COMMENTARY

The Triple Rule-Out: Pros and Cons

Elliot K. Fishman, MD

Disclosures

May 16, 2012

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Hi. This is Elliot Fishman. Welcome to our latest vodcast. In this one we'll cover the pros and cons of the triple rule-out.

What is a triple rule-out? It is a single study where you are trying to exclude the presence of coronary artery disease -- defined as stenosis over 50% -- ruling out or ruling in aortic dissection and the possibility of pulmonary embolism. It tries to cover the three main causes of chest pain in a single examination.

It's something that's been talked about the last couple of years, but if you look at the literature, not a whole lot has been written. There are really 10 articles, and it's interesting that they're clustered in 2009, when the question was, "could you do a triple rule-out?," and in 2011, when the question was, "is it worthwhile doing?"

Let's look at some of the features. Doing a triple rule-out poses some technical challenges compared with a coronary CTA [computed tomography angiogram]. In a triple rule-out you must scan about a third larger volume, and this requires a longer patient breath-hold. There is an increased radiation dose to the patient, a larger area of scan, and the timing becomes very difficult because you are really trying to scan 2 different vascular beds that are optimized at different times: the pulmonary artery, which enhances optimally about 10 seconds or so before the aorta.

To illustrate, here is a nice example of a perfectly timed pulmonary embolism study. You can see good opacification of the main pulmonary arteries to both the right and left lung, and the main trunk, but you also notice the lack of opacification to any degree of the ascending and descending aorta.

Because you can see that even in this image, that contrast is coming in: innominate vein, SVC [superior vena cava], SVC to the right atrium, to the right ventricle, to the pulmonary arteries. And you have beautiful pulmonary arteries, but that's at the time the heart is not pumping blood enough to really allow good opacification of the aorta. So it's all a matter of timing.

It's the same situation in the aorta. Here is a case where we were looking for aortic dissection. There was none present, but you can see that when I'm timing for the aorta, typically triggering at a preset point, the pulmonary arteries are washed out. You can wash them out additionally with coronary CTA when you give a saline chaser. You can see the right side of the heart causing less artifact, so you can visualize the right coronary artery, but when you simply are using timing, the point is that the patient's aorta will opacify.

We can look at it a little bit more scientifically. Here is a test bolus, and you can see the contrast in the pulmonary arteries, the pulmonary arteries are washing out, and now the ascending aorta is optimal. If you look at this chart you can see that if you want the pulmonary arteries or you want the aorta, you time things differently. And here it is again with a nice schematic. They were looking for triggering points every two seconds for the patient's ascending aorta for coronary CTA.

The first few examples nicely show the pulmonary arteries. Then pulmonary arteries start washing out. The aorta begins to opacify, and when the aorta is optimally opacified, the pulmonary arteries are washing out. So there is a challenge, and to meet that challenge, you must reconsider how you do things. When you look at this graph, you know something has to give if you want to be able to trigger and get both of the curves to match. There are several tricks.

One trick is just to give more contrast material, so you keep continually opacifying the pulmonary arteries, so instead of that curve dropping off, as you can see in this schematic, it will stay flat. Then, when the aorta curve comes up, you are going to have them both opacified.

Really what you need to do is perform 2 or 3 quality exams in one CT acquisition. Now, of course, doing the aorta and doing the coronaries in 1 examination is not a trick. But the other one does become a trick, so there are several solutions. One is to increase contrast volume to maintain optimal opacification. Remember coronaries are typically 70 to 80 cc; you can put it up to 130 cc. Some people have increased the injection rate to lengthen the transit of opacification time, maybe inject 4 cc/sec rather than 5 or 6, but again, there you are sacrificing the height of the peak.

With newer scanners, like the dual source, you can do a very-high-pitch value and get the scan done very quickly. You simply give more contrast. I'll show you some examples. People have come up with different techniques such as split bolus with different injection rates from the first to the second bolus, or varying the concentration from the first to the second. But you could see by the fact that there are many ways there is no one perfect way, and that increases the challenge of what you need to do.

Let's take a look at the literature. Here is an article by Hapern.[1] This is one of the earlier articles looking to compare image quality with a dedicated coronary CT to a triple rule-out. You can see in their protocol they used a bit more contrast, 95 mL as opposed to 70 mL. They looked at consecutive exams over a 1-year period. They tried to look and determine the quality of the individual studies looking at the coronaries, aorta, and pulmonary arteries individually.

They concluded that you can do a good study, that vascular enhancement was adequate for diagnostic evaluation of pulmonary arteries in all triple rule-out studies. But you can see from their numbers at least 1 coronary segment demonstrated suboptimal quality in 8% of exams. But they felt that this was not that surprising and not different than a coronary CT by itself, because in the coronary CTs they had essentially the same number of suboptimal exams as in the triple rule-out procedure. Their protocol involves biphasic injection. In fact, beta blockers are critical because you need to look at the coronary arteries, but it wasn't doable.

