- Email: [email protected]
Rapid Resolution of Hyperkinesis After Exercise
Rapid Resolution of Hyperkinesis After Exercise* 1\v~Dlrnensional
Normal Subjects
Echocarcliographic Studies In
Ricardo Ciniglio , M.D .; Mark Kime; Trudy L. Burns, Ph.D.; and Byron F. Vandenberg, M .D .
Abnormal wall motion detected with exercise echocardiography identifies ischemic myocardium, while normal myocardium exhibits hyperkinetic motion. The normal, hyperkinetic response to exercise is transient and is predictive of an exceUent prognosis. However, there are few data on the duration of the hyperkinesis after peak exercise. Our purpose was to determine the time course of wall thickening after exercise in eight normal subjects with two-dimensional echocardiography. Percentage of waD thickening increased
from 53 ± 24 percent at baseline to 82 ± 24 percent at 0 to 2 min postexercise (p
Exercise-induced wall motion abnormalities, visualized by two-dimensional echocardiography, suggest the presence of coronary artery disease with a sensitivity of 70 to 94 percent, and a specificity of 67 to 92 percent.v" Hyperkinetic wall motion , on the other hand, is predictive of an excellent prognosis.4 The normal, hyperkinetic response to exercise is transient; and there are few data on the time course of resolution. The duration of normal, hyperkinetic wall motion is important to recognize because of the implications regarding prognosis. Our purpose, therefore, was to measure regional wall thickening in normal subjects before and serially after exercise, and to determine the duration of exercise-induced hyperkinesis.
an echocardiographic machine (Hewlett-Packard Sonos 1(00), using 2.5- or 3.5-MHz transducers. Parasternal long-axis and short-axis, as well as apical four- and two-chamber views, were obtained prior to exercise. Subjects were exercised on a treadmill according to the maximal Bruce protocol to at least 85 percent of their predicted maximal heart rate for age and to completion of stage 5 of the protocol. Electrocardiograms were recorded during each of the five stages of exercise, then at immediate recovery, and at 1, 3, and 5 min postexercise. Immediately after completion of exercise, the subjects were placed in a left lateral decubitus position. Within 2 min of exercise, the echocardiographic examination was repeated. Acoustic windows for parasternal views were chosen to obtain similar views as baseline. At 2 to 4 and 5 to 7 min after exercise. additional imaging was performed. At each of the echocardiographic examinations, gain settings were optimized to identify endocardial borders without "blooming" of the surfaces.·
METHODS
Subjects
Eight normal male subjects (age, 29 ± 4 years; range, 25 to 33 years) were studied. All subjects gave informed consent. The institutional committee on human research approved the study protocol. All had a normal history, ph ysical examination, and 12lead electrocardiogram. In addition, they were screened to assure adequate acoustic windows prior to exercise and echocardiographic imaging. The chest wall was marked with a marker in order to approximate imaging of similar acoustic windows at baseline and after exercise.' Exercise &hocardiography Protocol
Two-dimensional echocardiographic images were obtained with .From the Cardiovascular Center, Departments of Internal Medicine and Preventive Medicine, College of Medicine, University of Iowa. Iowa City. Supported in part by Grant-in-Aid 1A-92-GS-57 from the American Heart Association, Iowa Affiliate, West Des Moines, Iowa. Manuscript received April 21, 1992; revision accepted February 9, 1993 Reprint requests: Dr: \&ndenberg. Department of Medicine. University of Iowa Hospital, Iowa City 52242
712
Image Processing and Measurements
Only the parasternal long- and short-axis views were used for wall thickening measurements; endocardial surfaces were not consistently visualized from the apical views at peak exercise. Enddiastolic and end-systolic frames were digitized from videotape using a frame grabber (Nova Microsonics Color-Vue II) (512 X 240 x 6 bit matrix). End-diastole was defined as the frame just prior to, or during, mitral valve closure.· End-systole was defined as the frame prior to mitral valve opening in long-axis views or as the smallest cavity area in short-axis views," Parasternal long- and short-axis views were divided into four and six regions, respectively (Fig 1).7 Regional end-diastolic and end-systolic wall thickness was measured by averaging ten lengths evenly distributed within each region, wing the leading edge-to-leading edge method.