Acute Regional Myocardial Ischemia Identified by 2-Dimensional Multiregion Tissue Doppler Imaging Technique

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1 Acute Regional Myocardial Ischemia Identified by 2-Dimensional Multiregion Tissue Doppler Imaging Technique Thor Edvardsen, MD, Svend Aakhus, MD, PhD, Knut Endresen, MD, PhD, Reidar Bjomerheim, MD, PhD, Otto A. Smiseth, MD, PhD, FACC, and Halfdan Ihlen, MD, PhD, Oslo, Norway Background and Objective: Tissue Doppler echocardiography (TDE) is a promising method for the assessment of regional myocardial function, but pulsed TDE does not provide quantitative data from multiple regions simultaneously. This feature is important for the objective assessment of regional differences in myocardial function. In the present study, we investigated a new off-line TDE method that provides quantitative pulsed velocity data from an unlimited number of regions selected within a 2- dimensional (2D) image. The goal of the study was to determine the ability of this new approach to quantify regional myocardial function during acute myocardial ischemia induced by balloon angioplasty. Methods: Twenty-two patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by 2D TDE from the apical 4-chamber view before, during, and after angioplasty. Images were sampled at a rate of 69 ± 15 frames/s, and the off-line analysis allowed simultaneous measurement of velocities in multiple myocardial segments. Results: There were 3 major alterations in the systolic velocity pattern during LAD occlusion. Peak early systolic velocities along the apical septum were significantly reduced during LAD occlusion (2.8 ± 1.2 cm/s to 0.6 ± 1.7 cm/s, P <.001). Myocardial velocities in mid systole suggested paradoxical wall motion (1.0 ± 1.2 cm/s to 0.8 ± 0.9 cm/s, P <.001). When comparing the ischemic regions of the left ventricle with the nonischemic regions, each patient demonstrated lower myocardial systolic velocities in the ischemic region. Furthermore, during early diastole, the wall motion of the ischemic segments showed a postsystolic contraction pattern with velocities changing from 0.9 ± 1.0 cm/s to 1.9 ± 1.3 cm/s (P <.001). Conclusion: This new 2D TDE approach is able to quantify detailed myocardial velocity profiles from multiple regions simultaneously. Single-beat comparisons of ischemic and nonischemic regions might enhance the sensitivity for diagnosing ischemic heart disease. Reversed systolic wall motion during midsystole and marked positive velocity during early diastole might be new and important markers of myocardial wall ischemia. (J Am Soc Echocardiogr 2000;13: ) Two-dimensional (2D) echocardiography with regional wall motion analysis is widely used in the assessment of left ventricular (LV) function. Different modifications of this method have been developed, but they all include visual interpretation of myocardial thickening and endocardial excursion and therefore are subjective From the Department of Cardiology, National Hospital, University of Oslo. Thor Edvardsen is a recipient of research fellowships from the Norwegian Council on Cardiovascular Diseases. Reprint requests: Thor Edvardsen, MD, Dept of Cardiology, The National Hospital, 0027 Oslo, Norway ( thor.edvardsen@klinmed.uio.no). Copyright 2000 by the American Society of Echocardiography /2000/$ /1/ doi: /mje and operator-dependent. 1 Tissue Doppler echocardiography (TDE) has recently been introduced as an alternative method for the assessment of regional myocardial function. 2-7 Pulsed Doppler velocities can be measured from the fibrous atrioventricular annuli and myocardial segments. Doppler tissue velocities can also be displayed in 2D or M-mode format with colorcoded velocities superimposed on the tissue image. Although present versions of TDE are promising, they do have significant limitations. The pulsed tissue Doppler mode allows sampling from only one myocardial region at a time.this complicates comparisons between various regions because of significant beat-to-beat variability and translational motion. In this study we used a new off-line method that provides quantitative velocity data from an unlimited 986

