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1 Department of Radiology, Onze Lieve Vrouw Ziekenhuis, Moorselbaan 164, 9300
Aalst, Belgium.
2 Cardiovascular Center, Onze Lieve Vrouw Ziekenhuis, Moorselbaan 164, 9300
Aalst, Belgium.
Received February 10, 2003;
accepted after revision July 8, 2003.
Address correspondence to L. Van Hoe
(lievenvanhoe{at}hotmail.com).
Abstract
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SUBJECTS AND METHODS. Eighteen infarct patients (mean age ± SD, 62 ± 8 years) with myocardial ischemia were examined using MRI before and after revascularization. The MRI study before treatment consisted of an evaluation of first-pass perfusion, contractile function at rest and during dobutamine stress, and delayed hyperenhancement. Findings were correlated with segmental and global cardiac function after revascularization.
RESULTS. In initially dysfunctional segments, the likelihood of functional recovery after revascularization was 91% for segments without delayed hyperenhancement, 43% for segments with delayed hyperenhancement with transmural extent of 75% or less, and 8% for segments with delayed hyperenhancement with transmural extent of more than 75% (p < 0.05). Improved function at dobutamine stress MRI indicated functional recovery in 87%, whereas functional recovery was observed in only 30% of segments not responding at dobutamine stress MRI (p < 0.05). No significant correlation was found between the results of first-pass perfusion MRI and functional recovery. The ejection fraction after revascularization was best predicted by the MRI-derived infarct volume (p < 0.001, R2 = 0.63).
CONCLUSION. A simple protocol consisting of baseline contractility and delayed enhancement MRI studies is adequate to differentiate dysfunctional but viable from nonviable myocardium. Dobutamine stress and perfusion MRI studies offer little or no additional information.
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In recent years, MRI has been proposed as an alternative test to assess the extent of myocardial injury. The MRI approach has been successfully based on either the assessment of tissue perfusion (first-pass contrast-enhanced MRI), the assessment of contractile reserve (dobutamine stress MRI), or the evaluation of cellular integrity (delayed contrast-enhanced MRI) [9–18]. At present, the relative value of these three approaches remains undetermined.
The purpose of our study was to compare different MRI techniques in a group of patients with suspected myocardial ischemia who were candidates for revascularization.
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Thirty-three consecutive patients fulfilling these criteria (age range, 46–85 years; mean age, 63 years) were enrolled in the study and were imaged with MRI before undergoing diagnostic coronary angiography. Coronary angiograms and MRIs were obtained within 48 hr without intervening cardiac events. MRI was always performed first. Informed consent was obtained.
In 26 of these 33 patients, revascularization was performed either by coronary artery bypass grafting (n = 7) or percutaneous transluminal coronary angioplasty (n = 19). In two patients, revascularization was technically unsuccessful. These patients were excluded from the study. Six other patients were unable or unwilling to undergo repeated MRI. The remaining 18 patients (10 men, eight women; mean age ± SD, 62 ± 8 years) were reexamined with MRI 9 ± 2 months (mean ± SD) after the first examination.
MRI
MRI was performed using a 1.5-T scanner (Symphony, Siemens, Erlangen,
Germany) with a maximum gradient strength of 25 mT/m and body phased array
coils.
The MRI protocol included bolus IV administration of a commercially available gadolinium-based contrast agent (Magnevist [gadopentetate dimeglumine], Schering, Berlin, Germany) at a dose of 0.025 mmol/kg, after which first-pass perfusion short-axis images were obtained at rest using an inversion recovery snapshot fast low-angle shot (FLASH) sequence (TR/TE, 2.4/1.2; inversion time, 200 msec; matrix, 48 x 128; 60 measures; average field of view, 320 x 400 mm; slice thickness, 8 mm). Three slices (one basal, one mid ventricular, and one apical) were imaged simultaneously. After the perfusion study, an additional IV bolus of 0.175 mmol/kg gadopentetate dimeglumine was administered as a preparation for the delayed contrast-enhanced study. As a next step, cardiac function was assessed at rest and during low-dose dobutamine infusion (10 mg/kg per minute) using a breath-hold cine sequence (40/4; acquisition time, 14 sec; matrix, 126 x 256; slice thickness, 8 mm). Short-axis images were obtained at contiguous slice positions covering the entire left ventricle. Finally, 30- to 40-min delayed contrast-enhanced short-axis images were obtained during breath-holding using an inversion recovery segmented FLASH sequence (12 heart beats; 8/4; acquisition time, 10 sec; matrix, 253 x 256; inversion recovery pulse, 180°; slice thickness, 8 mm) [19]. Images were obtained at contiguous slice positions. The inversion time was optimized individually to reduce the signal intensity of normal myocardial tissue without reducing the signal intensity of flowing blood. The inversion times used in different patients varied between 250 and 300 msec.
