Detection of restenosis with dobutamine stress test after coronary angioplasty Dobutamine ECG tests were serially performed before, at 15 days, and at 2 and 6 months after successful coronary angioplasty in 56 patients. The dose of dobutamine was progressively increased from 5 gglkglmin to a maximum of 40 pglkglmin every 5 minutes, with ECG and blood pressure control. Coronary angiography was performed at the end of the study. At 15 days after coronary angioplasty, the dobutamine test was of little value for the diagnosis or prediction of restenosis. At the end of the study, both the presence of angina and the results of the dobutamine test were related to coronary angiography, and their accuracy was calculated for the detection of mild (1 50%) and severe (2 70%) restenosis or new coronary lesions. The accuracy of angina was 66% for the detection of mild lesions and 70% for that of severe lesions, whereas the accuracy of the dobutamine test was 76% for mild lesions and 60% for severe lesions. It is concluded that the dobutamine stress test is a simple and useful method for the detection of restenosis when it is performed at 2 and 6 months after coronary angioplasty. However, it cannot distinguish between restenosis or new coronary lesions. (AM HEART J 1992;124:1196.)
Isabel Coma-Canella, Madrid, Spain
MD,a Nicolas Sobrino Daza, MD,b and Luis Calvo Orbe, MDb
Percutaneous transluminal coronary angioplasty (PTCA) is a widely used method of myocardial revascularization. It has a high rate of immediate success, but a major problem is the high incidence of restenosis during the first 6 months of follow-up.1-3 Although the gold standard for the diagnosis of restenosis is coronary angiography, repeat angiography throughout the follow-up period for every patient is expensive and impractical. For this reason it is interesting to have a noninvasive method that is highly sensitive and specific for the detection of this complication available. Furthermore, the method must provide useful information about the physiologic consequences of a given anatomic lesion.4s 5 At present, the simplest method that is available for the detection of ischemia in patients with coronary artery disease is the exercise stress test. However, its diagnostic accuracy in the detection of restenosis is rather 10w.~-~ Exercise thallium scintigraphy and radionuelide ventriculography are superior to exercise
From %he Coronary bthe Hemodynamic Spain. Received
Care Unit, Division of Coronary Artery Diseases, and Section, Cardiology Division, La Paz Hospital, Madrid,
for publication
Apr.
6, 1992; accepted
May
20, 199”.
Reprint requests: Isabel Coma-Canella, MD, Unidad Coronaria, Paz, Paseo de la Castellana 261, 28046 Madrid, Spain 4/1/40542
1196
Hospital
La
ECG.“,7,g However, thallium is expensive and scintigraphy is not available in every hospital. In addition, some patients who have undergone PTCA are unable to perform physical exercise. Since the dobutamine ECG test has been demonstrated to be a good alternative to exercise testing1°-14 and since it can be used in patients who are unable to exercise, we designed a prospective study to calculate its diagnostic accuracy for the detection of restenosis after coronary angioplasty METHODS Patient population.
Sixty-four patients who underwent complete revascularization by means of successful coronary angioplasty underwent serial dobutamine stress tests after informed consent was obtained. Six patients who were free of symptoms and whose dobutamine test results were negative throughout the 6 months of follow-up refused coronary angiography. For this reason, they were excluded from the analysis. Therefore the study group is biased in favor of those with recurrent coronary stenosis. The 58 remaining patients were 55 men and 3 women, with a mean age of 56 t 9 years (range, 31 to 75 years). Ten of them had an old myocardial infarction. The reasons for performing coronary angioplasty were the following: 14 patients had stable angina, 31 had unstable angina, 5 had postinfarction angina, and 8 patients had acute myocardial infarction. These eight patients had a predischarge dobutamine test that suggested the presence of ischemia.
