a Cardiovascular Centre, Vilnius University Hospital, Santariskiu Klinikos, Vilnius, Lithuania
b Department of Cardiology, University Hospital, Gasthuisberg, Leuven, Belgium
* Corresponding author. Tel.: +370-5-2365207; fax: +370-5-2365211
E-mail address: jelena.celutkiene{at}santa.lt
Received 14 July 2003; revised 12 March 2004; accepted 2 April 2004 This paper was guest edited by Dr Michael H. Picard, Massachusetts General Hospital, Boston, USA
Abstract
Aims Doppler myocardial imaging (DMI) has been suggested as a method of quantifying induced ischaemia during dobutamine stress echocardiography (DSE). The aim of the present study was to investigate both standard systolic and diastolic parameters, but more specifically to address the phenomenon of post-systolic motion (PSM) as a marker of acquired ischaemia during DSE using pulsed-wave DMI.
Methods and results We examined 60 patients without previous myocardial infarction who underwent DSE. Peak systolic, post-systolic, early and late diastolic velocities were measured at rest and during stress. Myocardial segments () were divided into ISCHAEMIC and NON-ISCHAEMIC groups according to the presence of significant angiographic coronary stenosis. ISCHAEMIC segments (
) compared with NON-ISCHAEMIC segments (
) demonstrated a reduced increase of systolic velocity (8.012.7 vs 9.316.4 cm/s,
), prominent PSM (5.88.3 vs 0.632.1 cm/s,
) and reduced early diastolic velocity (6.510.2 vs 7.913.2 cm/s,
) during stress. The peak velocity of PSM was the most accurate index of induced ischaemia (sensitivity 73100%, specificity 8297%) compared to systolic and early diastolic velocities (sensitivity 5277% and 6368%, specificity 6377% and 5981%, respectively).
Conclusion PSM derived by pulsed-wave DMI during DSE was the most sensitive index of acquired ischaemia compared to other functional DMI indices.
Key Words: Doppler myocardial imaging Dobutamine stress echocardiography Regional myocardial function Induced ischaemia Post-systolic motion
Introduction
Dobutamine stress echocardiography (DSE) is widely used both for the detection of coronary artery disease (CAD) and the evaluation of the functional significance of angiographically-proven coronary lesions. However, the subjective interpretation of stress echocardiography remains the most significant disadvantage of this technique.1,2 The lack of uniform diagnostic criteria remains a significant limitation in the agreement of even expert readers. This is especially true in situations where image quality is poor and wall motion abnormalities are subtle.1,3 Furthermore, recent studies have shown the physiological limitations of the human eye to resolve rapid, short-lived motion.4
A number of authors have proposed that the development of a user-friendly quantitative approach should overcome the limitations of subjective evaluation of DSE images.2,3 Several investigators have shown Doppler myocardial velocity imaging (DMI) to be a sensitive alternative to the present echocardiographic and scintigraphic imaging techniques to evaluate stress tests.5,6 Quantification of myocardial function by pulsed Doppler myocardial mapping during dobutamine stress has also been shown to be a feasible, accurate and reproducible technique.6 The peak velocity response for both systole and diastole has been shown to be significantly lower during either exercise or dobutamine stress in mal-perfused myocardial regions compared to normal.5,6 However, no quantitative approach is in widespread clinical use.
Prior investigations have shown that changes in post-systolic deformation are sensitive and early markers of acute ischaemia.79 However, there is a lack of data concerning post-systolic motion (PSM) and its diagnostic value during stress echocardiography. This prospective observational study explored both systolic and diastolic parameters but specifically focused on the induction of PSM as a marker of induced ischaemia during dobutamine stress. This was studied using pulsed-wave (PW) DMI.
Methods
Patient clinical profile
We prospectively enrolled 60 consecutive patients (pts) (29 males, mean age 60±10 years) with known or suspected CAD who were referred for diagnostic DSE. Patients with a prior history of myocardial infarction, dilated cardiomyopathy, increased myocardial mass index (MMI120 g/m2), significant valve disease, atrial or ventricular arrhythmia, pacemaker implantation, bundle branch blocks or left ventricular (LV) ejection fraction (EF)
45% were excluded from the study. All participants gave written informed consent before the examinations.
