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European Journal of Echocardiography 2003 4(4):279-285; doi:10.1016/S1525-2167(03)00009-X
© 2003 by European Society of Cardiology
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Copyright © 2003, The European Society of Cardiology

Isovolumic Contraction Time by Pulsed-Wave Doppler Tissue Imaging in Aortic Stenosis

R. Moreno, J. Zamorano, C. Almería, J. A. Pérez-González, L. Mataix, J. L. Rodrigo, D. Herrera, A. Aubele, L. Pérez de Isla, E. De Marco, L. Sánchez-Harguindey and C. Macaya

Laboratory of Echocardiography, Hospital Clinico San Carlos, Madrid, Spain

Received 24 September 2002; accepted after revision 22 January 2003.


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background: Doppler Tissue Imaging (DTI) has been evaluated in ischaemic heart disease and some cardiomyopathies. In patients with aortic stenosis (AS), left ventricular contraction is slowered. This study aimed to evaluate the possible role of the measurement of isovolumic contraction time (ICT) by DTI in the evaluation of AS severity.

Methods: The study population constitutes 30 patients: 15 with AS (nine severe and six non-severe) and 15 control subjects. All of them had normal systolic function, sinus rhythm, and absence of ischaemic heart disease of conduction abnormalities. ICT was defined as the time from the onset of the QRS complex to the beginning of the DTI systolic wave. The correlation between ICT and aortic area obtained by continuity equation, as well as the diagnostic value of ICT in the identification of severe AS were studied.

Results: ICT was significantly increased in patients with severe AS (98±27 versus 65±21 ms, p=0.024). There was a significant correlation between ICT and aortic area (r=–0.56; p=0.035). The receiver operator characteristic curve of ICT in the identification of severe AS yielded an area under the curve of 0.852 (95% confidence interval: 0.665–1.0). The two best cut-points were <73 ms (88% sensitivity, 77% specificity) and <85 ms (78% sensitivity, 83% specificity). A value of <41 ms had a 100% sensitivity, but only a 17% specificity, and <91 ms showed a 100% specificity, but only a 44% sensitivity.

Conclusions: ICT measured by pulsed-wave DTI is increased in patients with aortic stenosis.

Keywords: aortic stenosis; Doppler tissue imaging


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
In patients with an increased afterload, left ventricular contraction is slower than in control subjects[1,2]. Although an increase in the production of the slow form of beta-myosin heavy chain seems to play a key role[1,3], other potential mechanisms, such as an impaired subendocardial perfusion, have also been proposed[4,5]. Some studies have previously evaluated the possible role of the abnormalities on left ventricular systolic function in the assessment of AS severity[6–11]. However, most of the currently available echocardiographic techniques are not able to offer a precise quantification of left ventricular segmental motion velocity.

Doppler Tissue Imaging (DTI) allows the measurement of myocardial velocities throughout the cardiac cycle, as well as the time intervals with a high precision. The usefulness of DTI has been studied especially in patients with ischaemic heart disease and some cardiomyopathies[12–14]. The objective of this study was to evaluate the possible role of DTI in the study of severity of patients with aortic stenosis (AS). For this purpose, we prospectively studied 30 patients (15 with and 15 without AS) with DTI, trying to relate isovolumic contraction time (ICT) measured by DTI with the presence and severity of AS.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
Study population
The study population constitutes two groups of subjects: 15 with AS and 15 control subjects. All patients, both control subjects and those with AS, had an optimal acoustical window and trans-aortic continuous Doppler recordings.

Patients with AS fulfilled the following inclusion criteria: (1) trans-aortic peak gradient of 20 mmHg or more; (2) normal left ventricular systolic function by two-dimensional echocardiographic study; (3) absence of previously known ischaemic heart disease or chest pain; (4) sinus rhythm; (5) absence of atrioventricular or ventricular conduction abnormalities. Out of the 15 patients with AS, nine (60%) had severe AS.

Control subjects had a normal echocardiographic study, and had been referred to our Laboratory of Echocardiography to rule out valvular or myocardial heart disease in presence of murmur or syncope. All control subjects were also in sinus rhythm, and had no ventricular conduction abnormalities.

