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Cardiac Imaging |
1 From the Department of Cardiology, German Heart Institute Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany (A.W., I.P., S.R., C.K., E.F., E.N.); Department of Cardiology, Swiss Cardiovascular Center Bern, Bern, Switzerland (A.W.); and Department of Cardiology, Heart Center Osnabrueck-Bad Rothenfelde, Osnabrueck-Bad Rothenfelde, Germany (S.R.). Received March 25, 2003; revision requested June 18; final revision received February 6, 2004; accepted February 17. A.W. supported by a grant from the Swiss National Science Foundation and the Swiss Foundation for Grants in Medicine and Biology. Address correspondence to E.N. (e-mail: eike.nagel@dhzb.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: One hundred sixty consecutive patients (mean age, 59 years ± 8 [standard deviation]) who had undergone revascularization for CAD and have wall motion abnormalities at rest underwent stress cardiovascular MR imaging prior to clinically indicated invasive coronary angiography. Turbo gradient-echo MR images were acquired at rest and during a standardized high-dose dobutamine-atropine protocol with three short-axis and two long-axis views. Regional wall motion was assessed by a blinded observer by using a 16-segment model and a four-point scoring system. New or worsening wall motion abnormality in at least one segment was considered positive for myocardial ischemia.
RESULTS: Significant CAD (stenoses of at least 50% diameter at angiography) was found in 119 patients (74%). Target heart rate was not reached in nine patients (6%). Overall sensitivity and specificity for detection of significant CAD were 89% and 84%, respectively. Diagnostic accuracy was 88%, and positive and negative predictive values were 94% and 73%, respectively. Overall sensitivity for detection of significant CAD in patients with single-, double-, and triple-vessel disease was 87%, 88%, and 100%, respectively.
CONCLUSION: High-dose stress cardiovascular MR imaging can be used for follow-up of patients after coronary revascularization procedures. Diagnostic accuracy is similar to stress cardiovascular MR imaging data for patients suspected of having CAD and compares favorably with that of other established noninvasive techniques.
Supplemental material: radiology.rsnajnls.org/cgi/content/full/2331030463/DC1.
© RSNA, 2004
Index terms: Coronary angiography, comparative studies, 54.1244 • Coronary vessels, MR, 54.121412, 54.12142, 54.12143 • Coronary vessels, stenosis or obstruction • Heart, ischemia, 51.1939 • Magnetic resonance (MR), cine study, 54.12149
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The development of stress-induced regional wall motion abnormalities, which constitutes the rationale for both dobutamine stress echocardiography and dobutamine stress cardiovascular magnetic resonance (MR) imaging, is considered a sensitive and reliable early marker of myocardial ischemia that precedes the development of ST-segment depression and anginal symptoms (3).
Because of its versatility and relatively low cost, dobutamine stress echocardiography is widely used in clinical practice. In patients with baseline wall motion abnormalities at rest, however, its diagnostic accuracy is limited (4–6). Fast high-dose dobutamine stress cardiovascular MR imaging has been reported (7,8) to be superior to dobutamine stress echocardiography in patients suspected of having CAD (7), a result attributed to superior image quality.
However, patients with prior myocardial infarction (7,9,10) or wall motion abnormalities at rest (9,10)—that is, patients in whom detection of ischemia can be difficult—have been excluded from most previous stress cardiovascular MR imaging studies. Therefore, the purpose of the present study was to determine the value of high-dose dobutamine stress cardiovascular MR imaging for diagnosis of ischemia in patients who have undergone revascularization for CAD and have wall motion abnormalities at rest, with quantitative invasive coronary angiography serving as the reference standard.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Patients were excluded because of non–sinus rhythm, unstable angina, severely decreased left ventricular ejection fraction (<30%), significant valvular disease (ie, more than mild stenosis or regurgitation), severe arterial hypertension (blood pressure 
220/120 mm Hg), implanted pacemakers, or other general contraindications to cardiovascular MR examination. To ensure an adequate heart rate response to dobutamine, patients were requested to withhold beta-blockers on the day of the stress examination. Other antianginal medications were not discontinued.
