10.2 -> YSM Fitkin Auditorium: Okay,

12.38 -> YSM Fitkin Auditorium: So good morning, everyone.

23.44 -> YSM Fitkin Auditorium: Good morning, everyone.

38.79 -> YSM Fitkin Auditorium: Exactly.

43.07 -> YSM Fitkin Auditorium: Good morning. Everyone before we get started today. Um, I know all of you.

48.82 -> YSM Fitkin Auditorium: Um, are aware of really the tragic circumstances of uh, of last uh Thursday afternoon, and a loss of uh of uh,

59.68 -> YSM Fitkin Auditorium: Dr. Barry Zar, I did think we saw a wonderful showing at memorial services for his family, and how many of you have reached out to them?

69.23 -> YSM Fitkin Auditorium: Um! Directly. I thought it would be proper, and I will have many opportunities into the future to recognize the impact that he's had to organization into world and large. But I thought, before we started um with with your support. Uh that we might just spend a moment and just take a moment to reflect

88.77 -> YSM Fitkin Auditorium: uh, in a moment of silence in his honor before we get started this morning

124.64 -> YSM Fitkin Auditorium: for all of us

126.45 -> YSM Fitkin Auditorium: uh wake up every morning and think about how we can impact the world. The little things in the large things we do, and use that desired as a load star. I think we would be better for it, and with that um thank you for for uh, for uh supporting the family and the section, or it is difficult time, and we'll get started with the more.

148.17 -> YSM Fitkin Auditorium: Thanks, Eric. Um

150.54 -> YSM Fitkin Auditorium: uh, i'm glad everybody uh could come by this morning, and I'm I'm, i'm really happy that we didn't have somebody that uh, you know I look up to as a beer mentor and a and a friend here presenting uh uh to us this morning. So Dr. Sami Shah, you know he's a he's a fellow favorite cardiologist. He's a he's an educator, a researcher, and a scientist, and his his background. He went to college at Pennsylvania State University, Uh. Went to Uh got his Md. And via

179.98 -> YSM Fitkin Auditorium: at the University of Illinois. Uh, uh, and then certain, and after that he has been uh a constant at heel training for Residency. His fellowship is international cardiology, fellowship all here, Gio, and then staying on as faculty.

194.69 -> YSM Fitkin Auditorium: He has. He has a unique focus which you know, brings back his investigative background with a Phd. Into his clinical medicine. You know a true, true triple thread in that regards his focus is on quarter physiology, and how that impacts a healthcare uh decisions, especially among them and those with psychological stress. And he has a wonderful program at the Va. Which is a progressively, you know, gaining nationally fame, and i'm so glad to welcome you here with us today.

224.63 -> YSM Fitkin Auditorium: So me

231.32 -> thanks so much, everyone.

235.02 -> YSM Fitkin Auditorium: Thank you, Dr. Blasquez, and thanks all for being here today. So i'm honored to give this presentation about this program that we've been working on for the last several years. Um! And hopefully i'll give you a new way to look at an old problem. So um. The title is seeing the invisible Ischemia and the obstructive coronary artery disease.

253.54 -> YSM Fitkin Auditorium: So my disclosures are essentially funding for research. So um women's health Research at Yale I have a vascular, and then the um, the Food and Drug administration.

265.55 -> YSM Fitkin Auditorium: So I have three um main parts to this talk. So the uh objectives uh are: first to discuss the rationale for basic corner and physiology assessment.

274 -> YSM Fitkin Auditorium: After that i'll go on and talk about our program and the testing that we do. And then the last part i'll talk about some of our investigative efforts.

283.25 -> YSM Fitkin Auditorium: So the first part is titled the streetlight Effect. So this is a a type of observational bias where we tend to look for things where we're

292.53 -> YSM Fitkin Auditorium: he's seemingly more easily going to find them, even if it's not necessarily where we'll find the answers.

300.33 -> YSM Fitkin Auditorium: So i'll start with the case

302.33 -> YSM Fitkin Auditorium: a sixty-seven year, old man with hypertension and diabetes. Prior Covid, Nineteen infection presented the emergency department with chest pain and

310.45 -> YSM Fitkin Auditorium: his initial presentation the nikki. That was non-specific.

314.54 -> YSM Fitkin Auditorium: He had a proponent that was negative for Ischemia.

318.6 -> YSM Fitkin Auditorium: He underwent an indication exercise uh spec stress test where he did. Seven point two met on the uh treadmill. He had chest pain during exercise, and then he had in for your scheme on his for fusion imaging

330.37 -> YSM Fitkin Auditorium: as an inpatient, he was referred for diagnostic, ordinary and geography.

336.31 -> YSM Fitkin Auditorium: So it's going to be an aggram. You see his first picture, this total shot showing no significant obstructive disease, and the led here some mild black,

344.98 -> YSM Fitkin Auditorium: and then in his right corner. He He also had some wild black,

349.61 -> YSM Fitkin Auditorium: so based on the profusion imaging, he underwent further assessment of uh and uh instantaneous way-free ratio, or an ifr of the right corner yardtery, which is non-eschemic, so the value is zero point nine one which is greater than the reference for a scheme of zero point eight, nine.

364.15 -> YSM Fitkin Auditorium: So the patient was discharged home

366.46 -> YSM Fitkin Auditorium: for outpatient medical follow up. So he was actually followed very closely in cardiology

371.56 -> YSM Fitkin Auditorium: uh seen multiple times, and then over the course of the year he had three more er business, for, trust me, he was admitted again to the chest pain center.

379.33 -> YSM Fitkin Auditorium: He under what a repeat stress, um exercise, spec, or actually pharmacological uh spec uh stress test. And then finally, he was repeat, uh referred to as geography.

391.29 -> YSM Fitkin Auditorium: So the his second quarter in angiogram looks very similar to the first,

398.99 -> YSM Fitkin Auditorium: based on the angiographic findings you under what pressureware assessment of the led again.

403.88 -> YSM Fitkin Auditorium: So this time, uh the fractional full reserve of the led was zero point eight, seven

408.6 -> YSM Fitkin Auditorium: again, not aesthetic above the reference range of Point Eight.

412.14 -> YSM Fitkin Auditorium: So the patient is uh seeing again as an inpatient, and then discharged.

417.03 -> YSM Fitkin Auditorium: His total evaluation over the course of the year was two hospital admissions by vr visits for testing two hundred and ninety-two to spec stress tests, a gi referral and an endoscope.

428.17 -> YSM Fitkin Auditorium: So in this chart he was noted that should he have recurrent testing for the evaluation for microbes to the disease will be warranted

434.56 -> YSM Fitkin Auditorium: and turn off shortly thereafter. He represented the chest pain,

439.79 -> YSM Fitkin Auditorium: so I had the chance to do physiology, testing on him. So his quarry angiogram. This time we have a guide. Catheter

445.96 -> YSM Fitkin Auditorium: looks very similar, and then we did a cylinder in provocation.