The follow-up MRI study, which was performed 9 ± 2 months (mean ± SD) after the initial study, consisted of an evaluation of baseline contractility using the same cine sequence.
Analysis of MRI
Definition of segments.—For the analysis of contractile
function and delayed hyperenhancement per segment, the left ventricle was
divided into 16 segments according to the model of the American Heart
Association [20]. Three
representative short-axis slices obtained at the level of the apex, mid
ventricle, and base were divided into four, six, and six segments,
respectively. No attempt was made to include the apical segment (segment 17)
in the evaluation because this segment could not be adequately assessed on the
short-axis slices.
Images obtained after revascularization were carefully compared with those obtained before therapy, and corresponding segments were defined in consensus by two observers.
Analysis of segmental function and pattern of contrast uptake.—All images were viewed on a computer console after removal of identifying information and were presented in random order. In total, 288 segments were analyzed (18 patients, 16 segments per patient). Two observers independently analyzed the images. In cases of disagreement, they performed the analysis again, and a consensus opinion was obtained.
Wall motion at rest and wall motion during dobutamine stress were assessed visually and described as normal, hypokinetic, akinetic, or dyskinetic. A positive response to dobutamine was defined as any improvement in contractile status (e.g., akinetic to hypokinetic, hypokinetic to normal). For analysis of perfusion, the uptake pattern of contrast medium by myocardial tissue was assessed. Distinct uptake of contrast medium during the capillary phase was described as normal perfusion. The absence of uptake or clearly diminished uptake was described as abnormal perfusion. Delayed hyperenhancement was classified as absent or present. If delayed enhancement was observed, the transmural extent was determined in the middle of the segment and was classified as 1–25%, 26–50%, 51–75%, or 76–100%.
Analysis of global function and volume of hyperenhancing tissue.—For calculation of the end-diastolic volume and ejection fraction, all short-axis cine images were analyzed using commercially available software (Argus, Siemens). For each slice, end-systolic and end-diastolic phases were defined, and the inner and outer borders of the left ventricular myocardium were contoured manually.
The total volume of hyperenhancing tissue was calculated as follows. For each slice, hyperenhancing regions were contoured manually, and the area of hyperenhancing tissue was calculated. The volume was calculated by adding the areas and multiplying the resulting value with the slice thickness. Also, the number of enhancing segments was counted per patient.
Data Analysis
For MRIs obtained before treatment, the number of segments with abnormal
contractility (at rest and during stress), abnormal perfusion, or delayed
hyperenhancement was calculated and expressed as a percentage of the total
number of segments (n = 288). For MRIs obtained after treatment, the
same was done for contractility at rest.
Next, the subgroup of segments with abnormal contractile function at rest during the initial evaluation was used for further analysis. The status of segmental perfusion (normal or abnormal), contractility during dobutamine stress (improved vs not improved compared with baseline), and presence and transmural extent of delayed enhancement were compared with the presence or absence of improvement in contractile function after revascularization. The McNemar test with correction for clustered data was used for statistical analysis [21].
Differences in mean ejection fraction and end-diastolic volume before and after treatment in the same patients were assessed statistically using Wilcoxon's signed rank test.
Linear regression analysis and analysis of variance were used to correlate before-treatment ejection fraction, end-diastolic volume, infarct volume, and number of infarcted segments with ejection fraction after treatment and end-diastolic volume.
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After revascularization, no patient had any symptoms of angina. Maximal exercise test result was negative for residual ischemia.
Findings at MRI
Pretreatment MRI.—At rest, contractile function was scored
as normal in 171 segments (59%), whereas 85 segments (30%) were hypokinetic
and 32 segments (11%) were akinetic. During dobutamine infusion, contractile
function was scored as normal in 216 segments (75%), and 51 segments (18%)
were hypokinetic and 21 segments (7%) were akinetic. Perfusion was normal in
208 segments (72%) and abnormal in 80 segments (28%). Delayed hyperenhancement
was observed in 67 (23%) of 288 segments. The transmural extent was between 1%
and 25% in 15 segments, between 26% and 50% in 19 segments, between 51% and
75% in nine segments, and between 75% and 100% in 24 segments.
The distribution per patient was as follows: Segments with normal contractile function were observed in 14 patients (78%); hypokinetic and akinetic or dyskinetic segments were found in 13 and seven patients, respectively (72% and 39%). At dobutamine stress MRI, normally functioning segments were observed in 17 patients (94%), hypokinetic segments in 12 (67%), and akinetic or dyskinetic segments in seven (39%). Segments with normal perfusion were observed in 18 patients (100%). In 13 patients (72%), abnormally perfused segments were found. Finally, segments with normal signal intensity at delayed contrast-enhanced MRI were found in 18 patients (100%), and delayed hyperenhancement with transmural extent of 75% or less and more than 75% was found in 13 patients (72%) and eight patients (44%), respectively.
