Reprinted by permission from Primary Cardiology, 1995.
Paul Barone DO, Daniel Shindler MD, John Kostis MD.
CASE PRESENTATION
An 84 year old white man presented with crescendo angina. He had a long history of hypertension and diabetes. During the hospital stay he ruled in for myocardial infarction and underwent cardiac catheterization which reveled triple vessel coronary artery disease. It was decided to send him for coronary bypass surgery. At the time of surgery he underwent a transesophageal echocardiogram (TEE), which showed diffuse aortic plaques with a mobile atheroma. He underwent bypass surgery uneventfully, but on the second postoperative day he was found to be aphasic with new left sided weakness. CT scan confirmed a new left side CVA.
INTRODUCTION
There are many methods of detecting and quantifying aortic atherosclerotic plaques. Roentgenographic studies such as chest X-ray, CT scans, MRI and angiography have all been used. These studies do not provide real-time images. The use of transesophageal echocardiography has shown great promise because it does provide real-time images and is able to image arterial wall structure permitting plaque and wall characterization.
Aortic atherosclerosis by TEE has been clinically useful in the field of systemic and peripheral embolization.(1) Many studies have shown that protruding atheromas in the thoracic aorta are an independent risk factor for embolism.(2-5) Stroke data banks show that no cause can be found in 26-40% of all cerebral infarcts.(5) In this subgroup of patients, TEE is the study of choice to define the embolic source.(6) TEE has also found its way into the operating room. With respect to cardiopulmonary bypass surgery it has been shown that use of TEE has decreased the incidence of perioperative stroke.(7) Recent studies have also been done showing a relationship between aortic atherosclerotic disease and coronary artery disease.(8,9)
The following is a review of the history of TEE visualization of aortic atherosclerosis, of the present classifications of aortic plaques, and of the limitations of TEE in this area.
HISTORICAL PERSPECTIVE
Early studies of arterial atherosclerosis utilized ultrasonic tissue characterization. The use of techniques such as, analysis of attenuation properties, backscattered radio frequency signals and more recently pixel gray scale level brought new insights.
Picano et. al (10) studied formalin-fixed human aortic walls and found that by using backscattered signals they were able to differentiate normal from fibrofatty and calcific subsets. They went on to study the attenuation properties of human fresh aortic walls. This in vitro approach showed that integrated attenuation index was lowest in normal walls and progressively increased in fibrous, fibrofatty and calcific subsets.(11) Sarnelli et. al.(12) did comparative histology on aortic specimens utilizing both attenuated and backscattered indexes. This had the ability to differentiate deposition of biochemical components, such as collagen, and calcium from fatty tissue.
Grey level statistics by Pandian et. al. have been used to differentiate myocardium before and after infarction. McPherson et al. who were able to distinguish perivascular fat from atheroma or normal wall in human coronary arteries.(13,14) McPherson et. al used grey scale levels to differentiate plaques from plaque free regions in the aorta.(15) They were able to do so when comparisons were made in the same patient. In comparable visualization between patients, the plaques with lower mean gray scale levels required slightly higher gain settings to offset the lower brightness. As a result, the gray scale levels of the plaques and normal aorta were nearly identical. This finding reflects the difficulty in applying gray scale statistics across patients when there is no internal standardization of equipment for comparison.
PATHOLOGY AND ULTRASONIC IMAGES
Studies done looking at aortic atherosclerosis and systemic embolization utilized other criteria to diagnose atherosclerosis. One such criterion is intimal and medial thickness. Pignoli et. al. utilizing B mode images of intimal and medial thickness defined this area as two parallel echogenic lines separated by a hypoechoic space.(16) They showed that the inner line was the luminal/intimal transition and the outer line represented the adventitia. They also set out to determine the accuracy of intimal/medial thickness measurements by B mode imaging and correlating this with the thickness of different combinations of tunicae evaluated by gross and microscopic exam. They found, by gross pathologic exam, no statistically significant difference between the two measurements. There was a statistical difference when compared to the histologic measurements. This discrepancy may be due to artifacts introduced during the processing of tissue for histologic evaluation.
Nishino et. al. utilized maximal thickness of the intimal/medial complex as an index of atherosis.(17) They also compared the TEE results with pathologic measurements and found a linear relationship. Toyoda et. al. also utilizing intimal-medial thickness compared measurements recorded with TEE and histologic specimens. They found a sensitivity of echo detection of a complicated lesion to be 74% with a specificity of 94%.(4)
Thus, multiple studies have found the use of ultrasonic images in the measurement of intima/media complex to be pathologically accurate. However, none of the above studies supply pathological support for the concept of thickened intimal/media complex as it applies to atherosclerosis.