In 10 of 170 consecutive patients (6%), cardiovascular MR imaging could not be performed because of claustrophobia. Thus, the remaining 160 patients constituted the study population. Patient demographics are summarized in the Table. All patients had undergone coronary revascularization procedures previously—on the left anterior descending coronary artery in 105 cases, the left circumflex coronary artery in 71 cases, and the right coronary artery in 93 cases. The mean interval since the last revascularization procedure was 24 months ± 32 (standard deviation) (median, 7 months; range, 1–153 months). All patients had baseline wall motion abnormalities at rest. These were localized in the left anterior descending coronary artery territory in 110 cases, in the left circumflex artery territory in 87 cases, and in the right coronary artery territory in 82 cases.
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The time sequence of the examination is shown in Figure 1. A single-section segmented turbo gradient-echo technique (repetition time msec/echo time msec, 5.6/1.9; flip angle, 25°; spatial resolution, better than 1.6 x 1.6 x 8 mm; temporal resolution, <30 msec) was used. Electrocardiographic rhythm and symptoms were monitored continuously, and blood pressure was determined every 3 minutes. Dobutamine (Fresenius Kabi Germany, Bad Homburg, Germany) was infused intravenously during 3-minute stages at doses of 10, 20, 30, and 40 µg per kilogram of body weight per minute until at least 85% of age-predicted heart rate was reached. If at the peak dose of dobutamine the target heart rate was not achieved and the stress test results were still negative, 0.25-mg fractions of atropine (B. Braun Melsungen, Melsungen, Germany; maximal dose, 2 mg) were administered in the absence of contraindications, such as narrow-angle glaucoma or symptoms of prostatic obstruction.
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Image Analysis
All digital stress cardiovascular MR images were displayed as continuous synchronized cine loops by using a multiple-screen format (MASS software package, version 4.2; Medis, Leiden, the Netherlands) to compare corresponding rest, increasing stress, and peak stress levels. Regional wall motion was assessed off line by an experienced observer (A.W., with 2 years of experience in cardiovascular MR imaging in a high-volume facility and review of more than 500 stress cardiovascular MR imaging cases) who was blinded to clinical data and results of invasive coronary angiography. A 16-segment model (12) was used, and segmental wall motion was graded semiquantitatively with a four-point scoring system (1, normal; 2, hypokinetic; 3, akinetic; and 4, dyskinetic).
Stress cardiovascular MR imaging findings were considered positive for ischemia in cases of (a) development of a new wall motion abnormality in at least one segment with normal wall motion at rest or (b) a worsening wall motion abnormality or a biphasic response in at least one segment with abnormal wall motion at rest. In the absence of ischemia, failure to attain 85% of age-predicted maximal heart rate was identified as a nondiagnostic result. For comparison with invasive coronary angiography, segmental wall motion was related to the corresponding presumed coronary artery territories.
Quantitative Coronary Angiography
The results of stress cardiovascular MR imaging had no influence on the decision to perform clinically indicated invasive coronary angiography. Coronary angiograms were obtained in all patients within 24 hours of stress cardiovascular MR examination and were reviewed and evaluated by means of consensus between two senior invasive cardiologists (each with more than 15 years of experience in invasive cardiology in a high-volume center) who were blinded to the results of stress cardiovascular MR imaging.
Quantitative coronary angiography (Inturis Cardio Image Viewing Package, release 1.22; Philips) was performed by an additional observer (technician with 8 years of experience in quantitative coronary angiography) who was blinded to clinical data and the results of stress cardiovascular MR imaging. All native coronary arteries, side branches, and bypass grafts were evaluated, but for native coronary arteries, only lesions in vessel segments with a reference diameter (vessel diameter in nondiseased artery immediately proximal to the lesion) of at least 2 mm were included in the analysis.
Stenosis of at least 50% diameter reduction at quantitative coronary angiography was considered significant (13). Results were documented separately for the three major epicardial coronary arteries (left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery). Bypass grafts and side branches were included in the analysis of the respective coronary territory.