Standard coronary angiography was performed in all 60 pts referred for DSE within 1 month of the dobutamine challenge. Coronary angiographic data were analysed visually by two experts blinded to both the clinical data and the results of DSE. Significant coronary stenosis has been traditionally defined as equal to or more than 50% artery lumen narrowing, localised in the first or middle segments of the coronary arterial tree, observed in two orthogonal angiograms. When the evaluations of coronary angiography by two experts were discordant, the third expert was invited to achieve consensus.
According to the results of the coronary angiography, the patients were divided into two groups: the STENOSED Group comprised 37 pts with significant (50%) coronary stenoses, the NON-STENOSED Group comprised 23 pts with normal findings or non-significant lesions (
50%) in coronary arteries. The clinical and echocardiographic data of both groups are summarized in Table 1.
|
Data analysis
Myocardial wall segments were correlated to the coronary circulation supply according to three types of the coronary circulation.10
Doppler myocardial imaging data analysis
Fig. 1 shows the parameters recorded in case of normal (Fig. 1, top) and abnormal (i.e., demonstrating post-systolic positive wave) (Fig. 1, bottom) myocardial motion. All parameters were measured twice: at rest and during stress. Secondary parameters were calculated: and ratios peak velocity of post-systolic motion/peak systolic velocity (PSM/S) and peak velocity of early ventricular filling/peak velocity of atrial contraction (
). PSM was defined as positive wave, which appeared after the curve of systolic ejection had reached the zero line. End of ejection was defined as end of T wave on ECG.11
|
Due to heterogeneity of myocardial velocities in different myocardial walls and different levels of LV, all 16 segments were analysed separately. Averaging was performed only among all 1st segments, among all 2nd segments, etc. Thus, velocities of different segments are presented as range values.
When performing detailed segmental analysis, all segments (960) of the study population (60 pts) were divided into two groups, depending on the results of coronary angiography. The ISCHAEMIC group consisted of 373 segments supplied by stenosed (50% narrowed) coronary arteries, while the NON-ISCHAEMIC group consisted of 587 segments supplied by non-stenosed (normal or stenosis
50%) coronary arteries.
Statistical analysis
Unless specified, data was expressed as mean values±SD. A -value
0.05 was considered to be statistically significant. Factor analysis was used to identify underlying variables, or factors, that explain the pattern of correlation within a set of observed variables (i.e., within a matrix of measured velocities, for example,
). The pts with missing data were deleted, thus 50 pts were included in the factor analysis. Varimax method of factor rotation was selected, factor loadings (Varimax normalised)
0.700 were considered as significant weights of variables.
The MannWhitney test for independent samples was used as a non-parametric alternative to the
-test. The Wilcoxon matched pairs test was used as an analogue of the paired
-test for the sample measured under the two conditions of rest and stress. Two-sided tests were performed.
Logistic regression analyses were performed in order to assess the possibility of predicting coronary stenosis of a supplying coronary artery by segmental myocardial velocity parameters. The logistic regression model is a method of analysis concerned with describing the relationship between a response variable (coronary stenosis) and an explanatory variable (e.g., PSMstress). The form of the logistic regression model used was as follows:
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The diagnostic performance of DMI-derived indices for discriminating normal, as opposed to ISCHAEMIC LV wall segments was tested using ROC (receiver operating characteristic) curves. For each parameter investigated, an optimal cut-off value was determined to maximise the sum of sensitivity and specificity. All statistical analyses were undertaken using standard statistical software SPSS 9.0 version and Statistica 6.0.
Results
Dobutamine echocardiography and coronary angiography
The 85% age-predicted maximum heart rate was achieved in 14 pts of the STENOSED group (38%) and in 15 pts of the NON-STENOSED group (65%). Other reasons for terminating the dobutamine challenge were: chest pain (15 pts, 10 from the STENOSED group), wall motion abnormalities (6 pts of the STENOSED group), arrhythmia (3 pts), ECG changes (3 pts), hypotension (3 pts), and hypertension (1 pt). The haemodynamics of the tests are presented in Table 1.