· Wall thickening was measured after review of videotapes in order to identify endocardial and epicardial surfaces. Care was taken to exclude the chords and epicardium from the posterior wall endocardial surface; right-sided chords were excluded from the right ventricular side of the septum .' When these structures appeared to overlie the surfaces, the myocardial thickness was not measured. Wall thickness change was the dilference between end-systolic and end-diastolic thickness. I' Fractional systolic wall thickening was calculated using the following formula : RapId Resolution of HypeI1dne8I8 Alter Exercise (Cln/gllo et 8/)
Table l-Rnulta ofHeGrt Bate, SynoUc Bp, and HatePreaure Product (BPP) Baseline
Post
0-2 min Post
2-4 min Post
78:t 19
179:t2O* (94:t9%) 164:t 18t 29,422:t5,075*
129:t 18* (69:t9%) 159:t27t 2O,353:t 3,613*
104:t22* (55:t 12%) 146:t31t 15,299:t 4,683*
Immediately Heart rate, % maximum predicted Systolic Bp, mm Hg Rate pressure product
119:t 11 9,216:t 2,361
5-7 min
Post 98:t 17* (52:t9%) 119:t 18 l1,639:t2,924
*p
Data are expressed as mean z standard deviation. A two-factor repeated measures analysis of variance model (with factors subject and time) was fitted to the heart rate, systolic Bp, and rate pressure product data. A three-factor repeated measures analysis of variance model (with factors subject, time, and region) was fitted to the systolic wall thickness change and the percentage of systolic wall thickening data. lime by region interaction effects were also included in the three-factor model. lbst hoc multiple pairwise comparisons were conducted following the overall analyses using the Bonferroni procedure to control the overall experimentwise error rate at 0.05. Variability was calculated as the mean percent error (difference between two measurements divided by the mean of two measurements x 100). RESULTS
There were signi6cant (p
elevation and recovery of the rate pressure product was the same as for systolic BP with a significant elevation (p
Table 2-RegiontJl DiJfermca in WaD Thiclcening Of>erTime After lMk EzerciIe Postexercise
Basal anterior septum (long axis)t Thickness change Percentage of thickness change Basal posterior (long axis) Thickness change Percentage of thickness change Mid anterior septum (short axis)t Thickness change Percentage of thickness change Mid inferior lateral (short axis) Thickness change Percentage of thickness change
Baseline
0-2 min*
2-4 min
5-7 min
(n=8) O.4:tO.l 42:t 15 (n=8) 0.6:t0.2 75:t24 (n=8) O.4:tO.l 39:t21 (n=7) 0.5:t0.2 57:t 17
(0=6) 0.7:t0.2 72:t20 (n=5) 0.9:t0.l 92:t22 (n=3) 0.6:t0.l 72:t5 (n=5) 0.8:t0.3 91 :t33
(n=4) 0.5:t0.l 52:t8 (n=5) 0.8:t0.2 88:t 19 (n=4) 0.3:t0.l 34:t10 (n=4) 0.7:t0.2 76:t25
(n=8) 0.4:t0.l 42:t 16 (n=7) 0.7:t0.l 69:t 16 (n=6) O.4:tO.l 46:t1O (n=7) 0.6:t0.2 61 :t23
*p
713
Baseline
0-2
ins Post
2-4
ins Post
5-7
ins Post
FllaJKE 1. End-systolic parasternal long-axis (upper panel) and short-axis (lower panel] views of the left ventricle at baseline, 0 to 2, 2 to 4, and 5 to 7 min after peak exercise. The regions used for measurements are identified at baseline. In the parasternal long-axis view, wall thickness was measured in the basal anterior septal and mid anterior regions and also in the basal posterior and mid-inferior lateral regions. In the parasternal short-axis view, wall thickness was measured in (starting at I2-o'c1ock position, then clockwise) mid-anterior septal, mid-anterior, mid-lateral, mid-inferior lateral, mid-inferior, and mid-septal
re-gions .
indication that the time course was different from one region to the next for either variable since the interaction effects were not significant (p>O,80). Because the interaction effects were not significant, time comparisons were made by combining the data over all four regions. Overall systolic wall thickness change (Fig 2) and percentage of systolic wall thickening (Fig 3) increased from baseline to 0 to 2 min postexercise, but returned to baseline at 2 to 4 min . Percentage of wall thickening increased from 53 ± 24 percent at baseline to 82 ± 24 percent at 0 to 2 min postexercise (p
septum (long axis) and in the mid anterior septum (short axis) compared with the basal posterior (long axis) or the mid inferior lateral (short axis) regions (p
The major finding of this study was that maximal systolic wall thickening occurred within 2 min after exercise, then returned to baseline, corresponding to changes in hemodynamics.
