The SNMMI Podcast: A Heart-to-Heart on Women’s Cardiac Health

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Please read the full prescribing information for additional important safety information at visamil.com and in the show notes. Welcome to the SNMMI podcast. Get ready for a scintillating conversation. Hello and welcome to a special edition of the SNMI podcast for Heart Month, sponsored by the Cardiovascular Council. My name is James Thachry. I'm a Heisenberg professor of translational cardiovascular, molecular imaging at Hannaburg Medical School in Germany. Hi, everyone. Thank you for the invitation. My name is Thachry Gaeyegos. I'm an assistant professor of medicine at Yale University and I co-direct the Cardiac Emory Doses Program. Hi, everyone. I'm Rin Shetty. I'm an advanced multi-modality imaging cardiologist and director of the women's heart program here at the University of Louisville. Thank you for joining us. So I think it's an exciting time in the field of cardiovascular imaging. There's a lot of new developments emerging. And as a lot of changes in therapy have been developing, moving towards more personalized medicine, I think imaging really has a chance to be more directly involved in how clinical decisions are made. One example might be in cardiac amyloidosis where to familitis and imaging guided or imaging monitored therapy has really emerged. Yeah, I think that within that field, which is basically what I spend most of my time with, I think really, cardiac imaging has really enabled more accurate diagnosis, customized treatments. And not only that, also just the shift of invasive diagnosis to non-invasive diagnosis and then a prompt initiation of treatment. For the case of cardiac amyloidosis, you were mentioning the fact that we can have multi-parametric advanced imaging with different modalities and involve, you know, echo and MRI has been really unique. I think with the advent of bone centography now transitioning to cardiac amyloid radionucleid imaging really have resulted in earlier diagnosis and initiation of treatment. As, you know, these techniques continue to evolve, I think, we're kind of like shifting now from like, okay, we're getting where we probably like the diagnosis part, but also thinking about other things like progression of disease. Like, you know, now that we are able to treat these patients and I think it has been very unique and really like kind of what we're shifting towards, okay, we now we diagnose, now we're able to treat, now do we know if those treatments are working? Like what besides the patient having increased improvement in their mortality or their disease state, do we know if anything is happening at the, you know, molecular level that is actually more evident in objective ways, which the patient would love to have as in, you know, changes in echo is my ejection fraction improving and what is the impact of that clinically or in the case of MRI, you know, the change in ECV is, is it meaningful or is it just a change that we see in imaging does that translate to something clinical or even into are the treatments enough, right? Because I think the burden of answering that question will be in advance multi-modality imaging. Do you think that the bone avid tracers are sensitive enough to give you a meaningful readout to the response to a really specific anti anti-ATTR treatment? Probably not. I think we are shifting from the sense, the semi quantitative modality, which is what we typically have been using to diagnose as in trying to finesse the quantitative, you know, part of using SUV with spec CT and whatnot, but I don't think we're ready yet. And probably not necessarily the modality at this point to, you know, really derive a conclusion in terms of like progression of disease. Probably, you know, the answer will be with like either new tracers or the use of pet, like you mentioned, or, you know, even part of MRI were able, you know, to see there's a shift for example in parameters like, you know, ECV, for example. Is it this stage, DPD and the other bone avid tracers is more yes or no, not necessarily severity? Correct. And I think, I mean, still the case even with, you know, PYP as much as we like to put numbers for like the visual uptake and whatnot, I don't think we're there yet. And I think, I mean, in, in, even, you know, we talked about progression that, but with diagnosis, I do notice, you know, in my clinical practice too, that sometimes we get patients that come symptomatic. And, you know, the patterns are different. They're particularly when they're in the early disease, what the typical teaching of like diffuse uptake or, you know, very, you know, visual uptake of two to three is probably, you know, different in those patients with early disease. But obviously we're just starting to learn that because traditionally we've been diagnosing people that probably have had, you know, heart failure for years, not those patients that are starting with like very mildly elevated, anti-probe and P and very early disease in general. Right. So I think one of the other challenges in terms of personalized therapy works back towards another topic of interest to the cardiovascular council and to this group, which is in specific challenges within imaging in women's health, women's heart health. I think Marin, you add some, some points to make in that regard. Absolutely. I think this is such an important topic because we women traditionally, we've been disproportionately under diagnosed under treated because the traditional paradigm has always been around obstructive echocardial disease, but that's not often the biology that's driving symptoms in women. And I think cardiac peth has really been a game changer because now we're identifying more cases of the kind of more cases of my pro-vascular dysfunction. And yes, we can do that in the cardiac lab in an invasive sense, but cardiac peth has brought it to a wider audience in a non-invasive fashion where we go beyond just looking at echocardial disease. We can actually quantify and treat and then go back in quantifying and see if there's a response. So that to me is extremely exciting. And are there specific, certainly we look at the way that most patients with heart failure and after myocardial infarction are treated, it goes historically back to these large block blaster drug trials that were predominantly conducted in men of a specific background. Do you think that a larger exploration of women with cardiovascular disease changes the way that we can approach these types of treatments? Absolutely. I mean, something I always say is that women are not small men. Drug, that were created by men, for men, of course, work in men, but what about women, right? And I think that there's a general awareness in our community about that. And so there's a lot of effort and resources that are being pushed into trying to engulf women and also different ethnic groups because everybody doesn't respond the