Patients
with
residual
lesions
L 50% after
Volume 124 Number
5
angioplasty in at least one coronary artery were not included in the study. Other exclusion criteria were negative results of a dobutamine test before PTCA; ECG changes that precluded the correct int,erpretation of the test, such as left bundle branch block or preexcitation syndrome; and absence of sinus rhythm. Patients who had valvular heart disease, primary cardiomyopathy, or congenital heart disease were also excluded. No patient was taking P-blockers or digitalis at the time of the tests. Other antianginal drugs such as nitrates or calcium channel blockers were not withdrawn The dobutamine stress test was performed with patients in the supine position. A K&lead ECG and cuff blood pressure control were recorded at baseline, after each dose of dobutamine, and at 5 and 10 minutes after the infusion was completed. Dobutamine was infused at an initial dose of 5 gg/kg/min for 5 minutes, and the dose was progressively increased to 10, 15, and 20 pg/kg/min every 5 minutes. Further increases up to a maximum of 40 pg/kg/min were allowed if the heart rate was 5 110 beats/min or if after it reached 110 beats/min, it did not increase to at least 30 beats/min above the baseline value. The criteria for stopping the test were: a heart rate 1 130 beats/min, moderate to severe angina, ST-segment shift L 2 mm (1 mm = 0.1 mV), severe arrhythmias, systolic blood pressure 1 210 mm Hg, failure to increase the heart rate with higher doses of dobutamine, or disturbing symptoms that precluded higher doses of the drug. Test results were positive when typical angina1 pain or ST-segment shift L 1 mm at 0.08 second of the J point was present. An ST-segment elevation on ECG leads with pathologic Q waves that suggested the presence of necrosis was disregarded. An ST-segment depression on ECG leads that were opposed to those with ST-segment elevation was considered to be a benign mirror image,‘” and it was also disregarded. Positive test results were divided into groups of strongly positive and slightly positive results. A strongly positive test result was characterized by an ST-segment shift 2 2 mm or an ST-segment shift < 2mm plus dobutamineinduced typical angina1 pain. Except in cases of unstable angina that were not controlled with pharmacologic treatment, the dobutamine test was performed within 7 days before PTCA, and it was repeated whenever possible at 15 days, and at 2 and 6 months after PTCA. The total number of dobut.amine stress tests that were performed in the 58 patients was 194: 51 tests were performed before PTCA, 50 at 15 days, 49 at 2 months, and 44 at 6 months. Cardiac catheterization with coronary angiography was performed before PTCA and at the end of the study within a week of the last dobutamine stress test. Although the study was scheduled for a follow-up period of 6 months, coronary angiography was performed before this time in patients who had severe angina or strongly positive dobutamine test results. Regardless of the time at which it was performed, coronary angiography was compared with the simultaneous dobutamine stress test to calculate the accuracy of such a test for the detect,ion of restenosis. Coronary
Dobutamine
test in restenosis
1197
arterial lesions were measured with calipers by two expert observers who were unaware of the results of the test; they used a semiquantitative method. In cases of discrepancy, the arithmetical mean of the two different measurements was taken. Lesions from 50 o/r to 69 c/Oin a major coronary artery or an important branch were considered mild and lesions I 70% were severe. Lesions < 50% were considered nonsignificant. PTCA was performed in lesions 2 70°C through the femoral artery with a standard technique. It was successful in cases of residual stenosis < 50%. The number of dilated arteries was 75. This corresponded to one dilated vessel in 44 patients, two vessels in 11 patients, and three vessels in three patients. The revascularization was complete in every case. One patient with single-vessel disease had three lesions at three different levels, and another patient had two lesions in the same artery. Every lesion was dilated, which added up to a total of 78 dilated lesions. The dilated lesions ranged between 70 ‘?C and 100 90, and locations were as follows: 30 in the left anterior descending coronary artery, 5 in the first diagonal branch, 11 in the left circumflex coronary artery, 11 in a large marginal branch of the circumflex coronary artery, and 21 in the right coronary artery. In six patients a total (100%) occlusion was dilated. Treatment after PTCA consisted of nifedipine, 10 mg given orally three times a day, and aspirin, 250 mg daily, except in cases of drug intolerance of disturbing side effects. All of the tests were performed without withdrawing treatment. Exercise stress testing was performed whenever possible on a treadmill, according to a maximal, symptom-limited Bruce protocol. The test consisted of progressive stages, each of which lasted 3 minutes. A complete ECG was recorded at baseline and immediately after the exercise was completed. The ECG leads aVF, Vs, and Vs were continuously monitored during the test. Cuff blood pressure was recorded before exercise, at the end of each stage, and at l-minute intervals after the exercise was completed for up to 3 minutes or until return to baseline. The criteria for stopping the exercise test were similar to those for stopping the dobutamine test, except for the maximal heart rate that was allowed with the exercise test. In addition, hypotension (decrease in systolic blood pressure 2 20 mm Hg), severe dyspnea, or fatigue were other reasons for terminating the exercise test. Criteria for positivity were the same as for the dobutamine stress test. The exercise test was compared with the dobutamine stress test in terms of diagnostic accuracy in the detection of restenosis. For this reason, only the exercise test that was performed at the time of coronary angiography was assessed. Statistical analysis. Values are expressed as means * SD. Results before and after angioplasty were compared with the use of the Student’s t test for paired data. Chi-square analysis was used for comparison of proportions when appropriate. Sensitivity, specificity, predictive value of positive test results, predictive value of negative test results, and diagnostic accuracy were calculated according to the usual methods.16
1198
Coma-Canella,
Daza, and Orbe
ANGINA
NO
American
9
ANGINA
Test
positive
Test
negative
8
c
1
slight
5 +
strong
3
1 angio -+
positive
14 +
negative
27
2
RE 1 RE
angio
slight
- 1 no
c
November 1992 Heart Journal
~70%
1 no RE
14
41
Fig. 1. Results of dobutamine test and coronary angiography (angio) at 15 days of evolution in 50 patients, according to the presence or absence of angina at this time. RE, Restenosis.