451.83 -> YSM Fitkin Auditorium: So with twenty micrograms of acetal calling, you see that he has a significant basis for the led,

460.22 -> YSM Fitkin Auditorium: and then with a hundred micrograms of uh, you see that the led is essentially uh gone.

466.73 -> YSM Fitkin Auditorium: During this year chest, pain, and that's the elevation on his ekg.

472.03 -> YSM Fitkin Auditorium: You can see the difference when he's at the peak of his spasm, and then, when nitroglycerin is administered, and his symptoms and ekg change is resolved with nitroglycerin.

481.31 -> YSM Fitkin Auditorium: If you talk to the patient, this is exactly characteristic of the chest pain that kept bringing into the hospital.

488.41 -> YSM Fitkin Auditorium: So then we do uh guide wire based uh physiology with thermo dilution to drive as primary flow reserve, and it's index of micro circulatory resistance. So you see a number of pressure facing here. This is Um. Two pressure tracings in the possible quarter. In the the yellow line is the differential between the two. Um, and then we have thermal evolution curves on the bottom.

506.79 -> YSM Fitkin Auditorium: We derive this micro circulatory resistance, and his is elevated. So our cut off is twenty-five, and so he has this concurrent diagnosis of uh microvascular dysfunction you see in the snapshot here, where our wires all the way in the distal led.

523.78 -> YSM Fitkin Auditorium: So then it his next office visit we had um uh on discharge from the hospital. We had uh sort of the calcium channel blocker at a higher dose um than he had ever been on. We gave him short acting, nitrates and nitro patches for activity

535.74 -> YSM Fitkin Auditorium: mit ctl, and he had complete resolution of his chest pain. We stopped his beta block, or we stopped his isosaur by Mono nitrate, and he felt great, and he was back to a normal life, and has not represented after this one hundred and fifty.

549.61 -> YSM Fitkin Auditorium: So this is uh, actually a common problem. We've all encountered these patients in our practice. This is a patient that was taken care of in our health system. But if you go back and look at uh data that's historical. So uh the diamond forest criteria, which informed many iterations of stable engineer guidelines.

565.56 -> YSM Fitkin Auditorium: Um showed pre-test probabilities uh for people that presented with Angela. So if you look starting in the highest, pretest probabilities of people with typical angina. Men uh who are young uh

578.93 -> YSM Fitkin Auditorium: often have a trucking pulmonary artery disease, but looked at on autopsy or green and geography, if they present with typical engineer but younger men. A significant proportion will not have coronary artery disease, so that means that they have typical angina.

591.14 -> YSM Fitkin Auditorium: But no, it's like a form of artery disease. And then with women. And this really shows the uh implicit bias that goes into the way that we uh evaluate patients that even uh a woman who's uh forty to forty-nine years old, who presents a typical engineer? It's about a a coin flip whether that patient will come to the Cap lab

609.2 -> YSM Fitkin Auditorium: um with the

612.14 -> YSM Fitkin Auditorium: Then, when we go down to atypical symptoms, the numbers are even worse. So the majority of these to present with a typical symptoms for women. Uh, will not have obstructive corner or your disease, despite presenting with uh chest pain that could be angel.

624.8 -> YSM Fitkin Auditorium: And then with men it's uh almost half as well. So there's a significant number of patients, um informed by our diamond forest or criteria that present with chest pain from not obstructed.

641.23 -> YSM Fitkin Auditorium: If you look more recently in temporary cohorts. This was a page, a a paper published by Mash Patel Duke Um, and it showed that out patients who are referred to the Cap lab for evaluation of scheme of heart disease

651.85 -> YSM Fitkin Auditorium: uh, and this is excluding patients who are referred for pre-operative evaluation. But no one coronary is prior, mi prior, Pci, or bar a cabbage so de noble patients. They look at four hundred thousand patients at N cdr fifty-nine percent of the patients didn't have this to noses greater than fifty percent

667.51 -> YSM Fitkin Auditorium: and only thirty-eight percent of the patients who referred for an antigram uh had a stenosis greater than seventy.

673.61 -> YSM Fitkin Auditorium: If you use stress testing to try to uh change that result or modify that. Uh, if somebody has typical engine on a positive stress. They're getting just above fifty percent um probability of having instructing foreigner or disease. And then everything else is lower than that.

691.64 -> YSM Fitkin Auditorium: More recently the discharge study, published in the New England Journal of Medicine this year, looked at three thousand five hundred patients with intermediate pre-dest probability for trust pain, who presented to either an offices it or for inpatient evaluation.

704.18 -> YSM Fitkin Auditorium: Um! All of these patients had an intermediate uh pre-test probability for obstructing coronary artery. Disease, and then they were randomized to either receiving a coronary cta, or invasive binary and geography

714.67 -> YSM Fitkin Auditorium: in their cohort of three thousand five hundred patients. The prevalence of obstructive coronary artery disease greater than fifty was only twenty-six. So that means that seventy-five of these patients are presented.

731.15 -> YSM Fitkin Auditorium: Sorry So seventy-five percent did not have obstructed query order disease and so like we had another diagnosis for their symptoms.

737.87 -> YSM Fitkin Auditorium: Re-vascularization procedures in this cohort only occurred in a minority of patients fourteen in the Cta group and eighteen percent in the invasive forty and geography group.

750.68 -> YSM Fitkin Auditorium: So I want to expand uh our definition of isemic heart disease and and introduce a couple of terms. So if we're talking about stable scheme of heart disease uh, we've, we frequently talk about structural quarterly artery disease, but i'd also like to um mention this term of ischemia, and no obstructive quartery. Order, disease, which is abbreviated to Anoka.

770.2 -> YSM Fitkin Auditorium: If you look at a queue coronary syndrome, this is a different path of physiology. Patients can present with unstable angria and stem your stemme, and the term is myoardial infarction, and no obstructive coronary or your disease. So in noka is uh, frequently due to coronary microbes, either dysfunction, coronary bases spasm myo, cordial bridges, or other disorders of ordinary physiology,

789.65 -> YSM Fitkin Auditorium: Whereas Minoka is due to black erosion cardiomyopathies and can be due to vas a specimen as well.

797.48 -> YSM Fitkin Auditorium: There's a couple of myths here that i'd like to dispel, So the first is that Anoka is behind.

802.18 -> YSM Fitkin Auditorium: So there's a high uh burden of symptoms and patients with Anoka. If you look at Seattle and the question of summary scores which you see in this figure uh a lower score is worse people with an oak. I have some of the lowest uh summary scores of any population that we look at. So if you look at stable coronary over disease, people undergoing tci um patients with the noka end up with a very low um t l in a question or summary scores, reflecting a hybrid of symptoms and significant functional limitation.

831.26 -> YSM Fitkin Auditorium: There have been meta analyses and uh cohort studies that have shown a mortality risk in patients with microvascular dysfunction,

839.34 -> YSM Fitkin Auditorium: and all of these patients, as we saw in that case, um pose. This risk for increased health care utilization. The Mayo clinic is published on this that this group can be uh challenging in terms of cost due to repeat testing.

