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European Journal of Echocardiography 2004 5(3):196-204; doi:10.1016/j.euje.2003.09.004
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Copyright © 2003, The European Society of Cardiology

Comparison of early diastolic mitral annular velocity and flow propagation velocity in detection of mild to moderate left ventricular diastolic dysfunction

Tomas Palecek*, Ales Linhart, Jan Bultas and Michael Aschermann

2nd Department of Internal Medicine, General University Hospital, 1st School of Medicine, Charles University, U nemocnice 2, 128 08 Prague 2, Czech Republic

Received 24 February 2003; received in revised form 16 September 2003; accepted after revision 17 September 2003.

tpalec{at}hotmail.com

* Corresponding author. Tel.: +420-224-962-634; fax: +420-224-912-154.


   Abstract
Top
 Abstract
1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Study limitations
 6 Conclusions
 References
 
Background: Pulsed wave tissue Doppler echocardiography (PW-TDE) and color M-mode are new Doppler methods for left ventricular (LV) diastolic function assessment. To date, few studies have compared the data obtained by these methods in the same series of patients and compared them to the current clinical reference method of detecting LV diastolic function.

Aims: To determine the utility of PW-TDE and color M-mode parameters in the assessment of LV diastolic function in the typical patient population encountered in daily clinical practice and to compare their discriminating power.

Methods: Early diastolic septal mitral annular velocity (Em) determined by PW-TDE and color M-mode flow propagation velocity (Vp) were measured in 86 male patients and compared to LV filling patterns obtained using standard Doppler indices. Values of Em<0.08 m s–1 and Vp<0.5 m s–1 were considered as markers of abnormal LV diastolic function.

Results: A value of Em<0.08 m s–1 distinguished mild to moderate LV diastolic dysfunction with higher sensitivity and specificity than Vp<0.5 m s–1 (96% and 87% vs. 73% and 84%, respectively). A comparison of receiver operating characteristic curves showed a significant difference for areas under the curve in favor of Em (p<0.01). In a stepwise multiple logistic regression analysis, a pseudonormal filling pattern and an EF > 60% were identified as significant predictors of Vp false negative results (p<0.05).

Conclusions: Em appears to be superior to Vp in the detection of mild to moderate LV diastolic dysfunction. Vp failed to detect abnormal LV diastolic function in particular in patients with preserved LV systolic function and a pseudonormal filling pattern type.

Keywords: diastolic function; early diastolic mitral annular velocity; flow propagation velocity; echocardiography


   1 Introduction
Top
 Abstract
 1 Introduction
2 Methods
 3 Results
 4 Discussion
 5 Study limitations
 6 Conclusions
 References
 
Doppler echocardiography is the most commonly used diagnostic modality for assessing left ventricular (LV) diastolic function. Several indices derived from transmitral flow pulsed Doppler recordings have been used to characterize various patterns of LV filling. These include the measurement of the isovolumic relaxation time (IVRT), peak early (E) and atrial (A) filling velocities, the early-to-late filling (E/A) ratio, and the E wave deceleration time (DT).1 In patients, the interpretation of these indices can be difficult as they vary in response to either alterations in LV relaxation or left atrial (LA) pressure.2 A common example of this limitation is the inability to discriminate the normal Doppler filling pattern, seen in the presence of normal LV relaxation and normal LA pressure, from the almost identical "pseudonormal" filling pattern, caused by elevated LV filling pressures in the presence of impaired LV relaxation, indicating moderate LV diastolic dysfunction.3 The difference in the pulmonary venous and mitral A waves duration (Ardur–Adur) has been shown to be useful for predicting elevated LV filling pressures and has contributed to the understanding of LV diastolic dysfunction.4 However, accurate measurements of atrial flow reversal may be difficult and are not always possible, despite a recent report suggesting that they can be obtained in up to 90% of unselected patients.5