Temporal Variability in Thickening Exercise two-dimensional echocardiography is used to identify wall motion abnormalities that develop during ischemia in patients with coronary artery Rapid Resolution 01 Hyper1
1.2
""T"""------- -- - -- - -- -----,
* p c2·4 0.ll25 vs Baseline, mlns post
*
1.0
nd
5·7 mlns post
0.8
Well Thickness Chenge(cm)
0.8 0.4
0.2
o
l..a •••~....IL__I. . . . .L_.J. . . . .LJ Buellne
O·2111M Post
5.7111M
2-4 111M Post
Post 125
FIGURE 2. Bar Rrnph of systolic wall thickness change at baseline, 0 to 2, 2 to 4. and 5 to 7 min postexercise.
""T"""-- - - - -- - - - - - - - - - - - -.....
*
100
Percent
* p2c ·0.05 vs Baseline, 4 mlns post ...cI 5 • 7 mlns post
75
Systolic Well
thickening
50
25
FIGURE 3. Bar graph of percent systolic wall thickening at baseline. 0 to 2, 2 to 4. and 5 to 7 min postexercise.
disease. When myocardial perfusion is inadequate during the increased oxygen consumption associated with exercise, wall motion is reduced. I •3.11-17 In contrast, normal myocardium, after exercise, is hyperkinetic, with increased wall thickening, decreased systolic cavity size, and essentially normal diastolic dimensions." However, there are few studies on the time course of normal systolic function after exercise. In an M-mode echocardiographic study of normal subjects, Berberich et al l H demonstrated a trend toward baseline function by 3 min after exercise; by 4 to 5 minutes, function had returned to baseline. In their study, cavity dimensions, not wall thicknesses, were measured. In our study, the return of systolic wall thickening to baseline occurred with the return of hemodynamics toward normal. This reflects the influence of circulating catecholamines on both contractility (specifically, wall thickening) and heart rate .19 Since systolic wall thickening returned to baseline at 2 to 4 min after exercise, our study provides objective data in support of the recommendations of other authors that imaging should be completed within 2 min of peak exerciseI3.16.20 in order to assess maximal wall thickening. Regional Heterogeneity of Wall Thickening
Our findings of regional variability in wall thickening at baseline are similar to previous studies using Mmode echocardiography. Corya et al'? demonstrated that the normal septum thickened by 36 ± 12 percent
o i l.....__.....U Buellne
O· 2111n. Post
. . . .U . . . 2·4111ns Post
5· 7111ns Post
(range, 14 to 57 percent) compared with 47 ± 16 percent (range, 21 to 92 percent) in the normal posterior wall. A similar difference was also suggested in a study by Mason et al2 1 of normal subjects at rest and after exercise. Septal thickening increased from 56±3 (SEM) percent to 77±7 percent and posterior wall thickening increased from 89 ± 9 percent to 115 ± 8 percent with exercise. While these studies suggested a trend toward increased thickening in the posterior wall compared with the septum at rest, as well as with exercise, the statistical significance of the differences was not tested. Similar to the M-mode study by Corya et al,1O we calculated wall thickness change in addition to percentage wall thickening. Thickness change is useful since it may be readily applied to computer-based analysis systems of two-dimensional echocardiograms that have calibrated reference bars for the measurement of relative changes in endocardial motion ." In the study by Corya et al, wall thickeness change was 3 ± 1.2 mm (range, 1 to 5 mm) in the septum and 5 ± 1.88 mm (range, 3 to 11 mm) in the posterior wall. These measurements, obtained at rest, are similar to our results. The mechanism for the regional heterogeneity in systolic function between the septum and posterior wall is uncertain. Possible explanations include regional variation in the response to loading conditions'" or increased longitudinal shortening of the left ventricular free wall compared with the ventricular sepCHEST I 104 I 3 I SEPTEMBER. 1993
715
tum .23 These differences in regional loading conditions and longitudinal shortening probably explain the regional variation in recovery of normal function after exercise . Quantitative Two-Dimensional Echocardiography