854.33 -> YSM Fitkin Auditorium: Second myth is that Minoka is B. And I. So this is my partial fraction, and no obstructive coronary order disease. So we all take care of these patients. So patients who come to the Cap Lab is inpatient with the tropon and elevation, and then have no instructive coronary or disease.

868.07 -> YSM Fitkin Auditorium: Multiple cohort studies have shown a high rate of mortality in these patients

872.83 -> YSM Fitkin Auditorium: fatal heart attacks come to her in the absence of coronary stenosis,

876.58 -> YSM Fitkin Auditorium: and if you do advance testing, including optical coherence, tomography, imaging uh, of the coronary arteries. So this is shown in harp bonoka that was run out of Nyu um, and more than fifty percent of patients. You'll find an abnormality in the coronary arteries responsible for the presentation. And then, if you add Mri, you can actually find the eventual diagnosis, and eighty-five percent of symptoms.

896.42 -> YSM Fitkin Auditorium: But you can ask yourselves How often do we look so thoroughly? And these patients who have a normal engine?

904.62 -> YSM Fitkin Auditorium: This is a quote from Jay Wallace first in this book that I um found on the Internet many years ago. The books uh it's titled Chestn, and it's uh essentially a monograph um about all types of chest pain. And so in uh, Dr. Hirst's own words uh in the preface

919.75 -> YSM Fitkin Auditorium: mit

927.29 -> YSM Fitkin Auditorium: mit ctl, and patients know that those words are not diagnoses, as we're referring physicians who send their patients for the high-tech procedures. These designations, and the lack of resolution renders therapy impossible accordingly the patient's problem remains in completely addressed unresolved and unrelieved one hundred and fifty.

945.1 -> YSM Fitkin Auditorium: I want you to hear in a patient's own words. Um! What a typical chest being sounds like! And so this is a project that's um being done by one of our you know medical students, Um Mara Maya, who is actually going through and interviewing a lot of the patients that we take care of, so let's see if we can get the audio to work here.

961.88 -> YSM Fitkin Auditorium: I was walking down the hall, and and I just um! My heart was pounding. I was having trouble breathing. I'm thinking that I might have speak.

971.95 -> YSM Fitkin Auditorium: I thought it was the next room, but i'm gonna to the next room. I had this pain like this

981.12 -> YSM Fitkin Auditorium: pain pressure in my chest.

983.92 -> YSM Fitkin Auditorium: Um! I started sweating profusely, and started shaking. The pain was going across my back, down my arms. Um! And I was like something. Things rock here. This is not just me being out of shape from yet,

998.24 -> YSM Fitkin Auditorium: whatever. So I thought

1001.64 -> YSM Fitkin Auditorium: so. This patient called an ambulance. Um, She was at her place of employment.

1008.08 -> YSM Fitkin Auditorium: She goes to the er at first they're questioning her uh story, and then her blood root comes back, and her high sensitivity proponent. Um meets all criteria for a type one I

1018.71 -> YSM Fitkin Auditorium: so based on this Ri Kiji was fairly unremarkable. But with the blood work and her presentation, she was referred to urgent Orient and geography.

1026.329 -> YSM Fitkin Auditorium: Here's our angiogram.

1034.319 -> YSM Fitkin Auditorium: So after we see this in the chart, we say that There is Um, a small occluded diagonal branch here, and she has started on do on type plate with therapy, and described as having a typical sentence.

1044.16 -> YSM Fitkin Auditorium: She had a repeat presentation to the hospital was admitted.

1047.89 -> YSM Fitkin Auditorium: My colleague uh took care of her in the hospital, and then, uh, suggested that you know, with ongoing symptoms, she should have a physiology study. So we brought her back four months later.

1057.36 -> YSM Fitkin Auditorium: So here's your diagnostic angiogram.

1061.7 -> YSM Fitkin Auditorium: We give her acetal calling,

1063.78 -> YSM Fitkin Auditorium: and you see that the led is essentially gone from Osteom down to the apex, the entire vessels uh essentially spasm.

1071.04 -> YSM Fitkin Auditorium: And then with nitrogen,

1074.94 -> YSM Fitkin Auditorium: you see the vessel come back again another patient who had s the elevation in the lab on the table, and we were doing this,

1083.95 -> YSM Fitkin Auditorium: so we stopped a number of her medications. We stopped um blabbits. We stopped endorse. I think she was on her nose in as well, which she also stopped. Put her on. Uh Heido's telescope channel blocker, and then she, uh, she reliably, whereas metropolitan patches and likes to go for long walks with her husband uh taking their dogs out,

1099.38 -> YSM Fitkin Auditorium: and she's actually regained a complete quality of life and has no symptoms anymore.

1107.73 -> YSM Fitkin Auditorium: So in the second part, i'd like to go on and talk a little bit uh specifically about what we're doing in the Cap lab.

1121.32 -> YSM Fitkin Auditorium: So as you saw in the last um section when we're looking at coronary arteries in the Angiogram, there's a lot more um beneath the epipartial vessels. So uh, this is a corrosion cast from Dr. That um they published in uh an article on Microvascular Disease um in two thousand and seventeen uh. If you look past the epicordial vessels which are the largest vessels that we see on the surface of the heart,

1144.67 -> YSM Fitkin Auditorium: there's a rich network of uh arterials and uh microvascular vessels, and, in fact, most of the coronary resistance and profusion comes from the microvascular uh vessels

1157.8 -> YSM Fitkin Auditorium: coronary auto regulation of the body's ability to match coronary blood flow to oxygen. Demand depends on this microvascular network.

1166.46 -> YSM Fitkin Auditorium: The ability for the microvascular vessels and the epicordial vessels to respond to demand

1172.28 -> YSM Fitkin Auditorium: so vasodilation. And uh coronary uh profusion pressure are linked. So we have to have a balance between Vasa constriction and Bases dilation in order to optimize how much blood flow. We're getting.

1183.1 -> YSM Fitkin Auditorium: Any disorder of that system can lead to symptoms or people who have exertional intolerance

1190.24 -> YSM Fitkin Auditorium: even beyond um the uh, the anatomic level. If you look down to the cellular level

1196.5 -> YSM Fitkin Auditorium: uh, there's neural hormonal influences under theelium drive factors, mechanical factors um well stress and the metabolic influences, and the main ones that I want to talk about are acetal calling uh, which is a vase of dilator. Um when acting on the end of Theilian, but can be evasive. Constrictor and the V. Ask this with muscle, and then adenosine, which is a phase of dilator in the vascular smooth muscle.

1218.89 -> YSM Fitkin Auditorium: So in our Catholic protocol. What we do is we use two probe. So we use Adenosine

1223.87 -> YSM Fitkin Auditorium: to uh, look at, not into Billium dependent days of dilation. So we dilate to ask you this with muscle, and this is the the concept of fractional flow reserve. So we dilate the microbes through that with an exogenous compound with a dentistine,

1236.43 -> YSM Fitkin Auditorium: and then we're looking for a translational pressure, gradient with rational flow reserve.

