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Q: How accurate is Multislice CT angiography? Will it replace standard catheterization?
Dr. Zadeh: You have to look at what is available now, what is the evidence supporting CT now? At this point there are multiple single-center studies suggesting that the accuracy in detecting what we call obstructive coronary artery disease, usually defined as at least 50% diameter stenosis, usually associated with ischemia and symptoms, the detection of this is very high with CT.

There are certain limitations with these single center studies because they are all performed at very specialized centers. It's usually not at an independent core lab. So the question is how can you really generalize these data to your hospital around the corner? The best way to address this is to do a multi-center trial. This is currently underway for the most current generation 64-slice scanners and the results should be available in the next few months. We do have the results for the 16-slice CT scanners which kind of indicated that with this generation of scanners, at least, you would not be able to replace coronary angiography.

Johns Hopkins
Medical Center
in Baltimore, Maryland

Q: One of the most active topics in our Patient Forum is complications from angiograms -- arterial problems, nerve damage, people who have trouble walking. And I think that's under-appreciated.
Zadeh : I couldn't agree more. I was just pointing out the really severe life-threatening complications, but you're absolutely right. The vascular complication rate is really quite drastic and we all know of these cases. We've done hundreds of catheterizations and we've all experienced them and they are not trivial. Definitely there is a need, and I think that CT has great potential just to eliminate these unnecessary invasive procedures.

But again, it's a step process. You have to look at the data and the multicenter trial will help us a lot to document that this is a good tool to diagnose coronary artery disease. I am convinced that 5 years from now that we will not do a lot of diagnostic invasive procedures.

It will take a few years just to (A) provide the data; (B) to convince cardiologists and referring physicians that this technology really is ready. But it will happen. Maybe 5 or 6 years from now, but it will be there. And the reason I'm saying that, I am doing this every day and I see the CT angiograms and I see the referrals to the cath lab and my personal experience is also that correlation is very good. Now it all depends on the quality of the CT angiogram. If you have a good quality CT angiogram, the information you derive from the CT angiogram is superior to that of a coronary angiogram obtained by invasive angiography. And the reason I'm saying that is because there is evidence from comparisons with intravascular ultrasound that you do see small changes in the coronary tree which is not apparent by coronary angiogram. It's only seen by intravascular ultrasound. So we're getting information that we haven't been getting with invasive coronary angiograms. So it's extremely exciting to detect disease before it becomes obstructive.

But then that opens a new door and I want to stick to the discussion: the ability of CT to replace angiography. So the quality of the CT angiogram is critical. If you have a good quality CT angiogram then I think it's at least as good, and I think it's better than an invasive coronary angiogram. The problem is that you don't always get a good quality CT angiogram at the present time and that's where a lot of development is on the way right now.

Aquilion™ 64-slice CT scanner**

Q: What are the characteristics of a good quality CT angiogram? A: In 64 slice CT the main criteria are heart rate control, patient selection and the absence of heart rhythm abnormalities. These are the three key factors. There are differences in detector design but I would say overall, they're fairly small. More important is that you have a good heart rate control, meaning that you'd better look to patients with a heart rate less than 60. And that you have patient selection. And you have bigger problems with very obese patients. And lastly if you have atrial fibrillation that may cause trouble in terms of good image quality at the time.

Q: On a different subject, many times, women present differently than men with heart problems and chest pains. And often some of the ultrasound and thallium scan studies have more false positives with female patients.
A: I completely subscribe to that. Definitely women are more difficult in the sense of diagnosing CAD. We see a lot more women who had a thallium stress test where there was a suggestion of ischemia -- they have more breast intonation artifacts, particularly in the anterior wall, so they frequently present with an abnormal stress thallium and have absolutely normal arteries by CT angiogram.

The other problem with them is that they present more with atypical symptoms. And then they are have abnormal treadmill testing where also women are known for having more false positive EKG changes. The EKG changes are often more non-specific and they are harder to diagnose. You see more women with positive stress test results who then end up having normal coronary arteries. At the same time, women also create a problem for CTA in the sense that they are more sensitive to radiation, and you have to be more careful, because of the increased risk for breast cancer. Particularly for younger women it' more of an issue. And I'm more hesitant, especially with this generation of scanners, to scan women less than the age of 40.