RESULTS Clinical
One patient died suddenly outside of the hospital 3 months after PTCA, with symptoms that were suggestive of acute myocardial infarction. Five patients were readmitted: one had acute myocardial infarction 1 month after PTCA, and four had unstable angina. Three of these patients were readmitted within 15 days of PTCA, and one was readmitted at 2 months after PTCA. In this patient a new dobutamine test was not performed because of severe angina that was unresponsive to pharmacologic treatment. Six outpatients complained of angina at 15 days, 21 at 2 months, and 15 at 6 months after PTCA. The remaining patients were free of symptoms throughout the course of the study. Dobutamine stress test. Before PTCA, 51 patients underwent a dobutamine stress test. In seven patients it was not performed because of refractory unstable angina. Test results were positive in every case, inasmuch as a negative test result was an exclusion criterion. Results were strongly positive in 28 patients and slightly positive in 23. In 8 of these 23 cases the only criterion of positivity was stress-induced typical angina. The mean dose of dobutamine infused was 20.4 k 6 pg/kg/min. The heart rate changed from 68 + 12 beats/min to 104 f 18 beats/min, the systolic blood pressure from 122 +_ 17 mm Hg to 141 f 17 mm Hg, and the double product from 8355 + 2145 to 14,684 f 3222 (p < 0.00001 for every change). Fifteen days after PTCA, the dobutamine test was repeated in 50 patients. Results were negative in 28 patients and positive in 22: results were slightly positive in 19 and strongly positive in 3. In 10 of the 19 patients who had slightly positive test results, the only abnormality was stress-induced typical angina. The mean dose of dobutamine infused was 21.3 ? 3 evolution.
pg/kg/min. The heart rate changed from 67 +- 11 beatslmin to 112 + 13 beatsfmin, the systolic blood pressure from 127 f 16 mm Hg to 140 f 21 mm Hg, and the double product from 8570 +- 2044 to 15,734 ? 2743 (p < 0.00001 for every change). At 2 months the test was repeated in 49 of the 55 remaining patients. Results were positive in 23 patients (slightly positive in 17, strongly positive in 6) and negative in 26. In 10 patients the only criterion of positivity was stress-induced angina. The mean dose of dobutamine infused was 21 f 4 pglkglmin. The heart rate changed from 66 t 11 beats/min to 106 +_ 16 beats/min, the systolic blood pressure from 126 * 16 mm Hg to 146 t 25 mm Hg, and the double product from 8387 I 2222 to 15,600 +. 3672 (p < 0.00001 for every change). At 6 months the test was repeated in the 44 patients who reached this point in the follow-up period. Results were positive in 18 patients (slightly positive in 12, strongly positive in 6) and negative in 26. Six of the 12 patients with slightly positive test results had stress-induced angina as the only criterion of positivity. The mean dose of dobutamine infused was 23.2 + 6 pg/kg/min. The heart rate changed from 66 + 10 beats/min to 112 ? 13 beats/min, the systolic blood pressure from 132 rt 21 mm Hg to 150 +- 24 mm Hg, and the double product from 8828 +- 2227 to 16,721 + 3205 (p < 0.00001 for every change). Coronary angiography. At 15 days after PTCA, coronary angiography was performed in three patients because of severe thoracic pain that necessitated readmission to the coronary care unit. One of them had a 60 “c restenosis and added spontaneous vasospasm in several segments of the same coronary artery. Two other patients did not show restenosis or spontaneous vasospasm, and they continued the study until 6 months of follow-up. At this time,
Volume 124 Number 5
Dobutamine
slight
ANGINA
NO
Test
positive
16
Test
negative
5
21
Test
positive
Test
negative
28
ANGINA
12 +
strong
4 -+
slight
5
4 angio
- 4 RE ~70%
4 angio
- 4 RE ~70%
test in restenosis
7 c 21
strong
2--.+
2 anglo
- 2 RE 270%
Fig. 2. Results of dobutamine test and coronary angiography (angio) at 2 months of evolution tients, according to the presence or absence of angina at this time. RE, Restenosis.
