierhenrich R, Gauss A, Anhaeupl T, Schutz W. Analysis of diastolic function in patients undergoing aortic aneurysm repair and impact on hemodynamic response to aortic cross-clamping. J Cardiothorac Vasc Anesth 2005;19:165–72
153. Mahmood F, Matyal R, Maslow A, Subramaniam B, Mitchell J, Panzica P, Karthik S, Hess P. Myocardial performance index is a predictor of outcome after abdominal aortic aneurysm repair. J Cardiothorac Vasc Anesth 2008;22:706–12
154. Fayad A, Yang H, Nathan H, Bryson GL, Cina CS. Acute diastolic dysfunction in thoracoabdominal aortic aneurysm surgery. Can J Anaesth 2006;53:168–73
155. Mottram PM, Marwick TH. Assessment of diastolic function: what the general cardiologist needs to know. Heart 2005;91:681–95
156. Schnittger I, Appleton CP, Hatle LK, Popp RL. Diastolic mitral and tricuspid regurgitation by Doppler echocardiography in patients with atrioventricular block: new insight into the mechanism of atrioventricular valve closure. J Am Coll Cardiol 1988;11:83–8
157. Nagueh SF, Kopelen HA, Quinones MA. Assessment of left ventricular filling pressures by Doppler in the presence of atrial fibrillation. Circulation 1996;94:2138–45
158. Apstein CS, Grossman W. Opposite initial effects of supply and demand ischemia on left ventricular diastolic compliance: the ischemia-diastolic paradox. J Mol Cell Cardiol 1987;19:119–28
159. Koretsune Y, Corretti MC, Kusuoka H, Marban E. Mechanism of early ischemic contractile failure: inexcitability, metabolite accumulation, or vascular collapse? Circ Res 1991;68:255–62
160. Pagel PS, Grossman W, Haering JM, Warltier DC. Left ventricular diastolic function in the normal and diseased heart: perspectives for the anesthesiologist (2). Anesthesiology 1993;79:1104–20
161. Aroesty JM, McKay RG, Heller GV, Royal HD, Als AV, Grossman W. Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia. Circulation 1985;71:889–900
162. Carroll JD, Hess OM, Hirzel HO, Krayenbuehl HP. Exercise-induced ischemia: the influence of altered relaxation on early diastolic pressures. Circulation 1983;67:521–8
163. Mann T, Brodie BR, Grossman W, McLaurin LP. Effect of angina on the left ventricular diastolic pressure-volume relationship. Circulation 1977;55:761–6
164. McLaurin LP, Rolett EL, Grossman W. Impaired left ventricular relaxation during pacing-induced ischemia. Am J Cardiol 1973;32:751–7
165. Bolognesi R, Tsialtas D, Barilli AL, Manca C, Zeppellini R, Javernaro A, Cucchini F. Detection of early abnormalities of left ventricular function by hemodynamic, echo-tissue Doppler imaging, and mitral Doppler flow techniques in patients with coronary artery disease and normal ejection fraction. J Am Soc Echocardiogr 2001;14:764–72
166. Henein MY, Anagnostopoulos C, Das SK, O'Sullivan C, Underwood SR, Gibson DG. Left ventricular long axis disturbances as predictors for thallium perfusion defects in patients with known peripheral vascular disease. Heart 1998;79: 295–300
167. Bach DS, Armstrong WF, Donovan CL, Muller DW. Quantitative Doppler tissue imaging for assessment of regional myocardial velocities during transient ischemia and reperfusion. Am Heart J 1996;132:721–5
168. Derumeaux G, Ovize M, Loufoua J, Andre-Fouet X, Minaire Y, Cribier A, Letac B. Doppler tissue imaging quantitates regional wall motion during myocardial ischemia and reperfusion. Circulation 1998;97:1970–7
169. Pai RG, Suzuki M, Heywood JT, Ferry DR, Shah PM. Mitral A velocity wave transit time to the outflow tract as a measure of left ventricular diastolic stiffness: hemodynamic correlations in patients with coronary artery disease. Circulation 1994;89:553–7
170. Pai RG, Varadarajan P. Relative duration of transmitted mitral A wave as a measure of left ventricular end-diastolic pressure and stiffness. Echocardiography 2004;21:27–31
171. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527–33
172. Rivas-Gotz C, Khoury DS, Manolios M, Rao L, Kopelen HA, Nagueh SF. Time interval between onset of mitral inflow and onset of early diastolic velocity by tissue Doppler: a novel index of left ventricular relaxation—experimental studies and clinical application. J Am Coll Cardiol 2003;42:1463–70
173. Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M, Tschope C. Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 2007;116:637–47
174. Kim YJ, Sohn DW. Mitral annulus velocity in the estimation of left ventricular filling pressure: prospective study in 200 patients. J Am Soc Echocardiogr 2000;13:980–5
175. Nagueh SF, Mikati I, Kopelen HA, Middleton KJ, Quinones MA, Zoghbi WA. Doppler estimation of left ventricular filling pressure in sinus tachycardia: a new application of tissue Doppler imaging. Circulation 1998;98:1644–50
176. Sohn DW, Kim YJ, Kim HC, Chun HG, Park YB, Choi YS. Evaluation of left ventricular diastolic function when mitral E and A waves are completely fused: role of assessing mitral annulus velocity. J Am Soc Echocardiogr 1999;12:203–8
177. Lester SJ, Tajik AJ, Nishimura RA, Oh JK, Khandheria BK, Seward JB. Unlocking the mysteries of diastolic function: deciphering the Rosetta Stone 10 years later. J Am Coll Cardiol 2008;51:679–89
178. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63
179. Lester SJ, Ryan EW, Schiller NB, Foster E. Best method in clinical practice and in research studies to determine left atrial size. Am J Cardiol 1999;84:829–32
180. Douglas PS. The left atrium: a biomarker of chronic diastolic dysfunction and cardiovascular disease risk. J Am Coll Cardiol 2003;42:1206–7
181. Takemoto Y, Barnes ME, Seward JB, Lester SJ, Appleton CA, Gersh BJ, Bailey KR, Tsang TS. Usefulness of left atrial volume in predicting first congestive heart failure in patients ≥65 years of age with well-preserved left ventricular systolic function. Am J Cardiol 2005;96:832–6
182. Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. Am J Cardiol 2002;90:1284–9
183. Tsang TS, Barnes ME, Gersh BJ, Takemoto Y, Rosales AG, Bailey KR, Seward JB. Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol 2003;42: 1199–205
184. Tsang TS, Gersh BJ, Appleton CP, Tajik AJ, Barnes ME, Bailey KR, Oh JK, Leibson C, Montgomery SC, Seward JB. Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. J Am Coll Cardiol 2002;40:1636–44
185. Pagel PS, Hettrick DA, Lowe D, Tessmer JP, Warltier DC. Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs. Anesthesiology 1995;83:1021–35
186. Pagel PS, Hettrick DA, Warltier DC. Amrinone enhances myocardial contractility and improves left ventricular diastolic function in conscious and anesthetized chronically instrumented dogs. Anesthesiology 1993;79:753–65
187. Pagel PS, Kampine JP, Schmeling WT, Warltier DC. Alteration of left ventricular diastolic function by desflurane, isoflurane, and halothane in the chronically instrumented dog with autonomic nervous system blockade. Anesthesiology 1991;74:1103–14
188. Pagel PS, Kampine JP, Schmeling WT, Warltier DC. Reversal of volatile anesthetic-induced depression of myocardial contractility by extracellular calcium also enhances left ventricular diastolic function. Anesthesiology 1993;78:141–54
189. Pagel PS, Kehl F, Gare M, Hettrick DA, Kersten JR, Warltier DC. Mechanical function of the left atrium: new insights based on analysis of pressure-volume relations and Doppler echocardiography. Anesthesiology 2003;98:975–94
190. Pagel PS, Nijhawan N, Warltier DC. Quantitation of volatile anesthetic-induced depression of myocardial contractility using a single beat index derived from maximal ventricular power. J Cardiothorac Vasc Anesth 1993;7:688–95
191. Pagel PS, Schmeling WT, Kampine JP, Warltier DC. Alteration of canine left ventricular diastolic function by intravenous anesthetics in vivo: ketamine and propofol. Anesthesiology 1992;76:419–25
192. Doyle RL, Foex P, Ryder WA, Jones LA. Effects of halothane on left ventricular relaxation and early diastolic coronary blood flow in the dog. Anesthesiology 1989;70:660–6
193. Humphrey LS, Stinson DC, Humphrey MJ, Finney RS, Zeller PA, Judd MR, Blanck TJ. Volatile anesthetic effects on left ventricular relaxation in swine. Anesthesiology 1990;73:731–8
