Dr. Hayder Hashim, an interventional cardiologist with MedStar Heart & Vascular Institute at MedStar Washington Hospital Center, provides background and summarizes the importance of microvascular assessment, details the best way to manage CMD, and shares case study.
Thanks for the kind intro. Um I will just uh add one disclaimer. I'm not an expert in this field. I'm uh I'm learning with you. Um It's an area of interest to me um in, in uh in fellowship and in practicing uh before I joined the hospital center, uh I was telling the, the uh the team here. I um I was in private practice for a few years and then I um I switched to um to um and more in a academic setting where I have fellows uh big hospital um enjoy every day. Um Another disclaimer, I don't have a clinical practice. So, whatever I'm telling you now is um is accomplished by just being in the lab for five days. Uh I work in the lab as doctor Talreja knows, I work in the lab with the rest of my good friends. Um five days in the Cath lab, 7 to 7, just pump cases. But um towards understanding the micro circulation a step beyond an angiogram. It's, it's something we knew for years. I'm talking to Dr Goldberg here and it's microvascular disease or the micro circulation. It's been, it's been out there we studied in medicine in med school. We hear about residency fellowships and in practice and but we never understood exactly the mechanism, the problems, the treatment for it or even the diagnostics. This is the, this is the main story in this picture. For years, we have done the picture on the left and we still do it. We do an angiogram. We look at the main highways of the heart, we see the pic cardial arteries, we see the the main branches of the epicardial arteries. And that's what we are interested in. We are interested in this because that generates coronary artery bypass grafting that generates bifurcation, stenting. And then we are good at rule outs and you get a patient with chest pain on the table and you say, you know what? You don't have coronary disease, but we never told the patients what they have. If they have a stenosis, we could tell them you have a stenosis, a stent and I feel glorified after a stent and life is good. But we always, if you have a patient with chest pain on the table and everything is normal. And it's just going to say I ruled out coronary artery disease, but I didn't tell my patients what they have. And the reason for that is the picture on the right because you are truly missing with the coronary angiogram, the main circulation power of the whole coronary tree, which is the micro circulation. Now, to establish concepts moving forward. We all have to remember from med school that there are structural and functional changes that happen in the circulation. We are always interested in the conduit vessels. This part and the conduit vessels are the arteries that are larger than 400 micro millimeters. And when we are looking there, micrometers, I'm sorry when we are looking there, we look at the structure of those arteries and we know that they have endothelium, they have smooth muscles and they have adventitia. But guess what? These Kwood vessels are responsible for only 5% of the resistance and the functionality of the circulation. They are there because they are the floodgates. And without the Kwood vessels, without the 5% you won't be able to have the rest of the 95% working. Now, pre artery use and artery use might still share most of the structural characteristics and features of the Kwood vessels in a sense that they still have endothelial layer and they have smooth muscle layer. But once you get to the capillaries where the gas exchange happens, you are losing the smooth muscle layer. Why this is important? It's important because now we are establishing fact. Number one, whatever happens in the conduit will happen in the micro circulation, which means the diabetic, the hypertensive, the hyper epidemic, those risk factors, the smokers, the genetics while it is affecting the epicardial arteries with 30% stenosis, 60% stenosis, you could imagine what happens in the pre arteries and arteries because you definitely have less threshold for obstruction there with minimal plaque. So, structural changes that happen in the epicardial arteries could still translate because this will debunk the first myth that micro circulation or microvascular dysfunction is a disease of patients with no risk factors. That would be that's proven untrue whatever you have risk factors for epicardial disease, you should assume you have the same risk factors to the micro circulation and you will have microvascular dysfunction. The second thing that we will talk about is the functionality, which means if you have an endothelial dysfunction or your receptors are not working well. And the epicardial arteries, the arteries and the pre arteries still carry some endothelin dependent receptors. And these endotine dependent receptors are very sensitive to nitric oxide. You will have the same problem. So if someone is prone to have epicardial spasm, they will have micro circulatory spasm. Now, obviously, when you get to the capillaries, the endo receptors are gone. And now we are talking about and that independent receptors. Therefore, we use different medications to relax the microcirculation past the arterial where the capillaries are. But again, structural changes in the epicardial will translate into the micro circulation and the exact same functionality. If you have a dysfunction in the epicardial arteries, you have a dysfunction in the circulation. Um The question becomes now and I always challenged by um by Doctor Lord Sadler, who is the director in our lab. He always tell me. So you wanna tell me that micro circulation um is, is the precursor for every single thing. And I was like, that's not true. Now, we know that micro circulation could be the precursor. So micro circulatory dysfunction could be the precursor for diseases and it could also be a sli. Now, we all know in a cath lab, you are doing an anterior wall sty and if you're doing an anterior wall sty, you have distal liberalization and you have no ref flow and that's where we fall right here. And the aic so microvascular dysfunction could be a sequel or an end product of a disease. But at the same time, it could be the manifesting power or precursor for other diseases on this side of town. If you look here with AOC with Mya aoc means ischemia of ischemia with no obstructive coronary arteries, my nokia is obviously myocardial infarction. The only difference is with minoa with you have an objective findings of elevated enzymes and I guarantee you have seen those patients, we