Echocardiographic Evaluation of Diastolic Function

S. Michelle Bierig, MPH, RDCS, RDMS, FASE, FSDMS1, and Jeffrey Hill2, BS, RDCS, FASE

Journal of Diagnostic Medical Sonography 27(2) 65 78 The Author(s) 2011 Reprints and permission: http://www. sagepub.com/journalsPermissions.nav DOI: 10.1177/8756479311401914 http://jdm.sagepub.com

Abstract Left ventricular diastolic dysfunction is common in patients with heart failure. Echocardiographic evaluation of diastolic function provides the clinician with important information about ventricular relaxation and estimation of filling pressures. Optimal evaluation includes the integration of multiple echocardiographic parameters such as Doppler, M-mode, and volumes. This article aims to review the components of diastolic filling and ventricular performance, as well as discuss the techniques used for the assessment of left ventricular diastolic function. Keywords 2D, diastole, diastolic function, Doppler, echocardiography, tissue Doppler

Background
Evaluation of the diastolic phases in the assessment of cardiac function has become integral in the comprehensive echocardiogram.1 Abnormal findings in diastolic function may change treatment algorithms and aid in appropriate risk stratification. Asymptomatic patients can have diastolic dysfunction that precedes systolic dysfunction. Diastolic dysfunction has been reported in up to 27% to 30% of the general population.2,3 Those with diastolic dysfunction have associated cardiac risk factors such as obesity, diabetes, and hypertension, regardless of the presence or absence of systolic dysfunction.35 In patients with heart failure, normal ejection fraction (diastolic heart failure) is reported to be as high as 43% and is more common in women older than 60 years of age.4,5 Primary diastolic heart failure has a more favorable prognosis over systolic heart failure, with an annual mortality rate of 5% to 12%.4 The natural history of changes in the severity of diastolic dysfunction has been reported to remain the same in 52% of patients, worsened in 27%, and improved in 21%, with improvement in diastolic dysfunction being associated with a survival benefit.6,7 Symptoms of diastolic dysfunction are similar to those of heart failure and can include dyspnea (especially on exertion), palpitations, and exertional chest pain not related to coronary artery disease. Because dyspnea is a common symptom of congestive heart failure due to ventricular systolic impairment, it is important for sonographers to also evaluate diastolic dysfunction as a cause of dyspnea in this population.

Ventricular Diastolic Performance

The major determinants of left ventricular (LV) filling are ventricular relaxation and passive diastolic properties (compliance). Ventricular relaxation occurs when the LV pressure declines after aortic valve closure during the isovolumic period, represented by the rate and duration of the decrease in LV pressure after systolic contraction. Echocardiographically measured ventricular relaxation is assessed by measuring the early slope of the continuous-wave Doppler mitral regurgitation jet. This indirect measurement is the dP/dt (diastolic pressure over time). Normal dP/dt values are greater than 1200 mm Hg/s (Figure 1).8 The gold-standard direct measurement of ventricular relaxation is (time constant to relaxation) measured invasively, with normal values less than 50 ms. Tissue Doppler imaging (TDI) is an additional indirect echocardiographic measure of ventricular contraction and relaxation that has been validated against .911 In the early stages of diastolic impairment, ventricular filling slows because of prolonged relaxation, with the majority of filling occurring with atrial contraction at end diastole. More severe diastolic impairment is associated with increased LV and left atrial (LA) filling pressures.
1 2

St. Anthonys Medical Center, St. Louis, MO, USA Gibbs College of Boston, Boston, MA, USA

Corresponding Author: S. Michelle Bierig, St. Anthonys Medical Center, 10010 Kennerly Road, St. Louis, MO 63128 Email: michelle.bierig@samcstl.org

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Figure 1. Measurements of dP/dt in a patient with left ventricular (LV) dysfunction and moderate to severe mitral regurgitation. Continuous-wave Doppler was used in the apical three-chamber view. The dP/dt measurement begins at 1 m/s (upper horizontal dotted line), and the dP/dt slope (diagonal dotted lines) is extrapolated to 3 m/s (lower horizontal line). The average dP/dt in this patient is 699 mm Hg/s (normal >1200 mm Hg/s).

The term compliance is the sum of myocardial compliance, chamber compliance, and viscoelastic properties. Ventricular compliance describes the elasticity or ease of ventricular filling. Inadequate LV compliance caused by stiffness of the myocardium may occur with or without an increase in either end-diastolic or end-systolic volume.12 As LV compliance decreases, a gradual increase in filling pressures is required to maintain normal cardiac filling, volume, and output. Decreased compliance is seen with LV hypertrophy patterns, ischemia, and increasing LV volume.13 Increases in filling pressures are described by mean pulmonary capillary wedge pressures (PCWPs) of greater than 12 mm Hg and/or an LV end-diastolic pressure (LVEDP) of greater than 16 mm Hg.14

