(Circulation. 1998;98:2679-2686.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Long-Term Prognostic Value of Exercise Echocardiography Compared With Exercise 201Tl, ECG, and Clinical Variables in Patients Evaluated for Coronary Artery Disease
From the Section of Cardiology, Baylor College of Medicine and the Echocardiography and Nuclear Cardiology Laboratories of the Methodist Hospital, Houston, Tex.
Correspondence to William A. Zoghbi, MD, Director, Echocardiography Research, Baylor College of Medicine, 6550 Fannin, SM 677, Houston, TX 77030. E-mail wzoghbi{at}bcm.tmc.edu
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Abstract |
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Background—The accuracy of exercise echocardiography and 201Tl single photon emission computed tomography (SPECT) is similar in the diagnosis of coronary artery disease (CAD). However, comparative data on long-term prognosis are lacking.
Methods and Results—Clinical variables and exercise, echocardiographic, and 201Tl tomographic parameters were studied in 248 patients (age, 56±12 years [mean±SD]; 189 men) who underwent simultaneous treadmill exercise 201Tl SPECT and echocardiography. Follow-up was obtained in 225 patients (91%) at a mean of 3.7±2.0 years. A total of 64 cardiac events occurred. With the use of stepwise logistic regression, 4 models simulating clinical stress testing scenarios were evaluated in the prediction of all cardiac events, ischemic events, and/or cardiac death. The best clinical models were exercise echocardiography with exercise ECG and exercise 201Tl SPECT with exercise ECG. Both models were comparable in the prediction of cardiac events. For the exercise echocardiography model, exercise wall motion score index and induction of ischemia were the strongest predictors of events with ORs of 2.63 per unit increment (95% CI, 1.34 to 5.17; P=0.005) and 4.1 (95% CI, 1.32 to 12.79; P=0.015), respectively. For the model with exercise 201Tl SPECT, the strongest predictor was ischemic perfusion defect (OR, 4.93; 95% CI, 1.72 to 14.08; P=0.003). The absence of ST changes during exercise decreased the risk of events. For the prediction of ischemic events and/or cardiac death, echocardiographic and 201Tl parameters were the only predictive variables.
Conclusions—In patients evaluated for CAD, exercise echocardiography and 201Tl combined with ECG variables provide comparable prognostic information and can be used interchangeably for risk stratification.
Key Words: echocardiography • coronary disease • imaging • ischemia • prognosis
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Several studies demonstrated that in addition to conventional cardiac risk factors, resting left ventricular function and the presence or absence of stress-induced ischemia are among the most powerful predictors of cardiac events.1 2 3 Currently, exercise echocardiography and radionuclide perfusion imaging are the 2 best modalities for the detection of exercise-induced ischemia and are superior to conventional stress ECG.4 5 Although exercise echocardiography evaluates global and regional function and the radionuclide technique assesses relative myocardial perfusion, studies comparing these techniques have shown comparable results in the detection of coronary artery disease (CAD).4 6
Current literature suggests that exercise echocardiography and radionuclide perfusion imaging are both capable of detecting subgroups of patients at higher risk for future cardiac events.4 7 8 9 However, to date there has been no comparison of the 2 techniques for risk stratification in the same patients. The purpose of this study, therefore, was to compare the relative prognostic value of exercise echocardiography and exercise 201Tl single photon emission computed tomography (SPECT) in patients with suspected or known CAD. The incremental prognostic value of both techniques compared with clinical variables and exercise ECG was evaluated.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Patient Population
The population consisted of 248 patients (189 men; mean age, 56.3±12 years) evaluated between 1986 and 1993 during a single treadmill exercise session who underwent exercise echocardiography simultaneously with 201Tl SPECT. Most of these patients (85%) participated in a prospective study comparing the diagnostic value of exercise echocardiography with SPECT 201Tl.6 Patients were excluded if they had a recent myocardial infarction (<2 months), significant valvular heart disease, dilated or hypertrophic cardiomyopathy, or previous cardiac transplantation. This investigation was approved by the institutional review board of Baylor College of Medicine. Baseline characteristics are depicted in Table 1
. One
hundred ninety-four patients (78%) were receiving cardiac medications
consisting of calcium channel blockers in 47%, ß-blockers in 37%,
nitrates in 31%, and aspirin in 44%. Indications for the test were
evaluation of chest pain in 35%, screening for CAD in 52%, evaluation
of ischemia 2 to 3 months after acute myocardial infarction in
8%, palpitations in 3%, and heart failure in 2%. Historical data
were retrieved from medical records. Pretest probability of
CAD10 was low (
25%) in 58% of patients,
intermediate (26% to 69%) in 18%, and high (
70%) in 24%. Cardiac
catheterization was performed within 3 months in 84
patients, of whom 27 had single-vessel and 43 had multivessel
disease.
