risk stratification after acute myocardial infarction by means of exercise two-dimensional...

CLINICAL INVESTIGATIONS

Risk stratification after acute myocardial infarction by means of exercise two-dimensional echocardiography

To determine whether exercise two-dimensional echocardiography contributes to the prognostic information provided by exercise testing in patients recovering from acute myocardial infarction, 40 patients were prospectively studied by means of pre- and postexercise echocardiography 10 to 21 days after myocardial infarctlon. Patients were followed for 6 to 10 months or until one of the following clinical end points occurred: death, recurrent myocardiai infarction, unstable angina, or coronary artery bypass grafting. Results of treadmill exercise tests were negative in 13 of 20 patients with good clinical outcome (65% specificity) and positive In 11 of 20 patients with poor clinical outcome (55% sensitivity). The resting echocardiogram was abnormal in 37 of 40 patients. The exercise echocardiogram was negative in 19 of 20 patients with good clinical outcome (95% specificity) and positive in 16 of 20 patients with poor clinical outcome (60% sensitivity). We conclude that exercise echocardiography is more sensitive and specific than treadmill exercise testing for predicting the occurrence of subsequent cardiac events after acute myocardial infarction. (AM HEART J lS67;114:1305.)

Thomas Ryan, M.D., William F. Armstrong, M.D., Jacqueline A. O’Donnell, M.D., and Harvey Feigenbaum, M.D. Indianapolis, Ind.

Survivors of acute myocardial infarction comprise a heterogeneous group whose subsequent mortality risk varies widely. Risk stratification may be useful to identify those patients with increased likelihood of future cardiac events, so that appropriate thera- peutic measures can be undertaken.1*2 Conversely, demonstration of low-risk status provides significant physiologic benefits and allows some patients to be spared unnecessary invasive testinge3

Several investigators have shown that low-level exercise testing can be performed safely after myocardial infarction.4-g The test provides useful information on functional capacity,g can detect clinically important arrhythmias,4~5~g and may be predictive of subsequent coronary events.4-g It is assumed that the prognostic value of exercise testing depends on its

From the Department of Medicine, Indiana University School of Medicine, the Krannert Institute of Cardiology, and the Richard L. Roudebush Veterans Administration Medical Center.

Supported in part by the Herman C. Krannert Fund, Indianapolis, Ind.; grants HL-06308 and HL-07182 and Clinical Investigator Award HL-01041 (Dr. Armstrong) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.; the American Heart Associ- ation, Indiana Affiliate, Indianapolis, Ind.; and the Whitaker Foundation, Camp Hill, Pa.

Received for publication June 8, 1987; accepted July 10, 1987.

Reprint requests: Thomas Ryan, M.D., Indiana University Medical Center, University Hospital N-562, 926 West Michigan St., Indianapolis, IN 46223.

ability to provoke and detect reversible ischemia. However, some studies suggest that the development of angina during treadmill testing correlates poorly with exercise-induced ST segment depression.’ Furthermore, the significance of ST segment depression as a predictor of cardiovascular morbidity and mortality is not universally accepted.“12 One group of investigators13 has emphasized the importance of evaluating other manifestations of ischemia, such as exercise-induced decrease in ejection fraction, rather than relying solely on traditional indices, such as angina or ST segment depression. Finally, the ability of routine exercise testing to identify patients with multivessel coronary artery disease is limited.14

Two-dimensional echocardiography performed before and immediately after exercise can identify patients with inducible myocardial ischemia by demonstrating exercise-induced asynergy of dyssynergy. 15,16 Exercise-induced wall motion abnormalities correlate well with reversible thallium defects” and are a useful adjunct to the stress ECG for the detection of ischemic myocardium.

In this prospective study, exercise echocardiography was performed in a group of patients during the convalescent phase after acute myocardial infarction. The purpose of the investigation was to determine if exercise echocardiography contributes to the

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Table I. Criteria used for interpretation of exercise echocardiogram in patients with known myocardial infarction

Wall motion

Rest After exercise Znterpretation

Normal Normal

Hyperkinetic Normal

Negative Negative

Normal Normal

Hypokinetic Akinetic/dyakinetic

Positive Positive

Hypokinetic Akineticldyskinetic Negative*

Hypokinetic Akineticldyskinetic Positive?

Akineticldyskinetic Akinetic/dyskinetic Negative*

*As the sole wall motion abnormality. tin association with another wall motion abnormality.

prognostic information provided by exercise testing in this subset of patients. Specifically, the study was designed to examine whether exercise-induced wall motion abnormalities identify post-myocardial infarction patients at high risk for an unfavorable clinical course and to determine if exercise echocardiography can predict the extent of coronary artery disease after myocardial infarction.