Phases of Diastole
LV filling in diastole comprises four specific phases: (1) isovolumic relaxation time (IVRT), (2) early rapid filling, (3) diastasis, and (4) atrial contraction. The IVRT begins upon aortic valve closure (end of T wave on the electrocardiogram [ECG]) and ends upon mitral valve opening. The second phase of diastole is early rapid filling, which occurs when the initial LV diastolic filling pressures decrease below the level of LA pressure. At this time, the mitral valve opens, and blood begins moving from the LA into the LV. The extent of early filling is dependent on heart rate, LV relaxation, and

chamber compliance.12 Increases in either atrial or ventricular pressure may change the timing and volume of blood that moves from the LA into the LV. The third phase, diastasis, occurs after the initial ejection of blood into the LV. Because of near equalization of pressures, little blood moves from the LA into the LV during this period. The last phase of diastole is atrial contraction, which occurs due to atrial electrical stimulus, and the resulting atrial stroke volume is dependent on left atrial function and chamber compliance.12 This stimulus occurs after the activation of atrial systole (P wave on the ECG) and is represented by the final amount of blood moving from the LA into the LV, respectively. Each phase of diastole can be evaluated by a variety of echocardiographic techniques. For example, the first phase of diastole (IVRT) can be measured by continuous- or pulsed-wave spectral Doppler, as the time from the end of aortic flow to the onset of mitral flow. The second phase (early rapid filling) is measured by pulsed-wave Doppler and is represented as the mitral E wave velocity (Figure 2). Diastasis is represented on the mitral inflow spectral Doppler as the time between the E and A waves when the lowpressure gradient (<2 mm Hg normally) between the LA and LV results in lack of blood flow. The fourth phase (atrial contraction) is measured as the mitral A wave velocity. Echocardiographic representation of normal diastolic parameters is visualized in Figure 3, and diastolic function values are reported in Table 1.

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Figure 2. Using the mitral inflow pattern when measuring tissue velocity can aid in accurately measuring tissue Doppler imaging (TDI) velocities. The R-R interval can be separated in two, with the first half systole and the second half diastole. Diastole can be separated further with the first half of diastole displayed as early filling and the second half as late filling. The timing of mitral inflow is similar in timing to the tissue Doppler, whereas mitral inflow E and A wave velocities occur at the same time as tissue Doppler e and a wave velocities. Note in panel B that the TDI a wave velocity was measured incorrectly, after the QRS and into systole of the next beat. This peak waveform is actually the isovolumic contraction time waveform.

Grades of Diastolic Dysfunction

Echocardiographic measures of abnormal diastolic function severity can be described as grades evaluated by the following modalities: (1) pulsed-wave mitral inflow, (2) pulsedwave pulmonary venous inflow, (3) TDI, and (4) inflow propagation by color flow Doppler M-mode (CMM Vp). Mild diastolic dysfunction (grade I) is termed impaired relaxation. Increasing degrees of ventricular impairment and increases in filling pressures lead to intermediate diastolic dysfunction, or pseudonormal (grade II), with possible progression to severe diastolic dysfunction or restrictive reversible (grade III) and restrictive irreversible (grade IV) filling. Of those with diastolic dysfunction in the general population, an estimated 60% have impaired relaxation, 37% have pseudonormal patterns, and 1% have restrictive filling.3 Impaired relaxation (IR), the first stage of diastolic impairment, is the most common filling abnormality and is associated with coronary artery disease and hypertensive heart disease.35 Relaxation abnormalities are associated with an increase in LVEDP. During the rapid filling phase of diastole, the increase in LV filling pressures results in a decrease in the amount of blood moving from the LA to the LV. Because the same amount of blood is needed to maintain cardiac output for each cardiac cycle, the majority

of filling occurs during the atrial contraction phase. This results in a reduced mitral E wave velocity and increased E wave deceleration time with a tall A wave velocity. The pulmonary vein characteristics demonstrate a normal S/D ratio >1, and the atrial reversal velocity and duration may or may not be increased or prolonged. An increase in the velocity and duration is dependent on whether LVEDP is increased, whereas the E/A ratio may be less than 1 because of age rather than increased LVEDP.14 The TDI e velocity is usually reduced (<8 cm/s) because of abnormal compliance and relaxation abnormalities, and the E/e ratio is not increased significantly (<15). The CMM Vp may vary. Figure 4 demonstrates echocardiographic patterns of IR. The next stage of impairment is pseudonormal (PN). Recent studies have indicated that PN is associated with increases in mortality not previously described.15 In addition to an increase in LV pressure, increased LA pressure is present. Because the pressure in the left atrium is higher than in the left ventricle at the beginning of diastole in patients with intermediate diastolic dysfunction, a normal mitral E/A ratio (E/A ratio 12) is seen (Figure 5). The pulmonary vein pattern should demonstrate a taller diastolic D wave, with an S/D ratio <1 consistent with elevated LA pressure (PCWP). Prolongation of the pulmonary vein A wave duration is greater than the mitral A wave duration,

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Figure 3. Echocardiographic methods and measurements for the assessment of diastolic function in a healthy 22-year-old patient. (A) Mitral inflow E wave, E wave deceleration time, and A wave obtained at the leaflet tips (arrow) during apnea. (B) Doppler sample volume (SV) was repositioned toward the annulus (arrow) to improve visualization and demarcation lines of the A wave for measurement of the A wave duration. (C) Color flow Doppler M-mode velocity flow propagation (CMM Vp) slope. Depth was decreased, color Doppler was activated, color scale was increased (shifted upward to 30 cm/s), and a cursor was positioned across the inflow (arrow) of the left ventricle (LV). CMM Vp measurements begin at the onset of the first aliasing velocity in early diastole and extend approximately 4 cm into the LV. (D) Valsalva maneuver on the mitral E wave; E deceleration time and A wave showed a proportional decrease in both E and A wave velocities. (E) Pulmonary vein flow with the SV positioned at least 1.0 cm into the pulmonary vein (arrow) with a decrease in the Doppler filter. The S wave, D wave, Ar velocity, and Ar duration were measured. (F) Tissue Doppler imaging (TDI) with the SV positioned at the septal annulus (arrow). Note that in these examples, the peaks and slopes are clearly defined with minimal spectral broadening or signal contamination.