Early diastolic mitral annular velocity (Em) as determined by pulsed wave tissue Doppler echocardiography (PW-TDE) and the flow propagation velocity (Vp) of early LV filling measured by color M-mode are new Doppler indices of LV relaxation which have been suggested to be less dependent on preload.6,7 Thus these indices should allow to differentiate subjects with normal LV diastolic function (normal LV relaxation) from patients with LV diastolic dysfunction (impaired LV relaxation per se or more advanced dysfunction with decreased LV compliance and elevated LV filling pressures).8 To date, only few studies have compared the utility of these new Doppler methods in the assessment of LV diastolic function in the same population. Nagueh et al.9 have reported that LV filling pressures in patients with hypertrophic cardiomyopathy can be estimated with reasonable accuracy by measuring E/Vp or E/Em ratios. In the study of Rajagopalan et al.10 Em tended to have greater sensitivity and specificity than Vp in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. A close relationship between Em and Vp in patients after myocardial infarction has been recently reported by Møller et al.11 However, these studies were focused only on subjects with specific heart diseases. Therefore, the purpose of our study was to determine the utility of Em and Vp in the assessment of LV diastolic function in the typical patient population encountered in daily clinical practice and to compare the discriminating power of these indices. In the study population we did not include patients with LV restrictive filling pattern type, representing severe form of LV diastolic dysfunction, as—according to our opinion—recognition of this type of LV filling usually does not represent any major problem.


   2 Methods
Top
 Abstract
 1 Introduction
 2 Methods
3 Results
 4 Discussion
 5 Study limitations
 6 Conclusions
 References
 
2.1 Study population
The study population consisted of 86 non-consecutive male patients referred to our laboratory for echocardiographic evaluation. All were in normal sinus rhythm without ECG evidence of bundle branch block. In all, the LV filling pattern was clearly defined by using standard transmitral and pulmonary venous Doppler flow indices. We used these measurements as the clinical reference method.

A history of arterial hypertension (AHY) was present in 24 subjects. Coronary artery disease (CAD) was present in 24 patients. Hypertrophic cardiomyopathy (HCM), defined as a presence of unexplained LV hypertrophy or asymmetric septal hypertrophy, was present in 16 patients. There were two patients with a history of idiopathic dilated cardiomyopathy (DCM). The remaining 20 subjects were examined for other clinical reasons such as palpitations, preoperative evaluation for non-cardiac surgery etc. All patients were hemodynamically stable, without significant mitral or aortic valve pathology and with normal kinetics of the basal portion of interventricular septum. The consensus opinion of two experts was used to classify patients into each of the different types of diastolic function. This decision was based on the published criteria accepted by the Canadian Consensus on Diastolic Dysfunction.12 Group N consisted of 38 men with a normal LV filling pattern, i.e. subjects with normal LV diastolic function. Group A included 48 patients with mild or moderate LV diastolic dysfunction (31 subjects with impaired relaxation and 17 patients with a pseudonormal filling pattern).

2.2 Echocardiography
All patients were examined at rest lying in the left lateral decubitus position. The measurements were made using a Toshiba PowerVision 6000 (Toshiba Co, Tokyo, Japan) ultrasound machine with a broadband 2.0–4.8 MHz transducer. The machine was equipped with PW-TDE and second harmonic capabilities. Heart rate was measured at the time of echocardiography from the simultaneous ECG recording.

2.2.1 M-mode, 2-D and Doppler echocardiography
M-mode echocardiographic measurements were performed according to the recommendations of the American Society of Echocardiography.13 LV mass was calculated by the method described by Devereux et al.14 and then divided by body surface area to obtain LV mass index (LVMI).15 LVMI > 125 g m–2 was used as the limit for LV hypertrophy.16 Relative wall thickness (RWT) was calculated as 2 x PW/LVEDD. Asymmetric septal hypertrophy was defined as LV hypertrophy with IVS > 12 mm and IVS to PW thickness ratio ≥ 1.5. LV end-diastolic (LVEDV) and LV end-systolic (LVESV) volumes and LV ejection fraction (LVEF) were measured using the modified Simpson's method.17

Mitral flow velocities were recorded from an apical four-chamber view by placing the pulsed wave Doppler sample volume between the tips of the mitral leaflets. The following parameters were derived: peak early (E) and atrial (A) flow velocity, E/A ratio, A wave duration (Adur) and deceleration time (DT) of the E wave.18

Pulmonary venous flow velocities were obtained by placing the pulsed wave Doppler sample volume within the orifice of the right pulmonary vein with flow visualized with the guidance of color Doppler imaging. The pulmonary venous reversal A wave duration (Ardur) was measured and the difference between the pulmonary venous and mitral A waves duration (Ardur–Adur) was then calculated.18

2.2.2 PW-TDE
By placing the PW-TDE sample volume at the septal mitral annulus using an apical four-chamber view and by aligning long axis motion of the mitral annulus along the direction of the insonating ultrasound beam, recordings of early diastolic septal annular velocity (Em) were obtained. To obtain optimal recordings, the filter settings and gains were adjusted to minimize noise and to eliminate signals produced by the transmitral flow.19 A value of Em<0.08 m s–1 was considered to detect abnormal LV diastolic function (Fig. 1).20


Figure 1
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  		Figure 1 Representative examples of PW-TDE of the septal mitral annulus in a subject with normal LV diastolic function (Em≥0.08 m s–1) (left) and in a patient with abnormal LV diastolic function (Em<0.08 m s–1) (right). Em, early diastolic mitral annular velocity.