While there are few data on intraobserver variability in wall thickness measurements, the 8 percent interobserver variability was similar to the 6 to 8 percent reported by others. 22.24 These previous studies, however, used area-based methods for wall thickness measurements, tracing the endocardial and epicardial borders, and measuring myocardial area at end-dias tole and end-systole .22 •24 We used a linear method, since acoustic shadowing from ribs and lung at peak exercise prevented the visualization of the entire endocardial circumference. While an area method may be more robust than a linear method because of spatial averaging, we averaged multiple linear dimensions. Such clinically useful linear measurements of wall thickness obtained from two-dimensional echocardiograms are similar to those obtained with Mmode echocardiography. 2S Umitations
In our study, we were not able to quantitatively analyze wall motion because of the inability to visualize and trace the entire endocardium . The medial and lateral segments of the endocardium were not visible o to 2 min postexercise; thus, the center of the shortaxis cavity area could not be determined for wall motion analysis. The relationship of wall thickening to wall motion in recovery may be feasible with pharmacologic stress when respiratory artifact is minimized and the entire endocardium is demonstrated. There may be age-related differences in the time course of wall thickening after exercise; thus, our results may not apply to an older population. In our study, we selected young patients because of their lower prevalence of coronary artery disease.t" Since only normal subjects were exercised, we were not able to compare the time course of normal vs abnormal myocardial wall thickening. Such a study would be worthwhile in order to assess the influence of recovery time on return of wall thickening to normal in patients with coronary artery disease. CONCLUSION
Maximum wall thickening occurs within 2 min of peak exercise, then returns to baseline. Accurate identification of hyperkinetic, normal myocardium with exercise echocardiography requires immediate, postexercise imaging. ACKNOWLEDGMENTS: The authors are grateful for the assistance of Richard E . Kerber. M.D.• and David I. Skorton, M.D. In addition, they acknowledge the expert secretarial assistance of Diane Phillips and Ruth Lillie. 716
REFERENCES
1 Maurer G, Nanda NC . Two-dimensional echocardiographic evaluation of exercise-induced left and right venbicular asynergy : correlation with thallium scanning. Am I Cardiol 1981; 48:720-27 2 Sawada SG, Ryan T, Fineberg NS, Annstrong WF, judson WE, McHenry PL, et al. Exercise echocardiographic detection of coronary artery disease in women. I Am CoD Cardiol 1989; 14:1440-47 3 Presti CF, Annstrong WF, Feigenbaum H . Comparison of echocardiography at peak exercise and after bicycle exercise in evaluation of patients with known or suspected coronary artery diseases. I Am Soc Echo 1988; 1:119-26 4 Sawada SG, Ryan T, Conley MI, Corya BC, Feigenbaum H, Annstrong WF. Prognostic value of a normal exercise echocardiagram. Am Heart I 1990; 120:49-55 5 Feigenbaum H. Exercise echocardiography. I Am Soc Echo 1988; 1:161-66 6 Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H , et al. Recommendation for quantification of the left ventricle by two-dimensional echocardiograpby. 1 Am Soc Echo 1989; 2:358-67 7 Broderick T, Sawada S, Annstrong WF, Ryan T, Dillon IC, Bourdillon PY, et al. Improvement in rest and exercise-induced wall motion abnormalities after coronary angioplasty: an exercise ecbocardiography study. 1 Am Coli Cardioll990; 15:591-99 8 Wyatt HL, Haendchen RY, Meerbaum S, Corday E. Assessment of quantitative methods for 2-dimensional echocardiograpby. Am 1Cardioll983; 52:396-401 9 Sahn D , DeMaria A, Kisslo 1, Weyman A. Recommendations regarding quantitation in M-mode echocardiograpby: results of a survey of ecbocardiographic measurements. Circulation 1978; 58:1072-82 10 Corya BC , Rasmussen S, Feigenbaum H , Knoebel SB, Black MI. Systolic thickening and thinning of the septum and posterior wall in patients with coronary artery disease, congestive cardiomyopathy, and atrial septal defect. Circulation 1977; 55:109-14 11 Ryan T, Vasey C , Presti CF, O'Donnell jA, Feigenbaum H, Annstrong WF. Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest. 1 Am Coli Cardioll988; 11:993-99 12 Annstrong WF, O'Donnell 1, Ryan T, Feigenbaum H . Effect of prior myocardial infarction and extent and location of coronary disease on accuracy of exercise echocardiography. 