Author + information
- Received June 7, 1996
- Revision received December 17, 1996
- Accepted January 9, 1997
- Published online April 1, 1997.
- Eric H Steinberg, DOA,*,
- Lori Madmon, MSA,
- Chetan P Patel, MDB,
- Steven P Sedlis, MD, FACCA,
- Itzhak Kronzon, MD, FACCA and
- Jerald L Cohen, MD, FACCB
- ↵*Dr. Eric H. Steinberg, Division of Cardiology, New York Veterans Affairs Medical Center, 423 East 23rd Street, New York, New York 10010.
Objectives. This study sought to assess the long-term prognostic utility of dobutamine stress echocardiography in predicting fatal and nonfatal cardiac events.
Background. Although dobutamine stress echocardiography has improved sensitivity and specificity for detection of coronary artery disease, little is known of its predictive value for long-term cardiac events. Therefore, we followed up 120 consecutive patients who underwent dobutamine echocardiography for suspected coronary disease from March 1989 to August 1991.
Methods. All patients presenting for coronary angiography for chest pain were eligible for recruitment. Follow-up was 100% complete at 5 years (range 3.0 to 6.1). Cardiac events were defined as cardiac death or nonfatal myocardial infarction or the need for coronary revascularization (coronary angioplasty or bypass surgery).
Results. Positive (n = 78) and negative (n = 42) dobutamine test groups differed in their rates of coronary artery bypass graft surgery (37.2% vs. 9.5%, p < 0.001, respectively) and mortality. Of 26 total deaths, 22 occurred in the group with positive dobutamine test results (28% vs. 9.5%, p < 0.018); all 7 cardiac deaths occurred in this group as well (9% vs. 0%, p < 0.045). By multivariate regression analysis, positive results on dobutamine echocardiography remained independently predictive of future cardiac death after left ventricular ejection fraction and other clinical variables were accounted for.
Conclusions. A positive finding on dobutamine echocardiography is an independent predictor of long-term cardiac mortality, whereas a negative finding confers a significantly reduced likelihood of cardiac death as much as 5 years from initial testing. We conclude that dobutamine stress echocardiography can be used to predict which patients with suspected coronary artery disease are at low risk for cardiac death and do not require concurrent nuclear or invasive testing.
(J Am Coll Cardiol 1997;29:969–73)
© 1997 by the American College of Cardiology
Dobutamine stress echocardiography has been increasingly used to detect coronary artery disease, assess myocardial viability and predict cardiac risk in post-myocardial infarction patients and before major noncardiac surgery ([1–5]). The ability of dobutamine stress echocardiography to provide prognostic information regarding future cardiac events has been limited to 1- to 2-year follow-up studies ([6, 7]). One- to 10-year follow-up studies ([8–10]) of normal myocardial perfusion assessed by exercise thallium testing have demonstrated an excellent cardiac prognosis, with a likelihood of cardiac death or infarction ≤1%/year. An excellent prognosis has also been described ([11–13]) in long-term follow-up studies of coronary angiography in patients with normal or minimal coronary artery disease. However, although overall cardiac mortality rates remained low in these angiographic studies, patients with minimal or moderate disease had a significant increase in mortality, with a marked downsloping in their cardiac survival curve after 6 to 8 years ([12–14]). Dobutamine echocardiography has correlated well with angiographic and scintigraphic findings ([1, 2, 15]); however, its ability to predict cardiac events over a similar long-term follow-up period has not been determined. We therefore prospectively assessed 120 consecutive patients who underwent dobutamine stress echocardiography to determine its prognostic utility for predicting cardiac events over a 3- to 6-year period.
The methods and results of our initial studies involving this same patient cohort have been described in detail elsewhere ([1, 2]). Eligibility for participation in the study included patients presenting for coronary angiography to evaluate chest pain at the East Orange Veterans Affairs Medical Center between March 1989 and August 1991. These patients also had to successfully undergo dobutamine stress echocardiography. Exclusion criteria included unstable angina, cardiomyopathy, uncontrolled hypertension, significant valvular heart disease, known serious arrhythmia, congestive heart failure and previous coronary artery bypass surgery. The final cohort included 120 veterans (119 male; mean [±SD] age 66.9 ± 9.6 years, range 47 to 95). Patients were classified into two groups: 78 (65%) with positive and 42 (35%) with negative dobutamine test results.