METHODS

Patient populatlon. Survivors of uncomplicated myocardial infarction who would otherwise be considered candidates for submaximal stress testing were eligible for participation in this study. The series cannot be considered consecutive, since participation required referral from the primary physician. However, because most patients who experience uncomplicated myocardial infarction at the Indiana University Medical Center are subjected to submaximal treadmill testing, this cohort may be considered typical and representative of such a population. Forty patients were enrolled prospectively during the convalescent phase after acute myocardial infarction. Documentation of myocardial infarction required at least 2 of the following: (1) history of prolong- ed chest pain, (2) development of pathologic Q waves or evolutionary ST-T wave changes on the resting ECG, or (3) elevation of serum levels of creatinine kinase MB isoenzymes, lactate dehydrogenase (LDH, > LDHI), or both. Patients were excluded from the study because of: (1) angina occurring more than 48 hours after myocardial infarction, (2) moderate to severe congestive heart failure, (3) serious ventricular arrhythmias, (4) second- or third- degree atrioventricular block, (5) underlying valvular heart disease, (6) blood pressure >190/110 mm Hg, or (7) exercise-limiting noncardiac abnormalities.

Patients were recruited into the study if they fulfilled the entry criteria for documented myocardial infarction,

had no contraindication to treadmill exercise testing, had a technically satisfactory resting two-dimensional echocardiogram, and were willing to give informed consent. Patients who, on the basis of traditional clinical criteria or immediate postinfarction course, were thought to be at “high risk” for subsequent coronary morbidity were not referred for treadmill testing and, consequently, were not considered for participation in the study.

Treadmill protocol. Exercise testing was performed by means of a motor-driven treadmill and was conducted in 3-minute uninterrupted stages according to the following protocol: stage I, speed 1.5 m/hr with 3% grade (2.0 METS); stage II, speed 2 m/hr with 6% grade (3.7 METS); stage III, speed 2.4 m/hr with 9% grade (5.2 METS); and stage IV, speed 2.8 m/hr with 12% grade (7.5 METS). Three simultaneous ECG leads (bipolar Vz, Vg, lead II) were monitored continuously with an oscilloscope at rest, during exercise, and for 6 minutes after exercise. Direct writeouts were obtained and blood pressure was recorded at rest and during each exercise stage. Exercise was continued until achievement of 70% of the maximum predicted heart rate for sex and age or until one of the following end points occurred: (1) angina, (2) ~2 mm ST segment depression, (3) limiting symptoms, such as fatigue or leg cramps, (4) >lO mm Hg decrease in exercise blood pressure, and (5) increase in systolic blood pressure to >200 mm Hg. A positive test result was defined as: (1) development of typical angina during exercise, (2) 2 1 mm horizontal or downsloping ST segment depression 0.08 second after the J point in a lead normal at baseline, (3) exercise-induced negative u waves, or (4) >lO mm Hg decrease in blood pressure. Neither ST segment elevation nor ST segment depression in a lead with an abnormal ST segment at baseline was considered a positive response.

Exercise echocardiography. Two-dimensional echocardiograms were analyzed independently by two experienced observers who were blinded to both treadmill exercise results and clinical status. Left ventricular regional wall segments were identified in multiple views by means of standard nomenclature.1a Segmental wall motion was interpreted as either normal, hypokinetic, akinetic, or dyskinetic. A normal wall motion response to exercise was defined as the development of hyperdynamic wall motion or preservation of normal resting contraction after exercise (Table I). Because most patients (37 of 40) had a wall motion abnormality at rest, a positive exercise echocardiogram required fulfillment of one of two criteria: (1) development of a new wall motion abnormality (hypokinesia, akinesia, or dyskinesia) after exercise in an area normal at rest or (2) marked worsening of wall motion (hypokinesia to dyskinesia) in an area separate from a distinct, stable wall motion abnormality. This second criterion permitted identification of patients with multiple abnormal segments, one of which deteriorated significantly after exercise. Worsening of wall motion in a single abnormal segment, when all other segments of postexercise wall motion were normal, did not constitute a positive test result.