which is consistent with elevated atrial and ventricular pressures. The tissue Doppler e velocity is decreased because of a decrease in LV compliance and abnormal relaxation, with an E/e ratio >15. CMM Vp should be <50 cm/s. Restrictive filling is the last stage of diastolic dysfunction and can be dichotomized into restrictive reversible and restrictive irreversible. These two stages signify the highest increase in mortality and are represented by significant increases in filling pressures.6 In patients with severe diastolic dysfunction, the majority of LV filling occurs during the rapid filling phase of diastole due to significantly

elevated LA pressure and rapid equalization of pressures. Only a small portion of filling occurs during atrial contraction because of reduced atrial mechanical function. The mitral Doppler characteristics are restrictive in nature, reflecting a tall E wave velocity, shortened E wave deceleration time, and low A wave velocity (E/A ratio greater than 2). Restrictive filling defined by an E wave deceleration time <140 ms is associated with a 64% mortality rate and has been shown to be an independent predictor of death.6,16 The pulmonary vein pattern should demonstrate a tall diastolic D wave with a significant reduction in the S/D ratio,

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Table 1. Staging of Diastolic Function in Patients Older Than Age 50 Years Primary measures Mitral E/A ratio Mitral valve deceleration time, ms Mitral E/A ratio with Valsalva Tissue Doppler e, cm/s Tissue Doppler E/e Pulmonary vein flow Mitral A wave to pulmonary vein A wave duration Left atrial volume index, mL/m2 Secondary measures Color M-mode flow propagation, cm/s Isovolumic relaxation time, ms Normal 11.5 >160 No change >8 <8 Systolic predominance Mitral valve A wave longer <34 >50 60100 Impaired Relaxation <0.8 >220 <0.5 <8 8 Systolic predominance Mitral valve A wave longer <34 >50 >100 Pseudonormal 0.81.5 160200 0.5 <8 915 Diastolic predominance Pulmonary vein A wave 30 ms longer >34 <50 60100 Restrictive

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>2 <160 0.5 <8 >15 Diastolic predominance Pulmonary vein A wave 30 ms longer >34 <50 60

Adapted from Khouri et al.,12 Nagueh et al.,14 and Gilman et al.20

Figure 4. Impaired relaxation in a 66-year-old woman with longstanding hypertension and normal ejection fraction. Mitral E wave = 49 cm/s, E wave deceleration time = 349 ms, A wave = 70 cm/s, and E/A ratio = 0.7. (A) Mitral A wave duration = 137 ms. (B) Tissue Doppler imaging (TDI) e velocity = 6 cm/s, consistent with abnormal relaxation. E/e ratio = 9, normal. (C) Normal pulmonary venous pattern (S wave > D wave). (D) Normal Ar/A duration reflecting normal left atrial pressure.

consistent with elevated LA pressure and significantly reduced atrial mechanical function. Prolongation of the pulmonary vein A wave duration and an increase in the A velocity (>35 cm/s) are consistent with severely elevated LA pressure and LVEDP. Because of the inability of the LV to relax normally, the tissue Doppler e velocity is significantly decreased, and the E/e ratio is increased significantly (E/e > 15). The CMM Vp should be significantly reduced (Figure 6).

Technical Aspects for the Echocardiographic Assessment of Diastolic Function

As mentioned previously, 2D, M-mode, color, and pulsedand continuous-wave Doppler should be used for a comprehensive evaluation of diastolic function. The average time of acquisition of mitral inflow, pulmonary veins, TDI, and CMM has been shown to be an estimated four minutes.17

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Figure 5. Pseudonormal filling in a 54-year-old female with hypertension, recent myocardial infarction, no significant valvular disease, mild pulmonary hypertension, and mildly reduced EF. (A) Mitral inflow represented by a normal appearing pattern and E/A ratio. (B) The sample volume was repositioned toward the annulus for A wave duration measurement. (C) Abnormal flow propagation velocity < 50 cm/s. (D) Valsalva reduced the E wave, E/A ratio, and increased the A wave and E wave deceleration time. (E) Pulmonary venous pattern consistent with diastolic predominance and prolonged A wave duration. (F) TDI e velocity was significantly reduced, with a highly elevated E/e ratio. Findings are consistent with abnormal relaxation and elevated filling pressures.