2 Volume 13 Number 5 Edvardsen et al 987 Figure 1 Two-dimensional tissue Doppler image from apical 4-chamber view at baseline (center). Velocities toward the transducer are color-coded red, and velocities away from the transducer are coded blue. Left, Velocity profile from mid septum. Right, Simultaneous profile from mid lateral wall. (For further details about velocity spikes during cardiac cycle, see Figure 2.) The green dots indicate points of velocity measurements. number of regions selected within a 2D image. 8,9 Thus, by this method we could compare velocities in multiple regions from the same heartbeat.this is most easily done from the apical 4-chamber view, which allows measurements of longitudinal tissue velocities.the assessment of longitudinal velocities has been shown to minimize the effect of cardiac translation. 10 Furthermore, we included a tracking function that allowed partial compensation for cardiac translation.this new method should potentially enhance the sensitivity of TDE for detecting regional myocardial dysfunction. The goal of the study therefore was to determine the ability of this new approach to quantify regional myocardial function during acute myocardial ischemia induced by balloon angioplasty. METHODS Material Twenty-two consecutive patients undergoing coronary angioplasty were studied.the criteria for inclusion were a significant area of stenosis ( 75%) of the left anterior descending coronary artery (LAD) without any regional LV dysfunction at rest, as evaluated from the ventriculogram. Four patients had additional significant stenosis of the circumflex artery (Cx) and 6 had stenosis of the right coronary artery (RCA). If stenosis in the Cx or RCA was present, the lesion in the LAD was always treated by angioplasty first. All had stable angina pectoris verified with an exercise electrocardiogram (ECG). Patients with evidence of previous myocardial infarction or valvular heart disease as defined by echocardiography and/or left heart catheterization were excluded. All were in regular sinus rhythm. The regional ethical committee on human research approved the study. Written informed consent was given by all participants. Cardiac Catheterization Coronary angiography and left ventriculography were performed 3 to 6 weeks before angioplasty. The LV ejection fraction (LVEF) was calculated with a single-plane ellipsoidal formula. 11 Coronary angioplasty of the LAD stenosis was performed by the standard percutaneous transfemoral approach.the balloon inflations lasted 30 to 180 seconds and were repeated 1 to 6 times.there was a reperfusion period of 3 to 11 minutes between each occlusion. Coronary stenting was performed in 16 patients. Echocardiography Studies were performed with a phased-array ultrasonic device system (System Five, GE Vingmed Ultrasound, Horten, Norway) with use of a duplex transducer (3.75 MHz for TDE).The patients were examined in the supine position because a left lateral position would interfere with the angioplasty procedure. Recordings were performed before, during, and 10 minutes after the completed coronary angioplasty. Two-dimensional TDE images of the left ventricle were obtained from the apical 4-chamber views. Care was taken that all recordings were performed from the same apical window in each patient.