1.2 Baseline characteristics.
At the time of dobutamine stress echocardiography, baseline information regarding medical history and coronary risk factors were recorded for each patient and included age, tobacco usage, diabetes, hypertension, angina, family history of coronary artery disease, hypercholesterolemia, congestive heart failure, previous myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty and baseline left ventricular ejection fraction determined from the apical four-chamber view using the single-plane area–length method. Except for baseline left ventricular ejection fraction, these baseline characteristics did not differ significantly between the two patient groups (Table 1).
1.3 Cardiac catheterization.
Left-sided cardiac catheterization and coronary angiography were performed within 2 weeks of dobutamine stress echocardiography in the standard manner. Significant coronary artery disease was defined as >70% reduction in the lumen diameter of any of the three major epicardial coronary arteries or their primary branches, or >50% reduction of the lumen diameter of the left main coronary artery. Angiograms were reviewed in blinded manner by two angiographers who had no knowledge of the results of dobutamine echocardiography.
1.4 Dobutamine echocardiography.
Dobutamine stress echocardiography was performed using a Hewlett-Packard Sonos 500 echocardiography system and digitized on-line using a Nova Microsonics, PreVue analyzer. After baseline images were recorded, 2.5 μg/kg body weight per min of dobutamine was infused in 3-min increments to a maximum of 40 μg/kg per min. Images from the four standard views of the left ventricle (parasternal long- and short-axis, apical four- and two-chamber views) were recorded in a quad screen format and stored on a 5.25-in. floppy disk for later analysis.
A positive dobutamine stress test resultwas defined as the development of a new wall motion abnormality not present at baseline. For those studies with baseline wall motion abnormalities, a positive study result consisted of one showing either a higher grade wall motion abnormality in the baseline abnormal segment (i.e., from hypokinetic to akinetic) or any new wall motion abnormality in a different segment. Echocardiograms were read in blinder manner by two experienced observers who had no knowledge of the results of cardiac catheterization. There was 94% interobserver and 96% intraobserver agreement. Disagreements were resolved by consensus.
1.5 Patient follow-up.
Follow-up data were obtained from direct telephone contact, hospital and computer records and the Beneficiary Identification and Record Locator Subsystem (BIRLS) (). BIRLS is a computerized database that identifies veterans and their dependents who receive compensation, pension, education and other Veterans Affairs benefits. The accuracy rate is 95%. Follow-up was 100% complete for both morbidity and mortality.
All patients were followed up for a mean of 5 years (range 3.0 to 6.1). Evaluated end points included death, myocardial infarction, percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery (Table 2). Deaths were further classified as cardiac or noncardiac. Acute myocardial infarction was verified by hospital records using standard criteria of history, electrocardiogram (ECG) and cardiac enzyme levels.
1.6 Statistical analysis.
Variables were compared using chi-square analysis, with p < 0.05 considered significant. Logistic regression was used to compare the strength of the association of cardiac death with several other common clinical variables. In this multivariate analysis, the predictive value of dobutamine stress echocardiography was considered in combination with age, hypertension, angina, tobacco usage, diabetes, hypercholesterolemia, previous myocardial infarction, congestive heart failure, left ventricular ejection fraction <40%, rest wall motion abnormalities on echocardiography and family history of coronary artery disease. The least significant variables were removed from the model in a backward stepwise manner until only the two most significant variables remained as independent predictors of cardiac death.
Kaplan-Meier survival curves were performed for all-cause mortality, and equality of survival was compared using the Mantel-Cox test.
2.1 Coronary angiography.
Cardiac catheterization revealed that patients with positive dobutamine test results were significantly more likely to have multivessel coronary artery disease (66.7% vs. 7.1%, p < 0.0000) (Table 1). Importantly, no patient with three-vessel coronary artery disease had negative dobutamine test results. In contrast, dobutamine echocardiography was not a sensitive means of detecting patients with single-vessel coronary artery disease. This lack of sensitivity was demonstrated by 25.8% of patients with single-vessel disease with negative dobutamine test results.