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Exercise ECG
All patients underwent a multistage treadmill exercise with the
standard Bruce protocol. Criteria for interrupting the test were severe
chest pain, diagnostic ST-segment shift 2 mm,
extreme fatigue or dyspnea, systolic blood pressure >240
mm Hg, diastolic pressure >120 mm Hg, or the
reaching of maximal age-predicted heart rate. ECG was
diagnostic for ischemia when there was 1-mm flat
or downsloping ST-segment depression 0.08 seconds after the J point.
ST-segment depression in the presence of left bundle-branch block,
ventricular hypertrophy, or digoxin was
considered to be nondiagnostic.
Exercise Echocardiography
Two-dimensional echocardiograms were performed at rest and
immediately after exercise with digital technology as previously
described.6 The left ventricle was divided into
16 segments,6 and wall motion was semiquantified
as follows: 1=normal or hyperdynamic, 2=hypokinetic, 3=akinetic, and
4=dyskinetic. Images were interpreted by one of 2 experienced
investigators without knowledge of ECG, additional
diagnostic tests, or clinical outcome. Overall
interpretation was as follows: normal=normal or hyperdynamic function
with exercise, ischemia=new wall motion abnormality with
exercise, fixed abnormality=resting wall motion abnormality without
evidence of ischemia, and mixed abnormality=resting wall motion
abnormality with worsening function or contiguous or distant
ischemia during exercise. A wall motion score index (WMSI) was
derived as the sum of the individual scores divided by the total number
of segments, and ejection fraction was determined by subjective
estimation or with the multiple diameter
method.11
Exercise 201Tl SPECT
At peak exercise, 3 mCi 201Tl as thallous
chloride was injected intravenously, and the patient was
asked to exercise for an additional minute. After acquisition of the
echocardiographic images, SPECT was performed by use of
a large–field-of-view, single-crystal, rotating gamma camera (ADAC,
ARC 3000–3300).5 Redistribution images were
obtained 4 hours later. Reconstructed tomographic slices were oriented
in the short, horizontal long, and vertical long axes and displayed
sequentially to assess regional perfusion.5
Experienced observers unaware of the results of the echocardiography, additional tests, or clinical outcome performed the analyses. 201Tl uptake was scored as follows: 1=normal, 2=mildly reduced, 3=moderately reduced, and 4=severely reduced. Perfusion defects were analyzed for the presence of complete redistribution (ischemia), no redistribution (fixed defect), or partial redistribution (mixed defect). Computerized polar maps were generated and compared with a normal data bank.5 201Tl defect size (percent) was obtained by computer in most patients (n=228).5 In 20 patients studied in 1986 whose images could not be adequately processed, defect size was calculated as the number of exercise abnormal segments divided by the total number of segments (n=16) and expressed in percent. This semiquantitative analysis (percent abnormal segments) was also performed for all patients.
Clinical Outcome
Follow-up data were obtained by review of patient records,
personal communication with the patients' physicians, and telephone
interviews and were available in 225 patients (91%). The remaining 23
patients could not be contacted but had similar baseline
characteristics as the 225 patients. The following outcome events were
recorded: myocardial infarction,
revascularization procedures (angioplasty or
coronary artery bypass), congestive heart failure or unstable
angina requiring hospitalization, and death (cardiac and noncardiac).
Analysis was censored at the onset of the first event.
Statistical Analysis
Comparison of the prognostic power of exercise
echocardiography and exercise
201Tl was accomplished in 3 steps. Step 1
involved univariate testing to determine which
variables distinguished patients with from those without cardiac
events. These analyses used the 
2 test
for association or Fisher's exact test for categorical variables
and Student's t test or the Kruskal-Wallis test for
continuous variables.12
Step 2 involved using stepwise logistic regression to develop models capable of predicting events.13 Three definitions for cardiac events were used (1) all cardiac events, (2) ischemic events (myocardial infarction, hospitalization owing to unstable angina) and cardiac death, and (3) cardiac death alone. The reason for this approach was to analyze the group of "hard events" separately from events such as revascularization procedures and congestive heart failure, which may be viewed as "soft events" but are also important in terms of morbidity and healthcare costs.