1240.92 -> YSM Fitkin Auditorium: If we then go on and do a little bit more testing, like there more dilution, we can actually specifically localize uh the microvascular, and then come up with the index of micro circulatory resistance, and that whole circuit of the epic cardio vessel on the microvascular Uh bad is the coronary flow reserve

1259.26 -> YSM Fitkin Auditorium: on the other side, looking to endothelium dependent mechanisms for vasodilation acetylcholine binds to mushroomic receptors on the endothelium releasing nitric oxide. And then, uh, you should have base of dilation. In fact, most of our patients do have a vasiliatory response. But when there's some dysfunction of the endothelium,

1277.16 -> YSM Fitkin Auditorium: or a primary best of of muscle problem, you can get paradoxic or increase basal constriction to acetal

1287.07 -> YSM Fitkin Auditorium: So Practically what we do

1289.18 -> YSM Fitkin Auditorium: is if we have a patient with suspected this game of heart disease that comes to the cat lab

1293.39 -> YSM Fitkin Auditorium: almost universally. Now, if a patient gets referred to this indication, they get acetal calling testing. Then they get the guide while you're testing

1301.25 -> YSM Fitkin Auditorium: uh, and so uh with this protocol we can exclude um obstructive uh epic, cardio, coronary or disease, both anatomically and physiologically,

1310.09 -> YSM Fitkin Auditorium: we look at the end of billion dependent visa delegation um with uh acetal calling testing which gives us a really high resolution for epicardial basis, spasms, but also for microbes to the spasm as well. And then we um. We'll do a cornary flow, reserve uh and index of micro circulatory resistance to look at the microbes.

1331.16 -> YSM Fitkin Auditorium: I want to go over some technical considerations because this protocol that we do uh is a little bit different than other efforts that have been done in the past. So if you look at the Mayo Clinic, or Emory, or Cedar Sinai, who really pioneered a lot of this work.

1343.48 -> YSM Fitkin Auditorium: Most of these procedures have been done via bigger guiding. Catheter is usually the ephemeral access, and they're much more labor intensive than the corporate intensive. We we've been able to streamline this, so our access is almost always radial.

1355.94 -> YSM Fitkin Auditorium: We have very few ephemeral, and then really a minority of radio ephemeral transitions.

1361.86 -> YSM Fitkin Auditorium: We don't give radial visa dilators before we do this, which is different than other centers like Stanford

1368.5 -> YSM Fitkin Auditorium: guide catheter size matters. So there's some variability When we're doing these measurements. If we use small guide catheters uh most of our patients, we can get away with the six French if we use a smaller guide catheter, because we want to facilitate radial access,

1380.55 -> YSM Fitkin Auditorium: and then we can use other tools like a sheetless guide, which is really hydrophilic and able to get through most rate of arteries.

1387.95 -> YSM Fitkin Auditorium: Our procedure. Time is about fifty, six minutes for a physiology study, which is shorter than many of the prior reports,

1396.48 -> YSM Fitkin Auditorium: and it doesn't take a lot of contrast. And so this is a practical protocol that um should hopefully be uh scalable. These results. Um were uh presented as sky by Stephanie can recall who's one of our uh current interventional cardiology fellows,

1413.25 -> YSM Fitkin Auditorium: And then just a snapshot of what we found. So we our patients have um a fifty-three percent uh intermediate um b test probability of coronary or disease thirty one percent. We're low pretest probability, and then the balance um about fifteen or twenty percent or high pre-dest probability.

1429.28 -> YSM Fitkin Auditorium: If you look at the non-invasive testing almost all of our patients have had some sort of stress testing before they come to us.

1436.19 -> YSM Fitkin Auditorium: Of the people who have had stress testing twenty-three percent have had for fusion uh defects. And fifteen percent have that epg changes which really goes to show the low resolution for non-invasive functional imaging for people with inoga

1449.37 -> YSM Fitkin Auditorium: other sometimes have shown this. This is almost exactly similar to the data that's come out of Mayo Clinic and Stanford.

1459.04 -> YSM Fitkin Auditorium: And then our patients uh thirty-two percent have been diagnosed with microvascular dysfunction. Thirty-one percent with the basis fascinating.

1466.72 -> YSM Fitkin Auditorium: Thirteen percent have had a mix syndrome.

1469.55 -> YSM Fitkin Auditorium: Other is um other syndrome, such as uh myio cordial bridges or elevated resting flow and then normal micro-vascular function reflux, the history of what we've been doing where we were doing uh the guide wire part of this without doing a seed of calling, testing which we uh really initiated about two years ago.

1490.06 -> YSM Fitkin Auditorium: One of our most striking findings is that if you look at our entire cohort of patients, the time from the first Anna episode to diagnosis. The Median time is seventy-nine months,

1498.97 -> YSM Fitkin Auditorium: which really shows the work that we have to do. These are all patients taken care of in our health system,

1504.13 -> YSM Fitkin Auditorium: and it shows how hard it is to find a diagnosis.

1510.51 -> YSM Fitkin Auditorium: This is work that um Natasha cigar was here with us uh today. She's a medical resident has submitted to Acc. Looking at sex differences in our cohort. So the majority of the patients that we've tested are uh female twenty-nine percent are male.

1523.63 -> YSM Fitkin Auditorium: There's no um difference in the prevalence of each diagnostic phenotype which is important to recognize, because uh, we have this misconception that these are um disorders of women only. Um. But these uh these diagnoses occur both in uh males and emails uh, at least in our cohort with equal problems.

1542.2 -> YSM Fitkin Auditorium: We haven't seen any significant procedural differences in type of access or our ability to put a six French guide,

1548.66 -> YSM Fitkin Auditorium: and then we see lower rates of medical therapy. Uh in a female patients. So um male patients will come to us often on aspirin on beta blockers and android Henson receptor blockers or race inhibitors, whereas uh female patients are much less likely to be on medical therapy at the time of uh referral for their engineer.

1570.65 -> YSM Fitkin Auditorium: So um! Whether this testing is uh experimental or investigation, or whether this is guideline uh recommended care so as of um december of two thousand and twenty-one. Uh, with the latest chest pain. Guidelines. Uh: we now have an Acc. A. J. Guideline recommendation for guide where um based testing or invasive coronary function testing to improve diagnoses in these patients.

1591.68 -> YSM Fitkin Auditorium: This follows on the two thousand and nineteen Esp. Connect coronary syndrome guidelines, which also had a guideline recommendation for invasive functional testing and patients with uh suspected Anoga, or just being without a clear answer.

1604.54 -> YSM Fitkin Auditorium: I also want to add that in the two thousand and twenty-one uh a chest pain guidelines uh the term atypical testing um has been removed, and now it's been replaced with possibly cardiac testing. So the three types of chustain or engineer would be a typical engineer, possibly Cardiac and Jenna, or a non cardiac.

1628.68 -> YSM Fitkin Auditorium: The whole point of doing diagnostic testing is to guide therapy. And so this patient was, or this uh study was presented by Colin Barry at Grand Rounds about a year ago, so the Cor mica trial out of the Uk

1640.9 -> YSM Fitkin Auditorium: was a randomized trials, gratified medical therapy based on invasive uh physiologic testing.