Two-dimensional echocardiograms were obtained by

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Fig. 1. Negative exercise echocardiogram from patient with recent inferior myocardial infarction. End-diastolic (top) and end-systolic (bottom) frames are shown at rest (left) and after exercise (right). Inferoposterior akinesis is present at rest and is unchanged after exercise. Interventricular septum moves normally at rest and becomes hyperdynamic after exercise.

means of a commercially available go-degree mechanical sector scanner (Mark 300, Advanced Technology Labora- tories, Inc., Bothell, Wash.) and a 3 MHz transducer. Four standard views, including parasternal long- and short-axis and apical two- and four-chamber views, were obtained before and immediately after exercise with the patient in the supine left lateral position.

A MicroSonics CAD 888 frame grabber (MicroSonics, Inc., Indianapolis, Ind.) was used for data acquisition and analysis. Pre- and postexercise images were digitized off line in a 256 X 256 X 6 bit matrix with 64 shades of gray. The videotape was reviewed to select a single technically satisfactory cardiac cycle for each anatomic view. A triggering program was used to identify the R wave on the ECG that corresponded to this cycle. When the triggering program was activated, eight sequential fields were cap- tured at 50-msec intervals after the peak of the R wave, and a continuous loop recording of that cardiac cycle was created. Pre- and postexercise images of each standard echocardiographic view were displayed side by side in a quad-screen format.

Left ventricular ejection fraction was measured before and after exercise by means of a commercially available software measurement program. Ejection fraction was measured by a single-blinded observer from the apical four-chamber view. Left ventricular volumes were calculated at end diastole and end systole by means of Simp- son’s rule, from which the ejection fraction could be automatically derived.

Cardiac catheterization. Twenty-five of 40 patients underwent cardiac catheterization during the follow-up period. Coronary cineangiography was performed by means of the Judkins technique. Cineangiograms were interpreted without knowledge of the results of exercise echocardiography. Significant coronary stenosis was defined as L 70% reduction in the luminal diameter of the left main coronary artery, left anterior descending artery, left circumflex artery, right coronary artery, or one of their major branches. Single-vessel disease implied significant coronary stenosis confined to one of the three major epicardial vessels or its branches. Multivessel disease was defined as significant coronary stenosis in two or three of the major epicardial vessels, or the presence of left main coronary artery stenosis.

Follow-up. Patients were followed from the date of the index myocardial infarction until the occurrence of a cardiac event or, if no event occurred, for at least 6 months (range 6 to 10, mean 7.2 months). Physicians caring for the patients during this period had no knowledge of the exercise echocardiographic results. Clinical outcome was defined as either good or poor at the time of follow-up. End points used to define a poor clinical outcome included crescendo or unstable angina, recurrent myocardial infarction, need for coronary artery bypass grafting, or cardiac death. Patients who remained asymptomatic or who developed mild, stable angina (New York Heart Associa- tion functional class I) were classified as experiencing a good clinical outcome.

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Fig. 2. Positive exercise echocardiogram from patient with recent inferior myocardial infarction. At rest, septum moves posteriorly during systole (lower left). After exercise, end-systolic frame (lower right) demonstrates dyskinetic motion of distal septum and apex. Stable inferoposterior wall motion abnormality was documented by means of short-axis and apical two-chamber views.

Statistical analysis. Data are given as mean -t standard deviation. The relationship of measured variables to clinical outcome was examined singly for each variable followed by a multivariate analysis. Continuous variables such as age were compared by t test in the groups with poor and good clinical outcome. Discrete variables, such as history of myocardial infarction, were correlated with outcome by means of a contingency table and chi-square analysis. Stepwise linear discriminant analysis was performed to see if a subset of the variables would predict outcome better than any single variable. Cumulative survival curves were calculated by means of the product- limit method of Kaplan and Meier. The development of one of the events denoting poor clinical outcome was taken as the end point for purposes of analysis. Statistical differences between curves were assessed with the Mantel- Cox statistic. RESULTS

Patient data. The 40 patients (34 men) ranged in age from 38 to 73 (mean 55) years. Seven had historic and/or ECG evidence of previous myocardial infarction. Thirty-nine of 40 had significant elevation of creatinine phosphokinase MB isoenzyme. All patients had evolutionary ECG changes: 25 developed Q waves (10 anterior, 15 inferior) and 11 had ST segment or T wave changes only (four anterior, seven inferior). In four patients, the site of myocar-

dial infarction could not be localized by means of ECG criteria.