1 Am Coli Cardioll987; 10:531-38 13 Sawada SG, Iudson WE , Ryan T, Annstrong WF, Feigenbaum H . Upright bicycle exercise echocardiography after coronary artery bypass grafting. Am I Cardioll989; 64:1123-29 14 Iaarsma \v, Visser CA, Funke Kupper AI, Res ICJ, Van Eenige MI, Boos IP. Usefulness of two-dimensional exercise echocardiography shortly after myocardial infarction. Am 1 Cardiol 1986; 57:86-90 15 Limacher MC, Quinones MA, Poliner LR, Nelson IG, Winters WL, Waggoner AD . Detection of coronary artery disease with exercise two-dimensional ecbocardiography: description of a clinically applicable method and comparison with radionuclide ventriculography. Circulation 1983; 67:1211-18 16 Sheikh KH , Bengston IR, Helmy S, juarez C , Burgess R, Bashore TM, et al. Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography. I Am CoD CardioII990; 15:1043-51 17 Pandian NG, Kieso RA, Kerber RE . Two-dimensional echocardiography in experimental coronary stenosis: II . Relationship between systolic wall thinning and regional myocardial perfusion in severe coronary stenosis. Circulation 1982; 66:603-11 18 Berberich S, Zager IRS , Plotnick GD, Fisher ML. A practical RapId RelIoIutlon 01 HyperkInesIs Alter Exen:l8e(Cinlgllo
et a1)
19 20
21
22
approach to exercise echocardiography: immediate post exercise echocardlography J Am Coli Cardiel 1984: 3:284-90 Ellestad MH . Stress testing: principles and practice. Philadelphia : FA Davis. 1986; 13 Labovitz AJ. Lewen M. Kern MJ. Vandormael M. Mrosek DG . Byers SL. et aI. The effect of successful PTCA on left ventricular function : assessment of exercise echocardiography. Am Heart J 1989; 117:1003-08 Mason S. Weiss JL. Weisfeldt ML. Garrison JB. Fortuin NJ. Exercise echocardiography: detection of wall motion abnormalities during ischemia. Circulation 1979: 59 :50-9 Haendchen R. Wyatt HL. Maurer G . Zwehl \v, Bear M. Meerbaum S. et aI. Quantitation of regional cardiac function by
23
24
25
26
two-dimensional echocardiography: l. Patterns of contraction in the normal left ventricle. Circulation 1983: 67:1234-45 Kong Y. Morris JJ Jr. McIntosh HD. Assessment of regional myocardial performance from biplane coronary cineangiograrns. Am J Cardio11971: 27:529-37 Himelman RB. Cass idy MM . Landzberg JS . Schiller NB. Reproducibility of quantitative two-dimensional echocardiography. Am Heart J 1988; 115:425-31 Feneley Mp, Hickie JP. Validity of echocardiographic determination of left ventricular systolic wall thickening, Circulation 1984; 70:226-32 Wei JY. Gersh BJ. Heart disease in the elderly. Curr Prohl Cardioll987: 12:1-65
A M E R I C A N C O L L E G E OF C H E S T PHYSICIANS
59th ANNUAL SCIENTIFIC ASSEMBLY October 24 - 28, 1993 • Orlando
Save the Dates
CHEST I 104 I 3 I SEPTEMBER. 1993
717
Normal Subjects
Echocarcliographic Studies In
Ricardo Ciniglio , M.D .; Mark Kime; Trudy L. Burns, Ph.D.; and Byron F. Vandenberg, M .D .
Abnormal wall motion detected with exercise echocardiography identifies ischemic myocardium, while normal myocardium exhibits hyperkinetic motion. The normal, hyperkinetic response to exercise is transient and is predictive of an exceUent prognosis. However, there are few data on the duration of the hyperkinesis after peak exercise. Our purpose was to determine the time course of wall thickening after exercise in eight normal subjects with two-dimensional echocardiography. Percentage of waD thickening increased
from 53 ± 24 percent at baseline to 82 ± 24 percent at 0 to 2 min postexercise (p
Exercise-induced wall motion abnormalities, visualized by two-dimensional echocardiography, suggest the presence of coronary artery disease with a sensitivity of 70 to 94 percent, and a specificity of 67 to 92 percent.v" Hyperkinetic wall motion , on the other hand, is predictive of an excellent prognosis.4 The normal, hyperkinetic response to exercise is transient; and there are few data on the time course of resolution. The duration of normal, hyperkinetic wall motion is important to recognize because of the implications regarding prognosis. Our purpose, therefore, was to measure regional wall thickening in normal subjects before and serially after exercise, and to determine the duration of exercise-induced hyperkinesis.