1647.12 -> YSM Fitkin Auditorium: They took one hundred and fifty-one patients with an engine and no obstructive quartery, artery, disease, They underwent a physiology assessment with a protocol that's similar to ours.

1654.8 -> YSM Fitkin Auditorium: One hundred and seventy-five were randomized disclosure of the result, and the other seventy-five were blinded in terms, of the patient and the provider to the result. So all of these patients underwent the same testing, and the intervention was whether the results were disclosed. One hundred and fifty

1669.34 -> YSM Fitkin Auditorium: medical therapy was stratified, based on the diagnosis. So in the um first group, where the result was disclosed. Uh, it was a a conf confirmed diagnosis, and in the second group where the result Wasn't disclosed it was a suspected diagnosis.

1685.13 -> YSM Fitkin Auditorium: They looked at um Santa Cruz and quality of life. So um I wanted to start at the bottom of the baseline. So the Seattle and the questionnaire uh score of fifty um is really low. So if you look at Ischemia. They sorted at seventy, and they got them up to eighty with both the inv invasive of the Conservative arms.

1702.36 -> YSM Fitkin Auditorium: Uh, and so starting off at fifty, really shows that this was a very symptomatic population.

1707.14 -> YSM Fitkin Auditorium: The intervention for disclosing the results of the physiology study guides medical therapy, and you get a significant improvement in the Seattle engine. The question here, and this magnitude change is really um beyond anything that we've seen in this population, or even with the destructive coronary artery, disease, and the same finding is true for quality of life,

1724.99 -> YSM Fitkin Auditorium: and this is variable at least out to twelve months, and they're expanding this now with a much larger study.

1731.4 -> YSM Fitkin Auditorium: Our patients have said this to us as well, and so you know, One of the most rewarding things that I do is that I get to hear back from these patients when they finally get a diagnosis. And so you can imagine, if patients have been suffering from symptoms for seventy-nine months when they finally get on appropriate medical therapy and find symptom relief.

1749.65 -> YSM Fitkin Auditorium: They uh they like to share that,

1761.85 -> YSM Fitkin Auditorium: but there's still some work to do. So uh medical therapy is uh It's still kind of in its intensity for this, because we're just understanding these disorders. So uh, this is work from our show. Gopar was a medical resident also submitted to acc this year. So uh post procedure, medical therapy changes were recommended in eighty-nine percent of our patients that underwent testing

1782 -> YSM Fitkin Auditorium: if you look at ninety days, twenty percent or not on uh, recommended medical therapy regiments,

1788.42 -> YSM Fitkin Auditorium: and then it uh again, within that ninety days thirty either discontinue or change their medical, their every regiments.

1795.41 -> YSM Fitkin Auditorium: So, in order to better guide medical therapy, we need to know which phenotypes for creating, and we need to understand um the path of physiology of each of those phenotypes.

1807.74 -> YSM Fitkin Auditorium: So now, in the third part of this, I just want to talk about our current research efforts, and then introduce um the discover an oca multi-center registry.

1822.69 -> YSM Fitkin Auditorium: So uh I want to talk uh about expanding this paradigm of isemic heart disease so we focus so much on obstructive coronary artery disease uh as an interventional cardiologist, This is what I trained to look for. Uh, but what we found is that there's a much bigger world of isemic heart disease, including microvascular dysfunction

1842.57 -> YSM Fitkin Auditorium: phase of spasm and then other disorders, such as mental stress, induced bio-partial schema biocardo bridging and elevated resting flow. And so, when patients present with anginal symptoms, we should look comprehensively and try to find the cause.

1860.1 -> YSM Fitkin Auditorium: First, we need to define the hazard. And so when patients tell us this uh on interviews I feared for my life, and it was paralyzing. I felt like no one was believing me, and I doubted myself. It tells us that we need to do better.

1872.74 -> YSM Fitkin Auditorium: This is work. That, uh, again is done by Mar. My Our medical student um follows on work that Leslie signed it um as a medical student uh two years ago, and then Helen Gove is a school of public health student who's also working on this project.

1884.4 -> YSM Fitkin Auditorium: This is how a patient sounds We're like, uh uh heart attack to me at the time. Yeah, so um chest, pain, and uh difficulty breathing. And uh, yeah, I felt like I was dying. So I went to Yah! That's how it started,

1905.73 -> YSM Fitkin Auditorium: and these aren't just a few anecdotes.

1907.97 -> YSM Fitkin Auditorium: We've seen more than a hundred patients like this. They went to the er. They felt like they were dying, and we tell them sorry there's nothing wrong,

1916.01 -> YSM Fitkin Auditorium: so we need to move the needle. So what we're doing in one part of this is that we're interviewing all of our patients

1923.32 -> YSM Fitkin Auditorium: with a structured interview.

1925.09 -> YSM Fitkin Auditorium: We're coding the transcripts to identify common themes,

1928.55 -> YSM Fitkin Auditorium: and then we want to understand what our past come with, uh, and so either through publications Um. And getting these reports out there, or developing a new patient reported outcome measure. Uh, there's a lot of work to be done in terms of understanding symptoms.

1942.92 -> YSM Fitkin Auditorium: What about the hard outcomes. This is the part that, uh, you know, I think the hardest group to convince of the value of this type of testing is interventional cardiologists, because we say that obstructive corn, your artery disease must have the highest hazard but if you look

1956.99 -> YSM Fitkin Auditorium: uh, this is a meta-analysis that's um actively being done by Natalia. O'donovich is one of our recent graduates from our interventional cardiology. Um program. She's really put an exhaustive amount of work into this meta analysis of thirteen thousand patients really encompassing every study, both invasive and non-invasive that's been done in this area.

1976.31 -> YSM Fitkin Auditorium: If you look at the incidence of adverse events uh So Mace at five years is uh twelve percent

1984.1 -> YSM Fitkin Auditorium: hospitalization for um cardiovascular causes, twelve percent heart failure, twelve percent. And so

1991.45 -> YSM Fitkin Auditorium: over, follow up periods of five years or even greater. These patients are afflicted both with symptoms and hard outcomes.

2001.83 -> YSM Fitkin Auditorium: And so, looking at this data,

2003.95 -> YSM Fitkin Auditorium: we're able to develop an agenda for the future and come up with new new studies. So, number one, we need to develop a standardized protocol that can be performed to other medical centers. If you look at work that's been done in this area in the past. They were. They were protocols that really couldn't be extrapolated to other places, and that's why this didn't catch on

2024.68 -> YSM Fitkin Auditorium: two. We need to prospectively define phenotypes using consensus definitions. So what maybe microvascular dysfunction to me may be different than what's microwave basket is function to Dr. Young or Dr. Sinusis one hundred and fifty,

2036.73 -> YSM Fitkin Auditorium: and then we need to define the prognosis. So we need to know short term and long term. What's the prognosis in terms of patient report of outcomes? And what's the prognosis in terms of hard outcomes? What should we tell our patients to expect

2048.139 -> YSM Fitkin Auditorium: And should we be surprised when they come back to the emergency department.