Treadmill exercise testing. There were no complications during treadmill exercise testing. At the time of the test, four patients were taking digitalis and 19 patients were taking beta blockers. The patients exercised from 2 to 12 (mean 6.4) minutes. Peak heart rate obtained ranged from 79 to 146 bpm. Thirty-one of 40 patients (78%) reached the target of 70 % of maximum predicted heart rate. Only three patients developed typical angina during exercise; all three had diagnostic ST segment changes. In all, 18 patients had positive treadmill exercise test results. Of the nine patients who failed to reach the target heart rate, four had positive test results. In the remaining five patients, exercise was stopped because of either fatigue or leg pain.

Exercise echocardlogfaphy. Interobserver repro- ducibility for interpretation of the exercise echocardiograms was excellent. Agreement as to diagnosis occurred in 37 of 40 (93 % ) patients. Data reported henceforth are those of the first observer (T.R.).

The resting echocardiogram was abnormal in 37 of 40 patients. In nine patients, two distinct wall motion abnormalities were present at rest. In all nine, the second abnormal wall segment was hypoki-

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Table II. Clinical and historic parameters as predictors of clinical outcome

Table Ill. Treadmill exercise parameters as predictors of clinical outcome

Outcome Outcome

Parameter Good

Age h) 52 -c 12 Sex (M/F) 1713 Prior MI 0 Q wave 16 Non-Q wave 4 Anterior 6 Inferior 14

Poor p Value

57 f 10 NS 17/3 NS

7 0.008 9 NS 7 NS 8 NS 8 NS

MI = myocardial infarction; NS = not significant. Age is reported se mean k standard deviation. Anterior and inferior refer to location of MI. In four patients, the site and type of infarct could not be determined by ECG.

netic. Twenty-three (58%) patients had a negative exercise echocardiogram. In 21 patients, an isolated akinetic or dyskinetic wall segment at rest remained akinetic or dyskinetic after exercise (Fig. 1). In one patient, there was anterior akinesis and inferior hypokinesis at rest and no change after exercise. In another patient, an inferior wall that was hypokinetic at rest became dyskinetic after exercise, as the only wall motion abnormality.

The remaining 17 patients had a positive exercise echocardiogram. In nine patients, a wall segment moving normally at rest became hypokinetic, akinetic, or dyskinetic after exercise (Fig. 2). In eight patients, two wall motion abnormalities were present at rest, including a hypokinetic segment that became either akinetic or dyskinetic after exercise.

Clinical outcome. Twenty patients had an uneventful postmyocardial infarction course. At the time of follow-up, 17 were asymptomatic and three had stable functional class I angina. Twenty patients had one or more cardiac events during the follow-up period. Three patients died from cardiac causes and three had documented recurrent myocardial infarc- tions. Fourteen patients developed crescendo or unstable angina; seven of these patients underwent coronary artery bypass grafting and three patients underwent coronary angioplasty. Clinical variables that correlated with outcome included only history of previous myocardial infarction (p = 0.008). Nei- ther age, type of myocardial infarction (Q vs non-Q wave), nor site of myocardial infarction (anterior vs inferior) was predictive of clinical outcome (Table II). The inability of these clinical parameters to predict outcome likely reflects the relatively small size of the study population.

Parameter Good Poor p Value

Peak heart rate Heart rate = 70% * Duration ST depression/

negative u waves

121 t 11 114 2 14 NS 16 15 NS

5.9 k 2.8 7.0 +- 2.7 NS 7 11 NS

Values sre mean k standard deviation. ‘Number of patients in each outcome group who reached 70’; of age- predicted maximal heart rate.

Table IV. Predictive value of exercise echocardiography to identify patients with various clinical end points

Exercise echocardiography

End point Negative Positive (N = 23) (N= 17)

Good outcome (N = 20) Asymptomatic 16 1 Mild angina 3 0

Poor outcome (N = 20) Unstable angina 4 10 Myocardial infarction 0 3 Cardiac death 0 3 Coronary artery bypass grafting 1 6

Column totals are greater than N because some patients experienced more

than one end point.

Among treadmill characteristics, neither peak heart rate attained during exercise testing nor exercise duration was significantly greater among those patients with a good clinical outcome compared to those with a poor outcome (Table III). Angina during treadmill exercise occurred in only three patients, two of whom developed unstable angina during follow-up.

Results of treadmill exercise tests were interpreted as positive in 18 patients. Test results were negative in 13 of 20 patients with good clinical outcome (65 % specificity) and positive in 11 of 20 patients with poor clinical outcome (55% sensitivity). The predictive value of a positive treadmill exercise test result was 61%. Among six patients with “hard” clinical end points (either death or recurrent myocardial infarction), treadmill test results were positive in only three.