194. Plante E, Lachance D, Roussel E, Drolet MC, Arsenault M, Couet J. Impact of anesthesia on echocardiographic evaluation of systolic and diastolic function in rats. J Am Soc Echocardiogr 2006;19:1520–5
195. Goldberg AH, Phear WP. Halothane and paired stimulation: effects on myocardial compliance and contractility. J Appl Physiol 1970;28:391–6
196. Graham MR, Thiessen DB, Mutch WA. Isoflurane and halothane impair both systolic and diastolic function in the newborn pig. Can J Anaesth 1996;43:495–502
197. Graham MR, Thiessen DB, Mutch WA. Left ventricular systolic and diastolic function is unaltered during propofol infusion in newborn swine. Anesth Analg 1998;86:717–23
198. Skeehan TM, Schuler HG, Riley JL. Comparison of the alteration of cardiac function by sevoflurane, isoflurane, and halothane in the isolated working rat heart. J Cardiothorac Vasc Anesth 1995;9:706–12
199. Filipovic M, Wang J, Michaux I, Hunziker P, Skarvan K, Seeberger MD. Effects of halothane, sevoflurane and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation. Br J Anaesth 2005;94:186–92
200. Filipovic M, Michaux I, Wang J, Hunziker P, Skarvan K, Seeberger M. Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre-existing diastolic dysfunction. Br J Anaesth 2007;98:12–8
201. Neuhauser C, Muller M, Welters I, Scholz S, Kwapisz MM. Effect of isoflurane on echocardiographic left-ventricular relaxation indices in patients with diastolic dysfunction due to concentric hypertrophy and ischemic heart disease. J Cardiothorac Vasc Anesth 2006;20:509–14
202. Hanouz JL, Vivien B, Gueugniaud PY, Lecarpentier Y, Coriat P, Riou B. Comparison of the effects of sevoflurane, isoflurane and halothane on rat myocardium. Br J Anaesth 1998;80:621–7
203. Marsch SC, Dalmas S, Philbin DM, Ryder WA, Wong LS, Foex P. Effects and interactions of nitrous oxide, myocardial ischemia, and reperfusion on left ventricular diastolic function. Anesth Analg 1997;84:39–45
204. Vivien B, Hanouz JL, Gueugniaud PY, Lecarpentier Y, Coriat P, Riou B. Myocardial effects of desflurane in hamsters with hypertrophic cardiomyopathy. Anesthesiology 1998;89: 1191–8
205. Pagel PS. Anesthetics and echocardiographic assessment of left ventricular function: lessons learned from invasive analysis of cardiovascular mechanics. J Am Soc Echocardiogr 2007;20:440–1
206. Hanouz JL, Massetti M, Guesne G, Chanel S, Babatasi G, Rouet R, Ducouret P, Khayat A, Galateau F, Bricard H, Gerard JL. In vitro effects of desflurane, sevoflurane, isoflurane, and halothane in isolated human right atria. Anesthesiology 2000;92:116–24
207. Davies AE, McCans JL. Effects of barbiturate anesthetics and ketamine on the force-frequency relation of cardiac muscle. Eur J Pharmacol 1979;59:65–73
208. Frankl WS, Poole-Wilson PA. Effects of thiopental on tension development, action potential, and exchange of calcium and potassium in rabbit ventricular myocardium. J Cardiovasc Pharmacol 1981;3:554–65
209. Cook DJ, Carton EG, Housmans PR. Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle. Anesthesiology 1991;74:880–8
210. Riou B, Lecarpentier Y, Viars P. Inotropic effect of ketamine on rat cardiac papillary muscle. Anesthesiology 1989;71:116–25
211. Rusy BF, Amuzu JK, Bosscher HA, Redon D, Komai H. Negative inotropic effect of ketamine in rabbit ventricular muscle. Anesth Analg 1990;71:275–8
212. Urthaler F, Walker AA, James TN. Comparison of the inotropic action of morphine and ketamine studied in canine cardiac muscle. J Thorac Cardiovasc Surg 1976;72:142–9
213. Gare M, Parail A, Milosavljevic D, Kersten JR, Warltier DC, Pagel PS. Conscious sedation with midazolam or propofol does not alter left ventricular diastolic performance in patients with preexisting diastolic dysfunction: a transmitral and tissue Doppler transthoracic echocardiography study. Anesth Analg 2001;93:865–71
214. Komai H, DeWitt DE, Rusy BF. Negative inotropic effect of etomidate in rabbit papillary muscle. Anesth Analg 1985;64:400–4
© 2011 International Anesthesia Research Society