ANGINA
strong
15 Test
NO
ANGINA
negative
1199
1 d
6 ---b 1 no
in 49 pa-
6 RE ,70%
RE
29
Fig. 3. Results of dobutamine test and coronary angiography (angio) at 6 months of evolution tients, according to the presence or absence of angina at this time. RE, Restenosis.
repeat coronary angiography was performed. At 2 months, coronary angiography was performed in 10 patients: in four because of severe angina and in six because of strongly positive test results. Restenosis L 70 % was detected in all 10 patients. Three of them had undergone PTCA of two vessels, and restenosis of both vessels was present in all three cases. At 6 months coronary angiography was performed in the remaining 44 patients, regardless of symptoms or results of the test. Restenosis L 70 % was present in 17 patients, restenosis < 70% in 5, and new coronary lesions in 4 patients: two new lesions were
in 44 pa-
< 70 % and two were r 70 % . In eight patients PTCA had been performed in two vessels. Both vessels were free of restenosis in four patients. There was restenosis 1 70% in one of the two dilated arteries in three patients and < 70% in the remaining patient. In three patients PTCA had been performed in three vessels. One of them had two-vessel restenosis, and the two other patients did not have restenosis at all. Relationship and coronary
of clinical angiography.
symptoms,
dobutamine
test,
Figs. 1 to 3 show the relationship of the presence of angina, the results of the test, and the specific coronary lesion found at an-
1200
Coma-Canella,
Daza, and Orbe
American
3 angio
10
angio
18
angio
November1992 Heart Journal
26 angio
c pi-,,
2 no
CL
pCL(
116
2 no
CL
1101
16 no
CL
Fig. 4. Results of dobutamine test and coronary angiography (angio) at each moment of evolution. (+), Positive test result: (-). negative test result: RE. restenosis; AMI, acute myocardial infarction; SD, sudden death; CL, coronary lesions.
Table I. Diagnostic accuracy of angina and dobutamine test in the detection of coronary lesions after PTCA Lesions
Angina
Sensitivity (%) Specificity ( X ) Predictive value of a positive test (%) Predictive value of a negative test (?;I) Diagnostic accuracy
2 50% Dobutamine test
Lesions
Angina
2 70% Dobutamine test
58
72
89 91
89 93
63 78 74
79 80 82
52
61
68
77
68
78
70
80
(%I
giography at each moment of the clinical course. Fig. 4 shows a summary of the relationship between the dobutamine stress test and the presence of coronary lesions throughout the entire follow-up period. Usefulness of serial dobutamine stress tests. To assess the prognostic value of serial dobutamine tests throughout the patient’s clinical course, the results of the tests at 15 days and at 2 months were correlated with the results of coronary angiography at the end of the study. At 15 days, the results of 22 tests were positive. Mild restenosis was present in one of three patients who had undergone coronary angiography, future severe restenosis developed in 12 of 21 (57%), and future (15 days later) acute myocardial infarction in one patient. The remaining eight patients (36 % ) who had positive test results at 15 days after PTCA did not experience restenosis or other cardiac events
during the 6 months of follow-up. Negative test results were present in 28 patients, and 10 of them (36 % ) had late restenosis at 6 months. No significant difference in the presence of future restenosis was found between the group of patients with positive versus negative test results. At 2 months results of 23 tests were positive. Severe restenosis was detected by angiography in 10 patients. Restenosis I 70% was detected at 6 months in 8 of the 13 remaining patients (61% ), whereas five patients (22 % ) did not have restenosis. Twenty-six patients had negative test results. Seven of them (27 % ) had late restenosis and one patient had a fatal episode of sudden death 1 month later, whereas 18 were free of restenosis or cardiac events throughout the entire clinical course. No significant difference in the presence of future restenosis was found between patients with positive versus negative test results. Given the high proportion (2 of 3) of false-positive results at 15 days, we decided to disregard them for further analysis. For this reason, a total of 54 patients who underwent coronary angiography at 2 months (n = 10) or at 6 (n = 44) months were analyzed to calculate the accuracy of the dobutamine test. Diagnostic accuracy of symptomatology and dobutamine stress test for the detection of restenosis. To determine whether the dobutamine test adds something to the symptomatology of the patient in the detection of restenosis, the accuracy of angina and results of the dobutamine stress test were calculated for mild stenosis (L 50 % ) and severe stenosis (2 70%). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy are shown in Table I. The best diagnos-
Volume 124 Number 5
Table
Dobutamine
test in restenosis
1201
II. Parameters of oxygen consumption with dobutamine and exercise stress testing in 26 patients Parameter
Exercise test
Heart rate (beats/min) Systolic blood pressure (mm Hg) Rate-pressure product
136 T!T18 180 + 25 24,476 + 5,042