3 988 Edvardsen et al November 2000 Doppler Tissue Echocardiography The general principles that underlie the TDE modalities have been well described previously. 6,8,9,12 Briefly, by excluding the low-intensity flow signals, the strong tissue signals derived from myocardial motion are sent directly into the autocorrelator without high-pass filtering. Recordings were stored digitally as 2D cineloops and transferred to an optical disk medium for off-line analysis with use of commercially available postprocessing and analyzing software (Echopac, GE Vingmed Ultrasound). With this software, the images showing the velocity of tissue motion are superimposed on the 2D echocardiographic image for real-time display in color. By using the apical 4-chamber plane, the myocardial longitudinal wall motion velocities are assessed during the cardiac cycle. Velocities toward the transducer are colorcoded red, and velocities away from the transducer are coded blue (Figure 1).These color-coded velocities are automatically decoded into numeric values for analysis. By marking a region of interest on the 2D image, a velocity trace throughout the cardiac cycle for this area can be generated. This trace represents the mean of the instantaneous velocity spectrum. In this study, 2D tissue velocity images of the left ventricle were obtained at 69 ± 15 frames/s, which implies a temporal resolution of approximately 15 ms. Measurements were obtained from 3 regions along the interventricular septum (apical, mid, and basal septum) and from the corresponding regions on the lateral wall. Apical velocities were assessed from the most proximal part of the apical segment, as shown in Figure 1, because of potential problems with interpretation of apical velocities.technically adequate recordings were present when smooth velocity traces throughout systole and diastole could be obtained by repeated measurements in the different segments of the left ventricle.the TDE velocity traces were examined for numeric values, distinctive features, and velocity direction of myocardial movements throughout the cardiac cycle. The different phases of the heart cycle were defined in concordance with previous studies. 13,14 Systolic acceleration was measured from the end of isovolumic contraction (IVC) to the first peak systolic velocity. The isovolumic relaxation (IVR) was defined from the 2D loop as the period after systole and before mitral valve opening.the distinct signal from mitral valve movements could be assessed from the same 2D loop as velocity measurements from the myocardium. Measurements were taken from the mid portions of the LV wall. In patients with marked lateral displacement of the heart, compensation was made for this throughout the cardiac cycle by manual frame-to-frame marking of the region of interest on the 2D image.this corrected velocity trace was used for processing. Statistical Analysis Data are presented as mean value ± SD. Comparisons between velocities at different time points were analyzed Table 1 Clinical and hemodynamic characteristics Number 22 Age (y) 58 ± 8 Women/Men (number) 2/20 LVEDP (mm Hg) 14 ± 6 LVEF (%) 79 ± 7 HR (bpm) 58 ± 8 LAD lesion (area stenosis %) 85 ± 8 Mean values ± SD. LVEDP, Left ventricular end-diastolic pressure; LVEF, left ventricular ejection fraction; HR, heart rate; LAD, left anterior descending coronary artery. with a 1-way analysis of variance, and corrections were made for multiple comparisons with Bonferroni s criteria. Comparisons between different regions were analyzed with an unpaired Student t test. Differences were considered statistically significant when the P value was <.05. RESULTS Clinical and hemodynamic characteristics are shown in Table 1. Technically acceptable recordings were obtained in all patients before and during angioplasty. In 3 patients, data recordings after angioplasty were corrupted. One patient was not analyzed after angioplasty because of an emergent need for coronary bypass surgery. Left ventricular function was evaluated by objective quantification of regional myocardial velocities in 358 of the total 396 segments in the 22 patients. Velocity Pattern Before Angioplasty In all patients, the longitudinal velocity trace from each area of the myocardium had distinctive and similar features throughout the cardiac cycle (Figure 2, Table 2). There were 3 major myocardial velocities during a cardiac cycle. During systole the dominant velocity component was directed toward the apex. During diastole there were 2 major velocity components: an early (E) diastolic velocity and an atrial (A) induced velocity, both directed toward the base. During LV ejection, there was a large early systolic velocity (V SYS1 ), which peaked 103 ± 22 ms after peak R on the ECG.The timing of V SYS1 in different septal and lateral segments was not significantly different.v SYS1 did, however, decrease toward the apex (5.6 ± 1.5 cm/s versus cm/s,p <.001). After the early peak, a decrease in systolic velocity occurred and continued into a plateau-like phase. The velocity measured during this plateau, halfway during LV ejection, was defined as V SYS2 and was measured 180 ± 38 ms after peak R on the ECG. There were 2 minor myocardial velocity compo-