Some suggest taking measurements during apnea to improve the Doppler signal quality and reduce variation, whereas others have shown no difference in measurements taken at differing respiration times.1719 Overall, integration of multiple parameters is required for accurate evaluation of diastolic function (Table 1).9,10,12,14

Mitral Inflow
Mitral flow velocities are the most common way to evaluate diastolic function. Mitral flow velocities have low variability among readers, and these parameters are among the foundation for routine clinical integration.17 Sampling of the mitral velocities is accomplished by placing the pulsedwave sample volume (SV) at the leaflet tips of the mitral valve when closed (or in between the leaflet tips when open). The sample gate should be between 1 and 2 mm wide.1720 A good-quality Doppler tracing is characterized by a brighter

edge of the waveform with minimal spectral broadening indicating laminar flow. When a suboptimal tracing is obtained, it may be helpful to first add color Doppler over the mitral valve to identify the direction of flow into the left ventricle for more accurate placement of the SV and tracings.19 In addition, in patients with dilated cardiomyopathy where the annulus has repositioned (remodeled) toward the lateral wall or in patients with eccentric aortic insufficiency when the regurgitation contaminates the mitral Doppler signal, it may be necessary to move the SV slightly lateral to detect optimal mitral inflow (color flow Doppler will again aid in proper placement). Doppler sweep speed settings will vary depending on the absence or presence of disease. In patients with pericardial disease, a sweep speed of 25 to 50 mm/s is recommended to evaluate the changes in the mitral E wave velocity during respiration. If variation is not present, a Doppler sweep speed of 100 mm/s may be used.14 Patients with stenotic abnormalities of the mitral

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Figure 6. Restrictive filling in a 49-year-old man with coronary artery disease and severely reduced ejection fraction. (A) Mitral inflow represented by a tall E wave, rapid deceleration time, and an E/A ratio greater than 2. (B) Measurement of mitral A wave duration with the sample volume at the annulus. (C) Abnormal flow propagation velocity less than 50 cm/s. (D) Valsalva reduces the E wave (0.5) and unmasks the underlying relaxation abnormality and elevated filling pressures. (E) Pulmonary venous pattern with diastolic predominance indicating increased left atrial pressure. (F) TDI e velocity less than 8 cm/s and an E/e greater than 15, indicating increased filling pressures.

valve, including mitral stenosis, severe mitral annular calcification, and prosthetic valves, should have a mitral stenosis evaluation to include mitral valve area, pressure half-time measurement, and mean gradient reported instead of diastolic function grading. Changes in loading condition (i.e., increased afterload due to aortic insufficiency or increase preload in mitral regurgitation) can change the appearance of the mitral inflow patterns regardless of filling pressures. In addition, cardiac arrhythmias will change the mitral inflow patterns: tachycardia will shorten the E wave deceleration time and fuse the E and A waves, atrial fibrillation will result in no A wave because of the lack of atrial systole, and atrioventricular block can change the relationship of the E and A waves. In patients with tachycardia, the E wave deceleration time and A wave duration may be difficult to measure, but E/A ratio and IVRT may still be measureable.14 The mitral A wave will

be higher in velocity because of the shortened diastolic filling time.21 Because of these limitations to sampling mitral inflow and because mitral inflow velocities in patients with PN appear normal, it is necessary to perform a complete diastolic evaluation in all patients. Mitral valve A wave duration can be compared with the pulmonary vein A wave duration for estimation of filling pressures.22 The mitral A wave duration should be measured after the SV is repositioned toward the mitral valve annulus and the filters are decreased to improve the demarcation of the onset and ending of the A wave velocity.22,23 Normally, the mitral A wave duration is longer than pulmonary vein A wave duration. A pulmonary vein A wave duration that exceeds the mitral A wave duration greater than 30 ms is consistent with increased LVEDP regardless of other concomitant abnormalities.14,22

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Journal of Diagnostic Medical Sonography 27(2) e velocities are 13.3 + 3.3 cm/s, and normal septal e velocities are 11.5 + 2.6 cm/s.27 Tissue Doppler velocities less than 8 cm/s aid in the recognition of diastolic dysfunction and relaxation abnormalities associated with prolonged .911,14 Annular velocities less than 5 cm/s are associated with restrictive filling.14

Valsalva Maneuver
In patients with evidence of cardiac disease and a normalappearing mitral inflow defined by an E/A ratio between 0.8 and 2.0, the Valsalva maneuver can be performed to reveal a diastolic filling abnormality. LV preload is reduced, and changes in mitral inflow are observed to distinguish normal from PN filling.14 When PN or restrictive reversible filling is present, the E/A ratio will decrease with a reversal in the E/A pattern displayed as a smaller E wave and taller A wave. Studies indicate that 83% of patients can perform the Valsalva maneuver correctly.16 Optimal performance of the Valsalva maneuver would be for the patient to breathe out against a closed nose and mouth for 15 seconds while contracting the abdominal muscles.20 A decrease in the E/A ratio greater than or equal to 0.5 indicates increased filling pressures associated with a PN or restrictive reversible filling pattern. However, if no change is seen, this does not necessarily mean that filling pressures are not elevated.24