For each of the 3 definitions of events, 4 logistic models were
developed. The first had as its starting point the clinical and
exercise ECG variables important in univariate
analyses. The second model included resting
echocardiographic variables in addition to the
first model. The third model included exercise
echocardiographic variables in addition to clinical
and exercise ECG variables. The fourth model comprised
201Tl SPECT variables in addition to clinical
and exercise ECG variables. Variables that are highly
correlated (eg, WMSI and ejection fraction) should not be included in
the same model. In this situation, separate models with each of these
variables were constructed, and the 1 with the best fit was
reported. Pearson's 2 test was used to assess
the fit of each of the models.13
Step 3 consisted of comparing the predictive ability of the models using area under the receiver-operating characteristics curve (AUC). The AUC was determined by use of the trapezoidal rule.14 AUCs were compared by the method of Hanley and McNeil.14 15 A secondary aim was to compare event-free survival of patients on the basis of the results of exercise ECG, echocardiography, or 201Tl SPECT. The Kaplan-Meier curves are shown and were compared by use of the log-rank test.12 Significance was set at P<0.05.
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Results |
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During follow-up (up to 8 years; mean, 3.7±2 years), 64 cardiac events occurred: 7 cardiovascular deaths, 8 nonfatal myocardial infarctions, 9 hospitalizations for unstable angina, 11 hospitalizations for heart failure, 28 revascularizations (16 coronary bypass surgery and 12 angioplasty), and 1 cardiac transplantation because of ischemic heart disease and severe heart failure. One patient suffered a noncardiovascular death but was not considered an event for the purposes of this study. Most events (59%) occurred after 90 days. Most of the "early" events (<90 days) were revascularizations with either angioplasty (n=7) or bypass surgery (n=10). In contrast, ischemic events and cardiac death accounted for most of the late events (71%). Of the 17 patients with "early" revascularization, 15 had abnormal studies by both stress echocardiography and 201Tl, and 2 were normal by both. Of the 11 patients hospitalized with heart failure, 5 (45%) had normal ejection fractions (>50%) at the time of study, and only 2 had ejection fractions <35%. Of the 11 patients, 9 had abnormal exercise echocardiography, and 8 had abnormal exercise 201Tl studies.
Univariate Analysis
Clinical Parameters and Treadmill Exercise ECG
Among the clinical variables tested (Table 1
), smoking was the
only variable associated with all cardiac events
(P=0.02), with a trend observed for chest pain
(P=0.06) and hypertension (P=0.08). No clinical
variables were associated with ischemic events and cardiac
death. Diabetes mellitus was associated with cardiac death
(P=0.05), whereas old age was of borderline significance
(P=0.09).
Exercise duration in the 225 patients was 8.04±2.78 minutes. Peak
exercise heart rate was 146±23 bpm with maximal systolic and
diastolic blood pressures of 156±29 and 77±11
mm Hg, respectively. Sixty-eight percent of patients reached 85% of
their maximal age-predicted heart rate. A normal stress ECG and a
higher maximal exercise heart rate characterized a group of patients
with a lower risk for all cardiac events (Table 2). On the other hand, an
ischemic response on exercise ECG was a weak predictor of risk.
There was no association between exercise ECG variables and
ischemic events or cardiac death.
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Exercise 201Tl SPECT
The presence of a normal or an abnormal
201Tl study discriminated patients without events
from those with any cardiac event, ischemic events and cardiac
death combined, and cardiac death alone (Table 2). An abnormal exercise
201Tl was a predictor of all cardiac events
whether the study was classified as ischemia, fixed defect, or
mixed defect. Quantitative analysis of the perfusion defect
size or semiquantitative analysis with percent of abnormal
segments also differentiated patients with and without events in each
of the 3 cardiac events groups (Table 2).
