Keywords
The pharmacologic stress test, especially with echocardiography or radioisotope monitoring, is a tool that is frequently used for patients who are recuperating from an acute coronary event. The substances most frequently used are dobutamine, dipiridamol, and, more recently, arbutamine.1-3 For this test to provide satisfactory results, expensive equipment and experienced operators are required.4
The possibility of continuously monitoring the behavior of the ST segment with 12 electrocardiographic (ECG) leads simultaneously could provide a new, simple, and less expensive method of evaluating the consequences of a dobutamine infusion. Until now, few studies have been published in which ECG control is achieved with recordings every 3 minutes5 and with echocardiography monitoring.6 In 1991, Coma-Canella reported 95% sensitivity and 78% specificity by adding ECG monitoring to stress echocardiography with dobutamine.1 In 1994, Mairesse et al2 described the necessity of new criteria for pharmacological stress tests, but stated that diagnostic images are still required to predict the existence of coronary pathology with any certainty. In 1997, Martínez-Martínez et al3 proposed the use of dobutamine stress testing under standard ECG control in place of ergometry. In 1998, Coletta et al4 and De Felice et al5 studied standard ECG modifications with an intravenous (IV) dobutamine infusion and the possible impact of spontaneous contractile recuperation after an acute myocardial infarction. In 1999, Rambaldi et al6 investigated the T-wave modifications as a marker for myocardial viability, while Witchitz el al7 studied the sensitivity of this method. In our study we used for the first time the usual protocol of dobutamine with continuous real-time monitoring of the ST segment with 12 simultaneous ECG leads. Our objective was to evaluate the specificity and sensitivity of a dobutamine stress test with continuous real time monitoring of the ST segment with 12 simultaneous ECG leads in patients with heart disease.
PATIENTS AND METHODS
Patients
None of the patients in our study had a history of interventricular communication, valvulopathy, or myocardiopathy, or a known history of hypersensitivity to dobutamine or atropine, or both. Exclusion criteria were severe arterial hypertension, severe ventricular arrhythmia, or a clinical coronary status that would not allow temporary suspension of treatment.
Acute coronary events were produced in 36 patients (30 men and 6 women; average age 62±2 years) admitted to the coronary unit with a diagnosis of unstable angina within 10 days of the procedure. In all cases, total clinical and echocardiography stability were required during the 3 days preceding the test.
There were a total of 22 patients (20 men and 2 women, average age 64±4 years) with post-infarct angina who were also asymptomatic and stable 3 days prior to the test.
Three patients recuperated immediately (in less than 3 days) from successful transluminal angioplasty (3 men with an average age of 56±4 years).
A total of 6 patients presented with chronic stable heart disease (5 men and 1 woman; average age 66±6 years).
Eight individuals admitted for thoracic pain did not have a pathologic enzymatic curve or clear electrocardiographic evidence of acute heart disease (6 men and 2 women; average age 61±3 years).
Prior medication
Two days before the test, beta blockers, calcium antagonists, and long-acting nitrites were discontinued, with only sublingual nitrites being permitted on demand.
ST-segment monitoring
A Spacelab monitor was used, with simultaneous and continuous recording of 12 real time leads for the automatic quantification of the ST-segment levels. In addition to visualization on the screen and storage of all data, a paper recording at the rate of 25 mm/s was obtained, using 0.05 to 109 Hz filters.
An ischemic response was defined as the new appearance or worsening of an ST-segment depression greater than 1 mm horizontal or descending measured at 60 ms from point J in at least 2 leads in the same topographic area (anterior, inferior, or lateral).8
The same equipment allowed us to automatically control arterial pressure every 3 minutes.
Dobutamine/atropine protocol
All patients were studied in the coronary unit (CU), with all necessary emergency equipment available at all times.