The exercise echocardiogram was negative in 19 of 20 patients with a good clinical outcome (95%

1310 Ryan et al.

60 -

I 20 1

*p=NS

I I I 2 3 4 5 6 7 8 9 IO

Follow-up (months)

Fig. 3. Cumulative survival curves as function of treadmill exercise test results. Curves represent cumulative proportion of patients remaining event free. Solid line indicates patients with negative treadmill exercise test results. Broken line represents patients who had positive treadmill exercise test results. Follow-up is shown on abscissa. The two curves are not statistically different. Numbers represent total number of patients remaining at risk as function of time.

I

I L---1 I

L---, (I

I--- 5 -jPOsltlv*

pxoroho (*oh0 *

F40.00 1 I----------- 2 I

i

1 1

I I 2 3 4 5 6 7 S 9 IO

Follow-up (months)

Fig. 4. Cumulative survival curves as function of exercise echocardiographic results. Curves represent the proportion of patients remaining event free. Solid line indicates patients with negative exercise echocardiogram. Broken line represents patients with positive exercise echocardiogram. Follow-up is shown on abscissa. The two curves are statistically different at p < 0.001. Numbers under the curve represent total number of patients remaining at risk.

specificity) and was positive in 16 of 20 patients with poor clinical outcome (30% sensitivity). The predictive value of a positive exercise echocardiogram was 94 % (Table IV). Exercise echocardiography correctly identified all six patients who, during follow-up, either suffered recurrent myocardial infarction or died. There were four patients who developed unstable angina but had a negative exercise echocardiogram. Three of these four patients had single-vessel coronary artery disease at catheterization.

Survival analysis that used poor clinical outcome as the end point was performed as a function of both treadmill and exercise echocardiographic results, Cumulative survival curves that were based on

treadmill test results and showed the proportion of patients still maintaining an uneventful postinfarction course are shown in Fig. 3. The two curves are not statistically different. Survival curves as a function of exercise echocardiographic results are shown in Fig. 4. The curves are different for the two groups dp c 0.001).

Results of both the treadmill test and exercise echocardiography were positive in only 7 of 20 patients with a poor outcome. If either a positive treadmill exercise test result or a positive exercise echocardiogram was used to define a positive test result, sensitivity for identification of patients likely to experience a poor outcome increased to 90 % . This

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TME r

POS

NEC

Exercise echo post-AMI risk stratification 1311

POS

c

Fig. 5. Comparative ability of treadmill exercise test and exercise echocardiography to predict clinical outcome. Good and poor refer to clinical outcome groups. Numbers reflect total number of patients with each combination of test results as a function of outcome group. See text for discussion.

increase in sensitivity of the test to predict a poor outcome when the two tests were combined, compared to exercise echo alone, was not significant (80% vs 90% sensitivity, p = NS).

70

p=NS -,

,- PENS -,

1 70

Linear discriminant analysis was used to determine if any combination of clinical, treadmill, and echocardiographic variables could enhance our ability to predict outcome. Only the exercise echocardiographic results entered the equation (at p < 0.05). This suggests that no useful additional information is gained from clinical or treadmill data for assessment of risk of a poor clinical outcome.

- 60

- 50

- 40

Eight patients had positive treadmill exercise test results but a negative exercise echocardiogram. Six of eight had an uneventful clinical outcome. Seven patients had negative treadmill exercise test results but a positive exercise echocardiogram. All seven had a poor clinical outcome. Thus, among the 15 patients in whom there was disagreement between treadmill and echocardiographic results, the echocardiogram was predictive of clinical outcome in 13 (Fig. 5).

60 I -

z

s 50

.- ti I

5 40 -

.- t j $

1

30-

20

f f

Echocardiographic ejection fraction was determined in 38 patients and was a poor predictor of clinical outcome (Fig. 6). Neither resting ejection fraction, postexercise ejection fraction, nor percentage of change in ejection fraction was significantly different between groups. Ejection fraction de- creased after exercise in two patients with a good clinical outcome and five patients with a poor outcome.

Rest swesa Rest strrrr

Good Outcome Poor Dutcomo

Fig. 6. Echocardiographic ejection fraction before and after exercise in patients with good (left) vs poor (right) clinical outcome. There is no difference in either resting or postexercise ejection fraction between the two groups. Vertical bars represent mean f standard deviation.

ly without having undergone coronary cineangiography. Six patients who were asymptomatic after myocardial infarction also underwent cardiac catheterization.