an echocardiographic machine (Hewlett-Packard Sonos 1(00), using 2.5- or 3.5-MHz transducers. Parasternal long-axis and short-axis, as well as apical four- and two-chamber views, were obtained prior to exercise. Subjects were exercised on a treadmill according to the maximal Bruce protocol to at least 85 percent of their predicted maximal heart rate for age and to completion of stage 5 of the protocol. Electrocardiograms were recorded during each of the five stages of exercise, then at immediate recovery, and at 1, 3, and 5 min postexercise. Immediately after completion of exercise, the subjects were placed in a left lateral decubitus position. Within 2 min of exercise, the echocardiographic examination was repeated. Acoustic windows for parasternal views were chosen to obtain similar views as baseline. At 2 to 4 and 5 to 7 min after exercise. additional imaging was performed. At each of the echocardiographic examinations, gain settings were optimized to identify endocardial borders without "blooming" of the surfaces.·
METHODS
Subjects
Eight normal male subjects (age, 29 ± 4 years; range, 25 to 33 years) were studied. All subjects gave informed consent. The institutional committee on human research approved the study protocol. All had a normal history, ph ysical examination, and 12lead electrocardiogram. In addition, they were screened to assure adequate acoustic windows prior to exercise and echocardiographic imaging. The chest wall was marked with a marker in order to approximate imaging of similar acoustic windows at baseline and after exercise.' Exercise &hocardiography Protocol
Two-dimensional echocardiographic images were obtained with .From the Cardiovascular Center, Departments of Internal Medicine and Preventive Medicine, College of Medicine, University of Iowa. Iowa City. Supported in part by Grant-in-Aid 1A-92-GS-57 from the American Heart Association, Iowa Affiliate, West Des Moines, Iowa. Manuscript received April 21, 1992; revision accepted February 9, 1993 Reprint requests: Dr: \&ndenberg. Department of Medicine. University of Iowa Hospital, Iowa City 52242
712
Image Processing and Measurements
Only the parasternal long- and short-axis views were used for wall thickening measurements; endocardial surfaces were not consistently visualized from the apical views at peak exercise. Enddiastolic and end-systolic frames were digitized from videotape using a frame grabber (Nova Microsonics Color-Vue II) (512 X 240 x 6 bit matrix). End-diastole was defined as the frame just prior to, or during, mitral valve closure.· End-systole was defined as the frame prior to mitral valve opening in long-axis views or as the smallest cavity area in short-axis views," Parasternal long- and short-axis views were divided into four and six regions, respectively (Fig 1).7 Regional end-diastolic and end-systolic wall thickness was measured by averaging ten lengths evenly distributed within each region, wing the leading edge-to-leading edge method.· Wall thickening was measured after review of videotapes in order to identify endocardial and epicardial surfaces. Care was taken to exclude the chords and epicardium from the posterior wall endocardial surface; right-sided chords were excluded from the right ventricular side of the septum .' When these structures appeared to overlie the surfaces, the myocardial thickness was not measured. Wall thickness change was the dilference between end-systolic and end-diastolic thickness. I' Fractional systolic wall thickening was calculated using the following formula : RapId Resolution of HypeI1dne8I8 Alter Exercise (Cln/gllo et 8/)
Table l-Rnulta ofHeGrt Bate, SynoUc Bp, and HatePreaure Product (BPP) Baseline
Post
0-2 min Post
2-4 min Post
78:t 19
179:t2O* (94:t9%) 164:t 18t 29,422:t5,075*
129:t 18* (69:t9%) 159:t27t 2O,353:t 3,613*
104:t22* (55:t 12%) 146:t31t 15,299:t 4,683*
Immediately Heart rate, % maximum predicted Systolic Bp, mm Hg Rate pressure product
119:t 11 9,216:t 2,361
5-7 min
Post 98:t 17* (52:t9%) 119:t 18 l1,639:t2,924
*p