E/e Ratio for Estimation of Filling Pressures

An additional tool in the characterization of the stages of dysfunction and estimation of filling pressures divides the mitral E wave velocity with the tissue Doppler e velocity to calculate the E/e ratio. The E/e ratio has shown to correlate with several methods used for estimation of filling pressures, including mean LV pressure, PCWP, and LV diastolic pressure.911,26,3032 The e velocity decreases and E/e ratio increases with normal aging.14,18,26,30,31 In one study, the E/e ratio obtained from the septal annulus showed the best correlation with mean LV diastolic pressure compared to the lateral E/e ratio,10 whereas the E/e ratio obtained from the lateral annulus correlated best with PCWP, and an E/e >10 detected a mean PCWP greater than 15 mm Hg.9 An E/e ratio less than 8 indicates normal LV mean diastolic pressure, whereas an E/e ratio of greater than 15 indicates increased LV pressure with reasonable accuracy.10 It is important to recognize in patients with an E/e between 8 and 15 that additional measures of diastolic function (i.e., pulmonary vein, CMM, Valsalva maneuver, LA volumes) can be used to accurately grade diastolic function.10,14 An E/e ratio obtained from the lateral annulus of a value greater than 15 indicates increased PCWP, further isolating the degree of diastolic dysfunction to either pseudonormal or restrictive filling.9 A septal or lateral E/e ratio 11 correlates well with LV filling pressures and a PCWP >15 mm Hg even in the presence atrial fibrillation.32,33 In addition, combining the E/e ratio and estimation of ejection fraction can better identify high-risk patients who would be readmitted or associated with cardiac death.34 In contrast to mitral inflow, TDI is relatively load independent and useful in patients with tachycardia, atrial fibrillation, and hypertrophic obstructive cardiomyopathy (Figure 8). TDI is less useful in patients with ischemia in basal segments, previous cardiac surgery with paradoxical septal motion, and mitral valve repair and replacement.14 Despite other variables showing differences in young athletes and controls, tissue Doppler is consistent across these groups for displaying normal values.35 TDI may not be reliable in the following patients: normal patients with no cardiac abnormalities and those with mitral valvular abnormalities such as prosthetic mitral valve, mitral valve ring, annular calcification,36 severe mitral regurgitation, mitral stenosis, and constrictive pericarditis.14

Tissue Doppler Imaging

TDI has become an integral, easy, and accurate method to assess diastolic function by evaluating ventricular motion in diastole.911,17,18,2528 Tissue Doppler evaluates lowvelocity (<25 cm/s), high-amplitude movement of the mitral valve annulus.18,2528 During systole, the annulus moves toward the transducer, whereas the annulus moves away from the transducer in early and late diastole. This motion results in an upward and downward deflection with velocities being displayed above and below the baseline throughout the cardiac cycle. The early diastolic (e or em) velocity correlates with the timing of early filling of the left ventricle demonstrated by mitral E wave velocity. Not only does TDI aid in the assessment of filling pressures, but it is easily obtained and reproducible.18,25 Using the pulsed-wave tissue Doppler sampling equipment setting, the TDI velocity is obtained using a Doppler sweep speed of 100 mm/s with velocity scale optimized to be set from 20 to +30 cm/s.14 A 3- to 5-mm pulsed-wave SV is placed in the medial and/or lateral annulus at the mitral valve insertion points.14,17,18,20,27 A good-quality tracing is characterized by a brighter edge of the waveform with clear borders of the waveform delineated (Figure 7). When suboptimal tracings are detected, it may be helpful to first add color Doppler over the mitral valve annulus to evaluate the area of annular motion and to place the cursor at less than a 20-degree angle with the longitudinal motion of the left ventricle.14,18 In patients with normal LV function, a single site may be used, but in patients with regional wall motion abnormalities, the average of medial e and lateral e velocities should be reported.14,29 Normal lateral

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Figure 7. Optimization of tissue Doppler velocities is important in the accurate assessment of peak velocities. Poorly defined spectral tracing with decrease gain (A) can be optimized (B) by placing the sample volume in the annulus with the cursor parallel to the left ventricular longitudinal motion.

LA Volume
Measuring left atrial volumes using area length is the preferred method for estimating LA size.14,37 Increases in left atrial size correlate with increases in left atrial pressure. Measuring the left atrium in both the apical four- and twochamber views will provide the most accurate estimation of LA size and volume. When tracing LA volume, the atrial appendage, the confluence of the pulmonary veins, and the tenting area of the mitral valve should be excluded to avoid overestimation.20,14 An LA volume index >34 mL/m2 predicts death, heart failure, atrial fibrillation, and stroke (Figure 9).38 In addition, the E/e ratio combined with

LA volume estimation provides the best correlation with invasively measured cardiac pressures. Therefore, the most accurate evaluation of diastolic function requires utilization of multiple parameters. The LA may be dilated in mitral stenosis, atrial fibrillation, significant mitral regurgitation, and other cardiac abnormalities.38 Recognition of concurrent pathologic processes such as atrial septal defect, atrial fibrillation, and high-output states causing LA enlargement will help avoid misdiagnosis of diastolic dysfunction.12 Therefore, it is important to consider all etiologies of LA enlargement when diagnosing diastolic dysfunction. Using only two measures for the assessment

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Figure 8. Example of two patients with atrial fibrillation with and without suspected elevated filling pressures. The left atrial (LA) size and volumes are similar (panel A volumes = 101 mL; panel B volumes = 121 mL) and are increased. (A) The averaged mitral E wave velocity = 44 cm/s, which is low, and the E wave deceleration time = 202 ms. The averaged pulmonary vein D wave velocity = 42 cm/s; the TDI e velocity = 5 cm/s with an estimated E/e ratio of 10. The estimated pulmonary artery systolic pressure (PASP) was normal. In this example, five of five variables were obtained, all of which complemented each other and demonstrated abnormal relaxation (low e velocity), but no obvious evidence of elevated filling pressures (low mitral E wave, pulmonary D wave, e velocity, E/e ratio = 10, normal PASP). (B) The averaged mitral E wave velocity = 109 cm/s, E wave deceleration time = 204 ms. The averaged pulmonary vein D wave velocity = 90 cm/s; the TDI e velocity = 5 cm/s with an estimated E/e ratio of 20. The PASP was mildly elevated. In this example, five of five variables were obtained, of which four complemented each other and demonstrated abnormal relaxation (low e velocity) and evidence of elevated filling pressures (high mitral E wave, pulmonary D wave, low e velocity, E/e ratio = 20, elevated PASP). Note that increased LA volume does not necessarily indicate elevated filling pressures.