The modified Ohio State University protocol9 was used. The intravenous (IV) dobutamine infusion was begun at a dose of 5 µg/kg/min. At 3-minute intervals the dose was increased to 10, 20, and a maximum of 40 µg/kg/min. If the cardiac frequency did not reach a minimum of 85% of the theoretical level for the sex and body surface of the patient, 0.5 to 1 mg of IV atropine was added, without discontinuing the dobutamine infusion.
Criteria for interrupting the dobutamine infusion were: a) reaching 85% of the maximum cardiac frequency for the age and size of the patient; b) the appearance of angina; c) severe arterial hypertension (more than 220/120 mm Hg); d) decrease in systolic arterial pressure greater than 30 mm Hg; e) the appearance of severe ventricular or supraventricular arrhythmias; f) appearance of a significant ST-segment depression in 2 leads from the same area or worsening of pre-existing changes, and g) the end of the protocol.
The test was not considered diagnostic when:10 due to early interruption due to the appearance of c, d, and g in the preceding list, or a combination thereof; when collateral limiting side-effects were seen; when the protocol resulted in a normal test without having achieved 85% of the theoretical maximum cardiac frequency.
Coronary angiography
Coronary angiography was performed by interventionist cardiologists who did not participate in the investigations in all patients within 10 days of the dobutamine test. Lesions were estimated visually, with those greater than 70% considered significant.
Statistical evaluation
Our first objective was to answer the following questions:
-- If an ischemic condition existed, what would be the probability that the test would be positive?
-- If heart disease was not present, what would the probability be that the test would be negative?
If the ST-segment changes really constituted a continuous variable,9 for the purposes of our investigation we classified the results as positive or negative according to whether or not they were produced in accordance with the above-mentioned definitions. As a template or gold standard, coronary angiography was used.
Collateral side-effects
We defined as minor collateral side-effects that could not cause potential situations which compromised the life of the patient, were auto limited, or could be well controlled pharmacologically. On the other hand, we considered major collateral side-effects those situations that could potentially cause a clinical picture that compromised the patient´s life or prolonged hospitalization of the patient.
RESULTS
Seventy-five consecutive patients were analyzed prospectively. Table 1 lists the demographic and baseline clinical characteristics of these patients; the distribution by sex and age were similar in the 5 subgroups, and there were not very significant differences related to cardiovascular risk factors, with the exception of a minor prevalence of diabetes mellitus in the patients in with precordial pain under study.
The coronary angiography results are given in Table 2 (the clinicians did not know the results of the test being studied. The lesions were estimated visually, and those of more than 70% were considered significant. Obstructions of 100% were not included.
With the logical exception of the successful post-angioplasty patients, the 3 clinical forms of heart disease (unstable, chronic stable, and post-AMI angina) showed a significantly greater number of cases with arterial lesions.
Table 3 shows a comparison of the coronary angiography results with those with ECG/dobutamine tests; in the study population, 60% had abnormal coronary angiography and ECG/dobutamine test. This percentage increased to 80% with in the unstable angina group and decreased to 9% in the group with precordial pain of non-coronary origin (precordalgia under study), which we called the control group.
On the other hand, in 28% of the study population both tests were normal, which in the precordalgia group the percentage was 87.% (P<.001).
Table 4 shows the values that resulted from the calculation of the sensitivity and specificity of this method. Of the 49 patients with a positive ECG/dobutamine test, 45 (91.8%) also had significant lesions on angiography, while of the 26 patients with normal (or negative) ECG/dobutamine test, only 5 patients had significant angiographic lesions.
Table 5 demonstrates the clinical and hemodynamic response to the infusion of dobutamine and the eventual addition of atropine: the average length of the test was approximately 11 minutes, with a double product peak between 17 600 and 18 200, without any important differences between the 5 patient subgroups.
Atropine was needed in 83% of the patients with unstable angina, 73% who presented with post-AMI angina, in the 3 post-angioplasty patients, in 67% of the patients with chronic angina, and in 87% of the precordalgia group.
Of the 49 patients with a positive ECG/dobutamine test, 30 had typical angina. The presence of this symptoms did not change the specificity or sensitivity of the test (91% and 86%, respectively).
