Patient Population

The study was approved by the Human Investigation Committee at the University of Virginia , and all patients gave written informed consent .
Patients with previous MI ( > 6 weeks old ) who had a corresponding wall motion abnormality on left ventriculography underwent MCE at the time of diagnostic catheterization .
Twenty-one of these patients were also referred by their physicians for MPS within 4 weeks of catheterization .
These 21 patients form the basis of this report , and their clinical characteristics are provided in Table 1 .

MCE

We have previously described the method of performing MCE in the cardiac catheterization laboratory .
In brief , sonicated Renografin- 76 ( Squibb ) , which contains 500,000 + /-200,000 microbubbles of air with a mean diameter of 6 um , was injected into the left main ( 1.5 ml ) and right coronary ( 1.0 ml ) arteries during simultaneously performed transthoracic two-dimensional echocardiography in multiple views ( mid-papillary muscle short-axis and apical four- and two-chamber views ) .
In patients with a totally occluded artery , contrast patterns within the occluded bed were noted during injection of the nonoccluded arteries , which result from collateral flow as described by us previously .

MPS

MPS was performed with planar tl imaging in 17 patients and Tc-sestamibi single photon emission computed tomography in the remaining 4 .
For 17 patients 3 mCi of tl was injected during exercise 5 minutes before the initial images were obtained .
The delayed images were obtained 2 hours later .
Images were obtained in the anterior , 45-degree , and 70-degree left anterior oblique projections and were analyzed with a computer-assisted approach .
For four patients 8 mCi of Tc-sestamibi was injected at rest , and images were acquired 1 hour later .
Exercise images were acquired later in the day 1 hour after injection of 25 to 30 mCi of Tc-sestamibi during peak exercise .
Data were processed with Ramp and low-pass filters and back-projection , after which tomographic images were created in the horizontal and vertical long-axis views .
Quantitative measurements were then performed in different myocardial regions .
Only the delayed planar tl and the rest Tc-sestamibi images were analyzed for this study .

Image Interpretation

The left ventricle was divided into five regions for both forms of imaging : apex and interventricular septum and lateral , inferior , and anterior walls .
Each region was evaluated by two observers on MCE and MPS .
Similar scores were used for both methods of imaging : 0 = no opacification on MCE and severe defect ( < 50 % of maximal counts ) on MPS ; 0.5 = partial or patchy opacification ( including that seen only in the epicardial rim ) on MCE and mild to moderate defect ( 25 % to 50 % of maximal counts ) on MPS ; and 1 = homogeneous opacification on MCE and normal uptake on MPS .
The interobserver and intraobserver errors for MCE and MPS are small and have been previously reported .
Each region was also graded for wall motion as follows : 1 = normal , 2 = mild hypokinesia , 3 = severe hypokinesia , 4 = akinesia , and 5 = dyskinesia .
Our interobserver and intraobserver errors for wall motion score calculation are also small and have been previously reported .
The wall motion scores were assigned while the observers were blinded to the MCE and MPS data .

Statistical Methods

All data were analyzed with RS / 1 ( Bolt , Beranek , and Newman ) .
A weighted kappa statistic was used to assess concordance between MCE and MPS .
The weight favored fewer and penalized greater differences in scores between the methods .
Correlations between scores were performed with Spearman 's rank statistic .

Reasons for Concordance

The delayed 201tl image reflects the amount of 201Tl sequestered in the myocardium .
Because 201Tl enters the myocytes mostly by way of the Na/K pump , its presence within the myocardium indicates that the cell membrane is intact .
Similarly , at rest , Tc-sestamibi diffuses into the extravascular space and passively enters the myocyte before binding to the negatively charged mitochondrial membrane .
Consequently , its retention within the myocyte is dependent on intact mitochondrial function .
The relative activity of both tracers therefore provides an approximate estimate of the number of myocytes that are viable within a region .

