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J Am Coll Cardiol, 2000; 36:1557-1564 © 2000 by the American College of Cardiology Foundation |
Manuscript received September 27, 1999; revised manuscript received April 20, 2000, accepted June 19, 2000.
Reprint requests and correspondence: Dr. Eike Nagel, Internal Medicine/Cardiology, German Heart Institute & Charité Campus Virchow, Humboldt University, Augustenburger Platz 1, D-13353 Berlin/Germany
eike.nagel{at}dhzb.de
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Abstract |
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The purpose of this study was to determine the potential value of magnetic resonance myocardial perfusion in the follow-up of patients after coronary intervention.
BACKGROUND
In some patients a residual impairment of myocardial perfusion reserve (MPR) early after successful coronary intervention has been observed. In this study we evaluated an MPR index before and after intervention with magnetic resonance.
METHODS
Thirty-five patients with single- and multivessel coronary artery disease were studied before and 24 h after intervention. The signal intensity time curves of the first pass of a gadolinium-diethylene triamine pentacetic acid bolus injected via a central vein catheter were evaluated before and after dipyridamole infusion. The upslope was determined using a linear fit. Myocardial perfusion reserve index was estimated from the alterations of the upslope.
RESULTS
The MPR index in segments perfused by the stenotic artery was significantly lower than in the control segments (1.07 ± 0.24 vs. 2.18 ± 0.35, p < 0.001) and improved significantly after intervention (1.89 ± 0.39, p < 0.001) but did not normalize completely (p < 0.01). After intervention the MPR index remained significantly lower in the balloon percutaneous transluminal coronary angioplasty group (1.72 ± 0.38; n = 13) in comparison with the stent group (1.99 ± 0.36, n = 18, p < 0.05). In the stent group a complete normalization of the MPR index was found 24 h after stenting.
CONCLUSIONS
Magnetic resonance perfusion measurements allow a reliable assessment of MPR index. An improvement of MPR index can be observed after coronary intervention, which is more pronounced after stenting. Magnetic resonance perfusion measurements allow the assessment and may be useful for the follow-up of patients with coronary artery disease after coronary intervention.
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As chest pain has a low negative predictive value as a clinical marker for the detection of restenosis in these patients (25,26), an objective, noninvasive follow-up is required. Currently, single photon emission tomography or positron emission tomography (PET) are available for the evaluation of myocardial perfusion (11,14,19,26–28); however, these techniques are limited by their dependency on radioactive tracers, the long washout time for some tracers making repeated measurements impractical, attenuation artifacts in single photon emission computed tomography and the dependency on an on site cyclotron for PET. Cardiac magnetic resonance imaging (MR) is a promising noninvasive technique that has recently been shown to be more accurate for the detection of dobutamine-induced wall motion abnormalities than echocardiography (29). In general, evaluation of myocardial perfusion is even more promising since wall motion abnormalities occur later than the reduction of myocardial perfusion in the ischemic cascade. Cardiac MR allows the assessment of myocardial perfusion by an analysis of the first pass kinetics of a contrast agent bolus (3,30–33). We have shown in a previous study that myocardial perfusion reserve (MPR) can be reproducibly determined from the alterations of the upslope of a first pass gadolinium-DTPA bolus after dipyridamole vasodilation using a linear fit. In this prospective study of 40 patients we have shown a sensitivity of 92% and a specificity of 86% for the detection of significant coronary artery stenosis by the use of a previously defined ischemic threshold for MPR (3).
In reports of cardiac MR perfusion studies, Manning et al. (30) found an increase of maximal signal intensity after surgical revascularization, and Lauerma et al. (31) reported an increase of the upslope in a group of 11 patients with proximal single-vessel stenosis of the left anterior descending coronary artery (LAD) 3 months after PTCA or surgical revascularization. In principle, these studies have demonstrated that alterations of myocardial perfusion can be assessed noninvasively with MR.