Exercise Echocardiography
Concordance between exercise echocardiography
and 201Tl for normal and abnormal studies was
86% and for exact category of interpretation was 72%. The incidence
of abnormal exercise echocardiography was higher in
patients with any cardiac event (75%) compared with those without
events (37%; P<0.0001; Table 2). This incidence was also
higher in patients with combined ischemic events and cardiac
death (63%; P=0.018) and in those with cardiac death alone
(71%; P=0.069). An abnormal exercise
echocardiogram was a predictor of all cardiac events
whether the study was classified as ischemia or fixed wall
motion abnormality (Table 2). Parameters of resting
function, WMSI, and ejection fraction were predictors of all cardiac
events. On the other hand, exercise WMSI and ejection fraction were
significantly different in all subgroups of cardiac events, including
death alone.
Survival Analysis
Patients with positive exercise ECGs for ischemia and
nondiagnostic ECGs had worse survival than those with
normal ECGs. These results reached statistical significance for the end
points of all cardiac events and for cardiac death (P=0.02
to 0.001). For patients with normal stress ECGs, survival free from any
event at 5.5 years was 75%. Figures 1 and 2 depict the survival
analysis of the qualitative results of exercise
echocardiography and 201Tl
SPECT for the outcomes of all cardiac events and ischemic
events or cardiac death, respectively. A significant difference was
seen between patients with normal and abnormal studies for all end
points, including death alone (P=0.04), for both modalities.
The rates for various cardiac events in patients with normal
201Tl SPECT or normal exercise
echocardiography are shown in Table 3 and were comparable.
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Figures 3 through 5
depict the results with quantitative parameters. Event-free
survival in patients with perfusion defect size >15% (n=62) was
significantly lower than in those with smaller defects (n=163).
Similarly, the 67 patients with exercise WMSI 1.4, corresponding to 3
akinetic segments during stress out of the 16 segments or 18%, had
higher cardiac event rates compared with the 158 patients with less
extensive abnormality, regardless of the type of cardiac event
analyzed (Figures 3 through 5).
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Multivariate Analysis
Results of the multivariate analysis of
the 4 models tested and their incremental value in predicting cardiac
events are shown in Tables 4 through 6.
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All Cardiac Events
The multivariate predictors for all the
models are shown in Table 4. In the model of exercise
201Tl SPECT, the most significant predictor was
ischemia by 201Tl SPECT; normal exercise
ECG was still a negative predictor. The addition of perfusion defect
size did not improve the power of the model for all events (OR, 1.00;
P=0.36). For the exercise
echocardiography model, exercise WMSI was the
strongest predictor, followed by ischemia by
echocardiography and exercise ECG.
The incremental value for the 4 models tested, expressed as AUC and
global X2, is shown in Table 5 and Figure 6. The addition of resting
echocardiography to clinical and exercise ECG
improved the predictive power of the model but did not reach
significance (P=0.2). However, the AUCs for the models
including imaging during exercise were significantly greater
(P=0.05 to 0.017), confirming a true incremental power for
prediction of cardiac events for exercise
echocardiography and 201Tl
SPECT (Figure 6). The power of the exercise
echocardiography and exercise
201Tl models was comparable
(P=0.4).
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Ischemic Events and Cardiac Death
The first 2 models tested were not significant predictors of
ischemic events and cardiac death. For the model including
201Tl SPECT, the best
multivariate predictor was an abnormal
201Tl SPECT (Table 6). For the model comprising
stress echocardiography, an abnormal exercise
echocardiography was the only predictor (Table 6).
The power of these 2 models was comparable (Table 5).
Cardiac Death
Models including cardiac imaging during stress were the only
predictors of cardiac death (Table 6). In the model of
201Tl SPECT, perfusion defect size was the
strongest predictor, whereas for exercise
echocardiography, exercise WMSI was the only
significant predictor. The power of these 2 models was also similar
(Table 5).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The present study is the first to evaluate the comparative long-term prognostic power of exercise echocardiography and 201Tl tomography in patients undergoing both imaging modalities during the same exercise test. Parameters of cardiac function and perfusion by the respective modalities were equally powerful in separating patients with low or high risk for cardiac events, including hard cardiac events. Although exercise ECG discriminated between patients with and without events, the addition of cardiac imaging with either echocardiography or 201Tl during exercise improved the prognostic power and was similar for both imaging modalities.