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Figure 9. Measurement of the left atrial (LA) size and volume can be used to aid in the proper classification of diastolic function. Image A demonstrates normal LA size, whereas B demonstrates increase LA size associated with increased LA pressure.

of diastolic function rather than multiple ones can result in up to 25% of diastolic function misclassification.39

pressure.14 Atrial reversal velocities greater than 35 cm/s indicate increased LA pressure and are associated with PN and restrictive filling.22

Pulmonary Venous Flow

Sampling pulmonary vein flow velocities can aid in characterizing elevation in filling pressures.14,19,2023 The range of success rates for acquisition of pulmonary vein flow parameters is 49% to 84%.14,17 Other investigators have reported the success rate for obtaining pulmonary venous systolic and diastolic flow velocities to be as high as 95% with proper sonographer training and education.19 Difficulty in pulmonary vein Doppler recording is primarily associated with limitations of the pulsed-wave sample depth, enlarged cardiac structure, or artifact.19 A pulsed-wave SV is routinely placed 1 cm into the right upper pulmonary vein in the apical four-chamber view to measure systolic and diastolic flow patterns. A sweep speed of 50 to 100 mm/s is recommended.14 Pulmonary veins should be sampled with a 2- to 3-mm SV and the Doppler velocity filter set to 200 to 400 Hz.17 The SV size may be increased 4 to 5 mm with reasonable accuracy.19 Normal pulmonary venous flow in the adult (>50 years of age) population has a higher systolic flow and lower diastolic flow. Patients younger than 40 years of age may have a diastolic velocity higher than the systolic velocity because of normal diastolic suction and excellent ventricular compliance.40 When two systolic velocities are present (S1 due to early atrial relaxation), the second systolic velocity (S2) should be measured as the peak systolic velocity to compare with the diastolic velocity ratio.14,40 Increased LA pressure results in a lower systolic flow pattern with higher diastolic predominance. Diastolic predominance in pulmonary vein flow has been shown to be a predictor of increased heart failure readmissions and cardiovascular death.41 In young patients or in patients with atrial fibrillation, mitral valve disease, and hypertrophic cardiomyopathy, the diastolic predominance in the pulmonary vein pattern may not reliably reflect an increase in LA

Isovolumic Relaxation Time

The IVRT interval describes the time from aortic valve closure to mitral valve opening. It can be measured with either pulsed- or continuous-wave spectral Doppler, but continuous-wave Doppler usually provides a better display of valve closure depicted as brighter lines (artifact) crossing the Doppler zero baseline. This measurement is performed by placing the cursor between the mitral and aortic valves in the apical five-chamber view. IVRT is normally between 60 and 100 ms.14 The IVRT is longer in patients with impaired relaxation and decreased in patients with restrictive filling. The IVRT is also prolonged in patients with coronary artery disease, advanced age, and myocardial hypertrophy because of relaxation abnormalities. Conversely, the time is shortened in patients with tachycardia, as well as those on positive inotropes and catecholamine stimulation.

Color M-Mode Velocity Flow Propagation

CMM Vp represents the velocity of blood flow from the mitral leaflets into the LV cavity toward the apex during early diastole. The Vp is influenced by LV relaxation, LV systolic performance, and the end-systolic volume.42 In patients with reduced systolic function, the ratio of the mitral E wave velocity and the Vp (i.e., E/Vp) has been validated as a reliable method for the estimation of PCWP.42 CMM Vp can be obtained successfully in up to 100% of patients.17 In the apical four-chamber view, after placing a color Doppler sector over the left ventricular cavity, a cursor is placed through the ventricular apex and mitral valve leaflets with M-mode imaging activated. In diastole, the flow through the ventricular cavity is normally directed in a vertical pattern. With increasing diastolic dysfunction,

76 this flow from the annulus to the ventricular apex becomes more directed toward the lateral wall. The Vp is defined as the slope of the first aliasing velocity, which appears at the interface between the red and blue color velocities.14,17,42 Measurement of the Vp slope is made at the onset of mitral valve opening and is extrapolated an estimated 4 cm toward the apex.42 The color M-mode velocity scale baseline should be shifted upward to decrease the aliasing velocities directed toward the transducer for more accurate measurement of the Vp slope.42 A Vp greater than 50 cm/s is considered normal.14,43 Color M-mode flow propagation and its ratio has been noted to provide similar information as other markers such as E velocity and E/E ratio, but when other markers are inconsistent, the use of flow propagation can be helpful for final diagnosis.17,42,43

Journal of Diagnostic Medical Sonography 27(2) Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The author(s) received no financial support for the research and/ or authorship of this article.

