Thank you so much, Celina. This was a great overview of imaging. So our next presenter, I'll ask him to unmute and open his camera, is Dr. Creighton Dong from University of Washington. He will talk about coronary physiology guiding decisions in PCI. Thank you to the organizers and panelists for inviting me to speak today. I have the opportunity to discuss the 2021 rasterization guidelines as they pertain to using coronary physiology and to guide decisions in PCI. I have no disclosures. So here are the 2021 ACCHA guidelines, which state that in patients with angina or angina equivalent, undocumented ischemia, and angiographically intermediate stenosis, the use of fractional flow reserve or instantaneous wave-free ratio is recommended to guide the decision to proceed with PCI. And that was given a class one level evidence A recommendation. And a class three level of evidence BR was recommendation for instable patients with angiographically intermediate stenosis and FFR is greater than 0.8 or IFR is greater than 0.89, PCI should not be performed. So understanding why physiology matters starts with understanding how we quantify the severity of coronary artery disease. And this starts with knowing the origin of this magical 70% stenosis cutoff. In my training and in clinical practice, we often refer to a 70% coronary artery stenosis as being synonymous with significant flow in the coronary artery disease, and which justifies rasterization. But what is so magical about this stenosis? The original study to evaluate this is performed in 12 dogs where the circumflex was mechanically constricted through a thoracotomy and the associated coronary flow and flow reserve were measured. So an average coronary flow reserve began to decrease at a 45% stenosis, and the baseline flow began to decrease at 85%. So we know the average between 45 and 85 is somewhere around 70%. And this is really where we get this from. But the authors caution that the prediction of flow reserve from angiographic appearance of coronary lesion is difficult, and angiography is not sufficiently accurate for measuring small luminal changes, having major hemodynamic consequences. So here's the reason why. You can have a normal vessel, as in this one here, with normal flow, or you can have a vessel with severe stenosis with reduced flow, and this is what our expectation is. We also have a small vessel with diffuse disease, where there's no apparent relative stenosis, because stenosis is really a relative estimate of flow reduction. Or you can have a very large vessel, as in number six, that although there is a relative reduction in lumen area, there's actually normal flow. So remember that 70% is really just a surrogate for somewhere between 45 and 85% in the original study, which is really just a surrogate for coronary flow, which is really just a surrogate for myocardial perfusion, and ultimately the heart doesn't care about any of these things. It doesn't care what percent stenosis the vessel is upstream, it just cares about its blood flow. You can see here in the real world, in humans, not in dogs, we see that the situation in patients with native coronary disease is much more complex. Here you can see in this panel that the coronary flow reserve is poorly correlated with angiographic stenosis, and while there's a trend toward correlation with the degree of stenosis and FFR measurements, whether by QCA or CT quantified stenosis, or if you stratify them by less or greater than 50%, that there does tend to be some trend towards patients with less lower degree stenosis with a higher FFR. It is certainly not absolute, and there are many patients who have moderate stenosis with significant hemodynamic perturbations, and patients with high degree stenosis without any reductions in flow. So, what are the clinical outcomes if we practice with an angiographic-only strategy? One example of this is a current study which compared PCI driven by angiography alone versus medical therapy. While there was an improvement in symptoms and many patients in the medical arm crossed over to PCI, the overall results showed no difference in the primary outcome or survival. What is striking about this study is the fact that despite all patients having so-called angiographically significant coronary artery disease, in the sub-study of patients who had stress studies in the current study, in fact, very few of them had ischemia. You can see here that approximately two-thirds of patients in both arms had none or mild ischemia on their stress test. Compare this courage to fame, where we show this, where the superiority of FFR-guided PCI was shown over angiographic PCI. In the FAME-2 study at five-year follow-up, where the patients had a positive, or patients who had a positive FFR measurement, there was a superiority of physiologic-guided PCI over medical therapy in these patients. And where the five-year outcomes showed a persistence of this finding, primarily from a reduction in MI or an urgent revascularization. While in the medical therapy arm, you can see the rate of urgent and non-urgent revascularization are three times higher. For patients in the medical therapy arm, 50% of them had a revascularization by five years, and 35% of those were non-urgent. And this was statistically significant. And these were not simply trivial events. As you can see from the two-year results, that about a third of the patients here who presented in the medical therapy arm with urgent revascularization, it was due to an MI or chest pain with ECG changes. And this is a finding that I think mirrors what was seen in ischemia, where patients who had documented moderate to severe ischemia, who underwent revascularization, had a reduction in MI. And here, patients with more diffuse disease from the ischemia study, there was a reduction in the primary endpoint. And whether you use FFR or IFR, it appears to be equivalent. Data from the defined flare in Sweetheart study showed that these two strategies were very similar in their outcomes. And we know that patients who do not have ischemia based on physiologic evaluation, where the FFR is greater than 0.75, there does not seem to be any benefit from intervention. Here's a five-year data follow-up from defer, where they looked at patients who had FFR measurements greater than 0.75, and whether you got revascularization in red or deferred in blue, that the outcomes were similar. In fact, there was maybe a trend towards worse outcomes in the PERFORM arm, but overall, the p-value is 0.21, and there's no difference. And therefore, there is no benefit for PCI in such patients. Finally, although the study came out after the guidelines were finalized, it is worth mentioning the FAME 3 study, which evaluated 1,500 patients with multivessel disease, who were randomized either to CABG or FFR-guided PCR. It's important to note that 24% of the lesions in the PCI arm ended up not being treated, despite their initial randomization, due to the initial randomization due to the FFR being greater than 0.80. Overall, there was no difference in these strategies, although it does appear that PCI may be better in patients with a low-burden disease. We know that physiology can be used to improve the accuracy of the syntax score here, the low syntax score favoring PCI, potentially, p-value is not significant. We know that this physiology can be used to improve the accuracy of the syntax score, so it is something that may be useful in terms of determining which patients may be better suited for PCI or CABG. So, in conclusion, the guidelines recommend a class 1 level of evidence A, that in patients with angina or an angina equivalent, undocumented ischemia and angiographically intermediate stenosis, the use of fractional flow reserve or instantaneous wave-free ratio is recommended to guide the decision to proceed with PCI. Whereas a class 3 no-benefit level of evidence BR recommendation is that in stable patients with angiographically intermediate stenosis and FFR greater than 0.8 or IFR greater than 0.89, PCI should not be performed. Thank you.

coronary physiology

percutaneous coronary intervention

fractional flow reserve

instantaneous wave-free ratio

angiographically intermediate stenosis