Data are expressed as mean z standard deviation. A two-factor repeated measures analysis of variance model (with factors subject and time) was fitted to the heart rate, systolic Bp, and rate pressure product data. A three-factor repeated measures analysis of variance model (with factors subject, time, and region) was fitted to the systolic wall thickness change and the percentage of systolic wall thickening data. lime by region interaction effects were also included in the three-factor model. lbst hoc multiple pairwise comparisons were conducted following the overall analyses using the Bonferroni procedure to control the overall experimentwise error rate at 0.05. Variability was calculated as the mean percent error (difference between two measurements divided by the mean of two measurements x 100). RESULTS
There were signi6cant (p
elevation and recovery of the rate pressure product was the same as for systolic BP with a significant elevation (p
Table 2-RegiontJl DiJfermca in WaD Thiclcening Of>erTime After lMk EzerciIe Postexercise
Basal anterior septum (long axis)t Thickness change Percentage of thickness change Basal posterior (long axis) Thickness change Percentage of thickness change Mid anterior septum (short axis)t Thickness change Percentage of thickness change Mid inferior lateral (short axis) Thickness change Percentage of thickness change
Baseline
0-2 min*
2-4 min
5-7 min
(n=8) O.4:tO.l 42:t 15 (n=8) 0.6:t0.2 75:t24 (n=8) O.4:tO.l 39:t21 (n=7) 0.5:t0.2 57:t 17
(0=6) 0.7:t0.2 72:t20 (n=5) 0.9:t0.l 92:t22 (n=3) 0.6:t0.l 72:t5 (n=5) 0.8:t0.3 91 :t33
(n=4) 0.5:t0.l 52:t8 (n=5) 0.8:t0.2 88:t 19 (n=4) 0.3:t0.l 34:t10 (n=4) 0.7:t0.2 76:t25
(n=8) 0.4:t0.l 42:t 16 (n=7) 0.7:t0.l 69:t 16 (n=6) O.4:tO.l 46:t1O (n=7) 0.6:t0.2 61 :t23
*p
713
Baseline
0-2
ins Post
2-4
ins Post
5-7
ins Post
FllaJKE 1. End-systolic parasternal long-axis (upper panel) and short-axis (lower panel] views of the left ventricle at baseline, 0 to 2, 2 to 4, and 5 to 7 min after peak exercise. The regions used for measurements are identified at baseline. In the parasternal long-axis view, wall thickness was measured in the basal anterior septal and mid anterior regions and also in the basal posterior and mid-inferior lateral regions. In the parasternal short-axis view, wall thickness was measured in (starting at I2-o'c1ock position, then clockwise) mid-anterior septal, mid-anterior, mid-lateral, mid-inferior lateral, mid-inferior, and mid-septal
re-gions .
indication that the time course was different from one region to the next for either variable since the interaction effects were not significant (p>O,80). Because the interaction effects were not significant, time comparisons were made by combining the data over all four regions. Overall systolic wall thickness change (Fig 2) and percentage of systolic wall thickening (Fig 3) increased from baseline to 0 to 2 min postexercise, but returned to baseline at 2 to 4 min . Percentage of wall thickening increased from 53 ± 24 percent at baseline to 82 ± 24 percent at 0 to 2 min postexercise (p
septum (long axis) and in the mid anterior septum (short axis) compared with the basal posterior (long axis) or the mid inferior lateral (short axis) regions (p
The major finding of this study was that maximal systolic wall thickening occurred within 2 min after exercise, then returned to baseline, corresponding to changes in hemodynamics.
Temporal Variability in Thickening Exercise two-dimensional echocardiography is used to identify wall motion abnormalities that develop during ischemia in patients with coronary artery Rapid Resolution 01 Hyper1
1.2
""T"""------- -- - -- - -- -----,
* p c2·4 0.ll25 vs Baseline, mlns post
*
1.0
nd
5·7 mlns post
0.8
Well Thickness Chenge(cm)
0.8 0.4
0.2
o
l..a •••~....IL__I. . . . .L_.J. . . . .LJ Buellne
O·2111M Post
5.7111M
2-4 111M Post
Post 125
FIGURE 2. Bar Rrnph of systolic wall thickness change at baseline, 0 to 2, 2 to 4. and 5 to 7 min postexercise.
""T"""-- - - - -- - - - - - - - - - - - -.....
*
100
Percent
* p2c ·0.05 vs Baseline, 4 mlns post ...cI 5 • 7 mlns post
75
Systolic Well
thickening
50
25
FIGURE 3. Bar graph of percent systolic wall thickening at baseline. 0 to 2, 2 to 4. and 5 to 7 min postexercise.