tic accuracy was obtained with the dobutamine stress test for the detection of coronary lesions L 70%. Considering only these lesions, there were five falsepositive results. The test was slightly positive in these five cases. Three of these patients had lesions < 70 % and two other patients did not have significant lesions. There were six false-negative results at 6 months after PTCA. In three of them only one of the two dilated vessels had restenosis. In two other cases the restenosis was less severe than the previous lesion. Only one patient with negative test results had restenosis that was similar to the lesion before PTCA. Comparison
between
exercise
p Value
Dobutamine 108 + 15 151 + 25 16,406 + 3,693
Isabel Coma-Canella, Madrid, Spain
MD,a Nicolas Sobrino Daza, MD,b and Luis Calvo Orbe, MDb
Percutaneous transluminal coronary angioplasty (PTCA) is a widely used method of myocardial revascularization. It has a high rate of immediate success, but a major problem is the high incidence of restenosis during the first 6 months of follow-up.1-3 Although the gold standard for the diagnosis of restenosis is coronary angiography, repeat angiography throughout the follow-up period for every patient is expensive and impractical. For this reason it is interesting to have a noninvasive method that is highly sensitive and specific for the detection of this complication available. Furthermore, the method must provide useful information about the physiologic consequences of a given anatomic lesion.4s 5 At present, the simplest method that is available for the detection of ischemia in patients with coronary artery disease is the exercise stress test. However, its diagnostic accuracy in the detection of restenosis is rather 10w.~-~ Exercise thallium scintigraphy and radionuelide ventriculography are superior to exercise
From %he Coronary bthe Hemodynamic Spain. Received
Care Unit, Division of Coronary Artery Diseases, and Section, Cardiology Division, La Paz Hospital, Madrid,
for publication
Apr.
6, 1992; accepted
May
20, 199”.
Reprint requests: Isabel Coma-Canella, MD, Unidad Coronaria, Paz, Paseo de la Castellana 261, 28046 Madrid, Spain 4/1/40542
1196
Hospital
La
ECG.“,7,g However, thallium is expensive and scintigraphy is not available in every hospital. In addition, some patients who have undergone PTCA are unable to perform physical exercise. Since the dobutamine ECG test has been demonstrated to be a good alternative to exercise testing1°-14 and since it can be used in patients who are unable to exercise, we designed a prospective study to calculate its diagnostic accuracy for the detection of restenosis after coronary angioplasty METHODS Patient population.
Sixty-four patients who underwent complete revascularization by means of successful coronary angioplasty underwent serial dobutamine stress tests after informed consent was obtained. Six patients who were free of symptoms and whose dobutamine test results were negative throughout the 6 months of follow-up refused coronary angiography. For this reason, they were excluded from the analysis. Therefore the study group is biased in favor of those with recurrent coronary stenosis. The 58 remaining patients were 55 men and 3 women, with a mean age of 56 t 9 years (range, 31 to 75 years). Ten of them had an old myocardial infarction. The reasons for performing coronary angioplasty were the following: 14 patients had stable angina, 31 had unstable angina, 5 had postinfarction angina, and 8 patients had acute myocardial infarction. These eight patients had a predischarge dobutamine test that suggested the presence of ischemia.
Patients
with
residual
lesions
L 50% after
Volume 124 Number
5
angioplasty in at least one coronary artery were not included in the study. Other exclusion criteria were negative results of a dobutamine test before PTCA; ECG changes that precluded the correct int,erpretation of the test, such as left bundle branch block or preexcitation syndrome; and absence of sinus rhythm. Patients who had valvular heart disease, primary cardiomyopathy, or congenital heart disease were also excluded. No patient was taking P-blockers or digitalis at the time of the tests. Other antianginal drugs such as nitrates or calcium channel blockers were not withdrawn The dobutamine stress test was performed with patients in the supine position. A K&lead ECG and cuff blood pressure control were recorded at baseline, after each dose of dobutamine, and at 5 and 10 minutes after the infusion was completed. Dobutamine was infused at an initial dose of 5 gg/kg/min for 5 minutes, and the dose was progressively increased to 10, 15, and 20 pg/kg/min every 5 minutes. Further increases up to a maximum of 40 pg/kg/min were allowed if the heart rate was 5 110 beats/min or if after it reached 110 beats/min, it did not increase to at least 30 beats/min above the baseline value. The criteria for stopping the test were: a heart rate 1 130 beats/min, moderate to severe angina, ST-segment shift L 2 mm (1 mm = 0.1 mV), severe arrhythmias, systolic blood pressure 1 210 mm Hg, failure to increase the heart rate with higher doses of dobutamine, or disturbing symptoms that precluded higher doses of the drug. Test results were positive when typical angina1 pain or ST-segment shift L 1 mm at 