will talk about them in detail in a second. And you can also have angina which is anoca a for angina and no obstructive coronary arteries. So there is a large spectrum of diseases where the circulation is the driving force. But at the same time, this is what I find my research happening. My research happening now in cardiomyopathies, I work with our cardiomyopathy clinic, patients with amyloidosis with sarcoidosis with Fabris disease with genetic predispositions to cardiomyopathies. Those patients have microvascular dysfunction. They have nothing to do that. The circulation was completely intact. But now it's dysfunctional because of cardiomyopathy. Same thing with Takuto. I always ask myself if you close your eyes now and remember the last time you treated Takatsu patients, I guarantee it is. At least you treat one patient with Takato every week. It's a disease that we see it in, in, in the hospital. We see it on our units. Patients with Takata. Our patients also make it to the C lab. Um because most of those patients, they have chest pain syndrome, they have biomarkers, they have ugly looking EKG S, they end up on a calf table on a Friday evening when everyone is trying to go home because now am I gonna marinate those patients for a whole weekend until Monday to cal them? They are in semi technically and you go in and you take a picture and guess what? You don't find AAA any stenosis, significant stenosis in the coronary arteries. So what's happening Takato? Why is it always the led? These are the questions that are interesting me now in research because there has to be a link to the market circulation and I will share with you our experience from the hospital center in a second. Now, obviously, the rest I love there because it, if you definitely see patients with HEF PF what is micro circulation doing there? You see patients with obstructive C ad and so on and so forth. So I do believe this central illustration tell you that the microcirculation is the link between a lot of diseases that we treat on a daily basis. Now, you're gonna tell me, OK, um Enough with this, we understand. Um Is this um is this something that could uh explain everyone? Let's look at N CD R. This is N CD R data. I'm gonna skip through them quickly because I'm gonna explain it. Um Leaving fellowship and clinical practice. If you do a nuclear stress test on a patient, excuse me, you will send, you will send um four patients with positive stress. One of them will have uh a stenosis um that will receive a stent. So we know this one in four, you will find some sort of obstructive coronary artery disease. And those one in four could be, you could do an FFR to validate your stress test. You could do imaging or you could go ahead and put a stent because it's a stable coronary disease patient or medical therapy, positive stress test. You will, you will end up with stents. Now, what happened? The other three people, the other three people that were sent to the lab were told you have no obstructive coronary disease. Congratulations, but we didn't give them an answer. Now, if you take those three patients if we take the left over patients who left the cath lab without a obstructive coronary disease. And we look at the data, 50% of those patients will have microvascular disease or vasos spastic angina. So I'm not saying every single person comes to the lab leaves the hospital without testing. It means they have microvascular dysfunction, but at least a big chunk of patients leaving the lab will have if they are tested for micro circulatory dysfunction or vaso spasticity, they will have a problem and that is produced by many meta analyses and registries. Now, this is an entry for a business acumen for an idea that we had at the hospice center and we grew it. And that's when we linked to this disease because it affects mostly 60% of women and close to 4 million people in the United States. With this, with this condition, I tagged into our woman heart Center, which is a center that has been established at Georgetown. Many of my see patients there and obviously that the group of cardiologists that see patients there, they see scat patients, they see postpartum cardiomyopathy. They see patients with Tako, they see patients with cardio chemo induced cardiotoxicity from breast cancer immune check inhibitors, the emerging new cancer treatments with the NIH. So my colleagues were already seeing patients. All I did I said, you know what those patients that two thirds of patients with unexplained chest pain are women. Let's try to understand this disease together and that's how I partnered with them. And that was the supportive part uh portion of my um of the lack of my um um um clinical practice. I'm always in the lab. So you can ask me, where do you, when do you see patients, how do you treat them? And that's how I collaborated with my uh with my colleagues on the other side of town. Now, let's dig deep into um questions so far. By the way, doctor to, I don't know if you wanna open questions now or later, but you can interrupt me anytime and if it's too basic, I can move uh forward too, we'll do the questions at the end, maybe just for convenience. Perfect, excellent. So what do I understand? How, how do I understand the microcirculation? We all know something we all know something called CFR and CFR is coronary flow reserve. What I understand about CFR and how I explain it to my patients is the capacity of a human coronary circulation to augment in response to exercise. Which means if I am now resting and talking to you with coronary flow of 2 L per minute, I'm just using a number I should be able, if I start running out of this hospital to the garage, I should be able to augment my coronary flow by at least double. Hence, the cut off for historically is two. It's a ratio between what do you do when you exercise or hyperemic and then what do you do at rest? And that ratio is your coronary floor reserve. Coronary floor reserve now represents the entire coronary tree represents the conduits represents the micro circulation. Now, the conduits, we know how to tease out. We teased them out for years with afar and then we got sick and tired of using adenosine in the cath lab side effects. The time it takes we switch to non hyperemic indices. R, Fr IRDFPD over P for the interventionist in the audience, we know this very well. We have cut offs and then we have trials. And if you don't, if you see an FFR of more than 0.8 you leave the lesion, you can defer safely. And if you have an fr of 0.75 you better fix it because it's a problem. It could explain your ischemic symptoms or patient ischemic symptoms. So CFR represents that which means