Echocardiographic study
Echocardiographic study was performed with a Phillips Sonos 5500 or an Aloka SSD 870 equipment, with the patient in the left lateral position. The aortic valve area, and the maximum and mean trans-aortic pressure gradients were obtained. The internal diameter of the left ventricle outflow tract was measured from a freeze-frame image of the para-sternal long-axis view, taking the measurement as the distance between the trailing edge of the interventricular septum and the leading edge of the base of the anterior mitral leaflet just proximal to the aortic valve annulus during systole. The time-velocity integral of the left ventricular outflow tract was measured from the outer border or the spectral display of the pulsed-wave Doppler obtained from the five-chamber apical view. The maximum trans-aortic time-velocity integral was considered in apical, right para-sternal or subcostal views. Aortic valve area was calculated with the continuity equation, as follows:

Formula
where TVI1 is the time-velocity integral at left ventricular outflow tract and TVI2 is the time-velocity integral across the aortic valve.

AS was considered as severe in the presence of an aortic valve area of 0.8 cm2 or lower calculated by the continuity equation. Trans-aortic ICT was calculated as the time interval between the beginning of the QRS complex of the electrocardiogram and the beginning of the trans-aortic flow by continuous Doppler.

Pulsed-wave DTI was performed at the level of interventricular septum. ICT was defined as the time from the beginning of the QRS complex of the electrocardiogram to the beginning of the systolic wave ‘s’. Three beats were measured in each patient, the average between these values being considered for the analysis. The following were studied: (1) differences between patients with and without AS in the ICT; (2) correlation between DTI and aortic valve area as measured by continuity equation; and (3) value of ICT in the identification of severe AS. Interobserver and intraobserver variability in the measurement of ICT was 7±3 and 2±2 ms, respectively.

Statistical analysis
Continuous variables are expressed as mean ± standard deviation, and discrete variables as proportions (percentages). Comparison of continuous variables between two groups was studied with the Mann–Whitney U test, and comparison of proportions with the Chi-square test (Fisher's correction when necessary). The receiver operator characteristic (ROC) curves were obtained with the sensitivity and specificity for each cut-point of the ICT. Associations were considered statistically significant in presence of a p value lower than 0.05.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
Comparison between patients with and without AS and between patients with severe and non-severe AS
Table 1 shows differences between patients with and without AS. There were no significant differences regarding left ventricular diameters, wall thickness, and other two-dimensional echocardiographic measurements, as well as regarding transmitral flow Doppler data. Both trans-aortic and DTI ICT were slightly longer in patients with AS, but differences were not statistically significant.


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  		Table 1 Comparison between patients with and without AS.

 
Table 2shows the comparison between patients with severe and non-severe AS. There were no significant differences regarding left ventricular diameters, wall thickness, and other two-dimensional echocardiographic measurements between patients with severe and non-severe AS. Although trans-aortic ICT was similar in both groups of patients, DTI ICT was significantly longer in patients with severe AS (98±27 versus 65±21, p=0.024). DTI ICT was not statistically different in patients with non-severe AS and in control subjects (65±21 versus 82±23 ms, p=0.156) (Fig. 1).


Figure 1
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  		Fig. 1 Pulse-wave Doppler tissue imaging, showing systolic (s) and early (c) and late (a) diastolic waves. ICT: isovolumic contraction time.

 


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  		Table 2 Comparison between patients with severe and non-severe AS.

 
Correlation between DTI and aortic valve area as measured by continuity equation and diagnostic value of DTI ICT in the detection of severe AS
There was a significant negative correlation between DTI ICT and aortic valve area (r=–0.56; p=0.035) (Fig. 2). Fig. 3 shows the ROC curve with the sensitivity and one-specificity for each cut-point of DTI ICT in the diagnosis of severe AS among patients with AS. Area under the curve was high (area under the curve: 0.852; 95% confidence interval: 0.665–1.0). The two best cut-points were a DTI ICT < 73 ms (88% sensitivity, 77% specificity) and <85 ms (78% sensitivity, 83% specificity). A DTI ICT < 41 ms had a 100% sensitivity, but a 17% specificity, and DTI ICT <91 ms showed a 100% specificity, but with only a 44% sensitivity.


Figure 2
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  		Fig. 2 Correlation between aortic valve area and DTI ICT in patients with AS.

 


Figure 3
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  		Fig. 3 ROC curve of the usefulness of DTI ICT in the diagnosis of severe AS.

 
On the contrary, there was no significant correlation between trans-aortic ICT and aortic valve area (Fig. 4). Moreover, trans-aortic ICT showed a lower diagnostic value in the detection of severe AS (area under the curve: 0.712; 95% confidence interval: 0.513–0.911) (Fig. 5).


Figure 4
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  		Fig. 4 Correlation between aortic valve area and transaortic ICT in patients with AS.

 


Figure 5
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  		Fig. 5 ROC curve of the usefulness of trans-aortic ICT in the diagnosis of severe AS.