Statistical Analysis
Continuous variables were expressed as the mean value ± 1 standard deviation. Noncontinuous categorical variables were expressed as sums and percentages. The Student paired t test was used to assess hemodynamic differences at baseline and during stress cardiovascular MR imaging. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values were calculated according to standard definitions. Statistical significance was assumed with a P value of less than .05. All data were analyzed with the use of SPSS software (version 10.0; SPSS, Chicago, Ill).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Sixty-four percent (69 of 107) of patients with positive stress MR imaging results received atropine, and 54% (24 of 44) of patients with negative test results required atropine to reach target heart rate. Chest pain occurred in 66 patients (41%). Image quality was diagnostic in all patients. In the absence of ischemia, however, target heart rate was not reached in nine patients (6%). This resulted from maximum pharmacologic infusion in submaximal negative examinations in four patients (2%) and limiting side effects in five patients (3%), including ventricular extrasystoly (n = 2), severe chest pain (n = 1), nausea (n = 1), and asymptomatic decrease in blood pressure (n = 1).
There were 11 (7%) side effects in total, including those described in the previous paragraph, which led to interruption of stress MR imaging. These consisted of the following: one case (1%) of sustained ventricular tachycardia with hemodynamic compromise that required external defibrillation after imaging at peak dobutamine dose in a patient with triple-vessel disease and a severely diminished left ventricular ejection fraction of 35%, two cases (1%) of nonsustained ventricular tachycardia, one case (1%) of atrial fibrillation with rapid ventricular rate, three cases (2%) of ventricular extrasystoly, three cases (2%) of nausea, and one case (1%) of asymptomatic decrease in blood pressure.
Thus, a diagnostic-quality stress cardiovascular MR examination (ie, positive for ischemia or negative with achievement of at least a submaximal heart rate response) was achieved in 151 of 160 patients (94%). One hundred seven patients (67%) showed a new or worsening wall motion abnormality, while 44 (28%) did not. No stress cardiovascular MR imaging examination was terminated prematurely for a new or worsening wall motion abnormality that was ultimately not confirmed when evaluated off line. Images from positive examinations are shown in Figures 2 and 3.
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Detection of CAD in Individual Coronary Arteries
On the basis of the known anatomic correlation between coronary arteries and myocardial territories, disease of individual coronary arteries can be inferred. The sensitivity and specificity for detection of CAD in individual coronary arteries are shown in Figure 4 for all patients and in Figure 5 for patients with only one diseased vessel. Overall, 74 coronary artery stenoses in 58 patients were either missed or misdiagnosed. Forty-four of these patients had multivessel disease. However, most patients in whom an individual coronary artery stenosis was not recognized correctly were nevertheless identified as having significant CAD, either because they had multivessel disease and a dobutamine-induced wall motion abnormality in another territory or simply because the observed wall motion abnormality had been erroneously attributed to the wrong coronary artery (eg, right coronary artery instead of left circumflex artery). Thus, in a per-patient analysis, CAD was not identified in 12 patients. Eight of these patients had single-vessel disease, while four had double-vessel disease.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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Safety and Feasibility of Stress Cardiovascular MR Imaging
Extensive experience with other modalities in which similar dobutamine-atropine stress protocols were used, especially dobutamine stress echocardiography, has shown that severe complications may be expected in 0.25%–0.60% of patients, including sustained ventricular tachycardia, myocardial infarction, ventricular fibrillation (2,14–19), and even death (19). Clinically important arrhythmias have been reported to occur more frequently in patients with a history of ventricular arrhythmias or left ventricular dysfunction at rest (14). Thus, during stress cardiovascular MR imaging, monitoring of the patient within the magnet is mandatory and requires the same precautions and equipment as any other stress examination (11,20–22).