if I have a 90% osteo led my CFR would be abnormal. But what ha why? Because I can augment. And if you remember from the first two slides, if you, your conduit vessels are occluded or stenotic, you won't have the augmentation power because you cannot bring, bring blood to the micro circulation. So CFR represent epicardial and micro circulation. But what if your epicardial is normal? What if your epicardial has less than 50% in geographically? Then what's the problem? The problem in the micro circulation, true or false. That's probably true to a certain degree but could still remain false. And that's when it will take us to the next light. So to understand the problem in the micro circulation, CFR is part of the problem, ruling out epicardial disease is part of the problem. But to be very specific to the micro circulation, we are introducing the index of microvascular resistance, we got to have something that will check the actual resistance in the micro circulation because that will explain the CD or the coronary microvascular dysfunction. Now, the reason I was talking about this because I get challenged all the time by my non invasive images, we have a robust imaging program between cardi comar between pet CT, between CT scans and um and strain echocardiography. All my colleagues, they come back to me and said, Chill Man because I can give you CFR, send me someone with a pet CT and I will give you CFR in every single vessel I could give you the CFR and the led contribution and the circuit and the RC A and I could give you the global CFR. And then if you have normal um um CFR, you don't have microvascular circulation or if you have an abnormal CFR and then the patient get AC and the C is normal, then guess what? You have microvascular function that's debunked and I'll tell you why in a second. So how do we diagnose this before we get to the lab, you can get cardiac comar, pet CTS and some of my good friends in NYU in different institutions where we sit on the microvascular network. We always talk about this. Can I do pet CT and cr and if I do pet CT and your CFR is low and I do uh CTFFR and I rule out any Hepatitis disease, you have micro circulation. Not true. why? Because there are certain conditions that would drop your CFR without altering your microcirculation. There's something called, I'll get you back quickly. There's something called capillary fraction which means the muscle is getting thicker from hypertrophy from after load conditions of the heart such as severe aortic stenosis and but the capillaries are intact. The capillaries are the same number but the demand is getting is getting higher with capillary fraction. You could have low CFR, you cannot augment because of increased muscle mass while your circulation is normal. And I will demonstrate cases for you when the CFR is low. But the IMR which is very specific to the uh to the micro circulation is totally normal. For that reason, non invasive is a step ahead is a step more into details but not necessarily nailing down the diagnosis, which will lead us to why, how I make living, I make living because I'm in the lab and I'm trying to understand this condition invasively. There are two ways to do it first. There's something called Doppler wire, which is very simple. It's almost like an echo probe. It's an echo probe that is very tiny mounted on an intervention wire that goes down the coronary vessel. And all it does, it measures the velocity of every single heartbeat. And then we know from calculating ionic valve areas, for example, we track VVT and then we can take the time it takes and the time and go and then we take the velocity and I can give you flow. And if I know the flow through the lot, I could give you the stroke volume and then we can get cardiac output from echo. So same thing here, I'm checking the coronary flow bit to bit. So Doppler wire gives you an absolute coronary flow number so that patients Hashim coronary flow is 5 L per minute, but Lionel Messi is 10 L per minute. Um uh Serena Williams is 7 L per minute. So we give the absolute coronary flow. But guess what, I don't care about the number I care about the augmentation power and the preservation of the coronary flow, which is CFR. So what do we do? Excuse me, we do resting coronary flow and then I induce hyperemia or exercise the patient on a bike, which we don't do anymore. It's it's a pain in the neck. Uh So we give adenosine and we cause hyperemia and once you have hyperemia that's simulating not the physiologically in a comprehensive exercise scope, but it will at least simulate or paralyze the micro circulation. And you can calculate coronary flow before and after resting and hyperemic and you can get a cr or you can switch to something else called pressure wire. X for the interventions in the room. This is the old Saint Jude wire acquired by Abbot and we used this wire for many years. We used it because it has a pressure sensor. But then we realized that there is also a temperature sensor which took us back. Now is the same wire. There is no changes. All, all, all the new technology that was introduced now is saying that you have a pressure wire, you could do FFR, you could do RFR, you could do whatever you want to do just like you did many years ago. But we are also giving you a second step which is the temperature sensor that will allow you to do thermo dilution. Have we used thermodilution to understand flow? Of course, we've done this is the essence of Swan guns. Swan guns told us if you inject you're doing a right heart cath and you want to know the cardi caput, you inject 10 cc of room temperature saline, which is colder than the human body blood. And then that will leave the R A port, the proximal port reaches the distal port. The time it takes the volume is known I could give you the flow. And because I know the cardiac caput, I have the, but I'm sorry because I know the heart rate, I give you the flow every bit by the heart rate and I'll give you a card, the caput. And when we did the right heart cat, if I see an outlier, I'll delete it. I will take the most homogeneous two or three reads that I uh that I am obtained. Same thing here for the interventionist. The difference here, this is my reservoir. I don't have a standing bag. I don't tap into it and I don't inject 10 CCS. I inject three CCS. I'm in the coronary. I don't want to inject 10 CCS because we know normal saline is first hyperemic number one, number two, it's electro conductive. And for us in the lab, we know when we inject saline into the coronary, we see EKG changes, significant EKG changes sometimes. And if you keep injecting normal saline, such as in cases when you do