disease. When myocardial perfusion is inadequate during the increased oxygen consumption associated with exercise, wall motion is reduced. I •3.11-17 In contrast, normal myocardium, after exercise, is hyperkinetic, with increased wall thickening, decreased systolic cavity size, and essentially normal diastolic dimensions." However, there are few studies on the time course of normal systolic function after exercise. In an M-mode echocardiographic study of normal subjects, Berberich et al l H demonstrated a trend toward baseline function by 3 min after exercise; by 4 to 5 minutes, function had returned to baseline. In their study, cavity dimensions, not wall thicknesses, were measured. In our study, the return of systolic wall thickening to baseline occurred with the return of hemodynamics toward normal. This reflects the influence of circulating catecholamines on both contractility (specifically, wall thickening) and heart rate .19 Since systolic wall thickening returned to baseline at 2 to 4 min after exercise, our study provides objective data in support of the recommendations of other authors that imaging should be completed within 2 min of peak exerciseI3.16.20 in order to assess maximal wall thickening. Regional Heterogeneity of Wall Thickening
Our findings of regional variability in wall thickening at baseline are similar to previous studies using Mmode echocardiography. Corya et al'? demonstrated that the normal septum thickened by 36 ± 12 percent
o i l.....__.....U Buellne
O· 2111n. Post
. . . .U . . . 2·4111ns Post
5· 7111ns Post
(range, 14 to 57 percent) compared with 47 ± 16 percent (range, 21 to 92 percent) in the normal posterior wall. A similar difference was also suggested in a study by Mason et al2 1 of normal subjects at rest and after exercise. Septal thickening increased from 56±3 (SEM) percent to 77±7 percent and posterior wall thickening increased from 89 ± 9 percent to 115 ± 8 percent with exercise. While these studies suggested a trend toward increased thickening in the posterior wall compared with the septum at rest, as well as with exercise, the statistical significance of the differences was not tested. Similar to the M-mode study by Corya et al,1O we calculated wall thickness change in addition to percentage wall thickening. Thickness change is useful since it may be readily applied to computer-based analysis systems of two-dimensional echocardiograms that have calibrated reference bars for the measurement of relative changes in endocardial motion ." In the study by Corya et al, wall thickeness change was 3 ± 1.2 mm (range, 1 to 5 mm) in the septum and 5 ± 1.88 mm (range, 3 to 11 mm) in the posterior wall. These measurements, obtained at rest, are similar to our results. The mechanism for the regional heterogeneity in systolic function between the septum and posterior wall is uncertain. Possible explanations include regional variation in the response to loading conditions'" or increased longitudinal shortening of the left ventricular free wall compared with the ventricular sepCHEST I 104 I 3 I SEPTEMBER. 1993
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tum .23 These differences in regional loading conditions and longitudinal shortening probably explain the regional variation in recovery of normal function after exercise . Quantitative Two-Dimensional Echocardiography
While there are few data on intraobserver variability in wall thickness measurements, the 8 percent interobserver variability was similar to the 6 to 8 percent reported by others. 22.24 These previous studies, however, used area-based methods for wall thickness measurements, tracing the endocardial and epicardial borders, and measuring myocardial area at end-dias tole and end-systole .22 •24 We used a linear method, since acoustic shadowing from ribs and lung at peak exercise prevented the visualization of the entire endocardial circumference. While an area method may be more robust than a linear method because of spatial averaging, we averaged multiple linear dimensions. Such clinically useful linear measurements of wall thickness obtained from two-dimensional echocardiograms are similar to those obtained with Mmode echocardiography. 2S Umitations
In our study, we were not able to quantitatively analyze wall motion because of the inability to visualize and trace the entire endocardium . The medial and lateral segments of the endocardium were not visible o to 2 min postexercise; thus, the center of the shortaxis cavity area could not be determined for wall motion analysis. The relationship of wall thickening to wall motion in recovery may be feasible with pharmacologic stress when respiratory artifact is minimized and the entire endocardium is demonstrated. There may be age-related differences in the time course of wall thickening after exercise; thus, our results may not apply to an older population. In our study, we selected young patients because of their lower prevalence of coronary artery disease.t" Since only normal subjects were exercised, we were not able to compare the time course of normal vs abnormal myocardial wall thickening. Such a study would be worthwhile in order to assess the influence of recovery time on return of wall thickening to normal in patients with coronary artery disease. CONCLUSION
Maximum wall thickening occurs within 2 min of peak exercise, then returns to baseline. Accurate identification of hyperkinetic, normal myocardium with exercise echocardiography requires immediate, postexercise imaging. ACKNOWLEDGMENTS: The authors are grateful for the assistance of Richard E . Kerber. M.D.• and David I. Skorton, M.D. In addition, they acknowledge the expert secretarial assistance of Diane Phillips and Ruth Lillie. 716
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A M E R I C A N C O L L E G E OF C H E S T PHYSICIANS
59th ANNUAL SCIENTIFIC ASSEMBLY October 24 - 28, 1993 • Orlando
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