In the patient group, significant vessel disease was found: 16 pts had single vessel disease, 11 pts had 2-vessel disease and 10 pts had 3-vessel disease. Among those with significant disease (stenoses 50%), the left anterior descending artery was involved in 22 pts, 24 pts had significant left circumflex stenosis, and 22 had significant right coronary stenosis. According to visual assessment, stenoses
50% were found in 26 arteries (in six cases it was single vessel disease), stenoses
70% were found in 22 arteries and stenoses
90% were found in 20 arteries.
Doppler myocardial imaging common data
DMI velocity curves (spectra) were obtained in 908 segments (95% of scanned 960 myocardial segments), 357 segments (96%) of the ISCHAEMIC group and 551 segments (94%) of the NON-ISCHAEMIC group. Non-analysable Doppler curves occurred mainly during peak stress in mid-to-apical regions with decreasing frequency at the following sites: anterior (1.5%), inferior (1%), lateral and inferolateral walls.
Mean duration of DMI acquisition was 3±0.6 min at rest and at peak dobutamine.
Doppler myocardial imaging during dobutamine echocardiography
The factor analysis exploring ,
and
indices failed to reveal any significant results. The factor analysis exploring PSMstress had identified three characteristic hypothetical factors corresponding to the left anterior descending (LAD), left circumflex artery (LCX) and right coronary artery (RCA) territory. According to the significant weights of variables found by the factor analysis, the most informative segments were chosen for detailed analysis. In the LAD territory they were the mid-septal (2nd) and apical septal (3rd), basal anterior (12th) and mid-anteroseptal (15th), in the RCA territory the basal septal (1st), basal inferior (7th) and mid-inferior (8th), and in the LCX territory the basal inferolateral (13th) and mid-inferolateral (14th) segments.
All the myocardial segments studied demonstrated similar significant differences between the ISCHAEMIC and the NON-ISCHAEMIC groups for ,
,
,
,
,
and
. The entire set of measured and calculated parameters from three representative segments are summarised in Table 2.
|
|
The prominent parameter to discriminate ISCHAEMIC from NON-ISCHAEMIC segments was the magnitude of PSM (Fig. 3). At rest, PSM was significantly higher in the ISCHAEMIC group (2.74.9 vs 0.361.4 cm/s of the NON-ISCHAEMIC group, ). During stress, this difference between the two groups was markedly enhanced:
and
in ISCHAEMIC segments (5.88.3 cm/s and 0.540.84, respectively) were much higher than in NON-ISCHAEMIC segments (0.632.1 cm/s and 0.060.15, respectively,
) (Table 2).
|
Cut-off values of Doppler myocardial indices
The receiver operating characteristic curves constructed for ,
and
are shown in Fig. 4. The corresponding cut-off values and diagnostic accuracy are summarised in Table 3.
|
|
|
Previous investigators have incorporated DMI method in stress echocardiography and proposed the criteria for diagnosing induced myocardial ischaemia.2,3,5,6,12,13 These criteria included insufficient growth of peak systolic myocardial velocity and significant reduction of early diastolic velocity during stress in ISCHAEMIC segments. The present study confirmed the diagnostic value of these parameters during stress echocardiography. However, previously suggested criteria were not site-specific, though it is clearly shown that the velocity of appropriate segment depends on the site of the location in the left ventricle. Therefore, site-specific cut-off values of systolic and diastolic myocardial velocities were elucidated in the present study. To make DMI interrogation easier and more applicable in daily practice, the most representative myocardial segments for each of three coronary arteries were chosen using factor statistical analysis.
More importantly, in previous reports the characteristic element of the velocity profile of ischaemic myocardium has not been investigated as a potential marker of induced ischaemia. It is a phenomenon of post-systolic myocardial motion, which has been well described in numeral fundamental sono-micrometric studies as an early sensitive sign of ischaemia.79 This is the first correlative study in which peak systolic and diastolic velocities (including the velocity of PSM) have been studied during DSE and have been related to the results of coronary angiography. A close relationship between the peak velocity of PSM and coronary circulation has been demonstrated using logistic regression and factor analysis. The most informative segments for the diagnosis of coronary stenosis were determined. The proposed method is technically simple and can be easily performed using any echo machine equipped with conventional pulsed Doppler myocardial imaging.