2054.949 -> YSM Fitkin Auditorium: So i'm really uh proud to. Uh, you know, present the discover. And Okay, um multi-center registry which we just launched.

2062.55 -> YSM Fitkin Auditorium: So uh this is uh a ten cent multi-center registry that's being run um with Dr. Lansky as my co-princible investigator

2072.07 -> YSM Fitkin Auditorium: we have three goals with this. So number one. We want to describe the prevalence of specific physiologic phenotypes for patients who come to the cat lab um with chast pain, or is a a concern for the scheme of heart disease. But Don't have obstructive coronary order disease

2085.67 -> YSM Fitkin Auditorium: number two. We want to define the burden of obstructive coronary artery, disease, or sorry, not obstructive at those fluorosis, both and geographically, and by inter vascular imaging, which is something that has not been done in this population,

2097.72 -> YSM Fitkin Auditorium: and then number three we want. We want to characterize the natural history and the outcomes of patient. So we want to follow them for a long time. We want to do a serial assessment with patiently reported outcome measures, and then we want to characterize the hard uh outcomes for the prognosis.

2114.89 -> YSM Fitkin Auditorium: So there's a lot of data going into this. And so uh, we have a um, a patient interview at the beginning. We have patient reported outcome measures that are repeated at six months. Thirty days uh it's six months, one year uh, and then annually. For five years

2129.56 -> YSM Fitkin Auditorium: we have a ton of anatomic data. We have the angograms which are read by a core lab.

2134.43 -> YSM Fitkin Auditorium: We have intravascular imaging or optical coherence Tomography, that uh imaging of these vessels that are uh, angiographically, often right as normal. Um also being read by corelab. And then we'll get to see what the cloud black composition is,

2146.84 -> YSM Fitkin Auditorium: and then we'll have busy logic pina types uh following what I've shown uh and the prior sections, and so we'll be able to uh take these patients as a group and help inform what their outlooks are going to be

2162.01 -> YSM Fitkin Auditorium: the study team. Uh. So Dr. Lansky and I work with the all part of asking the research group which has been tremendous in making this a reality.

2169.3 -> We have ten enrolling sites,

2171.36 -> YSM Fitkin Auditorium: and then we have an executive committee with experts from around the world. Many of the people who did some of the foundational work in this field uh really helping to inform our protocol and making sure that we have a consensus.

2186.18 -> YSM Fitkin Auditorium: So uh, our target enrollment is five hundred uh participants at two years um, or at ten sites over two years.

2194.22 -> YSM Fitkin Auditorium: The assessment is a quarter of an angiogram and all patients. They have to have non-instructive disease, either anatomically with less than a seventy percent angiographic stenosis or physiologically so a fractional fluores or or a non hypothetical ratio that's non-eschemic.

2209.54 -> YSM Fitkin Auditorium: All the patients will get acetal calling provocation ordinary physiology and intercournary imaging

2218.2 -> YSM Fitkin Auditorium: so patients will have a baseline uh battery of patient reported outcome measures,

2222.36 -> YSM Fitkin Auditorium: but looking at Seattle and the question here, quality of life.

2225.95 -> YSM Fitkin Auditorium: Um. Phq. Eight for depression, and then the generalized anxiety sort of questionnaire.

2231.13 -> YSM Fitkin Auditorium: And then they'll be followed up. Uh for five years. Um, with repeats of these um issue reported outcome measures, and then we have a call center that actually reaches out to the patients um to find out if any new events occur.

2244.61 -> YSM Fitkin Auditorium: Our primary endpoint is major adverse, cardiovascular events, and we have a number of secondary endpoints as well.

2253.87 -> YSM Fitkin Auditorium: So we're including uh any patient that's male or non-pregnant female greater than eighteen years

2259.4 -> YSM Fitkin Auditorium: Patients who have a suspected ischemic heart disease who are referred to undergo clinically indicated corner and geography,

2265.29 -> YSM Fitkin Auditorium: and then the obstructive quarter of your disease Um, as I previously described.

2274.56 -> YSM Fitkin Auditorium: So um

2276.05 -> YSM Fitkin Auditorium: really uh happy to announce that we've been uh enrolled our first four patients. Um, hopefully uh, we'll have number five in tomorrow.

2286.83 -> YSM Fitkin Auditorium: So in conclusion,

2290.58 -> YSM Fitkin Auditorium: number one, we've had tremendous technological advances really over the last seventy years. If you think about one Corey and geography, for it started in one thousand nine hundred and fifty eight,

2299.34 -> YSM Fitkin Auditorium: we can now uh expand the yield of invasion and geography. We can incorporate physiology in real time, and it's a protocol that can be done almost to any center,

2309.82 -> YSM Fitkin Auditorium: and more than fifty percent of people who are referred to the cardiac C. Lab. This came in Heart disease may refer to to a process that doesn't include atroscalatic epic cardio obstruction,

2319.11 -> YSM Fitkin Auditorium: but may include a physiologic problem like bases, spas, and microbes. That is function or another syndrome.

2325.29 -> YSM Fitkin Auditorium: We're just beginning to understand the prognostic value of invasive physiology testing.

2330.04 -> YSM Fitkin Auditorium: And as we do this, we'll have a better understanding of medical therapy, and we'll be able to improve patient care and improve our outcomes.

2339.79 -> YSM Fitkin Auditorium: Uh, it's been a a ton of people that have helped um over really about six years, making this a reality. And so uh, too many people to to thank out loud my family. Um! Who you know their support, makes all of this possible

2354.64 -> YSM Fitkin Auditorium: uh, and the really incredible uh support from our own section the all cardiovascular research group,

2362.95 -> YSM Fitkin Auditorium: countless number of trainees who help with this work, and then I've really been um lucky to have great funding that's made this possible.

2370.74 -> YSM Fitkin Auditorium: So i'll stop there and take any questions. Thank you.

2388.17 -> We talked about this uh

2405.6 -> um.

2407.76 -> So

2409.31 -> yeah,

2411.61 -> you can be

2415.71 -> that. Why,

2419.58 -> uh

2421.25 -> that the

2423.93 -> YSM Fitkin Auditorium: part of our

2429.65 -> under that

2434.75 -> you have a

2438.25 -> that?

2439.16 -> These are.

2446.69 -> YSM Fitkin Auditorium: Yeah, that's a So it's a really um that questions on the No. So when we think about primary physiology, you're exactly right. So some of our patients present with Angela. But you wonder things like not a scheme of cardiomyopathy. Things like, are familiar with preserved injection. Fraction. What the disorder uh is that's causing that?

2463.6 -> YSM Fitkin Auditorium: So? Uh, John Blair at the University of Chicago is actually look specifically at half, and and patients with have path we're hospitalized with heartfelt. Your symptoms um are. Have a higher microbes to the resistance when they referred, friend geography than people who don't.