 
2.2.3 Color M-mode
From the same apical four-chamber view, the color Doppler sector map of the mitral inflow was adjusted to obtain the longest column of color flow from the mitral annulus to apex. An M-mode cursor was placed through the center of this flow, avoiding boundary regions. The color M-mode flow propagation velocity (Vp) was measured as the slope of the first aliasing velocity during early filling, from the mitral valve plane to 4 cm distally into the LV cavity.7 A value of Vp<0.5 m s–1 was considered to detect abnormal LV diastolic function (Fig. 2). We chose this average value between 0.45 m s–1 and 0.55 m s–1, as these represented the age-dependent cut-off values previously suggested by Garcia et al.20 Doppler velocity curves were recorded during end-expiratory apnea, with a sweep speed of 50 mm s–1. All measurements were based on the average of three consecutive cardiac cycles.


Figure 2
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  		Figure 2 Representative examples of color M-mode recordings with the method of measuring Vp as the slope of the first aliasing velocity during early filling (yellow or white line). The subject with normal LV diastolic function (Vp≥0.5 m s–1) (left) and the patient with abnormal LV diastolic function (Vp<0.5 m s–1) (right). Vp, flow propagation velocity.

 
2.3 Statistical analysis
Data are expressed as mean ± SD or as a percentage of subjects. Differences between groups were compared with the unpaired Student's t test. Sensitivity, specificity, positive and negative predictive values were calculated by a standard formula. The receiver operating characteristic (ROC) curves method was used to determine the summary measure of relative accuracy for Em and Vp as a function of specificity and sensitivity. Stepwise multiple logistic regression analysis was performed to determine significant predictors of Vp false negativity in the detection of LV diastolic dysfunction. A value of p≤0.05 was considered statistically significant. Statistical analysis was performed with commercially available JMP 3.2.2. statistical software (SAS Institute Inc).


   3 Results
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
4 Discussion
 5 Study limitations
 6 Conclusions
 References
 
3.1 Clinical characteristics
The clinical characteristics of the two study groups are listed in Table 1. As expected, the age of the subjects in group N was lower than in group A (p<0.001). There were no significant differences concerning heart rate between the study groups. Body surface area was greater in group A (p<0.05). The prevalence of AHY was similar in both study groups. However, CAD, HCM and DCM were more frequently present in patients with LV diastolic dysfunction.


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  		Table 1 Clinical characteristics of the study groups

 
3.2 M-mode and 2-D echocardiographic parameters
The M-mode and 2-D echocardiographic parameters are listed in Table 2. LA diameter was significantly larger in patients with diastolic dysfunction (p<0.05). Although there was a trend to higher LVEDD in group A, the difference did not reach the statistical significance. Nevertheless, LVEDV, LVESD, and LVESV were significantly greater and LVEF lower in patients with abnormal LV diastolic function (p<0.05). In addition, LVMI (p<0.01) and RWT (p<0.05) were greater in group A.


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  		Table 2 Basic echocardiographic parameters

 
There were no significant differences between subjects with impaired relaxation and pseudonormal filling pattern excepting LA diameter, which was significantly larger in patients with pseudonormalization (47±1 mm vs. 44±1 mm; p<0.001).

3.3 The comparison of Em and Vp
The comparison of sensitivity, specificity and positive and negative predictive values for Em<0.08 m s–1 and Vp<0.5 m s–1 for detecting mild to moderate LV diastolic dysfunction is shown in Fig. 3.


Figure 3
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  		Figure 3 Sensitivity, specificity, positive and negative predictive values for Em<0.08 m s–1 and Vp<0.5 m s–1 for the detection of mild to moderate LV diastolic dysfunction. Em, early diastolic mitral annular velocity; Vp, flow propagation velocity; Sens, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value.