4 Volume 13 Number 5 Edvardsen et al 989 Table 2 Myocardial velocities (cm/s) in septal and lateral wall segments during the cardiac cycle at baseline, during and after LAD occlusion Location V SYS1 V SYS2 V IVR V E V A Septum Basal Baseline 5.6 ± ± ± ± ± 1.5 Occlusion 4.4 ± 1.6* 2.8 ± ± ± 1.7* 5.5 ± 1.5 After 6.0 ± ± ± ± ± 1.6 Mid Baseline 4.1 ± ± ± ± ± 1.4 Occlusion 1.8 ± ± ± ± ± 1.5 After 4.2 ± ± ± 1.1* 5.4 ± ± 1.3 Apical Baseline 2.8 ± ± ± ± ± 1.3 Occlusion 0.6 ± ± ± ± ± 1.4 After 2.5 ± ± ± ± ± 1.9 Lateral wall Basal Baseline 5.6 ± ± ± ± ± 2.2 Occlusion 5.1 ± ± ± ± ± 2.0 After 5.6 ± ± ± ± ± 2.6 Mid Baseline 4.5 ± ± ± ± ± 2.4 Occlusion 4.1 ± ± ± ± ± 1.9 After 4.6 ± ± ± ± ± 2.0 Apical Baseline 3.5 ± ± ± ± ± 2.3 Occlusion 1.9 ± ± ± ± ± 1.6 After 3.7 ± ± ± ± ± 1.6 V SYS1, Early systolic velocity; V SYS2, midsystolic velocity; V IVR, velocity during isovolumic relaxation; V E, early diastolic velocity; V A, atrial induced velocity. *P <.01 compared with baseline. P <.05 compared with baseline. P <.001 compared with baseline. nents in the period between the peak of the R wave on the ECG and the onset of the large positive systolic velocity corresponding to the IVC period. The dominant velocity peak during IVR was negative (V IVR ). Velocity Pattern During Regional Ischemia Occlusion of the LAD caused significant reduction of early and mid systolic velocities (V SYS1 and V SYS2 ) in the segments supplied by this artery. The most marked changes occurred in the apical segment of the septum, where negative velocities indicating paradoxical motion were found in 27% of the patients during V SYS1 and in 73% during V SYS2 (Figure 3).Less marked reductions of systolic velocities were seen in the basal portion of the septum and lateral wall. The lengths of time to V SYS1 and V SYS2 were delayed during ischemia and measured 117 ± 25 ms (P <.05) and 201 ± 40 ms (P <.05), respectively, after peak R on the ECG. The pattern of V SYS2 was changed from a plateau at baseline into a more defined negative peak velocity in most patients in the ischemic segments. Systolic acceleration decreased from 85 ± 43 cm/s 2 to 30 ± 30 cm/s 2 (P <.001).This decrease was present in each patient, but the difference was less than 10 cm/s 2 in 3 patients. As demonstrated in Figure 4, LAD occlusion induced marked nonuniformity of regional myocardial tissue velocities. The velocities in the segments supplied by the occluded artery were significantly lower than in the presumably nonischemic segments. In mid and basal segments of the lateral wall, no significant change in velocities occurred. The velocities during IVR were considerable changed. The V IVR became paradoxical with positive velocities in all patients (P <.001) except one in the segments supplied by LAD.This patient had RCA occlusion and 75% area stenosis of the Cx.The V IVR remained unchanged in nonischemic parts of the lateral wall. The early diastolic velocity (V E ) and the atrial induced velocity (V A ) were easily recognized in the velocity profile in each patient during ischemia.the regional V E became moderately reduced in the basal and mid septal segments (P <.05), whereas no significant changes were found in other segments of the ventricle.the V A decreased moderately in the apical septum region (P <.05). Velocity Pattern After Angioplasty Reperfusion of ischemic myocardium was associated with rapid increases of systolic velocities and restoring of negative V IVR.Ten minutes after balloon deflation, the velocity traces were back to the control values except in 2 patients in whom V SYS1 became