laser arrect toy, you can actually induce a FB uh VFIB because you have VFIB. Um And the reason you in this because you are ischemic from all the electro conductivity and replacing the blood. For that reason, I use only three CC and it's as simple as this, this is 30 seconds. I don't need to go through the whole thing. But technically, I have a guide down the corner and all I'm doing is I I flush just like any guide hygiene I don't want to bore the non intervention interventions with this. But this is technically it, I fill my syringe and this syringe will inject down the Coron. That's all I need. What do I do? I do it multiple times. Uh This is more interventional. Um But this is what I get first. This is the picture I get. I have pressure sensors. This is the waveforms. I have the resting time, which means how long did it take for the three CC? Three amounts of normal saline to leave the guide catheter and to and to reach the tip of the wire and the tip of the wire is a sensor and you get the time at rest right there, I have 123 readings. They are pretty homogeneous. How do we define homogeneity in, in this study it's anything within 15%. So I think within 15% of each other I will take it. There is so much A I in this technology that if you have an outlier, the mean or the average time here will be highlighted in yellow. That's the machine telling you you need to repeat one of the outliers because you uh this is not an accurate measurement of the time we are using time at rest and time at hyperemia as a surrogate for flow. So how do I induce hyperemia? I use IV adenosine just like we did with ear, I induce hyperemia. I wait for hyperemia to kick in. There are multiple signs for hyperemia. The most specific is patients reporting symptoms. The second is you will have systemic hypertension. The third, you will have some sort of an arrhythmia. Certain patients respond with tachycardia in response to the systemic hypertension. Some patient responds with a V blocks some bradycardia um um um um manifestation and then the last is drop in PD over P A by more than 3 to 4 units. That's for the interventional when I'm in the lab. And I want to know I don't have time to wait for two minutes for hyperemia to kick in. So sometimes certain patients are very sensitive to adenosine, they go into hyperemia within a minute. And if I see one of these four things, all, all of them, I'm done. I don't have to wait for two minutes. It's recommended to use IV adenosine to have a more steady state high premie than using intra coronary adenosine. You can use intra cor adenosine, but you got to be pretty darn good in injecting because you need to inject three CC of saline three times at least. That's assuming no outliers while adenosine intra coronary is still under effect, which is pretty challenging. Now, once I have the time at rest time at hyperemia, I could calculate my CFR and then I could calculate my IMR and we'll talk about it in a second. So coronary flow reserve, this is technically it time, rest time at high premium, you get it. There are no normal values for the reason I said my absolute coronary flow is different from your absolute coronary flow and it's not specific to the micro circulation. Yes, it is a a AAA marker for um for micro circulatory dysfunction. If you have a problem with the, with the, with the circulation, but you could have it um but also in other conditions and obviously, it's affected by the epicardial coronary disease. So um which is something we know. Now the normal value is anything above two to be very more um more liberal. We're going with 2 to 2.5 based on the clinical presentation of the patients. No IMR because I have flow and I have voltage which is PD, I'm using ohm's law and resistance and I could get you the resistance and the normal value of IMR is less than 25. If you are mounting resistance of more than 25 you are not relaxing your micro circulation in response to adenosine. Now, this is variable in conditions and the heart transplant population that we have at the Washington Hospital Center. There is emerging data that an IMR of 16 signifies early signs of projections 16 while it's normal for me in my native heart. If I have a grafted heart or a transplanted heart, 16 is car for abnormality because now you are saying there are signs of micro circulation, structural and functional changes happening. You probably need to change your immune suppressant. Now, for post a someone who had just got treated for a large anterior wall sty, a large sty, the cut off for abnormality is 40. You can say why? Because I told you I expect some sort of embolization and microvascular dysfunction from edema from oxygen free radical damage to the microcirculation. I cannot treat everyone with a stem or an end stem with a thrombotic occlusion with an IMR of 25 that everyone has microvascular function. For that reason, the one that is the IMR value that's correlating with uh problem and and post stemi is 40. Now, this is reproducible, its validated in multiple trials. It's not affected by a cardio coronary disease which will take us to a different group of patients, the patients who are Sted but they still have chest pain and they start shopping around looking for an answer and you do a afar you do of the stent, you do ibis of the stent. You are questioning yourself. Did I put a good stent or not? But they still have chest pain because two conditions could coexist. You could have epicardial disease, you stent it, you stent it or you sent to coronary bypass grafting, but your microcirculation is still affected because structural changes could happen in both circulation or both levels of circulation. This whole talk does not complete or is not done unless you rule out vaso spasticity. So far, I just talked about microvascular dysfunction. I have not talked about endothelial dysfunction, slow flow or spasm for that. I performed something called Asty colic challenge. This is not ergotamine, this is not, it is scoline is a naturally occurring compound as we all know we make, we make it in the body. Um and what it does in a normal endothelium and a normal epicardial artery, acetylcholine should vasodilate, should make everyone have artery gets bigger. But in some, in patients with endothelial dysfunction or they have vaso spastic response, they will have vasospasm when I challenge them with the stock. What do I do for the left coronary? I give 2 mcg 20 mcg and 100 incremental dosages while I'm observing symptoms. EKG and geographic appearance of spasm for the r because it's less territorial. I do 2, 2050. The reason we do most of our micro vascular testing and I start calling in the led because