A trained physician, a defibrillator, and emergency medications must be present at the site of stress cardiovascular MR imaging (11). The main concern is the occurrence of arrhythmias. While ST-segment analysis is generally precluded by distortion caused by the magnetic field, cardiovascular MR imaging allows monitoring of cardiac rhythm and, thus, online assessment of stress-induced arrhythmias. In our patient population, which had a high pretest probability of inducible ischemia, stress cardiovascular MR imaging was mostly well tolerated, with major adverse effects occurring in only one patient, who developed a sustained ventricular tachycardia with hemodynamic compromise. This patient was removed from the magnet room, and cardioversion was performed successfully with a defibrillator located in the preparation room (23).
Overall Diagnostic Accuracy of Stress Cardiovascular MR Imaging
In the era of interventional cardiology, the major goal of a noninvasive test is the identification of all patients with significant CAD. Furthermore, the identification of patients with extensive CAD is particularly important, since these patients would benefit from coronary revascularization from a prognostic point of view. In the present study, the sensitivity for detection of significant CAD in patients with triple-vessel disease was 100%. A secondary objective would be the detection of stenoses in all vessels that would be potential candidates for revascularization. Thus, in the current study, all bypass grafts and all vessel segments with a diameter of at least 2 mm, including side branches, were included in the analysis.
Indeed, stenosis in a vessel smaller than 2 mm in diameter rarely constitutes a target for revascularization (24,25). A stenosis of at least 50% diameter at quantitative coronary angiography was considered significant (13), since most clinicians and third-party payers use this degree of stenosis as the threshold for revascularization procedures. In addition, this criterion has also been used in the vast majority of dobutamine stress-echo studies (2).
The results of the present study compare favorably with those in previous studies in which dobutamine stress echocardiography (2) and single photon-emission computed tomography were used. For dobutamine stress echocardiography in particular, approximately 10% of patients have nondiagnostic submaximal negative test results because of an insufficient hemodynamic response to dobutamine-atropine administration or limiting side effects, compared with 6% in our study. On the basis of a total of 2246 patients reported in 28 studies, the overall sensitivity, specificity, and diagnostic accuracy of dobutamine stress echocardiography were 80%, 84%, and 81%, respectively (2), compared with 89%, 84%, and 88% in our study, despite concentration on a patient population expected to be more difficult to assess. Mean sensitivities for detection of significant CAD in patients with single-, double-, and triple-vessel disease were 74%, 86%, and 92%, respectively, compared with 87%, 88%, and 100% in the present study.
The diagnostic accuracy of dobutamine stress echocardiography has been reported to be comparable to that of radionuclide perfusion imaging (2). In general, however, techniques based on assessment of regional left ventricular wall motion are less sensitive but more specific for detection of inducible ischemia (2,26), a finding in line with the "ischemic cascade" theory, which states that perfusion abnormalities precede wall motion abnormalities and electrocardiographic changes (27).
Detection of CAD in Individual Coronary Arteries
The localization of left ventricular segments with an abnormal response to stress cardiovascular MR imaging showed good correlation with the presence of significant stenoses in individual coronary arteries. In patients with single-vessel disease, the sensitivities of stress cardiovascular MR imaging for the identification of CAD in the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery were 76%, 74%, and 82%, respectively. For dobutamine stress echocardiography, the reported mean sensitivities are 72%, 55%, and 76%, respectively (2).
As for dobutamine stress echocardiography (2), our lower sensitivity for detection of left circumflex coronary artery disease might be explained by the variations in coronary anatomy (eg, variations in blood supply to the posterior wall by either the left circumflex coronary artery or the right coronary artery, depending on their relative size). In addition, coronary collateral vessels, which are encountered frequently in chronic CAD, were not quantitatively accounted for.
Previous Studies
Over the past decade, conventional intermediate-dose dobutamine stress cardiovascular MR imaging (9,10,28,29) has been shown to be feasible in small patient populations. However, intermediate-dose dobutamine alone (9,10,28,29) is considered insufficient to induce ischemia in many patients (30). Fast high-dose dobutamine-atropine stress cardiovascular MR imaging has been reported (7,8) to be superior to dobutamine stress echocardiography in patients suspected of having CAD (7), a result attributed to superior image quality. Of note, in the present study, image quality was diagnostic in all patients.