0.08 second of the J point was present. An ST-segment elevation on ECG leads with pathologic Q waves that suggested the presence of necrosis was disregarded. An ST-segment depression on ECG leads that were opposed to those with ST-segment elevation was considered to be a benign mirror image,‘” and it was also disregarded. Positive test results were divided into groups of strongly positive and slightly positive results. A strongly positive test result was characterized by an ST-segment shift 2 2 mm or an ST-segment shift < 2mm plus dobutamineinduced typical angina1 pain. Except in cases of unstable angina that were not controlled with pharmacologic treatment, the dobutamine test was performed within 7 days before PTCA, and it was repeated whenever possible at 15 days, and at 2 and 6 months after PTCA. The total number of dobut.amine stress tests that were performed in the 58 patients was 194: 51 tests were performed before PTCA, 50 at 15 days, 49 at 2 months, and 44 at 6 months. Cardiac catheterization with coronary angiography was performed before PTCA and at the end of the study within a week of the last dobutamine stress test. Although the study was scheduled for a follow-up period of 6 months, coronary angiography was performed before this time in patients who had severe angina or strongly positive dobutamine test results. Regardless of the time at which it was performed, coronary angiography was compared with the simultaneous dobutamine stress test to calculate the accuracy of such a test for the detect,ion of restenosis. Coronary
Dobutamine
test in restenosis
1197
arterial lesions were measured with calipers by two expert observers who were unaware of the results of the test; they used a semiquantitative method. In cases of discrepancy, the arithmetical mean of the two different measurements was taken. Lesions from 50 o/r to 69 c/Oin a major coronary artery or an important branch were considered mild and lesions I 70% were severe. Lesions < 50% were considered nonsignificant. PTCA was performed in lesions 2 70°C through the femoral artery with a standard technique. It was successful in cases of residual stenosis < 50%. The number of dilated arteries was 75. This corresponded to one dilated vessel in 44 patients, two vessels in 11 patients, and three vessels in three patients. The revascularization was complete in every case. One patient with single-vessel disease had three lesions at three different levels, and another patient had two lesions in the same artery. Every lesion was dilated, which added up to a total of 78 dilated lesions. The dilated lesions ranged between 70 ‘?C and 100 90, and locations were as follows: 30 in the left anterior descending coronary artery, 5 in the first diagonal branch, 11 in the left circumflex coronary artery, 11 in a large marginal branch of the circumflex coronary artery, and 21 in the right coronary artery. In six patients a total (100%) occlusion was dilated. Treatment after PTCA consisted of nifedipine, 10 mg given orally three times a day, and aspirin, 250 mg daily, except in cases of drug intolerance of disturbing side effects. All of the tests were performed without withdrawing treatment. Exercise stress testing was performed whenever possible on a treadmill, according to a maximal, symptom-limited Bruce protocol. The test consisted of progressive stages, each of which lasted 3 minutes. A complete ECG was recorded at baseline and immediately after the exercise was completed. The ECG leads aVF, Vs, and Vs were continuously monitored during the test. Cuff blood pressure was recorded before exercise, at the end of each stage, and at l-minute intervals after the exercise was completed for up to 3 minutes or until return to baseline. The criteria for stopping the exercise test were similar to those for stopping the dobutamine test, except for the maximal heart rate that was allowed with the exercise test. In addition, hypotension (decrease in systolic blood pressure 2 20 mm Hg), severe dyspnea, or fatigue were other reasons for terminating the exercise test. Criteria for positivity were the same as for the dobutamine stress test. The exercise test was compared with the dobutamine stress test in terms of diagnostic accuracy in the detection of restenosis. For this reason, only the exercise test that was performed at the time of coronary angiography was assessed. Statistical analysis. Values are expressed as means * SD. Results before and after angioplasty were compared with the use of the Student’s t test for paired data. Chi-square analysis was used for comparison of proportions when appropriate. Sensitivity, specificity, predictive value of positive test results, predictive value of negative test results, and diagnostic accuracy were calculated according to the usual methods.16
1198
Coma-Canella,
Daza, and Orbe
ANGINA
NO
American
9
ANGINA
Test
positive
Test
negative
8
c
1
slight
5 +
strong
3
1 angio -+
positive
14 +
negative
27
2
RE 1 RE
angio
slight
- 1 no
c
November 1992 Heart Journal
~70%
1 no RE
14
41
Fig. 1. Results of dobutamine test and coronary angiography (angio) at 15 days of evolution in 50 patients, according to the presence or absence of angina at this time. RE, Restenosis.