Q: Will the more advanced scanners have more or less radiation, for example the 256-slice scanner? I've read a study that shows it will have less radiation.
A: The technology is marching forth at incredible speed. Image quality is getting better and better, producing more consistently good quality, but at the same time, radiation is actually going down. There are several strategies right now to reduce radiation exposure to the patient and one is using the 256-slice scanner. It is true that, if you are reducing your scan time, you're also likely reducing your radiation exposure. We are actually very interested in exploring this, as soon as we have this scanner. We are going to get it in just a few weeks. And that is very exciting to see that we'll be getting better image quality at lower radiation exposure.

We are actually expecting to have quite drastic reductions because we also are doing all retrospective gating, meaning we are acquiring images throughout the cardiac cycle, whereas a lot of recent developments have shown that you may be able to obtain good quality images while you just obtaining images during a specific part of the cardiac cycle. Meaning that the radiation exposure will be further reduced to a very short fraction, well within the cardiac cycle. So there are several developments ongoing that are very promising. What we see right now is the peak of the radiation exposure and it will only get better and some studies are suggestions that it will get a lot better, meaning that radiation exposure will be cut by 60, 70 or even 80%.

The reason for that is the improvement in detector design, more coverage, prospective gating. The dual source CT apparently has shown quite a reduction in radiation dose. There are several strategies that we need to pursue and it is very exciting to see how it will all pan out in the next few months and years.

Q: There's some confusion out there about CT scans. Can you explain the difference between a Multislice CT angiogram and a CT calcium scoring test? And do you think calcium scoring exams, with no contrast, are useful?
A: They are useful because they provide us with prognostic data. Now we're going into the whole area of primary prevention, where we're trying to establish in asymptomatic people what is the risk of having obstructive or meaningful coronary artery disease.

Our current ways to assess this are extremely limited: we have the Framingham risk score, which has shown over and over and over that it works well in overall populations, but for risk protection in a given individual, it's extremely limited.

Q: There was a recent article in the NYT about vulnerable plaque and it talked a lot about CT as a way of visualizing vulnerable plaque. I've been told that this is not yet "ready for prime time".
A: We don't know. It's too early in the game. We do see a lot of things, we do see plaque, for instance, in the proximal LAD or left main which would be a "poster child" for what vulnerable plaque looks like. Or then we have a large non-calcified plaque burden with low-density content which you could think could be a lipid core, etc. So I have seen those, but we have no clues that these are really vulnerable, and you need a lot of data and pathology and intravascular ultrasound data, and long-term follow-up to know exactly what constitutes vulnerability by CT.

Having said all that, some people like Peter Libby doubt that there is such a thing as a vulnerable plaque. If you look at the pathology data, I spoke with Renu Virmani, first of all, only 50-60% of plaques done by pathology which we think were causing MI had these characteristics of the lipid core. There are a lot of other plaques which have fissures, a lot of other plaques which have none of these characteristics and which turn out to be the culprit lesions. It's not that straight-forward.

And there's data that turned up in another one of Dr. Virmani's publications that looked at patients who died of a non-cardiac death, clearly non-cardiac death, an accident or whatever. They found 10% of those had evidence of prior plaque rupture. So that tells me that plaque rupture is much more common than we think it is, but only in a minority of cases actually leads to a devastating event. It means even if we find plaques that are possibly at risk, it still doesn’t mean that they'll cause you a lot of harm. This data suggests that this is much more complex, this picture. It only leads to a catastrophic event if some other factors are involved as well: for example the whole coagulation and platelet function issues. This is a very complex issue and sometimes we try to make it too easy and say, you know, we have to chase after vulnerable plaque and you're going to solve the issue.

Q: What else is on the horizon for CT?
A: The other thing which is not well-publicized right now is the potential for CT also to do perfusion imaging. It's something we're very excited about. We're currently conducting a clinical trial here where we are looking at stress perfusion with CT. This would not be a higher dose than is currently seen with Thallium scans, hopefully a lower dose, and with much better resolution. And again, you're getting both: you're getting the coronaries AND at the same time, you're getting artery perfusion. This is extremely interesting. Why would you get a nuclear perfusion study when you could get it all with CT? Because if you look at the meta-analysis of nuclear stress perfusion, it's not that great. The sensitivity is something like 80-82%. And the specificity is 76%.

We've given millions of nuclear stress tests to people and never even thought about these things, and now radiation is a big issue, and rightly so, but it should have been a big issue ten years ago when all these nuclear stress tests were done. So the 256 actually will be very interesting for the whole stress perfusion research. Eventually I think there's not going to be much need for nuclear scans, if it pans out the way I think it will, that you can do these tests with CT better.