Angiographlc results. Twenty-five patients under- Of the 25 patients who underwent cardiac cathe- went cardiac catheterization 1 day to 5 months after terization, treadmill testing was positive in 14, nine exercise echocardiography (Fig. 7). Nineteen of 21 of whom had multivessel coronary disease. Exercise patients with poor outcome were referred for cathe- echocardiography was positive in 15, fourteen of terization because of an unfavorable clinical course. whom had multivessel disease. One patient in the poor-outcome group died sudden- Of the 19 patients with an unfavorable clinical


American Heart Journal

OUTCOME

EXERCISE ECHO .! a.. 1 is .! is .I a., (4) (0) (3) Cl) (2) (0) (1) (14)

RESTING ECHO ” 8V!\ SWMA MWMA MWMA

(1) (0) (8) (8)

Fig. 7. Clinical and echocardiographic results in patients with single-vessel and multivessel coronary artery disease. A single wall motion abnormality was detected in seven of eight patients with single-vessel disease. Exercise echocardiography identified most (14 of 15) patients with multivessel disease in whom a cardiac event occurred. Only six of these 14 patients had multiple wall motion abnormalities on resting echocardiogram. Test results were negative in two patients with multivessel disease who were asymptomatic at follow-up. MVD, Multivessel coronary disease; SVD, single-vessel coronary disease; Pos, positive; Neg, negative; SWMA, single wall motion abnormality; MWMA, multiple wall motion abnormalities.

course who underwent cardiac catheterization, 15 had multivessel coronary disease and four had single-vessel disease. Exercise echocardiography correctly identified 14 of 15 (93 % ) patients with multivessel disease and a poor outcome. Among four patients who developed post-myocardial infarction angina but had single-vessel disease, exercise echocardiography correctly identified three. That is, exercise echocardiography properly demonstrated only one wall motion abnormality in three of four patients with single-vessel disease. One patient with single-vessel disease had a false positive exercise echocardiogram. Thus, among 19 patients who developed recurrent symptoms or events after myocardial infarction and subsequently underwent cardiac catheterization, exercise echocardiography correctly predicted the presence or absence of multives- se1 disease in 17 (89 % ).

Of six patients who underwent cardiac catheterization despite a stable post-myocardial infarction clinical course, four had single-vessel disease and two had multivessel disease. All had a negative exercise echocardiogram. Thus, exercise echocardiography correctly predicted the extent of coronary artery disease in only four of six. However, the two patients with multivessel disease but a negative exercise echocardiogram were both without symptoms after at least 6 months’ follow-up.

In all, 17 patients had multivessel coronary dis-

ease. Fifteen of these 17 had a cardiac event during follow-up, 14 of whom were identified by a positive exercise echocardiogram. The resting echocardiogram was less sensitive for detecting the presence of multivessel coronary disease, demonstrating multiple wall motion abnormalities in only six of these patients.

Of eight patients with single-vessel disease, four developed post-myocardial infarction angina and four remained asymptomatic. Exercise echocardiography demonstrated an isolated wall motion abnormality in seven of these eight patients.

DISCUSSION

Prognosis for survivors of acute myocardial infarction is dependent on a variety of factors, including the severity of left ventricular dysfunction, the extent of coronary artery disease, the presence of inducible ischemia, and the occurrence of ventricular arrhythmias.’ Although no single test addresses all of these variables, several specialized tests have been used successfully for risk stratification. Because no method is perfect in its ability to predict outcome, the clinical value of any given technique depends on its safety, cost effectiveness, availability, and diagnostic yield.

In the current study, exercise echocardiography was shown to be a useful adjunct to treadmill exercise testing for the purpose of risk stratification

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after myocardial infarction. Most important, stress echocardiography improved the ability of the test to predict clinical outcome during the follow-up period. When compared to treadmill testing alone, exercise echocardiography resulted in an increase in sensitivity from 55% to 80% 0, = NS) and specificity from 65% to 95% (p < 0.05) for identification of those patients who would experience an unfavorable clinical course.

Several studies have examined the prognostic value of exercise testing in the post-myocardial infarction patient.4-‘4 In some, exercise-induced ST segment depression, angina, or both have been correlated with a variety of clinical end points, including development of unstable angina, recurrent myocardial infarction, sudden death, and the overall mortality rate.4-8 Other treadmill variables, such as development of ventricular arrhythmias> 5, s exercise duration,g, l1 abnormal blood pressure response,6r g, l* and maximum workload attained? have also been shown to predict outcome. Agreement as to which of these exercise variables are most useful predictors has not been universal. Several studiesg-12 have failed to demonstrate a significant relation betwen ST segment depression and outcome. Thus, while most investigators agree that exercise testing is useful after myocardial infarction, questions remain as to which exercise variables are most closely related to prognosis.