2476.47 -> YSM Fitkin Auditorium: And this, you know, i'm trying to get away from this term of microvascular disease, because it's really dysfunction. It can happen in any disease state. Uh, if you look at people with allegraft uh vasculop of the after a heart transplant the first um first place, that they have uh allegravascular, but

2493.74 -> YSM Fitkin Auditorium: and so we have tools that if that's the clinical question we can actually look at that. So anybody who's going to come down to the Cath lab and get an angogram.

2501.17 -> YSM Fitkin Auditorium: We should do this testing because there's a lot to learn, so it may help guide their he path management. If we also understand that they have microbes through this function. Um, At the same time

2533.35 -> mhm

2547.96 -> YSM Fitkin Auditorium: I haven't gone back and looked uh if you, I would say about half or have afterwards fluorosis. It's not uncommon to see through this in these patients. And then there's cases where we're pulled, You know the uh fourth discover and occupation that we enrolled had an led that looked like it had a thirty percent angiographic stenosis.

2564.88 -> YSM Fitkin Auditorium: Uh. But after giving her a sedal call and she has spasm at that site um which also goes with azure sclerosis, and then the end of the old. This function but once you give her nitrogen, it completely dilates, and it looks like a normal lesson.

2575.56 -> YSM Fitkin Auditorium: Um! On this you actually do see a mild amount of pl there. And so that's why I think the intravascular imaging in this cohort of five hundred patients, is really going to inform how prevalent at those fluorosis is, because I think it's it's either under appreciated um, and probably worse than than we think it is.

2597.27 -> Rachel Lampert: Hi, do you guys hear me?

2601.6 -> Rachel Lampert: Um! So maybe I missed the denominator. But I was really struck by one graph that you showed where there was a sixteen, only sixteen percent were normal. So i'm wondering like, Ha! Like, what about people that just have costochondritis, or you know, Gestritis, some people must have truly non cardiac, not non cardiac non coronary chess discomfort. So how are you getting such a high uh percentage

2624.87 -> Rachel Lampert: of uh positives.

2626.89 -> YSM Fitkin Auditorium: Thanks, Dr. Laper. So you have to look at the patients who are referred. So, uh, are actually our number of normal primary physiology. Patients uh is about the same as Korea, which is about fifteen percent

2638.54 -> YSM Fitkin Auditorium: Um, And so i'm seeing patients will get referred after having a number of Angstroms, a number of stress tests and extensive workup, and then they get sent in. And so we're not catching people early in their um presentations. And so the numbers are going to be skewed towards patients who really have something that's giving them persistent symptoms

2656.04 -> YSM Fitkin Auditorium: whereas many of those patients with uh non-party chess pain will either have improvement in their symptoms or kind of move on and find a a different cause. And so we're. We're only really seeing the refractory patients. At this point. Some of the people that we've tested have come in on their first

2670.64 -> YSM Fitkin Auditorium: presentation, but overwhelmingly the majority of people have had some sort of work up before they reach us.

2680.68 -> That's a great topic.

2688.95 -> So uh,

2694.84 -> this is obviously

2701.07 -> it started to tease out

2703.61 -> the first case there

2712.19 -> very confused quarter.

2716.17 -> Or is it

2719.62 -> to ask you this,

2722.13 -> and then

2732.34 -> i'm sure that

2733.93 -> see

2739.92 -> but

2742.89 -> experience in terms of

2744.86 -> so large.

2748.7 -> And what are your

2753.11 -> specific?

2759.02 -> YSM Fitkin Auditorium: Yeah. So i'll start with the the second question first. So uh, you know, the the whole uh concept of discover and okay

2768.41 -> YSM Fitkin Auditorium: is to be kind of this engine to allow us to do therapeutic trials. So, first defining what the patient reported outcome hazard and the hard outcome hazard is, and then, now, having a mechanism where we can have a standardized protocol at multiple sites, um and all patients, and then follow them, allows us to insert a therapy into this very easily, where we could essentially randomize people to either placebo or a therapeutic, and then have this the same follow up with a baseline cohort, and forming

2796.48 -> YSM Fitkin Auditorium: um the hazard without therapy,

2799.44 -> YSM Fitkin Auditorium: and then the first question, So what do we learn in terms of therapy? So a lot of the medical therapy that we use is based on um for mica or other uh data that's come out of Mayo clinic.

2809.92 -> YSM Fitkin Auditorium: I've learned that there's a lot of work that we have to do to understand therapy. I can't tell you why some patients respond. Better to calcium tunnel blockers when they have basis, spasm, but others don't um. I've learned that long acting nitrates barely work for any of these patients, and so I very rarely use them.

2825.92 -> YSM Fitkin Auditorium: Um! I learned this very humbling lesson in the beginning of this from Dr. Spats where uh I actually um was an acetal calling dialist. I I didn't think we had a lot to gain by adding that to our protocol, and So we were just doing guidewear-based testing. And I said, You know, once you rule out microbes for the disease the rest doesn't really matter. You can essentially say that it's phase of and recreate them for it empirically. But um, adding that component to it, and having a full um full protocol where we actually give a diagnosis is really informed.

2854.5 -> YSM Fitkin Auditorium: Um! What we're finding, and the you know. I wish I could make a therapeutic recommendation, but every single patient is different. Um. And so what I tell patients uh post procedure is Um!

2866.75 -> YSM Fitkin Auditorium: It's going to take a try or to. Sometimes we get it right on the first try, but sometimes it takes a couple of tries, and you know the overwhelming majority of patients. We get feeling better. Uh, but it does take some trial on there

2877.24 -> YSM Fitkin Auditorium: the highest risk. Patients so patients universally will ask this after their procedure. They'll say, what's my outlook? Am I going to die from this? And so in our cohort nobody has died of a party basket. The cause of the patients we've tested, but that's really a short follow up period, and it's a small sample,

2893.24 -> YSM Fitkin Auditorium: so we don't really know. Um. There is a mortality hazard, but all of these phenotypes, but i'm not sure what the cause of death is whether it's heart failure um from microvascular or dysfunction, or whether it's basis spas, and causing a card cardiac arrest. I don't think we have that level of precision, yet to understand what which risk factors lead to to bad outcomes.

2913.19 -> YSM Fitkin Auditorium: We also Don't understand why, for example, the second case, I showed that patient who's otherwise, uh, you know fairly medically well, had a high sensitivity proponent of four hundred, whereas the first case, who had it, you know, an equal burden of spasm only had a high sensitivity proponent of about one hundred.

2928.22 -> YSM Fitkin Auditorium: And so why do people have more necrosis? Um, in some cases compared to others, especially when they have a symptom onset somewhere in the middle of their life. Um!

2937.55 -> YSM Fitkin Auditorium: Why, all of a sudden, are they now presenting with such significant disease? We really don't understand it. Uh. And so the first step is kind of understanding the phenotypes. Then we can go back and try to find out which patients suffer the most.

2951.81 -> YSM Fitkin Auditorium: Dr. Uh, I think that this is at a stand up the first time.

2970.88 -> That's it,

2971.97 -> whether you can systematically apply those things.