Pathologic studies have been done looking at aortic intimal thickness and correlating it with atheronecrosis and coronary artery disease.(18,19) Fibroplastic intimal thickening is thought to be driven in experimental animals by smooth-muscle cells proliferating in situ. Studies done on postmaturity intimal changes have found that at a certain intimal thickness: 200-299um, the increase in cell number is complete.(19)
Tracy et. al. have shown that the probability of atheronecrosis emerging in the aorta was related to age and fibroplastic intimal thickness. Aortas with a mean thickness grater than 300um have a high probability of developing some foci of atheronecrosis. They also defined a threshold for necrosis as a mathematical equation, in which age and fibroplasia are variables. When years times the mean intimal thickness exceeded 17,000um-years the odds of finding a necrotic core exceeded unity.(18,19)
Thus, there is some pathological support for the theory of increased intimal/medial complex as a sign for atherosclerosis. This also supplies a intimal/medial critical thickness that is required to produce an atheronecrotic lesion. Whether this can be utilized as pathologic basis for ultrasound characterization of plaques remains to be answered by further study.
ULTRASONIC CHARACTERIZATION OF ATHEROSCLEROTIC PLAQUES
As stated earlier, a majority of studies done defined atherosclerosis as an increase of the thickening of the intima with luminal irregularities. Fazio et. al.(8) and Tribouilloy et. al.(9) were more specific in their respective studies and defined aortic atherosclerosis in grades I-IV and I-III respectively. Fazio et. al. do not place a figure on the exact measurement of the I/M complex. Tribouilloy et al. state that an I/M thickness of less than 5mm is stage II and greater than 5mm is stage III. The measurement of 5mm was used in an earlier study by Katz et. al. (7) Toyoda et. al.(4) looking at aortogenic embolic strokes, delineated a measurement of 3mm. Again, none of the above studies define any pathologic basis for these measurements.
Plaque thickening and its association with embolic events were looked at by Amarenco.(20) In a group of 78 patients with no known cause of cerebral infarction, 28% had plaques >4mm in thickness, as compared to 8.1% who had infarcts of known cause. They concluded that the association between atherosclerotic plaques in the aortic arch and the risk of ischemic strokes increased from less than 5 to more than 13 when plaque thickness was greater than 4.2 mm.
A final characterization first described by Karalis et. al.(3) and later studied by Tunick et. al is a protruding or mobile component to the atherosclerotic lesion, such as our patient.(1-3)
Multiple studies have shown that protruding atheroma to be an independent risk factor for systemic embolization.(2,6) Tunick et. al. showed that in the presence of a protruding atheroma, one was at a 3 times greater risk of having an embolic event.(2) Karalis showed and incidence of embolic events to be 31% with such a lesion. A prospective study by Tunick et. al. in which patients with protruding aortic plaques were followed for 13 months found that 33% developed embolic complaints compared to only 7% of the controls.(3,6)
No studies have been done to characterize the form of the atheroma, ie whether it is ulcerated. Amarenco et. al. determined the frequency of ulcerated plaques in the aortic arch in 500 postmortem patients with history of CVA and found the prevalence of ulcerated plaques was 26%.(21) TEE is, as shown in our patient, able to visualize plaques protruding into the lumen, but it is unable to identify ulcerations. With the advent of 3-D and 4-D imaging of the aorta, more accurate description of plaque morphology is expected.(22)
LIMITATIONS
As is true for all diagnostic tests, there are also limitations to TEE imaging of the aorta. A major limitation is the inability to visualize the ascending aorta due to the air filled trachea interposed between the esophagus and the aorta. One pathologic study has shown that in 97 specimens of ascending aorta from adults with coronary artery disease, the prevalence of atherosclerotic plaques was 38%.(23) Amarenco showed that plaques in the ascending aorta and proximal arch were associated with a greater increase in the risk of stoke than those found in the distal arch or descending aorta. With the use of biplane and multiplane probes the blind spot in the ascending aorta is even smaller.
Another limitation, artifacts, are inborn to all ultrasonic images. They are especially troublesome in the ascending aorta. As with all echocardiography, artifacts arise at multiple levels in the acquisition, processing, display, and recording of reflected ultrasound signals.(24) The ability to diminish the effects of artifacts on studies depends as much on the technique and skill of the echocardiographer performing and interpreting ultrasound images as on the anatomic challanges posed by a particular esophagus.
Other limitations include, the lack of a large scale study comparing TEE images with histologic or gross pathologic specimens, the inability to visualize the aortic wall that is closest to the transducer, and if a protruding atheroma is found, what is the optimal treatment? Only the anecdotal use of oral anticoagulants has been published with good results.(25)
CONCLUSION
The use of transesophageal echocardiography for aortic dissection, valvular pathology and visualizing posterior cardiac structures is well documented.(26) The use of TEE in the study of aortic atherosclerosis and its clinical implications is still in its infancy. The use of TEE for undiagnosed causes of CVA is well documented and should be utilized. Further study is needed in the aspect of effective treatment in patients with mobile or protruding atheromas. TEE in the operating room for cardiopulmonary surgery appears to be effective in decreasing post-operative stroke. The age of patients undergoing coronary artery bypass grafting has increased and the incidence of stroke after the procedure increases linearly with age.(27,28) TEE inspection of the aorta prior to cannulation is becoming routine. The emerging technology of 3-D and 4-D imaging will better depict the aorta, and more exactly characterize atherosclerotic plaques.
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