it is the sole supplier of the LV ventricular mass. And it could represent, it's almost like the delicate, that represents the higher population. For that reason. We go to the led. Now you are going to tell me, but what's wrong with you? You are going to wire an led. That's normal. You're going to inject that start calling an led, that's normal. Well, that's when the technical aspect comes when I as interventionist. If it's a tortuous led, I'm not going down that led. If it's a dual led, I'm not going down. That led. If it's an led, that doesn't reach the apex because the RC is the most dominant vessel. I'm not going down the led. I pick the led in most of my cases for the reasons I told you, but not necessarily all the time. And obviously, when you do research and you try to understand micro circulation, I usually do micro circulation assessment and cooling challenges. And the culprit vessel corresponding to my echo wall motion corresponding to my T wave inversion on. So you can pick and choose but for patients coming from home and you are trying to rule out or understand this disease. I always use the led. Now I start calling it's a ocular preparation. It's not FDA approved for intra coronary injection for that reason. You have to get to your pharmacy on board and you have to get an approval for using it. But again, it is proven by multiple meta analysis. One was published yesterday in Neuro intervention from the European experience and we have one from the US in Jack interventions. You could look into it. It's a meta analysis talking about the safety of estalone. What do I look for if you have chest pain and or ischemic changes without angiogram problem, I take a picture and there is nothing happening but the patients having tons of chest pain, you have microvascular spasm. How come there is no epicardial? You can't see it geographically. Because guess what angiogram shows the epicardial arteries only. So you could have microvascular spasm because some functional um um um uh uh features had happened in the micro circulation. So you have chest pain, EKG S, you could have chest pain EKG changes and epicardial spasm based on angiogram. Then you diagnose your patients with coronary vasospasm or pronounced endothelial dysfunction. The main reason here, I've been talking for 30 minutes and nobody got time for this. Who is going to wait all this hashem? Are you nuts? You do 10 cases a day? You have time to do this. Well, we looked into the data, the data was published many years ago and 67 years ago and it looked at doing a afar and measuring IMR and CFR by thermodilution does not take more than five minutes. Now, obviously, my 1st 10 cases I took longer. I was, it's just the same thing when II I remember my first day in fellowship, I couldn't get radio access. It took me 20 minutes in AEM. And my, my attendant was like, you know what uh go on access and come back. But uh obviously, with time, we got better. So the learning curve to put a wire down in in L AD it is very simple. I mean, we've done it as an interventionist to put a guide. We're better at that. So truly doing putting the wire down doing the injections rest and at hyperemia doesn't take more than five minutes and we will answer the questions later this year. Hopefully, we were part of this study. It is called the flow lab study, which is technically multi center. People like myself who love to do this in the cat lab. And we just recorded the time it takes which injections you usually delete as an outlier and it mostly I could tell you this anecdotally. It's usually the first why it's the first because by the time you put the guide in and you're prepping your wire to go down, some blood creeps back to the guide, which is a normal occurrence. If you are working in a lab, you know, this blood comes back from the coronary tree reflexing back into, into the guide. And by the time you do your injection, you is or the the saline column is already warm, you will get an outlier. But once you get into the habit of injecting, you will uh you will get your uh homogeneous uh reading. So fl la will shed the light on safety. How much radiation? Um How much did it take us? And um how many patients we went trans radial transfemoral. You will get the the data recently. After all this, you're gonna stop me and say, you know what? Hey buddy, I practice my guidelines. Is this in the guidelines? Am I doing something because you are in a research program? You are academically. Am I treating my patients? With guidelines. This is the European guidelines. They are usually ahead of us. And I believe everyone listening to me and in the room know that the Europeans are more progressive in their guidelines than us. In 2019, they said if you are doing calf for someone who has typical chest pain and you don't understand why their pericardial arteries are normal. We do, it is reasonable to proceed with wire based understanding of the micro circulation and that's how they propose their consensus of practice. You get the patient, you evaluate the patient the way you like non invasive. If you have nuclear in your office, if you believe in CT angiogram to and structural anatomy, go ahead and do whatever you like. But once you are convinced your patient needs to get to make it to the cat for an invasive coronary angio, you need to tell your interventionalist if you don't find anything, I'm pretty convinced this is Angina. You need to do guide wire and adenosine testing and alco testing and then you put your patient in one of these buckets which will aid in the treatment and I'll get to it in a second. Surprisingly, for the first time in history. Two years after the guidelines, European guidelines, the American guidelines comes out says, you know what guidelines of chest pain A H A ac case, chest ct um um um uh societies, cardio Commerce Society, they never sat down for the first time. They sat down so C MD. Unite everyone. Apparently. So now they sit down and they say the exact same recommendation. It's a, it's reasonable if you are highlighted that in yellow. If you don't find cardial disease, you should follow up with understanding the ma circulation. Why are we doing this? Because it's bad prognosis. We know if you have low FFR you, your prognosis is bad from Pha one F two and you need to stand and life is good and your FFR is, is above 80.8 or or 80. Your life is good. Why? Because you can defer and your prognosis is good. Now, same thing applies for CFR patients with low C for any reason, it doesn't matter. You walk in, you get a pet city, your CFR is less than your neighbor. You're going to die before your neighbor. You will have an event before a neighbor. Why