The aim of this study was to evaluate the changes of MPR within 24 h of a successful coronary intervention in a patient population with coronary artery disease (CAD). Another purpose of this study was to determine the possible diagnostic impact of this technique in the diagnosis and follow-up of patients with CAD who have undergone balloon PTCA or stenting.
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Methods |
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75% area stenosis) referred for elective coronary intervention were prospectively included in the study after written informed consent. All patients had a stenosis of a major coronary artery.
Patients were excluded if they had a history of prior myocardial infarction, unstable angina, hemodynamic relevant valvular disease, ventricular extrasystole Lown III, atrial fibrillation, ejection fraction <30%, blood pressure >160/95 mm Hg or <100/70 mm Hg, obstructive pulmonary disease, known claustrophobia or a contraindication for an MR examination such as incompatible metallic implants. Antianginal medication was stopped, and patients refrained from drinks containing caffeine or theine for at least 12 h before the examination.
Coronary angiography.
After the MR examination, all patients underwent left-sided cardiac catheterization and biplane selective coronary angiography by the Judkins’ technique. Coronary stenoses were filmed in the center of the field from multiple projections, and, as much as possible, overlap of side branches and foreshortening of relevant coronary stenoses was avoided. Coronary angiograms were quantitatively assessed with the QANSAD QCA system (trademark of ARRI, Munich, Germany) for high-grade stenosis (75% area stenosis). The examiner was blinded to the MR examination. Coronary intervention was performed with or without stenting based on the decision of the physician performing the procedure.
MR imaging. All patients had a central vein catheter placed in the superior vena cava via the right cubital vein. The position of the catheter was controlled with x-ray and corrected if needed. Patients were then examined in the supine position with a 1.5 Tesla whole body MR tomograph (ACS NT, Philips, Best, the Netherlands), which used a five-element phased array cardiac surface coil. After two rapid surveys to determine the exact position and axis of the left ventricle, a short axis slice at the height of the origin of the papillary muscles was chosen for perfusion imaging using an electrocardiogram (ECG) triggered Tl-weighted inversion recovery single shot turbo-gradient echo sequence (inversion pulse, prepulse delay 360 ms, acquisition duration 360 ms, flip angle 15°, echo time 1.7 ms, repetition time 9 ms). Slice thickness was 8 mm with a spatial resolution of 1.7 x 1.9 mm. During a short expiratory breath hold of 10 heartbeats, 10 dynamic images without contrast agent were acquired. During a second expiratory breath hold, a bolus of gadolinium-DTPA 0.025 mmol/kg body weight (Magnevist, Schering AG, Berlin, Germany) was rapidly injected manually and flushed through with 0.9% NaCl 10 ml. Sixty dynamic images (one image per heart beat) were acquired during the first and second pass of the contrast agent (Fig. 1). Care was taken to achieve breath holding during the first passage of the contrast agent through the myocardium to minimize breathing artifacts. During the acquisition of later images, the patients were allowed to take single deep breaths when needed. After 15 min to allow for the clearance of the first contrast agent injection, dipyridamole 0.56 mg/kg body weight was administered for 4 min. Image acquisition was repeated 2 min after the end of dipyridamole infusion. During dipyridamole infusion an ECG rhythm strip was continuously acquired by the use of standard MR equipment. Blood pressure was measured once a minute with standard equipment outside the scanning room by the use of a pneumatic extension with the patient remaining in the scanner. The dipyridamole infusion was discontinued upon patient request or when chest discomfort occurred that was indicative of progressive or severe angina or dyspnea, when there was a decrease in systolic pressure (>40 mm Hg), when there was severe supraventricular or ventricular arrhythmias or other adverse effects. Aminophylline was administered as clinically required. The MR study was repeated 24 h after coronary intervention using an identical protocol to that used before intervention.
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Statistical analysis. If not otherwise stated, continuous data are presented as mean ±1 standard deviations. An unpaired or paired two-tailed Student t test was used for differences between groups. A two-way repeated measurement analysis of variance was used to test for group (control, stent, balloon) and intervention (before/after) effect and their interactions. In addition an univariate analysis of variance was performed to compare the measures of the stent after intervention and balloon PTCA group and the control group. To adjust for multiple testing, Sidak’s test was applied. A p value of <0.05 was considered statistically significant.