2.2 Clinical follow-up.
Cardiac and all-cause mortality were significantly higher in patients with positive dobutamine test results (9.0% vs. 0.0%, p < 0.045 and 28.2% vs. 9.5%, p < 0.018, respectively) (Table 2). All seven cardiac-related deaths occurred in the group with positive dobutamine test results (five secondary to coronary artery disease, two due to congestive heart failure). Of 19 noncardiac deaths, 7 were due to malignancy, 2 to renal disease, 2 to liver disease, 2 to pneumonia, 2 to unknown causes (both in the group with positive dobutamine test results) and 1 each due to AIDS, stroke, cellulitis and gastrointestinal bleeding. Patients with positive dobutamine test results were more likely to undergo coronary artery bypass surgery than those with negative dobutamine test results (37.2% vs. 9.5%, p < 0.001). Coronary artery bypass surgery and percutaneous transluminal coronary angioplasty procedures were performed a mean of 14.8 and 11.8 months after dobutamine echocardiography, respectively. The incidence of nonfatal myocardial infarction and percutaneous transluminal coronary angioplasty did not differ significantly between the two groups.
Dobutamine echocardiography had a sensitivity and specificity of 78.8% and 51.9%, respectively, for identifying all cardiac events; a sensitivity and specificity of 100% and 37.2%, respectively, for identifying cardiac-related death; and a negative predictive value of 100% and 95.2%, respectively, for cardiac death and myocardial infarction (Table 2).
Multivariate regression analysis showed that positive findings on dobutamine echocardiography and an ejection fraction <40% were the only independent variables associated with cardiac death. Kaplan-Meier survival analysis revealed a significant difference in cumulative percent survival between groups (71.8% with positive vs. 90.5% with negative dobutamine test results, p = 0.02) that became apparent at 3 years into the follow-up period (Fig. 1).
To our knowledge, this is the first report to describe the 5-year prognostic value of dobutamine echocardiography in evaluating patients with coronary artery disease. Our data demonstrate the ability of normal findings on dobutamine echocardiography to predict which patients with a high pretest probability of coronary artery disease are at low risk of long-term fatal cardiac events. These findings are similar to several long-term follow-up studies of cardiac and all-cause mortality in patients with either normal exercise thallium results or angiographically normal or minimally diseased coronary arteries (Table 3). In these studies, patients with either normal myocardial perfusion or ≤50% coronary lumen narrowing had an annual cardiac mortality rate ≤0.5%/year and an all-cause mortality rate ≤0.9%/year. Our study shows similar results, with annual 5-year cardiac and all-cause mortality rates of 0%/year and 1.9%/year, respectively.
The finding that patients with positive dobutamine test results were more likely to require future surgical revascularization is consistent with the ability of dobutamine echocardiography to accurately distinguish between patients with multivessel versus lesser degrees of coronary disease. However, the poor sensitivity of dobutamine echocardiography for detecting patients with single-vessel coronary artery disease may help to explain why this test was less predictive of the need for future coronary angioplasty.
Although cardiac survival in the group with negative dobutamine test results was excellent, nonfatal myocardial infarction occurred with a similar frequency in those with negative (4.8%) or positive (3.8%) findings on dobutamine echocardiography. This frequency is similar to that described in studies of patients with either normal thallium exercise test results or coronary lumen narrowing, where the majority of hard events (cardiac death or nonfatal infarction) have been nonfatal infarctions ([8–13]). Possible explanations for these events could include either the progression of an existing lesion that was physiologically “silent” or the development of a new, obstructive lesion within an artery with previously undetectable disease. Several invasive studies ([17–19]) have demonstrated the development of new, obstructive coronary lesions in areas of an artery with only minor disease on initial angiography.
3.1 Study limitations.
Some limitations should be considered in interpreting this study. Because we did not know the number of patients referred who may have had abnormal results on previous exercise electrocardiography, the relative prognostic value of the stress ECG together with wall motion analysis could not be assessed. Also, because all patients in the study had a high pretest probability for coronary artery disease by virtue of their presentation with chest pain and selection for cardiac catheterization, these results may not be applicable to a more general referral population. A posttest referral bias can not be eliminated from this study because dobutamine echocardiographic results were available to the clinicians caring for these patients. Finally, these results will need to be reproduced in further studies involving a larger patient cohort before the precise role of dobutamine stress echocardiography in long-term cardiac risk stratification can be determined.
- Beneficiary Identification and Record Location Subsystem
- Received June 7, 1996.
- Revision received December 17, 1996.
- Accepted January 9, 1997.
- The American College of Cardiology
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