Exercise Echocardiography Versus Exercise
201Tl SPECT
Improvements in ultrasound technology and digital image capture
have propelled the use of stress echocardiography
in the evaluation of patients with CAD. Although exercise
echocardiography evaluates ventricular
function and 201Tl scintigraphy
reveals relative myocardial perfusion, studies comparing both
techniques showed a similar accuracy in the diagnosis of
CAD.4 6 A paucity of data exists, however, on the
prognostic power of exercise echocardiography. The
prognostic impact of exercise echocardiography in
patients with chronic CAD followed for 1 year was initially reported by
Krivokapich et al.8 More recently, longer-term
follow-up was reported and demonstrated that a positive stress
echocardiography is a strong independent predictor
of outcome.9 The present investigation
extends these observations and demonstrates that the long-term
prognostic power of exercise echocardiography is
similar to that of exercise 201Tl SPECT. The
addition of imaging by either technique provided significant
incremental value over that available solely from clinical and exercise
parameters for all events and particularly for spontaneous
cardiac events.
The impact of systolic ventricular function on prognosis is well established. Exercise WMSI, a parameter that incorporates resting function and extent of myocardium at risk during stress, was the main predictor of events and the sole echocardiographic predictor of cardiac death by multivariate analysis. Patients with an exercise ejection fraction of <60% had a worse prognosis. It is worth noting, however, that the impact of exercise ejection fraction on prognosis was not better than that of exercise WMSI, the latter being easier to determine during stress. The present study extends earlier observations with exercise radionuclide angiography3 to exercise echocardiography, further emphasizing the importance of evaluating the extent of ventricular dysfunction during stress, in addition to detection of ischemia.
Since the initial report by Brown et al2 in 1983, several studies have demonstrated the prognostic significance of exercise 201Tl scintigraphy.7 16 17 18 In recent studies in which 201Tl SPECT was performed, the size of the perfusion defect was shown to be a powerful predictor of ischemic events and cardiac death.16 17 18 Iskandrian et al16 have shown that a perfusion defect size of >15% identified patients with a high likelihood of cardiac events. In the present investigation, similar findings were observed. Ischemia was the main multivariate predictor of all cardiac events. However, perfusion defect size successfully separated the study population into low and high risk and was the sole multivariate predictor of cardiac death. These findings further demonstrate that exercise 201Tl SPECT provides excellent risk stratification of patients with suspected CAD.
The association between exercise echocardiography
and cardiac events was remarkably similar to that of
201Tl SPECT. Exercise WMSI (the counterpart of
perfusion defect by 201Tl SPECT) separated the
study population into low and high risk and was the best
multivariate echocardiographic
predictor of cardiac death. An important goal of any stress modality is
the ability to identify patients with a low cardiac event rate in
addition to those at high risk. The cardiac event rate in patients with
normal exercise 201Tl SPECT was similar to that
for exercise echocardiography, regardless of the
type of outcome analyzed (Table 3), and further support that
the 2 modalities are comparable in risk stratification.
Study Limitations
Most patients did not have angiography to evaluate the prognostic
power of coronary anatomy. This stems from the design
of the present investigation, which was to compare stress
echocardiography and 201Tl
SPECT in a clinical setting. However, the addition of coronary
angiography to stress perfusion imaging was shown not to improve risk
stratification.7 Availability of the stress test
information to the clinician undoubtedly influences patient management.
This may have triggered a revascularization
procedure or alteration in medical management. For this reason, results
were analyzed with all cardiac events and spontaneous events
included. Furthermore, because this investigation is a comparative
study, the influence on outcome affects the risk stratification of both
modalities.
Conclusions
In patients evaluated for CAD, both exercise
echocardiography and 201Tl
SPECT significantly improve the prognostic power of exercise ECG in
assessing subsequent cardiac events and provide comparable prognostic
information. The choice of imaging modality in a particular
institution, however, depends on several factors, including
availability, feasibility, expertise, and cost considerations.
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Acknowledgments |
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We thank Eula Landry for her assistance in preparing the manuscript.
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Footnotes |
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Guest editor for this article was Richard L. Popp, MD, Stanford University Medical Center, Stanford, Calif.
Received May 29, 1998; revision received August 19, 1998; accepted September 2, 1998.