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Results |
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The clinical data of the patient population are given in Table 1. Fifty-two coronary artery stenoses were found by angiography. Twenty-one patients had stenoses of the LAD, 15 of the LCX and 16 of the RCA. Twenty patients (57%) had single- and 12 had (34%) double-vessel disease. In three patients (9%) triple-vessel disease was found despite previously expected double-vessel disease, and two of them were referred for surgical revascularization. In the remaining patients coronary intervention was successfully performed (residual area stenosis of <75%) in all but two who had a subtotal occlusion of the coronary artery. In 20 vessels of 15 patients with multivessel disease, no intervention was performed; thus, 22 stenotic vessels remained during follow-up. The characteristics of the coronary arteries before and after intervention are given in Table 2. All patients had normal wall motion on ventriculographic examination.
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In 793 of 840 segments (94%) evaluated before and after dipyridamole, a linear fit was performed. Forty-seven segments could not be analyzed due to noise or artifacts.
Before intervention the MPR index was 1.13 ± 0.25 in segments supplied by a stenotic coronary artery and 2.18 ± 0.35 in control segments (p < 0.001). Forty-seven of the 53 territories supplied by stenotic coronary arteries and 43 of the 52 territories supplied by nonstenotic coronary arteries were correctly diagnosed as ischemic and nonischemic, respectively, by the use of the previously defined threshold of 1.5. This resulted in a sensitivity of 89% and a specificity of 83% with a diagnostic accuracy of 86%.
The group effect for the three groups—controls, stent and balloon revascularization—was significant (p < 0.001). The intervention effect of the balloon and stent groups showed significant differences, comparing before and after intervention (p < 0.0001). Between the three groups (control, stent and balloon) there was a significant interaction effect (p < 0.0001) showing the different effects of stent and balloon treatment.
After intervention, the MPR index increased significantly in segments supplied by successfully treated vessels (1.07 ± 0.24 before and 1.89 ± 0.39 after intervention, p < 0.001); however, it remained below the levels of the control segments (p < 0.01) (Fig. 3). The subgroup of patients treated with stents (n = 18) showed no significant differences of the MPR index (1.99 ± 0.36 vs. 2.18 ± 0.35, p = 0.54), whereas those treated with balloon PTCA (n = 13) had levels that remained below the control group (1.72 ± 0.38, p = 0.003) and also below the patients treated with stents (p = 0.029). The increase in the MPR index was significantly higher in patients treated with stents (206 ± 67%) when compared with those without stents (164 ± 49%, p = 0.02) (Fig. 4). In three patients (11%) who had undergone a successful intervention and who were in the balloon PTCA group, the MPR index increased after angioplasty but remained below the ischemic threshold of 1.5. After coronary intervention, sensitivity and specificity for the detection of a stenotic coronary artery were 82% and 84%, respectively, which resulted in a diagnostic accuracy of 84%.