Posttreatment MRI.—Contractile function was scored as normal in 227 segments (79%). Thirty-two segments (11%) were hypokinetic, and 29 segments (10%) were akinetic or dyskinetic.
Global function and volume of hyperenhancing tissue.—The mean ejection fraction was 52% ± 16% before treatment and 58% ± 11% after treatment. Differences in ejection fraction before and after therapy were statistically significant (p < 0.05). The mean end-diastolic volume was 104 ± 22 mL before treatment and 102 ± 16 mL after treatment. Differences were not significant. The mean infarct volume was 11.4 ± 10.4 mL (range, 0–33 mL).
Prediction of Segmental Function
The likelihood of improved contractile function after revascularization is
given in Table 1 (data for
initially dysfunctional segments, n = 117).
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Our findings show that the likelihood of functional improvement is highest if no delayed enhancement was found (92%). The proportion of segments with improved contractility after revascularization was significantly lower if delayed hyperenhancement was observed (p < 0.05). The differences between the segments with transmural extent of 75% or less (functional improvement in 43%) and transmural extent of more than 75% (functional improvement in only 8%) were also statistically significant (p < 0.001). The differences among the groups with transmural extent 1–25%, 26–50%, and 51–75% were not statistically significant. Improved contractile function at low-dose dobutamine stress MRI also indicated a high likelihood of recovery (87%) (p < 0.05).
The results obtained using perfusion and dobutamine stress MRI were analyzed separately for the subgroup of initially dysfunctional segments with delayed enhancement with transmural extent of 1–75% (n = 32). This analysis was done because, in this group, findings at delayed enhancement MRI had a low predictive value. Sixteen of these segments were normally perfused. The likelihood of functional recovery was 50% in segments with normal perfusion (8/16) and 43% in segments with abnormal perfusion (7/16). Also in this subgroup, 27 segments showed improved function during dobutamine stress. The likelihood of functional recovery was 60% (3/5) if dobutamine stress could improve contractile function and 41% (11/27) if the function remained unchanged. Thus, no additional information was obtained with the use of perfusion MRI or dobutamine stress MRI.
Prediction of Global Function
There was a statistically significant correlation (p < 0.05)
between ejection fraction, number of enhancing segments, and infarct volume
before treatment and ejection fraction after treatment when compared for the
same patients.
A particularly strong correlation was found between MRI-derived infarct volume and ejection fraction at follow-up (p < 0.001, R2 = 0.63) and between the number of hyperenhancing segments and ejection fraction at follow-up (p < 0.001, R2 = 0.60). Ejection fraction at follow-up was less strongly correlated to the ejection fraction before treatment (R2 = 0.42).
We also analyzed the correlation between infarct volume and ejection fraction after treatment. We found that patients with an infarct volume of at least 25 mL had ejection fraction values below 50% after revascularization (Fig. 2).
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Several other studies have assessed the value of different MRI techniques in the evaluation of myocardial viability. Cine MRIs obtained during rest can be used to assess diastolic wall thickness and systolic wall thickening—parameters that are associated with viability classified by nuclear medicine techniques [22]. Viability has also been assessed by documenting functional reserve during pharmacologic stress. Baer et al. [15] assessed results obtained with dobutamine MRI and obtained a sensitivity of 89% and a specificity of 94% in defining viability. Currently, this technique has not been widely used, probably because of the possible side effects.
Other investigators have assessed the value of first-pass and delayed contrast-enhanced MRI, either alone or in combination. Rogers et al. [17] monitored myocardial enhancement in 17 patients with reperfused acute myocardial infarction on first-pass and 7 ± 2 min delayed MRI and observed three distinct patterns of abnormal enhancement. On first-pass MRI, hypoenhancement was found to be predictive of a poor functional outcome after 7 weeks, particularly in the absence of delayed hyperenhancement. On the other hand, the presence of hyperenhancement on delayed MRI without hypoenhancement on first-pass MRI was associated with good functional recovery. However, the results for enhancement on delayed MRI obtained in that study cannot be compared with our results because of the different time delays used after contrast injection. After extensive preliminary experiments, we decided to use a time delay of 30–40 min. The rationale for the long delay time is that the accumulation of contrast medium in necrotic tissue is a process mediated by diffusion, not perfusion, and that this process is slow. Sandstede et al. [14] evaluated the relationship between enhancement and functional outcome on first-pass and 15-min delayed MRI. These authors found that the presence of delayed hyperenhancement had a positive predictive value of 96% for dysfunction at follow-up and 83% of the segments without hyperenhancement showed mechanical improvement. In their study, hypoenhancement during first-pass MRI did not serve as a reliable criterion of viability. Kim et al. [9] used delayed contrast-enhanced MRI to identify reversible myocardial dysfunction. In an analysis of 804 dysfunctional segments, the likelihood of improvement in regional contractility after revascularization decreased progressively as the transmural extent of hyperenhancement before revascularization increased. Ramani et al. [18] examined 24 stable patients with coronary artery disease and contractile abnormalities and also found that delayed hyperenhancement correlated with nonviability.