CFR is important? Now, if you combine low CFR because of an elevated resistance with, you will actually be in trouble. You are the worst of everyone else. So if having low CFR, you're not doing well. But if you have low CFR and you have low IMR, which means your micro circulation is ok. You are worse than this everyone else. But guess what? You're still in the same group. But the minute you drop your CFR because of the micro circulation that is responsible for 90% of the resistance, you will be in trouble. Post PC IR is also playing a prognostic value and that's what we talked about. If a PC, that you've done that elevated the, the IMR your patients at a higher risk of events, how do I understand it to simplify it and end this and go to treatment high CFR low IMR normal FFR patient is out done. Why you're augmenting you're not resistance and you don't have epicardial disease. And if I do, I start calling and there's no changes. This is not cardiac chest pain. There are patients that visited the emergency room nine times in the last year and they start going from hashem to Dr Goldberg to leaving to Amy and coming back, they are stopping, you cut the chase, you get tested, you have everything normal, it's not cardiac out of the cardiology clinic. Now, low CFR high IMR normal FFR, that's typical C MD. You cannot augment because of high resistance while your led is totally normal. Low CFR you cannot augment low IMR you have no resistance in the micro circulation. You have abnormal of of R this is doctor Tre Specialty. Send them in. We will do it oct guided stent IVIS, guided stents and we're done. Now, you have low CFR low IMR normal FFR. What, what are you talking about? Um You told us that you know they go CFR represents both. So how come you have a normal circulation and a normal epicardial? So, where is the CFR coming from? This is why pet CT is not conclusive. It's a step towards but it's not the actual diagnosis. The reason for that, if you have high output states, if your resting flow is at maximum, how do you assume if I give you heparin um sorry, adenosine or if I make you exercise, you will bring your cognitive flow. Higher patients with thyrotoxicosis, anemia, Paget disease, avi fistulas. How many patients with end stage disease? You see in the lab a lot, how many patients with end stage liver disease? Those patients are at high output states at the beginning. So they, they won't be augmenting because they already augmenting and the CFR would be low or find other E allies. Maybe when I tested the patients, I injected warm saline and my CFR is abnormal. So there are multiple ways that CFR could tease you away from the real diagnosis, either linked to the patients or linked to the technical aspect of doing things. So don't be surprised if you see the last pattern. And obviously this is Esta Colin. This is I put it in a different one chest, an E no spasm, you have micro circulation, spasm usually comes in with high IMR two, which will demonstrate in a second chest pain with angiographic spasm, epicardial. And then if you don't dilate to the low dose or you create slow flow, then you have pure endothelial dysfunction. Very rare that you will find pure endothelial, very rare. It's a small percentage of patients and this is a paper that we published two weeks ago. This is the comprehensive came at Jack. It's a state of the art has two parts. The first part talks about building a program, talking about the journey from receiving the patient all the way out to the diagnosis. And part two talks about the treatment of those patients. If you look here, uh I will leave you to look at it for 20 seconds for the sake of time. But it's exactly what I just presented to you. You have chest pain, you get cath, you have less than 50% stenosis. You do your epicardial tease out physiology. FFR non hyperemic. And then you go ahead with, with uh coronary flow reserve and IMR testing and Tyco and then you come up with buckets to put your patients in and that's the definition of every bucket I did not address the green box on the far, right, which is myocardial bridge. That's a lecture by itself. But that's one of the most interesting findings because I struggle this morning this morning. What to do with myocardial bridge? It's a cause of pain. You hear it in reports, you read it in reports coming back from the cat lab a lot. There is significant bridge in the middle. Now what unroofing beta blocker negative inotropes. What do you do with that? There is a full section in the paper on how to diagnose this and how we believe we are heading into the treatment. And obviously, the I do in the lab, I use intravascular ultrasound to see the change in diameter with every single heartbeat. And obviously you do the beam to challenge your thought process or hypothesis that is inotropic, dependent and heart rate dependent different lecture. I don't want to spend more time here. Now we're gonna say treatment. OK. Move. We're done. We understood it's prognostically bad people are dying. Um And there's a lot of patients out there. OK? We get it. How am I gonna treat my patients? Man? This is what, what matters. I wanna know what to, what to use. I'll start with the Cormier trial. Kya trial is a very simple study. It took 100 51 patients. Everyone has chest pain, seeing a cardiologist got tested with AC T angiogram, nuclear stress echo debut. I mean, I don't care. They made it to the Cath lab with a chest pain syndrome trying to understand what they have. They all underwent C MD testing the way I just showed you, they went from acetylcholine, reverse acetylcholine with nitroglycerin, put the wire down injections of normal saline thermodilution. IMR all of them, one group was told what they had. They sat, we've done no blockages. You have microvascular dysfunction and your cardiologist will be told what you have. And this is the treatment we're recommending the other group was told, don't worry, no blockages. Everything is good. Looks perfect. Yeah. So, what do I have? I don't know, go to CV S pick up amLODIPine, nitroglycerin beta blockers. And let's see which one works better. Sent home regular practice. They follow them for six months and 12 months. And what they found that the angina severity is less perception of illness is less. And the patients who were told the diagnosis, then they looked at the global treatment satisfaction or adherence to medications. The patients who were told what they have and the cardiologist told how to treat they did much better. Now, I don't want you to believe this. But what I believe from this, the take home message that giving a diagnosis is almost half way into treatment because