 

   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
Left ventricular systolic function in patients with AS
The key physiopathologic point in AS is an increased left ventricular afterload, that produces a hypercontractility and subsequently a pressure gradient between left ventricle and aorta. The initial response of left ventricular myocardium consists of an increase in wall thickening with a preserved systolic function, and only at end stages a systolic dysfunction occurs[15,16]. Also, in patients with significant AS, a delayed peak of myocardial wall contraction may be present, as a reflection of the prolonged effort of the left ventricle in ejecting the blood through the obstructed aortic valve. Some experimental studies have shown that an increased afterload produces a slowered myocardial contraction[1]. Similarly, Harding and Poole-Wilson[2] have demonstrated that the myocytes from left ventricle of patients undergoing aortic valve replacement for severe AS had a slowed contraction velocity. This could be mostly due to an increase in the slow form of beta-myosin heavy chain[1,3]. However, other potential mechanisms, such as a subendocardial ischemia, have also been involved[4,5].

Some previous studies have evaluated the possible role of left ventricular systolic function in the evaluation of AS severity. Sheppard et al.[6] compared the systolic and diastolic slopes of the posterior left ventricular wall, reflecting the slower filling and emptying of the ventricle in patients with AS. In the study of Schwartz et al.[7], the systolic wall thickness and systolic left ventricular dimension were studied, showing a good relation in children and young adults, but not in older adults. Zoghbi et al.[8] found a significant inverse correlation between the aortic area and the difference between the ejection time measured by pulsed-wave Doppler and the predicted ejection time derived from the regression equation of Harley. Mann et al.[9] developed an index based on the percent fractional shortening and the peak instantaneous Doppler-derived flow velocity across the aortic valve. Recently, Antonini-Canterin et al.[10] have used the same principle, but taking into consideration left ventricular ejection fraction instead of fractional shortening, in order to overcome the limitations that may be present in patients with regional wall motion abnormalities. Finally, using a new automated segmental motion analysis system (A-SMA), we have recently found a delayed peak of fractional area shortening in patients with AS, especially in those with severe AS[17].

Additionally, it has been postulated that the time from the aortic valve opening to the peak trans-aortic velocity evaluated by continuous-wave Doppler could be useful in the assessment of AS severity[18]. However, the results of those studies were contradictory, probably because those parameters are also dependent on left ventricular and aortic pressures, peripheral artery resistance and left ventricular systolic function[19,20].

Limitations of continuity equation and usefulness of ICT measured by DTI in the evaluation of patients with AS
The continuity equation constitutes the gold standard in the non-invasive quantification of AS[21]. However, this method may not be accurate in all clinical settings, especially in patients with heavily calcified valves, deficient acoustical window, or inadequate continuous-wave Doppler recording. The continuity equation is sometimes poorly reproducible and shows high interobserver variability, especially in patients with heavily calcified valves[22]. The location of the sample volume when measuring left ventricle outflow tract velocity can also affect the reproducibility of aortic valve area calculation[23].

DTI allows the measurement of myocardial velocities and time intervals with a high precision. In the present study, we have measured with ICT using DTI, and have obtained a stronger correlation with aortic valve area than trans-aortic ICT (coefficient correlation –0.56 versus –0.015, respectively). Although there were no significant differences in DTI ICT between patients with and without AS, a significantly longer DTI ICT was found in patients with severe AS in comparison with patients with non-severe AS, indicating that only in patients with severe AS DTI ICT is significantly increased. The presence of severe AS could be, therefore, a pre-requisite for the occurrence of left ventricular dysfunction even at early stages non-evident at conventional echocardiography. We tried to use this increased DTI ICT in the identification of patients with severe AS calculating the ROC curves. A DTI ICT < 73 ms showed 88% sensitivity and 77% specificity, and a DTI ICT <85 ms a 78% sensitivity with an 83% specificity. Although these values may not be considered very high, DTI could complement the Doppler evaluation of AS, especially when continuous-wave Doppler recording is not adequate, or in patients with poor acoustical window in which measurement of left ventricular outflow diameter may be difficult. In such patients, for example, a DTI ICT < 55 ms, could potentially exclude the presence of a severe AS (see Fig. 3).

Study limitations
This study has several limitations. First, the sample of patients is relatively low. However, it was large enough to detect significant differences in DTI ICT between patients with severe and non-severe AS, as well as a significant correlation between aortic valve area and DTI ICT. Second, all study patients had an optimal acoustical window and trans-aortic continuous Doppler recording. The application in patients with suboptimal conventional echocardiographic study is to be demonstrated. Finally, all study patients had a normal left ventricular ejection fraction. The interest of a possible role of DTI ICT in the diagnosis of patients with depressed left ventricular ejection fraction warrants further studies.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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