In another article, by Charlie White[2] at the University of Maryland, they looked at a typical chest pain in low-to-intermediate-risk patients. They mentioned that a triple rule-out may be the ideal thing to do, but they cautioned that it has a higher radiation dose, so you really want to be careful how you select the patients. In older patients with a low risk of lifelong radiation-induced cancer this might be ideal, provided you have an optimal protocol. But in patients who were younger, one would have to really think about whether this was the right thing to do.

In terms of quality, Charlie wrote another article which said the image quality of triple rule-out CTA is comparable to that of a dedicated coronary CTA.[3] Triple rule-out showed no statistically significant difference in motion artifact or opacification, and therefore may be an alternative and a useful study in a select group of emergency patients. In this article, they had a 64-slice scanner, 130 cc of contrast, and split-bolus injections.

Another article, in 2009, by Schertler,[4] finds that triple rule-out is feasible in patients with suspicion of PE [pulmonary embolism], reveals a wide range of vascular and nonvascular chest disease, and offers an excellent overall diagnostic performance. This study was the first that really used the dual source scanner, so they were able to use a single volume of contrast at a fixed rate of 4 cc/sec with some saline push, but not a whole lot. [Another] article, by Urbania,[5] found that triple rule-outs can be done, but they also made the point that we should all recognize, that the appropriate clinical use of these protocols remains to be shown by randomized controlled trials. That's hard to do, but really, it is the right thing to do.

In 2011, there have been several articles. An article by Curry[6] and the group in Baptist in Miami looked at coronary CTA in triple rule-out in the ER setting, and tried to provide some algorithms for the effective use of these techniques. And they said that although they weren't great advocates of triple rule-out, it may be considered if additional suspicion of PE or dissection is present. They said it was possible, but it wasn't their ideal study.

Yoon and Wann found that while triple rule-out can be very useful and potentially cost-effective when used appropriately, there is a concern regarding overuse of this technology.[7] That really is one of the big issues.

Who is the right patient? Perhaps a low-to-intermediate individual at increased risk for acute coronary syndrome, and who has chest pain that might be attributed to acute pathologic conditions of the aorta or the pulmonary arteries. The authors said CT should not be used as a routine screening procedure, and that is a very good point. Their concern is whether it is the right thing to do, and that's where the authors left the question.

There were 2 other articles that actually looked at numbers. Here is an article by Madder[8] in JCCT. In patients with acute chest pain, a triple rule-out results in higher radiation exposure with the cardiac CT, but was not associated with improved yield, reduced clinical events, or diminished downstream resource use.

These researchers looked carefully at 2068 patients, about 10% with triple rule-out and the rest with cardiac CTs. The composite diagnostic yield was 14% with triple rule-out, and 16% with cardiac CT, and was driven by a diagnosis of COPD [chronic obstructive pulmonary disease]. So in this series, doing triple rule-outs wasn't that helpful. They had a 50% higher dose, a higher incidence of subsequent emergency center evaluations, and more downstream PE protocol CT angiographies. It was not something that they could recommend.

Finally, we have something from Mass General, and Rogers[9] is the first author. They conducted a randomized trial to compare the efficiency of comprehensive CT examination in patients presenting to the ER with undifferentiated chest pain or discomfort, or dyspnea. They divided patients into 2 groups where they received a dedicated CT of the coronaries, or a triple rule-out.

They found that comprehensive cardiac CT scanning was feasible, with similar results to dedicated protocols in terms of diagnostic yield. However, it did not reduce the length of stay, it did not reduce the rate of subsequent testing or cost. Their conclusion: although triple rule-out might be helpful in the evaluation of select patients, these findings suggest that it should not be used routinely with the expectation that it will improve efficiency or resource use. These are very, very important statements.

So where do we stand now? Triple rule-outs can be done. You need to learn how to do a good protocol, you need an experienced tech, and it's great to have a dual source scanner. Triple rule-out can be done successfully in a select patient population where the differential diagnosis for acute chest pain is nonspecific but suggests coronary or cardiac or aortic problems or even PE. So in the right patient, where you really are up against the wall, you can't figure out what's going on, but you think it is cardiac-related, it is a reasonable study to do, particularly in patients over age 40.

Radiation dose is a consideration, but you need to do the right thing for the individual patient. I think at this point, however, the articles and the numbers suggest that triple rule-out is not a routine ER study, it's not like a PE, it's not for everyone, and before you order one and you do one, you really need to think about whether you need one.

Thank you for your attention.

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