5 990 Edvardsen et al November 2000 Figure 2 Tissue Doppler imaging from a patient before (top) and during (bottom) occlusion of the left anterior descending coronary artery. V IVC, Isovolumic contraction period; V SYS1, early systolic velocity; V SYS2, midsystolic velocity; V IVR, velocity during isovolumic relaxation; V E, early diastolic velocity; V A, atrial induced velocity. slightly lower than during LAD occlusion.the V SYS2 and V IVR, however, returned to baseline values in both these patients. Electrocardiograms During LAD occlusion, ST-segment depression in the standard ECG lead II was 1.6 ± 0.7 mm. STdepression 1 mm in at least one precordial lead was present in all. Reproducibility Twenty-three recordings from 10 patients were randomly selected and analyzed later by another investigator. The kappa values within 1 cm/s range for intraobserver and interobserver agreement for V SYS1 were 0.53 and 0.48, respectively.the corresponding values for V SYS2 were 0.44 and 0.44 and for V IVR were 0.58 and 0.64, respectively. The interobserver agreement regarding timing parameters was 0.60 for V SYS1, 0.57 for V SYS2, and 0.66 for V IVR. No systematic differences existed in these measurements. DISCUSSION In the normal myocardium, there is systolic shortening of all myocardial segments, and therefore TDE from an apical window shows uniformly positive sys-

6 Volume 13 Number 5 Edvardsen et al 991 tolic velocities. In the present study, 2D TDE showed consistent and marked reductions in early systolic tissue velocities in ischemic myocardium. In most patients,v SYS2 became reversed in the apical septum, indicating severe ischemia with systolic lengthening of the ischemic segments. In the remaining patients, a reduction was found in systolic velocities consistent with regional hypokinesis. Regional myocardial tissue velocities represent the net effect of the contractile and elastic properties of the whole area under investigation.therefore, tethering effects from adjacent segments could influence the velocity results, and this might explain why V SYS1 is positive in most patients during ischemia. A supplementary sign, which is consistent with severe ischemia,was an early diastolic positive velocity.this most likely represents delayed contraction or passive collapse of the dyskinetic segment during IVR. In those patients in whom systolic velocities remained positive during ischemia, there was overlap with preischemic velocities on a group basis. Importantly, however, each of these patients demonstrated marked nonuniformity in velocities between the ischemic and nonischemic regions.taken together, these findings indicate that 2D TDE is a powerful diagnostic method for regional ischemia when the absolute velocities as well as the spatial velocity distinction are taken into account. In particular, the finding of reversed systolic velocities (ie, velocities directed away from the apex) should be an unequivocal sign of injured myocardium. Two-Dimensional Doppler Tissue Imaging We used a recently developed 2D TDE program that has the ability of recording 2D images of the heart with high frame rates. 8 The high frame rate makes this program very accurate and suitable for determining regional changes during an ischemic condition.for the first time,we have been able to measure velocities simultaneously from ischemic and nonischemic myocardium. This reduces variability caused by beat-to-beat differences in tissue velocities. In the present study as well as in a previous study, substantial overlapping between velocities measured before and during acute ischemia from the same location in different patients were found. 15 Comparing a nonischemic part of the myocardium with an ischemic part from the same cardiac cycle, however, revealed considerable differences in all patients. Most of the quantitative TDE studies so far have been based on M-mode or pulsed Doppler. The pulsed Doppler tissue imaging technique is good for measuring myocardial velocities because of the high frame rate. 13,16 The 2D TDE technique used in the Figure 3 The early systolic velocity (top) and midsystolic velocity (bottom) in apical septum at baseline and during and after occlusion of the left anterior descending coronary artery (LAD) in each patient. present study has a lower frame rate, but it offers the advantage of real-time image acquisition of the entire left ventricle with off-line analysis of an optional location from the same time interval. Circumferential and Longitudinal Wall Motions: Previous Studies It is well established that normal LV contraction and relaxation is a result of the interplay between longitudinal and circumferential myocardial fibers. 17 The myocardial concentric contraction pattern has been studied with the TDE technique from the parasternal short-axis view. Low systolic myocardial velocities in ventricles with myocardial damage, hypertrophy, and cardiomyopathy have been demonstrated by several authors. 4,6,14,18 Bach et al 15 studied systolic and diastolic myocardial velocities during angioplasty from the short-axis view.their findings of reduced systolic and diastolic velocities during transient ischemia corresponded to our findings of decreased V SYS1 and V E. The apical 4-chamber view allows simultaneous measurements of normal and ischemic regions from