References
1. Maestre A, Gil V, Gallego J, Aznar J, Mora A, MartnHidalgo A: Diagnostic accuracy of clinical criteria for identifying systolic and diastolic heart failure: cross-sectional study. J Eval Clin Pract 2009;15:5561. 2. Kuznetsova T, Herbots L, Lpez B, et al: Prevalence of left ventricular diastolic dysfunction in a general population. Circ Heart Fail 2009;2:105112. 3. Samdarshi TE, Taylor HA, Edwards DQ, et al: Distribution and determinants of Doppler-derived diastolic flow indices in African Americans: the Jackson Heart Study (JHS). Am Heart J 2009;158:209216. 4. Chinali M, Joffe SW, Aurigemma GP, Makam R, Meyer TE, Goldberg RJ: Risk factors and comorbidities in a communitywide sample of patients hospitalized with acute systolic or diastolic heart failure: the Worcester Heart Failure Study. Coron Artery Dis 2010;21:137143. 5. Garcia MJ: Diastolic dysfunction and heart failure: causes and treatment options. Cleve Clin J Med 2000;67:727729, 733738. 6. Mandinov L, Eberli FR, Seiler C, Hess OM: Diastolic heart failure. Cardiovasc Res 2000;45:813825. 7. Achong N, Wahi S, Marwick TH: Evolution and outcome of diastolic dysfunction. Heart 2009;95:813818. 8. Chen C, Rodriguez L, Lethor JP, et al: Continuous wave Doppler echocardiography for the noninvasive assessment of left ventricular dP/dt and relaxation time constant from mitral regurgitant spectra in patients. J Am Coll Cardiol 1994;23:970976. 9. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quiones MA: Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:15271533. 10. Ommen SR, Nishimura RA, Appleton CP, et al: 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;102:17881794. 11. Sohn D, Chai I, Lee D, et al: Assessment of mitral annulus velocity by Doppler tissue imaging in evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30: 474480. 12. Khouri SJ, Maly GT, Suh DD, Walsh TE: A practical approach to the echocardiographic evaluation of diastolic function. J Am Soc Echocardiogr 2004;17:290297.

Additional Tools for the Assessment of Diastolic Function

Integration of multiple parameters as well as understanding the patients clinical status at the time of the diastolic evaluation provides the optimal diagnosis. In patients without right heart disease such as pulmonary stenosis or primary pulmonary hypertension, the right ventricular systolic pressure correlates with increased left ventricular end-diastolic pressure. The estimated pulmonary pressure is derived from the tricuspid regurgitation continuous-wave Doppler peak pressure and added right atrial pressure.14,44 Some studies indicate that in the presence of normal cardiac output and absence of pulmonary disease, an increase in pulmonary artery pressure may be a more accurate method to evaluate changes in left ventricular filling over the E/e ratio.14,44,45 A combination of tissue Doppler velocities and strain imaging has been proposed to be a more accurate method to evaluate LV filling pressures.46 Evaluation of LA strain has been proposed to more accurately identify patients with heart failure than other diastolic function parameters such as LA volume.47 The evaluation of segmental strain has been proposed to be a better marker for early detection of dysfunction, but this has not yet been routinely accepted or implemented.4648

Conclusion
Echocardiography is a useful imaging modality to detect abnormal relaxation and elevated filling pressures in patients with suspected cardiac disease. This article aims to outline a comprehensive evaluation for sonographers. Education, practice, and current equipment will aid the sonographer in obtaining high-quality and accurate echocardiographic recordings. Integration of multiple echocardiographic parameters with the clinical scenario may improve accuracy and detection in diagnosing diastolic dysfunction.

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13. Rost C, Flachskampf FA: Diagnosing left ventricular diastolic dysfunction by echocardiography: Reverend Bayes lends a hand. J Am Soc Echocardiogr 2010;23:162163. 14. Nagueh SF, Appleton CP, Gillebert TC, et al: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009;10:165193. 15. Somaratne JB, Whalley GA, Poppe KK, Gamble GD, Doughty RN: Pseudonormal mitral filling is associated with similarly poor prognosis as restrictive filling in patients with heart failure and coronary heart disease: a systematic review and meta-analysis of prospective studies. J Am Soc Echocardiogr 2009;22:494498. 16. Rauns J, Mller JE, Kjaergaard J, et al: EchoCardiography and Heart Outcome Study (ECHOS) Investigators: Prognostic importance of a restrictive mitral filling pattern in patients with symptomatic congestive heart failure and atrial fibrillation. Am Heart J 2009;158:983988. 17. Bess RL, Khan S, Rosman HS, Cohen GI, Allebban Z, Gardin JM: Technical aspects of diastology: why mitral inflow and tissue Doppler imaging are the preferred para meters? Echocardiography 2006;23:332339. 18. Hill JC, Palma RA: Doppler tissue imaging for the assessment of left ventricular diastolic function: a systematic approach for the sonographer. J Am Soc Echocardiogr 2005; 18:8088. 19. Jensen JL, Williams FE, Beilby BJ, et al: Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr 1997;10:6066. 20. Gilman G, Nelson TA, Hansen WH, Khandheria BK, Ommen SR: Diastolic function: a sonographers approach to the essential echocardiographic measurements of left ventricular diastolic function. J Am Soc Echocardiogr 2007;20: 199209. 21. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ: The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246270. 22. Rossvoll O, Hatle LK: Pulmonary venous flow velocities recorded by transthoracic Doppler: relations to left ventricular diastolic pressures. J Am Coll Cardiol 1993;21:687696. 23. 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;10:271292. 24. 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;30:459467. 25. Isaaz K, Munoz del Romeral L, Lee E, Schiller NB: Quantification of the motion of the cardiac base in normal subjects by Doppler echocardiography. J Am Soc Echocardiogr 1993;6:166176.