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 R. B. McCully, V. L. Roger, S. R. Ommen, D. W. Mahoney, K. N. Burger, W. K. Freeman, and P. A. Pellikka Outcomes of Patients With Reduced Exercise Capacity at Time of Exercise Echocardiography Mayo Clin. Proc., June 1, 2004; 79(6): 750 - 757. [Abstract] [PDF]
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 J. H. Ix, M. G. Shlipak, H. H. Liu, N. B. Schiller, and M. A. Whooley Association between Renal Insufficiency and Inducible Ischemia in Patients with Coronary Artery Disease: The Heart and Soul Study J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3233 - 3238. [Abstract] [Full Text] [PDF]
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A.F.L Schinkel, J.J Bax, M.L Geleijnse, E Boersma, A Elhendy, J.R.T.C Roelandt, and D Poldermans Noninvasive evaluation of ischaemic heart disease: myocardial perfusion imaging or stress echocardiography? Eur. Heart J., May 1, 2003; 24(9): 789 - 800. [Full Text] [PDF]
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A. Elhendy, K. M. Modesto, D. W. Mahoney, B. K. Khandheria, J. B. Seward, and P. A. Pellikka Prediction of mortality in patients with left ventricular hypertrophy by clinical, exercise stress, and echocardiographic data J. Am. Coll. Cardiol., January 1, 2003; 41(1): 129 - 135. [Abstract] [Full Text] [PDF]
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T. H Marwick Stress echocardiography Heart, January 1, 2003; 89(1): 113 - 118. [Full Text] [PDF]
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A. Elhendy, D. W. Mahoney, B. K. Khandheria, T. E. Paterick, K. N. Burger, and P. A. Pellikka Prognostic significance of the location of wall motion abnormalities during exercise echocardiography J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1623 - 1629. [Abstract] [Full Text] [PDF]
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R. B. McCully, V. L. Roger, D. W. Mahoney, K. N. Burger, R. L. Click, J. B. Seward, and P. A. Pellikka Outcome after abnormal exercise echocardiography for patients with good exercise capacity: Prognostic importance of the extent and severity of exercise-related left ventricular dysfunction J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1345 - 1352. [Abstract] [Full Text] [PDF]
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M. S. Lauer The "exercise" part of exercise echocardiography J. Am. Coll. Cardiol., April 17, 2002; 39(8): 1353 - 1355. [Full Text] [PDF]
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R. Wayhs, A. Zelinger, and P. Raggi High coronary artery calcium scores pose an extremely elevated risk for hard events J. Am. Coll. Cardiol., January 16, 2002; 39(2): 225 - 230. [Abstract] [Full Text] [PDF]
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R. J. Krone, R. M. Hardison, B. R. Chaitman, R. J. Gibbons, G. Sopko, R. Bach, and K. M. Detre Risk stratification after successful coronary revascularization: the lack of a role for routine exercise testing J. Am. Coll. Cardiol., July 1, 2001; 38(1): 136 - 142. [Abstract] [Full Text] [PDF]
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A. Elhendy, A. M. Arruda, D. W. Mahoney, and P. A. Pellikka Prognostic stratification of diabetic patients by exercise echocardiography J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1551 - 1557. [Abstract] [Full Text] [PDF]
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S. Shimoni, W. A. Zoghbi, F. Xie, D. Kricsfeld, S. Iskander, L. Gobar, I. A. Mikati, J. Abukhalil, M. S. Verani, E. L. O'Leary, et al. Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography J. Am. Coll. Cardiol., March 1, 2001; 37(3): 741 - 747. [Abstract] [Full Text] [PDF]
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G. P. Rodgers, J. Z. Ayanian, G. Balady, J. W. Beasley, K. A. Brown, E. V. Gervino, S. Paridon, M. Quinones, R. C. Schlant, W. L. Winters Jr, et al. American College of Cardiology/American Heart Association Clinical Competence Statement on Stress Testing : A Report of the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine Task Force on Clinical Competence Circulation, October 3, 2000; 102(14): 1726 - 1738. [Full Text] [PDF]
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G. P. Rodgers, J. Z. Ayanian, G. Balady, J. W. Beasley, K. A. Brown, E. V. Gervino, S. Paridon, M. Quinones, R. C. Schlant, W. L. Winters Jr, et al. American College of Cardiology/American Heart Association clinical competence statement on stress testing: A report of the American College of Cardiology/American Heart Association/American College of Physicians-American Society of Internal Medicine Task Force on Clinical Competence J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1441 - 1453. [Full Text] [PDF]
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Z.-X. He, T. D. Hedrick, C. M. Pratt, M. S. Verani, V. Aquino, R. Roberts, and J. J. Mahmarian Severity of Coronary Artery Calcification by Electron Beam Computed Tomography Predicts Silent Myocardial Ischemia Circulation, January 25, 2000; 101(3): 244 - 251. [Abstract] [Full Text] [PDF]
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