2978.47 -> And so

3009.54 -> YSM Fitkin Auditorium: So the the first question, Um! And I think there's a chat comment. So i'll just repeat the question. So it was about the technical challenges and things like contrast uh causing Hyperemia the

3019.74 -> YSM Fitkin Auditorium: There's a misconception about fractional flow. Reserve that it's a a binary test. You put the wire down and it fits out a number, and then that tells you um whether your result is a scheme, if or not, or your vessels scheme it or not.

3032.13 -> YSM Fitkin Auditorium: There's a lot of data about best practices, about the technical um considerations. And so uh, you know, Dr. Pal and I talk about this all the time. That uh, you have to be really careful with the way that uh, these numbers are interpreted. And so we try to follow all these best practices. So number one. Um, I say that i'm an expert in saline flushing because I flush uh contrast and blood out of the guide continuously because it can affect um these numbers. It can affect your epicardial pressure gradient.

3057.9 -> YSM Fitkin Auditorium: And then for thermal evolution. We also want a study stream um of the same temperature uh, of sailing in the guide, and so paying attention to those things, making sure we don't have pressure dampening from our guide, um et cetera, and then checking for pressure wire drift at the end. We do that for our own program.

3074.24 -> YSM Fitkin Auditorium: All those are in the discover. I know the protocol, and then we actually have for the first time a physiology for lab where we're going to be able to go back and look to see how much variability there was uh in the pressure measurements, and whether people follow the best practices. The software actually captures each step that was performed. And so we can see, did people flush saline? Did they zero the temperature. Sensor. Um, Because this you know, the value of this is that people are doing it well, and being very meticulous about it once

3101.02 -> YSM Fitkin Auditorium: we get it out there, and other people are doing this protocol. Um! Who knows what data we're going to get?

3106.24 -> YSM Fitkin Auditorium: Um. Sorry. What was the

3109.01 -> YSM Fitkin Auditorium: That's all right. They're not. Yeah, So I I really wanted to put a slide about non-invasive testing. But I feel um very bashful about uh telling this group about non-invasive testing So Um, you know you've done a a ton of amazing work. That's um really uh complementary to the work that we do invasively.

3128.03 -> YSM Fitkin Auditorium: I see a number of outpatient uh that get referred for evaluation, and i'd say less than half of them end up going to the Cap Lab because we are able to utilize on invasive testing um, whether clinically it's a pet flow reserve. And then hopefully, we have other tools.

3140.51 -> YSM Fitkin Auditorium: Um, I think there's really a big role for anatomic imaging. So when you have patients with a remote pre test probability, you come with new symptoms and an atomic test like a corner of a cta like the discharge trial showed can be really useful for excluding obstructive quarterly disease. So then, if they end up going to the capabilities

3163.74 -> YSM Fitkin Auditorium: um getting these tests, and so. Um! Hopefully, there's more on the future. I actually had a Twitter exchange with the principal investigator of the discharge trial, asking if they had any sense of what caused the symptoms in that seventy-five percent of people who came with Anglo without structure, disease, and they had some.

3178.85 -> YSM Fitkin Auditorium: It. Was. It was above my head. That's why I can't really speak to it. But fractal analysis to look um for potential causes of of microvascular. This function,

3188.51 -> YSM Fitkin Auditorium: Um, Dr. Spats

3190.29 -> Yeah.

3206.24 -> For

3236.9 -> Yes,

3240.33 -> you

3247.51 -> Um.

3268.05 -> YSM Fitkin Auditorium: Yeah, that's a It's a great question. I wish we had some sort of not invasive testing that we could use clinically. I'll i'll defer to um allen attella, and uh John, about anything that's in the pipeline. I really don't know. Experimentally I will say the the one thing that we do have coming from our group is uh the patient reported. Um symptoms. So we'll be structured. Interviews and the qualitative studies that you're helping with. Um. We are uh trying to formally characterize symptoms. So then, hopefully, we'll have some discriminatory ability. So

3297.12 -> YSM Fitkin Auditorium: we'll say that the patient gives a a certain subset of symptoms. You know exertional and and shortness of breath.

3303.55 -> YSM Fitkin Auditorium: Um relative to, for example, rust Angela Um. Perhaps we can tell if somebody is more likely to have microbes get this function, or more likely to have visa spasm just from their symptoms. And then, once you add testing to that, maybe you can have another layer. So, for example,

3317.55 -> YSM Fitkin Auditorium: um add a pet flow reserve, and then uh eventually start to kind of chip away. So before they end up in the Cat Lab we can have some sense of what they have, and then really only take the refractory patients for the ones that we still don't have an answer for um for functional testing.

3350.69 -> See what?

3358.45 -> Okay

3360.92 -> YSM Fitkin Auditorium: Mit. Ctl: And I haven't seen it. Yeah, it would be really interesting to take the Vasel spas on patients. And then Yeah, Um, look specifically at that group. I will say it's a very motivated patient population. And so, if you have any ideas that many of these patients would be willing to to help inform science. One hundred and fifty.

3377.86 -> YSM Fitkin Auditorium: We're going to take a last minute or so for the online things. And i'm just trying to review if we've already addressed them. There's one along for Marty's out for about a Lvd. Being Echo wall thickness and discovering No.

3390.11 -> YSM Fitkin Auditorium: So um thanks, Dr. Slter. So uh we are recording an Edp. It's a at the registry, so we're not mandating uh that people dip into the ventricle, but if it is uh um performed during the catheterization. We are capturing it, and then we are capturing um for uh echo uh hypertrophy. But again not capturing the images, just capturing the report.

3413.82 -> YSM Fitkin Auditorium: Okay, uh, and then uh, so do. Yeah. So Dr. Sede? He asked about uh systemic issues. So um, you know, you wonder if patients often ask about cerebral microbes to the disease, and whether it correlates uh to cardiac microbes for the disease. We have a number of Mris that are red as small vessel disease. Uh, and we don't know if it's a systemic issue, but it's um an area that we're actively looking at,

3434.47 -> YSM Fitkin Auditorium: and then the familiar pattern. So um, I actually uh I There's so many patients who ask about this, and i'm glad that somebody asked this question. Um, whether they have a family history patients, and told stories about their grandmother's carrying um electricalistering pills for a diagnosis of Angela, but never undergoing any sort of um bypass surgery or intervention, never having a heart attack, but just carrying Nitro, another woman from the Uk. She's actually looking for a provider in the Uk, because her mother has the same symptoms that she has

3463.28 -> YSM Fitkin Auditorium: um, and she presented the visa spasm um, and so we don't know um, and it's not something that anybody has really looked at, and we now have this population where it'd be great to go back and look um either their genetics or their family um histories to see if there is a familiar predisposition.

3481.5 -> YSM Fitkin Auditorium: Uh thanks. So thanks so much for taking the time to walk through your program and all the great work uh, you know, and I I I really look forward to seeing everyone back here next week as well. We have a visiting speaker uh about discussing a poly pharmacy, polyter, polyfield, strategy, and managing cardiovascular diseases. Uh: from Bring women's, hospitals. So thanks again. Uh and uh, thanks, Everyone here.

3505.28 -> Thank you.