 
Analysis of the areas under the curve (AUC) using ROC curves was computed to determine the relative accuracy of the Em and Vp as a function of sensitivity and specificity. The results are given in Fig. 4. The AUC for Em was 0.94 (95%CI 0.87–0.98) and 0.81 for Vp (95%CI 0.71–0.88). The difference between the AUC was statistically significant (p<0.01). The cut-off values with optimal sensitivity to specificity ratio were 0.08 m s–1 for Em (94% sensitivity, 92% specificity) and 0.48 m s–1 for Vp (73% sensitivity, 90% specificity).


Figure 4
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  		Figure 4 Receiver operating characteristic (ROC) curves for Em (solid line) and Vp (dashed line) for the detection of mild to moderate LV diastolic dysfunction. Em, early diastolic mitral annular velocity; Vp, flow propagation velocity.

 
A false negative result for the detection of mild to moderate LV diastolic dysfunction was found in 2 (4%) patients by using the PW-TDE and in 13 (27%) patients by using color M-mode. In stepwise multiple logistic regression analysis only pseudonormal filling pattern (OR 7.0; 95%CI 1.4–53.5; p<0.05) and EF > 60% (OR 10.5; 95%CI 2.0–89.9; p<0.05) were associated with Vp false negative results. The diagnosis of HCM was present in almost half of the Vp false negative results (46%). Patients with AHY and CAD together represented 46% of the Vp false negative results. There was no patient with DCM in the Vp false negative group.


   4 Discussion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
5 Study limitations
 6 Conclusions
 References
 
To our knowledge this study is the first to directly compare PW-TDE and color M-mode in the assessment of LV diastolic function in the same series of patients with various heart diseases typically encountered in daily clinical practice. Our results show that early diastolic mitral annular velocity Em measured by PW-TDE is a better indicator of mild to moderate LV diastolic dysfunction diagnosed by established standard pulsed Doppler criteria than color M-mode flow propagation velocity Vp. Incorrect diagnosis of normal LV diastolic function by using color M-mode was associated with pseudonormal filling pattern, which reflects an impaired relaxation with compensatory increase in LV filling pressures, and with a presence of normal LV systolic function. These conditions are frequently associated in patients with HCM.

TDE is an echocardiographic tool that uses low-velocity and high-amplitude Doppler signals, thus allowing to obtain myocardial wall velocities during examination.20 To date, several studies have suggested that early diastolic mitral annular velocity Em provides a relatively preload-independent assessment of LV relaxation allowing for diagnosing of diastolic dysfunction regardless of its severity. Oki et al.21 recorded transmitral flow and myocardial Doppler velocities and measured the time constant ({tau}) in patients undergoing cardiac catheterization. Various parameters calculated from transmitral flow Doppler correlated well with {tau} except in the group of patients with elevated LV end-diastolic pressure who had a pseudonormal filling pattern. In contrast, all patients with abnormal relaxation (prolonged {tau}) had a low Em. Accordingly, in patients with restrictive cardiomyopathy, low Em values have been found in the presence of high transmitral flow E velocities in patients with pseudonormal or restrictive filling pattern.22 In the same study, patients with constrictive pericarditis and normal systolic function had normal Em velocities, indicating a normal ventricular relaxation. Discordance between E/A ratios and Em have also been found in patients with hypertrophic, dilated, and hypertensive cardiomyopathies.6,23 Age-related changes of Em in the population of healthy subjects were reported by Alam et al.19 The results of our study confirm the high accuracy of septal mitral annular PW-TDE in identifying subjects with abnormal LV relaxation due to various cardiovascular diseases, regardless of increase in LV filling pressures. The value of Em<0.08 m s–1 identified with high sensitivity, specificity and both predictive values patients with mild and moderate LV diastolic dysfunction. However, attention must be paid to interpreting the hemodynamic significance of Em regarding LV diastolic function in the presence of mitral regurgitation. Ohte et al.24 demonstrated a paradoxically higher Em in patients having LV dysfunction with moderate to severe mitral regurgitation. A significant increase in volume flow across the mitral valve during early diastole resulted in faster early diastolic mitral annular motion, masking the presence of abnormal LV relaxation. The same limitation was described in patients undergoing regular hemodialysis.25