Hundley et al (8) studied 153 patients with poor acoustic windows that prevented adequate transthoracic echocardiographic imaging. In the 143 patients who received dobutamine, the test was terminated prematurely due to side effects in 26 patients (18%), including two cases of ventricular tachycardia (1%) and one case of atrial fibrillation (0.7%). Only 41 of 143 patients (29%) underwent invasive coronary angiography within 6 months of stress cardiovascular MR examination. In these patients, the sensitivity and specificity for detection of a stenosis more than 50% in diameter were 83% and 83%, respectively.
Furthermore, in the study of Hundley et al (8), 29 of 143 patients (20%)—that is, 42% (22 of 53 patients) of those taking beta-blockers and 8% (seven of 90 patients) of those who did not, failed to reach submaximal age-predicted heart rate despite maximal pharmacologic stress, thus yielding a high number of nondiagnostic examinations. Since their patients had relatively similar baseline characteristics, our higher number of diagnostic examinations (94%) most likely resulted from withholding of beta-blockers prior to testing and the more frequent administration of atropine (61% vs 27%), which allowed achievement of a higher heart rate response.
Limitations
The major limitation in the validation of noninvasive techniques aimed at detection of myocardial ischemia is the lack of an optimal reference standard. A possible disagreement between quantitative coronary angiography and stress cardiovascular MR imaging may be explained in part by different pathophysiologic approaches. It is well recognized that the functional relevance of intermediate coronary artery stenoses cannot be determined accurately by means of either conventional visual interpretation (31) or quantitative coronary angiography (32). This inaccuracy, which has been attributed mainly to the diffuse nature of CAD, the occurrence of arterial remodeling (33), and the development of coronary collaterals, may lead to underestimation of the diagnostic accuracy of noninvasive tests.
Furthermore, stress cardiovascular MR imaging was regarded as positive for ischemia and dobutamine infusion was consequently stopped if a new or worsening wall motion abnormality was seen in one territory during the examination. Thus, in patients with multiple coronary artery stenoses, it is likely that only the most significant stenosis was detected. As for dobutamine stress echocardiography (15,17), the interruption of the test once new or worsening wall motion abnormalities are detected, even if these are neither severe nor extensive, might improve safety when compared with an approach that involves only maximal dose or achievement of target heart rate as end points.
In our study, among patients with positive results, stress testing was stopped before administration of the highest dobutamine dose in 23 patients (21%). If, in order to detect all coronary artery stenoses in a particular patient, some positive tests were continued to reach target heart rate despite positivity, the incidence of side effects may have risen.
Wall motion was assessed only semiquantitatively in the present study. Currently, in most dobutamine stress echocardiographic and stress cardiovascular MR imaging studies and in clinical practice, wall motion analysis is based solely on qualitative criteria. This allows for immediate online analysis with termination of the test once ischemia has been detected, as well as rapid off-line analysis and reporting. While quantitative analysis has been shown to be feasible during stress cardiovascular MR imaging in patients without resting wall motion abnormalities (10,34) and might increase reproducibility and user independence, it is time-consuming, and its superiority has not yet been established.
Newer developments such as steady-state free precession imaging, which allows for better endocardial delineation (35) on long-axis views in particular, may support our findings even more. In addition, the use of myocardial tagging with high-dose dobutamine stress cardiovascular MR imaging has been shown to increase the detection rate of new wall motion abnormalities (36) when compared with stress cardiovascular MR imaging without tagging.
In conclusion, high-dose stress cardiovascular MR imaging can be used for the follow-up of patients after coronary revascularization procedures. Diagnostic accuracy is similar to stress cardiovascular MR imaging data reported for patients suspected of having CAD and compares favorably with other established noninvasive techniques.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, A.W., E.N.; study concepts, E.N.; study design, A.W., E.N.; literature research, A.W.; clinical studies, A.W., I.P., C.K.; data acquisition, A.W., I.P., S.R., C.K.; data analysis/interpretation, A.W., S.R.; statistical analysis, A.W.; manuscript preparation, A.W.; manuscript definition of intellectual content and editing, A.W., E.N.; manuscript revision/review and final version approval, all authors
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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