The normal myocardial response to dobutamine
Previously, Wilkenshoff et al.12 reported a significant increase of mean systolic myocardial velocities during exercise in normal subjects. The research by von Bibra et al.6 showed that catecholamine stimulation similarly induced significant increase in systolic (6.3±3 cm/s) and diastolic (3.5±2 cm/s) myocardial velocities in healthy persons. Such increase of velocities during peak stress was identical to the lengthening rate during dobutamine challenge in young normal subjects.6 Thus, this increase can be considered as a normal functional response, not dependent on the patient's age.
Our results appeared to be similar to those published earlier: the increase of systolic and diastolic myocardial velocities during peak stress ranged from 3.5 to 6.0 cm/s and from 0.8 to 2.0 cm/s, respectively. These findings confirm that dobutamine stress induces a uniform response in normal regional function. This is a pre-requisite for understanding the results of stress tests.6
The normal ranges of longitudinal velocities and the base-apex gradient of longitudinal velocities observed in this study are also consistent with previous findings (Fig. 6).6,13,14
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Ischaemic myocardial response to dobutamine
It has been suggested that when sub-endocardial ischaemia occurs, impaired long-axis shortening is evident before changes in short-axis shortening because of the myocardial fibre orientation.15 The differential placement of the longitudinal fibres in the sub-endocardium may render longitudinal velocity uniquely sensitive to mild or early ischaemia during stress.12 The present data demonstrate three discriminating features of ischaemic myocardial response to dobutamine stress:
The regional heterogeneity of myocardial velocities suggests a quantitative interpretation of DSE using site-specific cut-off values of DMI.16
Systolic motion
Several investigators have shown that a reduced increase of systolic myocardial velocities during stress echocardiography can be a sensitive marker of ischaemic myocardial segments.5,6,12 Using a peak systolic velocity of 12 cm/s to define an abnormal response, the sensitivity and specificity of DMI for ischaemia has been shown to be 86% and 96% for basal segments and 81% and 89% for mid segments.5 This threshold is similar to the site-specific cut-off values of peak systolic velocity (111314 cm/s) found in the present study. The absolute magnitude of peak systolic velocity during stress is significantly related to the stenosis of the supplying artery (
).
Some investigators suggest that the absolute magnitude of peak systolic velocities is not necessarily the parameter needed to distinguish between normal and impaired myocardial contraction in chronic ischaemia.12,14 However, changes in these parameters can be used for quantitative monitoring of ischaemia-induced wall motion abnormalities.12 A number of previous reports confirmed that, if compared with non-ischaemic segments, the stress-induced increase of peak contraction velocity was approximately 4050% less in segments with acute ischaemia.6 This has been described as a diagnostic parameter for significant coronary artery stenosis in studies using colour Doppler imaging with post-processing for both bicycle ergometry and dobutamine stress.12
Accordingly, our data showed that the increase in systolic velocities () was significantly lower in ISCHAEMIC than in NON-ISCHAEMIC segments (2.03.7 vs 3.46.0 cm/s,
).
Diastolic motion
Currently, the evaluation of regional diastolic wall motion has not been possible with semi-quantitative stress echocardiography. This is due to its low frame rate with respect to the short duration of early diastolic events. Quantification of regional diastolic myocardial function by pulsed Doppler myocardial mapping during dobutamine stress has been shown to be a feasible, accurate and reproducible technique.6
Early diastolic relaxation is known to be an active phenomenon, which takes place at a higher energetic expenditure than passive late diastolic motion.13 This may constitute the physiological basis underlying our findings of a low wave velocity and an inverse
ratio as sensitive signs of hypoperfusion.
Post-systolic motion
Post-systolic thickening/shortening associated with reduced systolic contraction have been recorded in pts with chronic CAD with significant narrowing of the vessel,17 in pts with acute myocardial infarction18 and during ischaemia induced by coronary angioplasty.19
Recently, Ilic and co-workers20 reported the value of index of PSM during DSE. They concluded that PSM, developed in segments with stress, provoked visually detectable myocardial ischaemia and that an index of PSM could be used as a marker of the severity of myocardial ischaemia. However, these authors have not verified the presence of PSM with the results of coronary angiography.