At present, only a few studies have compared contrast enhancement patterns and contractility in the same patient group. Lauerma et al. [16] performed cine MRI of the left ventricle at rest and during dobutamine infusion in 10 patients with multivessel coronary artery disease. Contrast uptake was assessed at first-pass and 5 min later. On dobutamine MRI only, unviable myocardium was detected with a sensitivity of 79% and a specificity of 93%. Analysis of first-pass MRI increased these values to 97% and 96%, respectively; analysis of enhancement 5 min later did not improve these results.
As far as we know, our study is the first to compare cine MRI at rest and during dobutamine infusion with first-pass perfusion and 30- to 40-min delayed enhancement. In our study, the results obtained on dobutamine stress MRI were not better than those obtained on delayed contrast-enhanced MRI. Also taking into account the potential side effects associated with stress examinations, we conclude that there is no reason to include stress studies in the MRI protocol for the assessment of myocardial viability. The results obtained on first-pass perfusion MRI were disappointing. Although abnormal perfusion was observed in many segments, the prognostic significance of this finding was limited. It should be noted that, like another group of researchers [23], we used a low dose of contrast medium for the perfusion studies (0.025 mmol/kg). Other investigators may prefer to use a dose of 0.05 mmol/kg. To the best of our knowledge, no formal comparative studies about the effects of contrast dose on perfusion MRI in patients with myocardial ischemia have been published.
The results obtained on MRI in this study seem to compare favorably with those obtained on PET, a technique that is commonly used as the gold standard to assess viability. Although determination of the relative value of these techniques warrants further study, MRI has several advantages over PET. First, no ionizing radiation is used for MRI. Second, the superior spatial resolution of MRI allows direct distinction between subendocardial and transmural infarction and a more accurate calculation of total infarct volume. Finally, with the use of state-of-the art equipment, MRI can become a fast "push-button" examination. If, for instance, only breath-hold multislice cine MRI and delayed MRI are performed, contrast medium can be injected as a preparatory step outside the scanning room, and the duration of the actual examination can be reduced to approximately 10 min.
This study has limitations. First, a relatively small number of patients were included. However, despite this limitation, several statistically significant results were obtained. Studies in more patients are needed to confirm these data. In particular, the precise prognostic significance of the transmural extent of hyperenhancement in function of infarct age should be studied. In older infarcts, infarct shrinkage occurs, whereas the thickness of viable tissue usually remains unchanged or even increases. Therefore, the apparent transmural extent of an infarct may change (decrease) as a function of time. In patients with old infarcts, we observed extremely thin and dysfunctional segments with relatively low transmural extent (e.g., 50%). In this patient group, wall thickness should probably also be included in the evaluation of viability.
A second limitation is that we did not study perfusion 1–2 min after contrast injection. It is possible that hypoenhancement at 1–2 min correlates better with microvascular obstruction than first-pass hypoperfusion. Indeed, hypoperfusion on first-pass MRI can also be expected in patients with severe coronary artery stenosis, even without associated structural myocardial abnormality. Also, like contractile function, perfusion was assessed qualitatively rather than quantitatively. We cannot exclude the possibility that better results would have been obtained if quantitative methods had been used.
In conclusion, the results of our study clearly indicate that MRI can be used to assess patients with ischemic heart disease who are being considered for revascularization. At the segment level, MRI helps to distinguish between myocardial infarction (characterized by delayed contrast enhancement and segmental contractile dysfunction), viable but ischemic myocardium (characterized by segmental contractile dysfunction without delayed contrastenhancement), and normal myocardium. For the entire myocardium, the relative volume of normal, diseased but salvageable, and nonsalvageable myocardium can be calculated and used to compare treatment options. Because we found that good results can be obtained with the use of cine and delayed enhancement studies only—that is, without the addition of dobutamine stress or perfusion studies—MRI could become a simple, fast, noninvasive, and stressless standard test to assess myocardial viability. Moreover, the extent of hyperenhancement can add prognostic information in the workup of these patients.
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