RESULTS Clinical
One patient died suddenly outside of the hospital 3 months after PTCA, with symptoms that were suggestive of acute myocardial infarction. Five patients were readmitted: one had acute myocardial infarction 1 month after PTCA, and four had unstable angina. Three of these patients were readmitted within 15 days of PTCA, and one was readmitted at 2 months after PTCA. In this patient a new dobutamine test was not performed because of severe angina that was unresponsive to pharmacologic treatment. Six outpatients complained of angina at 15 days, 21 at 2 months, and 15 at 6 months after PTCA. The remaining patients were free of symptoms throughout the course of the study. Dobutamine stress test. Before PTCA, 51 patients underwent a dobutamine stress test. In seven patients it was not performed because of refractory unstable angina. Test results were positive in every case, inasmuch as a negative test result was an exclusion criterion. Results were strongly positive in 28 patients and slightly positive in 23. In 8 of these 23 cases the only criterion of positivity was stress-induced typical angina. The mean dose of dobutamine infused was 20.4 k 6 pg/kg/min. The heart rate changed from 68 + 12 beats/min to 104 f 18 beats/min, the systolic blood pressure from 122 +_ 17 mm Hg to 141 f 17 mm Hg, and the double product from 8355 + 2145 to 14,684 f 3222 (p < 0.00001 for every change). Fifteen days after PTCA, the dobutamine test was repeated in 50 patients. Results were negative in 28 patients and positive in 22: results were slightly positive in 19 and strongly positive in 3. In 10 of the 19 patients who had slightly positive test results, the only abnormality was stress-induced typical angina. The mean dose of dobutamine infused was 21.3 ? 3 evolution.
pg/kg/min. The heart rate changed from 67 +- 11 beatslmin to 112 + 13 beatsfmin, the systolic blood pressure from 127 f 16 mm Hg to 140 f 21 mm Hg, and the double product from 8570 +- 2044 to 15,734 ? 2743 (p < 0.00001 for every change). At 2 months the test was repeated in 49 of the 55 remaining patients. Results were positive in 23 patients (slightly positive in 17, strongly positive in 6) and negative in 26. In 10 patients the only criterion of positivity was stress-induced angina. The mean dose of dobutamine infused was 21 f 4 pglkglmin. The heart rate changed from 66 t 11 beats/min to 106 +_ 16 beats/min, the systolic blood pressure from 126 * 16 mm Hg to 146 t 25 mm Hg, and the double product from 8387 I 2222 to 15,600 +. 3672 (p < 0.00001 for every change). At 6 months the test was repeated in the 44 patients who reached this point in the follow-up period. Results were positive in 18 patients (slightly positive in 12, strongly positive in 6) and negative in 26. Six of the 12 patients with slightly positive test results had stress-induced angina as the only criterion of positivity. The mean dose of dobutamine infused was 23.2 + 6 pg/kg/min. The heart rate changed from 66 + 10 beats/min to 112 ? 13 beats/min, the systolic blood pressure from 132 rt 21 mm Hg to 150 +- 24 mm Hg, and the double product from 8828 +- 2227 to 16,721 + 3205 (p < 0.00001 for every change). Coronary angiography. At 15 days after PTCA, coronary angiography was performed in three patients because of severe thoracic pain that necessitated readmission to the coronary care unit. One of them had a 60 “c restenosis and added spontaneous vasospasm in several segments of the same coronary artery. Two other patients did not show restenosis or spontaneous vasospasm, and they continued the study until 6 months of follow-up. At this time,
Volume 124 Number 5
Dobutamine
slight
ANGINA
NO
Test
positive
16
Test
negative
5
21
Test
positive
Test
negative
28
ANGINA
12 +
strong
4 -+
slight
5
4 angio
- 4 RE ~70%
4 angio
- 4 RE ~70%
test in restenosis
7 c 21
strong
2--.+
2 anglo
- 2 RE 270%
Fig. 2. Results of dobutamine test and coronary angiography (angio) at 2 months of evolution tients, according to the presence or absence of angina at this time. RE, Restenosis.