The recovery time for 50% of the ST segment was significantly shorter in the post-angioplasty patients (0.8 vs 2.9 minutes in the unstable angina group).
The peak of depression of the ST segment was 1.8 mV in 91.7% of patients with unstable angina, 1.6 mV in nearly 50% of patients with post-AMI angina and 1 of the 3 patients with angioplasty, 1.3 mV in 66% of the chronic patients, and 0.8 mV in 1 of the 8 individuals with precordial pain.
Side-effects
Following the definitions given in the Patients and methods section, during the dobutamine infusion (with the eventual addition of atropine) 75% of patients experienced minor side-effects: facial pain, nausea, and headache, principally). The test did not have to be suspended in any of these cases.
We did not record any cases of severe arterial hypotension (decrease in systolic arterial pressure greater than 20 mm Hg) and there was a 6% occurrence of supraventricular arrhythmias that did not require specific treatment or the suspension of the test.
DISCUSSION
This study is, at the moment, the first prospective clinical investigation to evaluate the specificity and sensitivity of continuous real-time ST segment monitoring with 12 simultaneous leads with dobutamine infusion.
It was not our intention to compare the efficacy of this diagnostic method with other well-proven tests, such as stress echocardiography and the various radioisotope resources, but to investigate the efficacy of a method that, because of its simplicity and cost to benefit ratio, could be a special tool that would useful in hospitals with limited technological resources.
The results obtained from a population with different forms of heart disease and a group of individuals admitted with precordial pain (with normal arteries on angiography) showed that the ECG/dobutamine test has a 90% sensitivity and 84% specificity, with 10% false negatives and 16% false positives. These results suggest the use of coronary angiography as a valuable diagnostic gold standard.
A decisive element at the time of evaluating the patient was the fact that the test was performed in the coronary unit, without the need to transfer the patient, with equipment that was easy to use and that provide objective results, eliminating the factor of personal interpretation.
As was expected due to the considerable international experience accumulated regarding diagnostic IV infusion of dobutamine/atropine under echocardiography or radioisotope control, there were no significant side-effects, giving the these a high level of safety.
Perhaps the percentage of false positive was somewhat higher than was expected (16%); nevertheless, it must be kept in mind that being a diagnostic development without antecedents, many doubtful recordings were considered negative in order not to negatively influence the protocol.
This can be confirmed with new experiences that involve a greater number of patients.
The ECG/dobutamine test, which is habitually used to investigate residual ischemia, is an evaluation that produces serious complications in less than 1% of patients.11 The test has a sensitivity of 80% and a specificity of 84%, the first varying between 74%, 86%, and 92% for lesions of 1, 2, and 3 vessels, respectively.10 Nevertheless, it is not an evaluation that is easy to perform, especially if experienced operators are not available.
Another limiting factor of the stress echocardiogram with dobutamine is that the subendocardial resolution is not always adequate, which is an indispensable requirement for an adequate interpretation of the changes in the regional parietal dynamic.12
Finally, it must be remembered that approximately 5% of patients do not have an adequate ultrasonic window.18,13-15
It is just as important to clearly specify the admission criteria for the CU as it is the discharge criteria. Possessing a simple diagnostic strategy that is available 24 hours a day allows good categorization of the patient´s discharge risk, as well as the correct selection of the immediate diagnostic-therapeutic strategy to follow.
CONCLUSIONS
With the specificity and sensitivity obtained and the simplicity and security of the procedure,16,17 the ECG/dobutamine test appears to have an important diagnostic and prognostic value in patients who recover from acute coronary events. If we add to this the simplicity and cost to benefit ratio18-21 (both for the patient and for the institution where they are admitted), the tendency that has been observed justifies new studies in larger study populations to prove definitively prove this hypothesis and establish this method as a new and useful diagnostic resource for heart disease.
Correspondence: Dr. E. Beck.
Ciudad de la Paz, 163. (1426) Buenos Aires. Argentina.
Correo electrónico: ebeck@ciudad.com.ar