those patients seek diagnosis. That's why they keep getting back to you and then they have frustration with you. You have frustration with them because you walk into the office. There's a sticky note um that Hashem. Um Miss Mrs Hashem called and she is miserable again. Oh, she called again. I don't know, man, I don't know what to do with this patient. Miss Hashem is admitted into the hospital on observation. The nurse practitioner saw the patient negative troponin times too. The last trust form was six months ago, cio gram was three months ago. She got cut by tre seven times already. What do you want us to do? What do I do? With these patients. Those are the patients who are seeking diagnosis and that's what K market trial told us giving a diagnosis. They will go away. Now, the disease might not go away. But guess what their perception to the illness is better, the quality of life is better. They will be settled by the fact that they got a diagnosis. So that's what the KYA trial tested was the treatment. This is, this is the treatment that was suggested by the Kya trial. Number one lifestyle factors. Ok. We've done this, bro. We're done, we're done with this. I've, I've, my patient is not gonna do uh yoga. Move on. Ok. Risk factor management, risk factors. This is microvascular function. Well, guess what we talked about it. Structural risk factors could still exist between the epicardial and micro circulation. And then we're gonna go talk about antianginals, statin and a arm is being tested in the warrior trial to conclude soon. It's a trial that got women with this condition, statin of ace inhibitors or arms and keep going. Then if I give you the diagnosis of microvascular angina, what's missing from 1 to 6? There is no natural. Do you know why? Because nitro is endo dependent, nitric oxide works on endo dependent that exists only in the epicardial arteries does not exist in the micro circulation. That's why when I measure a aar, I don't give nitro as an hyperemic agent, I give nitro to, to relax the epicardial arteries because I engage the RC A with a guide because I put a stent and at the edge of the stent, there is a tight area. That's when I give Nitro to vasodilate the epicardium. So if you have high IMRLCFR nitrates don't work. Tell me how many of your patients with microvascular dysfunction or you thought they have microvascular dysfunction. You gave nitro in all forms. Sublingual indoor is the cornerstone of my treatment. Before I realized I give everyone nitro, you have chest pain, pop nitro because if it's esophageal spasm, nitro should work. But guess what, when you have a diagnosis that doesn't work. Now, which beta blocker do I use? I use carvedilol. The reason I use carvedilol, I need some beta blockade with alpha blockade. I need something very non selective. Metoprolol is very good. We love metoprolol, heart rate or succinate. We love it. It's also proven in heart failure management, especially succinate. But here I use carvedilol because I need to take that alpha receptors also in case they are causing some vasoconstrictions. Boom. Done. If you are vasos spastic angina, which means your tyco challenge was abnormal. Then the mainstay is calcium chain blockers and long acting nitrates. And to be more comprehensive, we introduce this to you. I cannot read it. I do practice by this. I'm part of the paper. But now because we are so young in this treatment algorithm and we're still testing whenever we saw AAA case report, not case report, case series, uh small study from Italy, small study from Spain. We included it here. So the exact same thing you could try Ranolazine, you could switch to Ssris. There's nothing wrong with that. L arginine. You could use PD five inhibitors. There are a long list of things. Hopefully, one day we can get a dentist and antagonist um and, and a preparation that might help as well. Question so far. Good. So our experience, when did I start doing this? August 2021. That's why my disclaimer was my disclosure was I'm not an expert. I have an interest in it, but it's that simple to perform that I start doing it. We did 250 cases so far. I started with this is Maar um um ad that the marketing team told me I'm, I'm showing you this because I do see a lot of potential in, in, in, in growth. Um and, and um affecting patients um um everywhere in, in um in this area. So I started with calling my center, unexplained chest pain, but then you get a lot of patients unexplained chest pain. I have unexplained chest pain and walk around having some chest pain. So I switched to Comprehensive Coronary Function Testing Center. So that's how I'm envisioning the future of this field. This is myself, Brian case, Itzik Ben or some of you probably in the area knows who they are. Brian was one of our fellows. He joined us in one of the Mets star hospitals itsi works next to me. I work in lab one. He works in lab two. We are all part of this. Then this whole fed the research need in our institution. And we built the which is corn microvascular Dysfunction registry. It's sponsored by, it's our money. It's our grant, it is not sponsored by any industry. We built this out of our own effort and grants. It's free to participate. It's National International. There are multiple centers that are now feeding into our registry in an attempt to understand the disease better. I led the before I finish, I led the effort with the CDC to recognize microvascular dysfunction as a disease. And as of October 1st, I'm happy to announce that they actually recognize recognizing the disease. Now with an code, this has nothing to do with reimbursement. I'm not talking reimbursement. I'm talking about your patient comes in and hashem. Give a diagnose that diagnosis is not syndrome X anymore. That diagnosis is not angina anymore. That diagnosis is either angina with cardiovascular dysfunction or myocardial if the patient has acute presentation with biomarkers. So now this is a very good way for us to follow patients to understand the magnitude of the disease, the prevalence, the incident and how to treat those patients. I'm gonna end with one case. Do I have time doctor to radio or? Absolutely, we'd love to hear it. Ok. Here we go. 75 hyper hyperlipidemic GERD cervical radical apathy. Do you know why she has the last two diagnoses GD and cervical tacy because she's having chest pain forever. She saw a G I and AAA Ortho spine um before pain that nobody can explain. And if you do AAA cervical MRI on me now, I have cervical Ory, we all have it. So guess what? She continued to have chest pain one day she got very lucky why she got chest pain and end sty. So no one can deny her anymore. She has