In the current study, development of ST segment depression, negative u waves, or angina was used to define a positive treadmill test result. Although these findings were more prevalent among patients with an unfavorable clinical outcome, the positive predictive value of the treadmill test was only 61% . Furthermore, no other treadmill variables were useful predictors of subsequent cardiac events.

Exercise echocardiography. Exercise echocardiography significantly increased the predictive value of a positive test result as compared to the treadmill test (p < 0.05). More important, exercise echocardiography identified all six patients who either died or suffered recurrent myocardial infarction during follow-up, whereas treadmill testing alone identified only three of these six patients. Seven patients in whom the exercise echocardiogram detected an exercise-induced wall motion abnormality, but in whom treadmill test results were negative, experienced an ischemic cardiac event during follow-up. This finding suggests that, in the post-myocardial infarction patient, exercise-induced wall motion abnormalities may be more sensitive than the stress EGG for detecting latent ischemia.

Abnormal wall motion occurs promptly with the

induction of ischemia and can be accurately recorded with echocardiographic techniques.lg A major limitation of the ECG in the post-myocardial infarction patient is the presence of an abnormal baseline ST segment or T wave. The relative frequency of such a resting abnormality may render the exercise ECG of lesser value. A further potential problem in our study was the use of only a three-lead system. Others20 have demonstrated that the diagnostic yield is increased by increasing the number of monitored leads. These factors may partially account for the relatively greater sensitivity of the exercise echocardiogram compared to the treadmill test alone.

The ambiguity introduced by the abnormal resting ECG may also explain the relatively greater specificity of exercise echocardiography compared to treadmill exercise testing. Exercise echocardiography was more accurate for predicting low-risk status than treadmill testing alone. Only one patient with a positive exercise echocardiogram had an uneventful post-myocardial infarction course. In contrast, there were seven false positive treadmill test results. Similar improvements in specificity compared to treadmill testing alone have been demonstrated with the use of thallium scintigraphy.21

When the results of the exercise ECG and the exercise echocardiogram were discordant, the exercise echocardiogram was superior for predicting clinical outcome. In 13 of 15 patients, the exercise echocardiographic results correlated accurately with outcome. Most important, among the nine patients with a poor outcome in whom the test results disagreed, exercise echocardiography was correct in seven.

Comparison with previous studies. Two-dimensional echocardiography is useful after acute myocardial infarction to identify patients at increased risk for earlyz2s 23 and late24 complications. The value of echocardiography lies in its ability to detect and localize wall motion abnormalities, presumably resulting from ischemia or infarction, and thereby to quantitate the degree of left ventricular dysfunction, an important determinant of prognosis. Additionally, the presence of a wall motion abnormality outside the infarct zone has been correlated with a poor clinical outcome.22 The resting echocardiogram alone may fail to identify the patient with jeopardized myocardium. In the current study, a total of nine segments that functioned normally at rest, became abnormal only after exercise. Thus, the resting echocardiogram provides useful prognostic information by its ability to quantitate left ventricular dysfunction, whereas the stress echocardiogram


American Heart Journel

enhances the yield of the test by addressing another important prognostic variable, inducible ichemia.

Jaarsma et al.25 recently used two-dimensional echocardiography to examine the significance of exercise-induced transient remote asynergy in the post-myocardial infarction patient. Although duration of follow-up was considerably shorter than in the current study, the sensitivity of stress echocardiography to identify patients with recurrent ischemic events was comparable to our results. The specificity of the test was not reported. These investigators also demonstrated that left ventricular ejection fraction was of liiited value in this patient population and was only useful to identify patients with three-vessel coronary artery disease. In the current study, mean ejection fraction at rest was nearly identical in the two outcome groups. The increase in ejection fraction was greater among patients who experienced a good clinical outcome, although this trend did not reach statistical significance.

Predicting extent of coronary artery disease.

Because many of the patients enrolled in the current study experienced an uneventful post-myocardial infarction course, only 25 of 40 (63%) were referred for cardiac catheterization. An important finding was the demonstration that the exercise echocardiogram significantly enhanced the ability of the stress test to separate single-vessel from multivessel coronary artery disease. Treadmill testing alone is of limited value for detecting the presence of multives- se1 disease.” In the patient recovering from myocardial infarction, this may be an important clinical issue, because of the poorer prognosis associated with multivessel disease.26 Thallium scintigraphy has been used successfully as an adjunct to treadmill testing to improve the ability to detect multivessel disease.21s27’28 In the current study, exercise echocardiography correctly identified 82% of patients with multivessel disease and 88% of those with single- vessel disease. It is important to note that the two patients with multivessel disease but negative exercise echocardiograms both remained asymptomatic during follow-up. OtherP have demonstrated that functional assessment is more important to prognosis than merely the number of stenotic vessels. These findings emphasize the importance of evaluating the functional significance of the coronary anatomy as a determinant of outcome.