Color M-mode Doppler differs from spectral pulsed Doppler in that it allows the acquisition of spatial information in addition to velocity and time along an entire line across the LV cavity. There are two general color M-mode Doppler indexes reported in published reports. The first approach evaluates the slope of the flow wave front that determines a flow propagation velocity Vp.7,26 The second method is based on the assessment of a time delay between maximal velocity at the mitral leaflet tips and ventricular apex.27 Several different approaches have been described for identifying Vp of LV filling manually or in a (semi) automated way.28 Regardless of the method, Vp is always identified as a slope in the spatio-temporal color M-mode Doppler image. However, the quantification of Vp is not yet standardized. Takatsuji et al.29 suggested a complex approach for calculating Vp by using both the distance and time delay to the most apical point of the aliasing boundary. This method appears to be more suitable for measuring Vp in dilated ventricles where a curvilinear delay of flow propagation to the apex may be present. On the other hand the method described by Garcia used in our study is based on the isovelocity contour of the first aliasing velocities measured 4 cm distally into the LV cavity which is assumed to be linear. The method has a high reproducibility, uses more velocity information leading to less noise-sensitivity and has been used for quantifying Vp in most of the recent work.7 Previous studies have demonstrated that color M-mode Doppler indexes of LV filling are inversely related to LV relaxation and directly to LV systolic function.26,27 Garcia et al.30 demonstrated that Vp is not significantly affected by preload and thus may differentiate patients with abnormal LV diastolic function and pseudonormal Doppler indexes. Two mechanisms that determine Vp have been proposed, the presence of intraventricular pressure gradients and the formation of vortexes.31,32 Intraventricular pressure gradients, showing consistent apex-to-base gradients in pressure during early filling, are responsible for the mechanism of suction, allowing adequate LV filling. Vorticity is generated by shear between inflowing blood and the stationary blood already in the ventricle. Vortex formation increases in dilated ventricles or in those with wall dyssynergy, resulting in a reduced Vp. However, in a recent study in patients with coronary artery disease, Ohte et al.33 suggested that Vp is determined mainly by LV systolic performance and partly by LV relaxation and LV filling pressure. Barbier et al.34 also demonstrated that prolonged relaxation per se does not influence Vp in an unselected clinical population if LV systolic dysfunction and/or wall dyssynergy is absent. These authors also described the relationship between Vp and LV geometry. Normal systolic function and cavity elongation, which enhance the LV elastic recoil mechanism, may increase Vp despite LV hypertrophy and prolonged relaxation in patients with HCM or aortic valve disease. Accordingly, results of our study show that Vp fails to detect abnormal LV diastolic function, in particular, in patients with normal LV systolic function and pseudonormal filling pattern, mainly in patients with HCM. Due to a relatively high frequency of false negative results in this type of patients, color M-mode appears to be a less suitable method for identifying subjects with LV pseudonormal filling pattern and normal LV systolic function as compared to PW-TDE.


   5 Study limitations
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Study limitations
6 Conclusions
 References
 
The most important limitation of the current study is the lack of correlative invasive intracardiac pressure data to determine the precise magnitude of LV filling pressures. Our patients were classified on the basis of established pulsed Doppler echocardiographic grounds alone.12 However, previous studies had repeatedly shown the validity of these criteria in various patient groups.35

The manual method of Vp slope measurement can be problematic. Several algorithms have since been developed which permit the numerical decoding of color-encoded velocities and allow automatic measurements of the slope.36 However, the computer software required to obtain these measurements was not commercially available at the time of our study. Moreover, the data from the study of Garcia et al.7 indicate that the manual method of measurement is both reproducible and valid.

Another limitation of our study is a selection bias introduced by inclusion restricted to individuals with a clear LV filling pattern type defined by the comparison of standard transmitral and pulmonary venous Doppler flow indices. However, the main objective of the study was not to assess the accuracy of the methods in an unselected population but the comparison of their discriminating power between patients with normal LV diastolic function and those with mild to moderate diastolic dysfunction.


   6 Conclusions
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Study limitations
 6 Conclusions
References
 
Our study is the first to show on a population of patients with a wide range of heart diseases that early diastolic mitral annular velocity Em measured by PW-TDE is a more reliable index for differentiation of mild to moderate LV diastolic dysfunction than color M-mode flow propagation velocity Vp. Vp appears to be relatively insensitive in detecting abnormal LV diastolic function in patients with preserved LV systolic function and pseudonormal filling pattern.


   References
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Study limitations
 6 Conclusions
 References
 

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