ANGINA
strong
15 Test
NO
ANGINA
negative
1199
1 d
6 ---b 1 no
in 49 pa-
6 RE ,70%
RE
29
Fig. 3. Results of dobutamine test and coronary angiography (angio) at 6 months of evolution tients, according to the presence or absence of angina at this time. RE, Restenosis.
repeat coronary angiography was performed. At 2 months, coronary angiography was performed in 10 patients: in four because of severe angina and in six because of strongly positive test results. Restenosis L 70 % was detected in all 10 patients. Three of them had undergone PTCA of two vessels, and restenosis of both vessels was present in all three cases. At 6 months coronary angiography was performed in the remaining 44 patients, regardless of symptoms or results of the test. Restenosis L 70 % was present in 17 patients, restenosis < 70% in 5, and new coronary lesions in 4 patients: two new lesions were
in 44 pa-
< 70 % and two were r 70 % . In eight patients PTCA had been performed in two vessels. Both vessels were free of restenosis in four patients. There was restenosis 1 70% in one of the two dilated arteries in three patients and < 70% in the remaining patient. In three patients PTCA had been performed in three vessels. One of them had two-vessel restenosis, and the two other patients did not have restenosis at all. Relationship and coronary
of clinical angiography.
symptoms,
dobutamine
test,
Figs. 1 to 3 show the relationship of the presence of angina, the results of the test, and the specific coronary lesion found at an-
1200
Coma-Canella,
Daza, and Orbe
American
3 angio
10
angio
18
angio
November1992 Heart Journal
26 angio
c pi-,,
2 no
CL
pCL(
116
2 no
CL
1101
16 no
CL
Fig. 4. Results of dobutamine test and coronary angiography (angio) at each moment of evolution. (+), Positive test result: (-). negative test result: RE. restenosis; AMI, acute myocardial infarction; SD, sudden death; CL, coronary lesions.
Table I. Diagnostic accuracy of angina and dobutamine test in the detection of coronary lesions after PTCA Lesions
Angina
Sensitivity (%) Specificity ( X ) Predictive value of a positive test (%) Predictive value of a negative test (?;I) Diagnostic accuracy
2 50% Dobutamine test
Lesions
Angina
2 70% Dobutamine test
58
72
89 91
89 93
63 78 74
79 80 82
52
61
68
77
68
78
70
80
(%I
giography at each moment of the clinical course. Fig. 4 shows a summary of the relationship between the dobutamine stress test and the presence of coronary lesions throughout the entire follow-up period. Usefulness of serial dobutamine stress tests. To assess the prognostic value of serial dobutamine tests throughout the patient’s clinical course, the results of the tests at 15 days and at 2 months were correlated with the results of coronary angiography at the end of the study. At 15 days, the results of 22 tests were positive. Mild restenosis was present in one of three patients who had undergone coronary angiography, future severe restenosis developed in 12 of 21 (57%), and future (15 days later) acute myocardial infarction in one patient. The remaining eight patients (36 % ) who had positive test results at 15 days after PTCA did not experience restenosis or other cardiac events
during the 6 months of follow-up. Negative test results were present in 28 patients, and 10 of them (36 % ) had late restenosis at 6 months. No significant difference in the presence of future restenosis was found between the group of patients with positive versus negative test results. At 2 months results of 23 tests were positive. Severe restenosis was detected by angiography in 10 patients. Restenosis I 70% was detected at 6 months in 8 of the 13 remaining patients (61% ), whereas five patients (22 % ) did not have restenosis. Twenty-six patients had negative test results. Seven of them (27 % ) had late restenosis and one patient had a fatal episode of sudden death 1 month later, whereas 18 were free of restenosis or cardiac events throughout the entire clinical course. No significant difference in the presence of future restenosis was found between patients with positive versus negative test results. Given the high proportion (2 of 3) of false-positive results at 15 days, we decided to disregard them for further analysis. For this reason, a total of 54 patients who underwent coronary angiography at 2 months (n = 10) or at 6 (n = 44) months were analyzed to calculate the accuracy of the dobutamine test. Diagnostic accuracy of symptomatology and dobutamine stress test for the detection of restenosis. To determine whether the dobutamine test adds something to the symptomatology of the patient in the detection of restenosis, the accuracy of angina and results of the dobutamine stress test were calculated for mild stenosis (L 50 % ) and severe stenosis (2 70%). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy are shown in Table I. The best diagnos-
Volume 124 Number 5
Table
Dobutamine
test in restenosis
1201
II. Parameters of oxygen consumption with dobutamine and exercise stress testing in 26 patients Parameter
Exercise test
Heart rate (beats/min) Systolic blood pressure (mm Hg) Rate-pressure product
136 T!T18 180 + 25 24,476 + 5,042
tic accuracy was obtained with the dobutamine stress test for the detection of coronary lesions L 70%. Considering only these lesions, there were five falsepositive results. The test was slightly positive in these five cases. Three of these patients had lesions < 70 % and two other patients did not have significant lesions. There were six false-negative results at 6 months after PTCA. In three of them only one of the two dilated vessels had restenosis. In two other cases the restenosis was less severe than the previous lesion. Only one patient with negative test results had restenosis that was similar to the lesion before PTCA. Comparison
between
exercise
p Value
Dobutamine 108 + 15 151 + 25 16,406 + 3,693