Among eight patients with single-vessel disease, exercise echocardiography correctly demonstrated a single wall motion abnormality in seven. Whereas four of these patients were asymptomatic after myocardial infarction, the remaining four developed

chest pain during follow-up and subsequently underwent cardiac catheterization. Although these patients had single-vessel disease, the development of post-myocardial infarction angina suggests the presence of viable but jeopardized myocardium within the infarct zone. Gibson et alzl have shown that reversible thallium defects occur in patients with single-vessel disease. This finding identifies a subset of patients with high risk for future cardiac events. The ability to exclude significant multivessel disease in the post-myocardial infarction patient with recurrent chest pain may be of significant clinical value. In some instances, cardiac catheterization might be avoided. If ischemia within the infarct zone is suspected, cardiac catheterization with anticipation of possible coronary angioplasty might be undertaken.

Limitations. There are several limitations to exercise echocardiography, as performed in the current study. First, a small percentage of patients must be excluded because of technically inadequte echocardiograms. The prevalence of such technically unsatisfactory postexercise studies varies, but in a previous study from this laborato+ it was only 8 % . It is worth noting that in the current study no patient with a technically satisfactory resting echocardiogram was excluded from analysis because of an unsatisfactory postexercise echocardiogram.

A second limitation of this technique is the requirement for specialized computer-processing equipment, Although postexercise echocardiography can be performed without such computer processing, the technique greatly enhances ease of interpretation. The ability to compare each resting and postexercise view side by side allows more subtle abnormalities to be appreciated, thereby enhancing sensitivity.

The role of exercise echocardiography in the patient with single-vessel disease and angina war- rants special comment. Although the presence of single-vessel disease can be accurately confirmed, the ability of exercise echocardiography to detect ischemia within the infarct zone is limited. Once a segment has undergone partial infarction, a wall motion abnormality develops. Further ischemia within this area may or may not be detected as a worsening of wall motion. Thus, although exercise echocardiography can be utilized to exclude func- tionally significant multivessel disease in the patient with post-myocardial infarction angina, it cannot be relied on to detect ischemia within the infarct zone.

A final limitation is the reliance on postexercise imaging to detect exercise-induced changes in wall

Volum* 114 Number 6 Exercise echo post-AMI risk stratification 1315

motion. A previous studyI has demonstrated that exercise-induced transient dyssynergy tends to per- sist for several minutes after termination of exercise. Although postexercise imaging does not appear to significantly lower the sensitivity of the two-dimensional echocardiography to detect transient wall motion abnormalities, it is possible that a greater percentage of abnormal test results would be obtained if imaging were performed during peak exercise. This issue was not addressed in the current study.

Clinical implications. Because of the myriad of factors that may affect prognosis after acute myocardial infarction, no single test can be perfect in its ability to predict outcome. Exercise echocardiography is being used increasingly as a readily available, noninvasive, relatively inexpensive test to detect inducible myocardial ischemia. In the current study, exercise echocardiography was shown to be a useful adjunct to treadmill testing for purposes of risk stratification. This was not unexpected. Regional left ventricular function is an important determinant of prognosis after myocardial infarction. Any technique, such as two-dimensional echocardiography, that accurately records regional contractility would be expected to be a useful prognostic test.

For predicting clinical outcome, exercise echocardiography was superior to treadmill testing alone. The test also helped to identify those survivors of myocardial infarction with increased likelihood of having multivessel coronary artery disease. Multi- vessel coronary disease was unlikely in the absence of multiple exercise-induced wall motion abnormalities. This may be particularly useful in the approach to the patient who develops recurrent angina during the postinfarction period. In conclusion, two-dimensional echocardiography is an ideal technique to assess global and regional left ventricular function in the patient recovering from myocardial infarction. When used in conjunction with exercise testing, it becomes a reliable means to address another important functional predictor of prognosis, inducible myocardial ischemia.

The authors thank Ms. Judy Stanton for secretarial support and Naomi Fineberg, Ph.D., for expert statistical analysis of the data.

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