7 992 Edvardsen et al November 2000 A Figure 4 A, Tissue velocities in apical septum and apical lateral wall at baseline and during LAD occlusion. Each line represents one patient. The squares and vertical lines indicate mean ±2 SD. B, Tissue velocities in mid septum and mid lateral wall at baseline and during LAD occlusion. LAD, Left anterior descending coronary artery; V SYS1, early systolic velocity; V SYS2, midsystolic velocity; V IVR, velocity during isovolumic relaxation. 3 levels of the left ventricle (basal, mid, and apical) and was preferred in this study. Mitral annular and myocardial longitudinal velocity measurements have been used in several recent studies to characterize systole in healthy persons and in subjects with different heart diseases. 9,13,19-22 Generally, systolic longitudinal velocity was reduced in most heart diseases. This longitudinal approach has also been useful to describe the diastolic function in healthy subjects and in patients with LV hypertrophy, showing a decrease in V E with age and in LV hypertrophy. 23 The prominent postsystolic positive velocity during IVR in acute ischemia is in accordance with a gray-scale M-mode study of the mitral annulus in acute coronary occlusion. 24 Alterations of IVR velocities have also been demonstrated in an experimental study during acute ischemia by use of the pulsed Doppler tissue technique from the mid septum. 16 Several conditions are thus responsible for decreased myocardial systolic and diastolic velocities, and myocardial ischemia is difficult to diagnose from a single finding of reduced velocity.most studies so far have focused on the highest systolic velocity.the present study indicates, however, that to diagnose ischemia, both systolic and early diastolic velocities should be taken into account and compared with other regions of the left ventricle that are expected to be normal. Possible Clinical Implications The results of this study indicate that the assessment of myocardial Doppler velocities may be an important supplement to the visual assessment of regional LV dysfunction. The ability of the 2D TDE program to compare multiple segments from the same heartbeat could increase the diagnostic power of tissue Doppler during stress echocardiography.

8 Volume 13 Number 5 Edvardsen et al 993 B Figure 4 Cont d, B, Tissue velocities in mid septum and mid lateral wall at baseline and during LAD occlusion. LAD, Left anterior descending coronary artery; V SYS1, early systolic velocity; V SYS2, midsystolic velocity; V IVR, velocity during isovolumic relaxation. Limitations The angle between the Doppler beam and the different myocardial segments varies in this study. However, characteristic features in the temporal velocity pattern, such as velocity reversal, are not angle dependent. 8 The problems with cardiac translation and rotation are inherent in all TDE techniques. Because velocities in the nonischemic myocardium remained unchanged during LAD occlusion, we believe that the translation and rotation movements were of minor importance for the velocity assessment in the ischemic regions. Assessment of velocities in the LV apex is ambiguous.therefore apical velocities in this study were measured close to the mid segments. A total assessment of the left ventricle requires measurements from 3 ultrasonic apical views. In this study, measurements of ischemia were obtained during a short period of balloon inflation. All our efforts therefore were made to provide reliable data in the apical 4-chamber view, which visualizes considerable parts of the LAD perfused area. Conclusions This study demonstrates the ability of 2D TDE to quantify myocardial velocities from multiple regions simultaneously. This modality appears to enhance the sensitivity of TDE for diagnosing myocardial ischemia and regional dysfunction. Reversed systolic wall motion during the second part of systole and marked positive velocity during early diastole might be new and important markers of myocardial ischemia. Prospective trials are needed to determine whether the TDE approach has incremental clinical value over conventional wall motion analysis with gray-scale 2D echocardiography.

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