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Discussion |
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Comparison of balloon PTCA and stenting. Although the MPR index improved in all revascularized segments, it remained impaired when compared with control segments (1.89 ± 0.44 vs. 2.18 ± 0.35). A similar impairment of myocardial or coronary flow reserve was reported in 20 to 45% of the patients after PTCA (4,15,19–22,35,36). This fraction may reflect patients with suboptimal results of PTCA (10,11,19) who are at higher risk of developing restenosis on subsequent follow-up (13,27). An early impairment of myocardial perfusion after PTCA has been explained by several factors either directly related to the barotrauma, such as perivascular edema, small intimal dissection, recoil, mural thrombus formation, microembolization, or to alterations of vascular tonus and flow, reduced vascular response to vasodilators, abnormal autoregulation of the resistive vessels or the release of vasoconstrictors (9,28,37–41). However, the amount of impairment of coronary flow reserve after coronary intervention has been found to be mainly related to the degree of residual stenosis (10), which lead to the observation that better coronary artery blood flow is achieved after stent implantation when compared with balloon PTCA due to the larger and more circular lumen, the inhibition of recoil and to overcoming intimal dissection (42–44). This partially explains the lower incidence of restenosis after stenting when compared with balloon PTCA (45,46). In this study an impairment of MPR index after balloon PTCA with complete normalization after stenting was observed. This impairment reflects suboptimal results after balloon PTCA, even though this may not be visible during the procedure. In this analysis three treated patients had an MPR below the threshold value for significant coronary artery stenosis in the territory of the revascularized coronary artery. One of these patients had a residual stenosis of 58%, another one had a small dissection that was not visualized initially during the procedure. Thus, these patients may indeed have myocardial ischemia during dipyridamole infusion rather than false positive cardiac MR results. No significant differences of hemodynamic parameters were found that could explain the remaining impairment of MPR index after intervention. An influence of the delay of the measurements after intervention can be excluded because all measurements were performed 18 to 26 h after intervention.
MPR index after intervention. After intervention, four of the 22 remaining stenotic coronary arteries were diagnosed as nonstenotic by cardiac MR perfusion imaging. In two of these patients the same segment had already been classified as ischemic by the perfusion measurements before intervention. In contrast, the other two segments were correctly classified as ischemic before intervention but improved to normal after intervention of a different vessel without treatment of the vessel defined to supply this segment. Thus, these two segments may indeed have developed normal perfusion reserve index due to better collateralization after intervention.
Study limitations. Several limitations apply to this study. For technical reasons at the time of the study, only a single slice technique was used; thus, small perfusion defects at basal or apical segments may have been missed. However, only patients with stenoses of major coronary arteries, who were expected to have rather large perfusion defects, were included. New techniques enable the acquisition of multiple slices with good spatial resolution within one heartbeat, which should further improve the diagnostic accuracy of cardiac MR myocardial perfusion imaging (47).
No comparison of the cardiac MR perfusion measurements with scintigraphy or PET was performed. However, although cardiac MR shows a greater failure rate mainly due to claustrophobia, scintigraphic methods are limited by known problems, such as low spatial resolution and attenuation artifacts that lead to a decrease of diagnostic accuracy, especially of the posterior regions, with a low specificity. Despite the low spatial resolution, PET may currently be the optimal reference standard. In clinical practice angiography serves as the reference standard to decide whether a significant coronary artery stenosis is present and if an intervention is required. Thus, in this study cardiac MR perfusion measurements were compared with invasive angiography.
To optimize the kinetics of the contrast agent bolus, a central venous catheter was placed in all patients, which cannot be done if this technique is used routinely in larger patient populations, due to the semi-invasiveness of this procedure. However, the results of this study show that a linear fit of the upslope can be reliably used to detect significant coronary artery stenoses and to assess alterations of MPR after angioplasty. In contrast with previously suggested fitting procedures (33) that require a sufficient number of data points in the downslope of the first pass contrast agent curve (32), the analysis of the upslope can also be performed with peripheral injection and will be used in further studies in our institution.
Currently, analysis time is approximately 60 min per patient. Further optimization and automatization of postprocessing analysis is required before this technique can be introduced into clinical routine. However, prototype software is available at several institutions, which reduces evaluation time dramatically.
The long acquisition time results in a significant through plane motion during acquisition and may result in discrepancies in the assignment of the segments to the territories and an error in comparing similar segments. However, large segments were compared rather than a pixel to pixel analysis, which will be more sensitive to through plane motion. Improvements of the MR hard- and software allow much faster data acquisition, which will minimize this effect (47).
Conclusions. Cardiac MR perfusion measurements allow for accurate evaluation of MPR index. Significant coronary artery stenoses can be detected with high diagnostic accuracy. After coronary intervention an improvement in MPR index was found, which was more pronounced after stenting. This technique may be useful for the follow-up and control of patients with CAD after coronary intervention.
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