There's never enough time to talk about physiology. We could probably make a breakfast session last till noon. So I'm going to try and cover you a few future applications of physiology, which will come to our lab and hopefully make it a little easier and be helpful to the patient's outcome. So let me take you right through that. So we have right now, today, which is the near future, two methods available to us to look at physiology in an angiographically derived manner. So on the left, you're familiar with CT-FFR based measurements. I won't take you through the whole derivation of it, but it goes using a regular CT scan. The slices are sent for analysis, a matrix is generated, a net computational fluid analysis is applied, and a map of physiology through the vessel structure is made, and the correlations to wire-based FFR are pretty good, fairly high, and outcomes using the technology have demonstrated benefit as well. On the right, inside the lab, again, using a similar method of angiographic reconstruction of a vessel into three dimensions and applying a mesh network for point-by-point calculation, either with computational fluid dynamics or a fast flow technique, a number of companies have generated, or generate now, a color-coded map of a vessel, either all the vessels or a single target vessel, and again, the correlation with the wire-based FFR is very good. Not 100 percent, but pretty close. So I think going forward, the angiographically derived FFR information is going to be absolutely key and critical to our practice, easy to use, and available to every single patient, which is a remarkable feat. I want to remind you that CTA and CTFFR have interesting properties, and that they can detect a lot of things that regular angiography cannot. So it has help for perivascular structures, vulnerable plaque, of course assessment of coronary disease in ways that we can't see it, and then the computational fluid dynamics going from left to right. So it's got a lot of things we can use. Unfortunately, interventional cardiologists don't own the CT scanner, they don't use it very much, and the money goes somewhere else. But if it came to your cardiology section, you'd probably use it more. It's also interesting that if you correlate of all the modalities testing ischemia, and if we say FFR is your ischemic index, then the highest AUC and ROCs are shown here with CTFFR at the top, PET scanning second, regular CT just to show the angiographic findings third, and then single photon emission spec scanning at the bottom. So FFR-CT, according to these kind of data, could replace a lot of stress testing, again since the reimbursement problem is dominant, it's not going to replace your nuclear scanner in your office, but I think it has true value. Now shifting into the angiographic FFR, this is just a series of slides. This is from CathWorks that takes and maps the steps. Optimal angiography into planes, a reconstruction done by the computer, a stenosis assessment, and then finally the translation of that data into your projected FFR on the artery. There are a number of ways to do this. Each one has its methodology, clicking, identifying, moving the markers of the angiographic information down, but the outcome is pretty close to the same. This is a very, I think, future, not far future, application which is going to be of high value. Here's the meta-analysis a couple years ago from several different studies showing the correlation between the FFR by angio on the vertical and the FFR wire on the bottom, and the discordance in the red show it's about a 20% discordance in these particular studies, but that data will get tighter and tighter over time as the technology improves. So remember that the resting ratios correlate 80% to the FFR, this correlates 80% to the FFR, you're in business, and you don't have the struggle of having to do wire and adenosine because you don't need that with this model. Recently, I think, a very nice study that was just released at TCT in the fall, the FAVR3 China study where they compared QFR guidance for treatment or no treatment to angiographic guidance for treatment or no treatment, and the event rates were lower and outcomes were better for the QFR strategy, very similar to that when we did wire-based FAME studies where the physiologically directed ischemia-treated patients did better than the angiographic-treated patients without that knowledge. Okay, the future also consists of us being able to assess those patients without obstructive coronary disease who may have either infarct without obstructive disease or ischemia with no obstructive disease, and we get into the world of microvascular dysfunction. This is a large little summary slide that tells you where you find patients with microvascular disease in cardiomyopathies, in heart failure, variably coexisting with obstructive disease, in acute coronary syndrome, in the non-obstructed vessel, takotsubo, etc. So there's lots of opportunity for us to expand our knowledge and actually improve our treatment, especially for those patients with the non-obstructive chest pain syndromes. So from the epicardial vessel, we use the hyperemic or non-hyperemic pressure ratios to tell us about epicardial lesions, and we can use either Doppler or thermodilution flow to compute coronary flow reserve, and with thermodilution, you can also compute the index of microvascular resistance, and I'll just show you a case in one second. Now, in the far right with the advent of the core flow system that permits measurement of all of these at one time, you have the complete picture of the coronary physiology for your patient. Here's just a quick example. This individual had a chest pain syndrome, angiographically normal arteries, and when you do coronary flow here, you can see that the speed of flow down the vessel by the curves on the bottom, the blue is the rest, the gold is the hyperemic, it's much faster. The time of arrival is shown across the two areas, and the ratio of those produces coronary flow reserve. In this case, it was 2.2, with a high index of microvascular resistance, 58 was the value shown here, the upper limit being 25, and of course, the pressure is transmitted nearly completely through the vessel. So this is microvascular disease, and easy to do, quick to find out, and at least you could explain to the patient there may be something to do. Here's another example which was a little more, I think, dramatic. Again, this is an asymptomatic man with a decrease in his left ventricular ejection fraction, a highly calcified right coronary artery, scary-looking lesion, we're ready to do shockwave, but I think let's just measure this first, because the man is completely asymptomatic. No evidence of ischemia, do I need to treat this? Maybe this is just benign. Okay, so then we, again, apply the method, pass our pressure wire down, there was a gradient this time, but at maximum hyperemia, the FFR dropped only to 0.82, the coronary flow reserve rose to 3.8, and the microvascular resistance is 14, again, normal. So I don't think he would obtain benefit by putting a shockwave into that right coronary blasting away, putting in a stent. We're not going to change his flow, we're not going to change his microvascular disease except for the worse, so this was a very helpful study that we should apply frequently when needed. Okay, in the myocardial infarction world, the IMR is something we don't measure routinely, but if you did, you would be able to provide prognostic information for myocardial infarction. Will Ferron and his colleagues have pioneered this concept, IMRs of less than 40 associated with better outcome than those infarct patients having higher. And again, the best of the indices to talk about prognosis for the post-infarct patient was the IMR. Now just to close the discussion on future activity, wouldn't it be nice not to use a wire to measure microvascular disease and get that information again from our angiographically derived information, and there are some individuals, studies, and centers that are promoting this science. I don't think it's quite here yet. This was the only study I found that had decent graphics, and indeed, I think we will be able to calculate index of microvascular resistance and others based on angiographically derived parameters. Okay, just to sum up, what is the future impact of the information we just talked about? So I don't think anybody should doubt that CTFFR is here. It has wide applicability, and I think it has large value. I think it is limited by its business model. Angiographic FFR will be here within a couple years. It should be here widely, and I think its impact will be huge. There will be skeptics, but I think if you are a physiology-derived practitioner, you're going to like what you see. Invasive CMR with a wire is here now. It's not used widely because it's not distributed as widely as it could be, but I think the impact of this is also going to be very large, particularly if people apply studies and then therapies and see that improvement can occur. And lastly, angiographic corneal microvascular disease is not here yet, but it could be in the future, and I'm not sure what the impact is going to be beyond what we learned from the invasive CMD at the moment. So I'm going to stop there, and we'll talk about the future as we go through the present. Thank you very much.

physiology applications

cardiology

CT-FFR

angiographic reconstruction

microvascular dysfunction