In comparison , microbubbles used for MCE reside entirely within the vascular space .
They do not enter the extravascular space , nor are they extracted by myocytes .
They do not enter regions where microvessels are absent such as in scar tissue .
Microbubbles are also not seen in regions with other forms of microvascular disruption , plugging , and obliteration , which is frequently noted in areas with infarction .
The high degree of concordance between MCE and MPS should therefore not be surprising and has also been found in studies with venous injections of microbubbles .
Mild differences in score ( 1 grade ) noted in our study can be explained on the different methods of image representation ( tomographic vs planar ) .

Reasons for Discordance

Although complete discordance between the two techniques was exceptional , it could be most dramatic as in the example shown in Fig .
3 .
There are several possible reasons for this discordance .
Although no clinically documented events occurred between cardiac catheterization and MPS , there is a small chance that a new MI could have occurred .
The likelihood of an artifact on MCE is small , particularly if it encompasses the entire apex .
It is possible that the microvasculature within the apex was so sparse as not to be detected on MCE .
The low level of myocardial perfusion may , however , still have allowed accumulation of 201Tl over several hours within viable myocardium .
Thus unless very low levels of flow are detectable on MCE , an extractable tracer may have an advantage in terms of assessing myocardial viability .
It is likely , however , that more sensitive methods of detecting the presence of microbubbles in tissue such as intermittent harmonic imaging will make it possible to measure low levels of flow on MCE .

Microbubbles are destroyed on ultrasound exposure .
During the process of destruction , they produce an " acoustic noise , " which contains many frequencies including the frequency to which they were exposed ( fundamental frequency ) .
Selective acquisition of the nonfundamental frequencies ( including harmonics of the fundamental frequency ) results in increased signal-to-noise ratio and better imaging of the microbubbles .
The signal-to-noise ratio is further increased when microbubble destruction is minimized by obtaining images intermittently rather than continuously .
Experimental data from our laboratory indicate that this method can be used to measure very low levels of flow .

Advantages of Contrast Echocardiography

In the cardiac catheterization laboratory MCE offers a practical advantage over other techniques in that it can provide more immediate viability assessment , which can then be used to guide clinical decision making and obviate the need for a noninvasive viability test done on another day , which can increase hospital stay and cost .

Because of its superior spatial resolution , MCE can define the transmural location of viable tissue , which can have prognostic implications .
For instance , in Fig .
2 both techniques demonstrated partial viability .
However , on MCE it is clear that opacification is limited only in the epicardial rim .
Because wall thickening is dependent on endocardial viability , this patient is unlikely to demonstrate improvement in regional function after revascularization .
The 201Tl image does not provide this potentially important information because it cannot distinguish between reduced perfusion caused by low flow from that caused by partial MI .

Limitations of the Study

Except for four patients , the MPS data were not tomographic .
Data registration between the two techniques was therefore not optimal .
It is for this reason that we reduced the data to regions of the left ventricular myocardium instead of comparing segments to each other .
This approach , however , did not detract from the way we would have read each study clinically .
Despite the use of two different isotopes , no differences were seen in the results , although the number of patients studied was small .

We did not perform a revascularization procedure to determine which method predicts recovery in function .
Revascularization was not clinically indicated in many of these patients , and follow-up studies were not performed in those who received such a procedure .
We and others have demonstrated the predictive value of both techniques for improvement of regional function after revascularization in similar kinds of patients .
This is the first study , however , that compares the results of the two techniques in the same patients .

This study was performed in the cardiac catheterization laboratory with selective coronary injections .
Recent experimental data indicate that similar results can be obtained with aortic root injections when intermittent harmonic imaging is used , which will make the technique easier and simpler to perform .

Conclusions

MCE provides similar information as MPS for the putative assessment of myocardial viability in patients with coronary artery disease and old MI .
We and others have previously demonstrated similar results in patients with recent MI .
These findings potentially broaden the role of this technique for the assessment of myocardial viability in the cardiac catheterization laboratory .

Presented in part at the Seventh Annual Scientific Session of the American Society of Echocardiography , Chicago , Ill .
, June 10-12 , 1996 .

Reprint requests : Michael Ragosta , MD , Cardiovascular Division , Box 158 , Medical Center , University of Virginia , Charlottesville , VA 22908 .

Table 1 - Clinical characteristics of the patient population