Voigt et al.21 investigated strain-rate imaging during DSE and found that the ratio of post-systolic shortening to maximal segmental deformation is the best quantitative parameter to identify stress-induced ischaemia. Although strain/strain rate imaging better reflects true myocardial thickening/thinning, the use of myocardial velocities is far more practical, as the analysis can be performed on-line and does not require sophisticated time-consuming post-processing.
In the present study, we extend the findings of previous investigators by showing that PSM can be the most sensitive marker in the diagnosis of significant coronary stenosis during DSE. The factor analysis revealed that the values of the only parameter () are influenced by characteristic factor appropriate coronary territory. This result illustrates the relation of PSM to coronary circulation.
It has been reported that some amount of asynchrony of the wall motion is observed during LV contraction and relaxation, even under normal physiological conditions.22 It agrees with our data showing the presence of PSM to a mild extent in the NON-ISCHAEMIC segments (0.361.4 cm/s). In contrast, PSM was significantly higher in the ISCHAEMIC group already at rest (2.74.9 cm/s), .
The estimated cut-off values of PSM velocities in representative myocardial segments derived from ROC curves had both a high sensitivity (73100%) and specificity (8297%) (Fig. 4, Table 3). This accuracy is superior to the reported diagnostic accuracy of the visual evaluation of wall motion abnormalities among six experienced institutions (sensitivity 6285%, accuracy 6683%).23 In addition, PSM can be seen easily and quickly on-line during stress echocardiography, thus allowing early diagnosis of ischaemic changes.
The present study has confirmed the high feasibility of DMI both at rest and during stress 95%. To make the application of estimated regional diagnostic criteria more convenient and useful in daily practice, the most informative segments for the diagnosis of coronary stenosis have been selected. At the same time, these segments are easy for DMI scanning.
Previous reports have reported that image acquisition and off-line analysis required similar times consuming echocardiographic stress tests with off-line quad screen analysis as standard.6 In our study, the mean duration of DMI acquisition was 3±0.6 min both at rest and at peak dose of dobutamine infusion. Our suggested approach to DMI analysis should take approximately 510 additional minutes after the completion of challenge; it does not substantially prolong the time of challenge.
Although a number of authors have pointed out that spectral Doppler curves derived from the left ventricular apex are often non-analysable,6 we did not refuse an interrogation of apical segments. Indeed, the Doppler angle sometimes exceeded the acceptable magnitude in these segments, however, we could obtain spectral recordings of sufficient quality in the majority of apical segments.
Study limitations
We are aware that angiographic coronary stenosis does not always reflect the potential alteration in the regional myocardial perfusion. The relationship between stenosis severity and physiological reduction of coronary flow is quite variable even when there are no imaging limitations (e.g., eccentric stenosis or hazy areas due to thrombus).
Furthermore, the correlation between the distribution of coronary arterial anatomy and the echocardiographic myocardial wall segment location is also limited.13 Radionuclide methods would be more accurate than coronary angiography in defining ischaemic myocardial wall segments, and the accuracy of pulsed-wave DMI may be different when compared with this perfusion technique.
The PW DMI modality has a number of limitations compared to the colour mode. When using the pulsed Doppler technique, much more time is required to obtain velocity recordings from the 16 standard myocardial segments. In our study, for every separate myocardial segment, spectral recordings were acquired and stored during different time frames and heart rates. Thus, we could not measure the time of cardiac events, which was a substantial limitation in detecting myocardial ischaemia.
The defined cut-off values of peak systolic, post-systolic and early diastolic velocities require a validation in another group of pts; this should be completed in further studies. A statistical limitation of the study would be that the significance level has not been adjusted for the multiplicity of testing, which can result in the increased probability of wrong decisions, i.e., the inflation of -value.
Besides, the accuracy of myocardial velocities in the analysis of myocardial contractility is limited compared to strain/strain rate imaging, as the latter method eliminates tissue tethering and motion of cardiac translation.
Conclusions
The PW DMI is feasible during DSE and allows accurate discrimination between ischaemic and non-ischaemic myocardial segments. Transient myocardial ischaemia is characterised by simultaneous changes in systolic, diastolic and post-systolic velocities. The PSM appears to be the most sensitive index of induced ischaemia compared to other indices derived from PW DMI. The most informative segments and site-specific cut-off values of three major DMI parameters are herein suggested, which makes the method useful for daily clinical practice.
References