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26. Alam M, Wardell J, Andersson E, Samad BA, Nordlander R: Characteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects. J Am Soc Echocardiogr 1999;12:618628. 27. Waggoner AD, Bierig SM: Tissue Doppler imaging: a useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function. J Am Soc Echocardiogr 2001;14:11431152. 28. Waggoner AD: Alternative echocardiographic methods to assess left ventricular diastolic function. J Diagn Med Sonography 2002;18:218230. 29. 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;91:780784. 30. Tighe DA, Vinch CS, Hill JC, Meyer TE, Goldberg RJ, Aurigemma GP: Influence of age on assessment of diastolic function by Doppler tissue imaging. Am J Cardiol 2003;91: 254257. 31. De Sutter J, De Backer J, Van de Veire N, Velghe A, De Buyzere M, Gillebert TC: Effects of age, gender, and left ventricular mass on septal mitral annulus velocity (E) and the ratio of mitral early peak velocity to E (E/E). Am J Cardiol 2005;95:10201030. 32. Sohn DW, Song JM, Zo JH, et al: Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation. J Am Soc Echocardiogr 1999;12:927931. 33. Kusunose K, Yamada H, Nishio S, et al: Clinical utility of single-beat E/e obtained by simultaneous recording of flow and tissue Doppler velocities in atrial fibrillation with preserved systolic function. JACC Cardiovasc Imaging 2009; 2:11471156. 34. Hirata K, Hyodo E, Hozumi T, et al: Usefulness of a combination of systolic function by left ventricular ejection fraction and diastolic function by E/E to predict prognosis in patients with heart failure. Am J Cardiol 2009;103:12751279. 35. Teske AJ, Prakken NH, De Boeck BW, Velthuis BK, Doevendans PA, Cramer MJ: Effect of long term and intensive endurance training in athletes on the age related decline in left and right ventricular diastolic function as assessed by Doppler echocardiography. Am J Cardiol 2009;104: 11451151. 36. Soeki T, Fukuda N, Shinohara H, et al: Mitral inflow and mitral annular motion velocities in patients with mitral annular calcification: evaluation by pulsed Doppler echocardiography and pulsed Doppler tissue imaging. Eur J Echocardiogr 2002;3:128134. 37. Lang RM, Bierig M, Devereux RB, et al: Chamber Quantification Writing Group; American Society of Echocardiographys Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiographys Guidelines and Standards Committee

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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;18:14401463. 38. Abhayaratna WP, Seward JB, Appleton CP, et al: Left atrial size: physiologic determinants and clinical applications. J Am Coll Cardiol 2006;47:23572363. 39. Dokainish H, Nguyen JS, Sengupta R, et al: Do additional echocardiographic variables increase the accuracy of E/e for predicting left ventricular filling pressure in normal ejection fraction? An echocardiographic and invasive hemodynamic study. J Am Soc Echocardiogr 2010;23:156161. 40. Klein AL, Tajik AJ: Doppler assessment of pulmonary venous flow in healthy subjects and in patients with heart disease. J Am Soc Echocardiogr 1991;4:379392. 41. Ren X, Na B, Ristow B, Whooley MA, Schiller NB: Usefulness of diastolic dominant pulmonary vein flow to predict hospitalization for heart failure and mortality in ambulatory patients with coronary heart disease (from the Heart and Soul Study). Am J Cardiol 2009;103:482485. 42. Garcia MJ, Ares MA, Asher C, Rodrigues 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: 448454.

Journal of Diagnostic Medical Sonography 27(2)

43. Yotti R, Bermejo J, Antoranz JC, et al: A noninvasive method for assessing impaired diastolic suction in patients with dilated cardiomyopathy. Circulation 2005;112:29212929. 44. Bouchard JL, Aurigemma GP, Hill JC, Ennis CA, Tighe DA: Usefulness of the pulmonary arterial systolic pressure to predict pulmonary arterial wedge pressure in patients with normal left ventricular systolic function. Am J Cardiol 2008; 101:16731676. 45. Weeks SG, Shapiro M, Foster E, Michaels AD: Echocardiographic predictors of change in left ventricular diastolic pressure in heart failure patients receiving nesiritide. Echocardiography 2008;25:849855. 46. Wang J, Khoury DS, Thohan V, Torre-Amione G, Nagueh SF: Global diastolic strain rate for the assessment of left ventricular relaxation and filling pressures. Circulation 2007;115:13761383. 47. Kurt M, Wang J, Torre-Amione G, Nagueh SF: Left atrial function in diastolic heart failure. Circ Cardiovasc Imaging 2009;2:1015. 48. Pavlopoulos H, Nihoyannopoulos P: Regional left ventricular distribution of abnormal segmental relaxation evaluated by strain echocardiography and the incremental value over annular diastolic velocities in hypertensive patients with normal global diastolic function. Eur J Echocardiogr 2009; 10:654662.