troponin, high sensitivity, low sensitivity, it doesn't matter. She walked into the emergency room feeling very good with chest pain and sty and she was like, yes, I'm not crazy. So what did they do? They put a stent in her first om and then she continues to have chest pain. What we stinted the OM. But she continued. So she got a repeat angiogram in 2019 by another cardiologist. They're like, we don't know what's wrong with you. Maybe the stent has severe ISR. She gets ac nothing. Then she got frustrated. She saw a different cardiologist who said, you know what? Ha huh. I looked at the, see this from 2018 to 2019. There's a mid L ad lesion. I bet you if they have done FFR on it, that's the cause of your chest pain. Let's go back in, they go back in 2020 they do FFR of the mid led which was 50%. They get insignificant. She seeks help. She wants us. She feels miserable with nitrate, she gets dizzy the minute she takes the nitrate and absolutely miserable with extended release. Uh nitro preparations, RC. A mild disease. No doubt. There is something anyone wants to put a stent. No, looks good. OK. The, as you see, there is a stent in the uh in the om you see the shadow and the stent is not good. It's perfect with positive remodeling. The stint is bigger than the vessel itself now, so the stent is not the issue. Then we took a picture of the led. Do you see where the diaphragmatic silhouette crosses the heart silhouette, the cardiac silhouette. There is something of that led. Do you agree? It's hazy. It's not normal. It's am I gonna put a stent? No, with someone with chest pain, I'll do a afar. So I said, you know what this is the lesion they looked at in 2020. They don't know how to do a fa far. I know Afaf far better than anyone else. Let me do a fa far. That's what I'm thinking. So I put a wire down pressure Rx the wire that has a temperature and the pressure sensor. And first thing I did, I did RFR resting full cycle ratio, no high premium or nothing. This is just for me to understand if the narrowing is significant or not? The cut off is 0.89. What's, what's my value? 0.93. So is there a gradient loss? Yes, there is. Of course, there's a lesion. Is it clinically significant based on trials? No, it's not. But guess what hashem? This is resting. I bet you if you exercise the patients when she gets her chest pain, she will have an abnormal gradient. Well, OK. That's called a afar and a aar is 0.91. The cut off we use historically is 0.8 from fame one, fame to fame three. So all, all uh trials. So now that lab I confirmed in 2022 that what they did in 2020 was completely normal. So I went ahead and I measured her micro circulation function. What do you see here? Half of far we know who cares? OK. Time at rest, homogeneous, time at hyperemia, homogeneous. If you look at the curves here, this is, these are similar to the right heart curves. The right heart curves is usually um um um on the positive side of the axis, this is on the negative, it doesn't matter. So my my blue it takes time and it's not dagger shaped, it looks like a bell curve. So here comes here and goes down three of them. Imagine us when I became faster with hyperemia, I see significant drop and climbing back. And that's one of the signs of time and hyperemia. What's the CFR 2.5 normal or abnormal border Lish. But remember I said 20 to 25, that's what we're taking. But what's the most specific to the micro circulation is my IMR what's my IMR my IMR here is 39. The cut off of 25 is abnormal in general population. So she has microvascular dysfunction. How come she has a stent? Yes. Those are the patients where you stent and they continue to have chest pain because they could uh the the problem could coexist last case. And I will conclude in a minute, 59 same story. Lots of chest pain takes nitro feels good. Life is perfect. And I said, you know what, go get a pet city. Pet CT is very good. It'll tell you that you have no coronary classification. So calcium score comes out perfect. And then I don't know, I just copy paste the impression. I don't read the report. I'm an internationalist. I read the impressions and the impression it says no evidence for ischemia. Hallelujah. No evidence of transmural infarction. Oh God bless normal LV function. Oh, great. And the flow of the led CFR is 2.84 above 2.5 or above 20 the circ above two, the RC A above two. So each zip code, each highway, whether it's 66 whether it's beltway, whether it's the 95 they're all working and the whole area globally total CFR for the whole circulation 2.94. So she doesn't have microvascular dysfunction. Does she normal CFR? No calcium score. Her chest pain is in her head done. She continued to have chest pain. No one can explain it. We did a cat, no calcium, we know there's no calcium. This is the led, this is the RC A. So now what her CFR is normal if I do my CFR measurements, would I expect it's validated invasive and pet CT is validated. So this is an indication for esta chic testing now because she does not have microvascular dysfunction. Maybe she has something else. I gave her two mics small tiny dose and then she has uh uh no change in our symptoms. Life is good. I gave her 20 no change, no symptoms, same flow. There's no spasm and geographically I gave her 100. She's, there's no change in the epicardial spasm. She has lots of chest pain, lots of EKG changes. I gave her nitro to reverse the ni the Esta Colline and she did well. Then I proceeded with finishing. So, so far, what did I diagnose her with chest pain? EKG changes but no spasm on the corna. Is she vaso dilated to the low dose? She has microvascular spasm. So let's see if that's true. RFR 0.96 there's nothing done that L ad FFR 0.94 there's nothing needs treatment done that led when I continued CFR normal or abnormal normal 3.8. How come? Well, the city told you the CFR is normal. So she is compensating for her spasm by normal CFR but her IMR is 35. It's above 25. Why? Because she has micro vascular spasm. Not everyone has microvascular dysfunction, high IMR low CFR this woman, she has normal CFR but she has a lot of tens of chest pain because of acetyl Colline provocative testing revealed that she has microvascular spasm. How do you treat this? Microvascular angina, microvascular spasm, Bezos, spastic angina should be treated by calcium chain blockers and nitrate. And guess what? She was feeling better with sung nitro. So why did I do this? She was seeking a diagnosis. She was sick and tired of normal pet CT normal no calcium score. She wanted an answer. Why is she taking nitro? And that was the answer. I have other uh examples. But I'm gonna open up for questions for sake of time.
BROADCASTMED