same. And I think that comes down to precision medicine again. There's no one answer for everybody. And I'd love to hear your thoughts James, when it comes to precision medicine in some fewer work that you do. Yeah. So in with regards to the differences between female and male, we see that from a preclinical standpoint as well within, even within mice. There traditionally a lot of research was also conducted just in male mice because of the protection involved in estrogen signaling that changes the way they respond to coronary artery occlusion or to transverse aortic constriction pressure overload heart failure. What we've done in our own lab is really tried to move towards doing both sexes with as much of our research as we can. certainly a difference in the inflammatory response after myocardial infarction between female mice and male mice, which mirrors exactly what you would see clinically. The inflammatory response in a female mouse is less profound, and that actually adds some level of cardioprotection. In a mouse after coronary artery occlusion, they can develop an acute response, which is left ventricle rupture, which does happen in patients, but not very often. It is really a kin uses the same mechanisms that are involved in infarction expansion. So as part of why you see smaller infarction in females, what we see in the mice is that if you interfere with the inflammatory pathway, more male mice will experience left ventricle rupture, so they would end up with much larger infarction. And less female mice die of the acute rupture. There is some kind of protection mechanism, which we don't fully understand, and that speaks towards what differences in how you would approach the treatment would affect the acute response and the acute outcomes within those animals, and within, as by extension, within the patient population. Which is interesting just like thinking about the whole estrogen history and HRT that, like for decades, it goes up and down as a positive negative and kind of like a little bit in a positive note. There's some very interesting studies in overreactimized mice where the female mice then look very similar to the way that the male mouse responds to the injury. So there is certainly something involving the estrogen receptor signaling that is just throwing things into a different loop. And that's a new layer of complexity to our statistical models for doing power studies for how many animals we need for an experiment. But it's definitely worth understanding in a little bit more clarity and a little bit less nuanced. I was almost wondering about whether you guys study postmanopausal mice, or even a thing in whether they're just on the same. It's tricky and mice because of the age problems. And that's actually another layer of complexity in mouse studies. Most of these studies are also based on pretty young mice. So you do most of these operations at 12 weeks of age, which is basically an old adolescent mouse. And that's not with none of the complications that you get in the clinical population. So some of that's changing. There's a lot more emphasis on bridging through large animal models and through pigs and through other translational models that give you more of the manifestations of clinical disease. But I think you still can learn a lot when you go into these mouse models, even in genetically identical mice. So these are inbred black six mice. They're all genetically the same. You still get a range of different infarct sizes when you operate them exactly the same way. There's still something going on on an individual basis where they see a different response based on the individual biology that some of the imaging techniques that were under development and are starting to emerge give you a clearer idea of what's going on in the early stage post infarction. Things looking at acute inflammation or looking at fibroblast activation as markers of early changes to the cardiac milieu that then contribute to the severity of the remodeling and are also intriguing therapeutic targets. Especially in complex or borderline cases, confidence matters. With the Amaloid Pet Tracer Visamil, clinicians are supported by GE Health Care's commitment to diagnostic excellence, offering reader training, peer-to-peer preparation, and reimbursement support services to help streamline adoption and interpretation. Learn to read Visamil at readvisamil.com. I was going to actually ask a question, you know, like how, you know, to change just because I find that, you know, it's super interesting. Like, has there been a role of M-I-B-G, for example, in kind of like tying all of this, particularly as, you know, the different endotypes for I know come. And no cover for particularly for women is our being steady. It's M-I-B-G's a tricky example because it is still really struggle to find a clinical foothold in regular or routine use, despite what is what ended up being published evidence of its value for kind of stratifying patient risk. The struggle has still been, which patients do we actually need to scan? The cutoff threshold is still pretty, reads off is very arbitrary, even though it is the 1.96 standard deviations off of normal. And the meaning, as I recall, it's kind of these intermediate phases or the intermediate range of the M-I-B-G heart to mediusdinal ratio that are the patients at the higher risk of, of at least to a ventricular arrhythmia are patients who are in this middle ground, which still is a little bit of a mystery. It probably has to do with heterogeneity would be my guess that you don't have, if you have no innervation, you're not getting any sympathetic drive into any specific component of the last ventricle, then you get a, you don't end up driving into the ventricle arrhythmia that you end up developing if it's signaling into one area of the left ventricle and not in another. But those are studies that need to be matched up to EP and are complex to kind of come around. The other challenge there is that the therapy that you're often dealing with is not like in inflammation and fibrosis. These are treatments that are readily available, not overly expensive, and are what these patients are all getting anyway. So the, I think the real benefit of imaging is when you start looking at much more novel and molecular-based therapies that are starting to emerge, immune therapies and immunomodular psory therapies, that may work in one patient and not work in another. With inflammation as the example in MI, you get a wide range of inflammatory responses across different patients in a fairly narrow time window after the initial, after the initial stemmy. And that probably dictates who would benefit from an anti-inflammatory, an aggressive anti-inflammatory approach. Some inflammation needs to still be there because it helps with the healing. But if you treat all patients the same way, like we were saying before, you probably lose the benefit. And it's probably why a lot of anti-inflammatory therapeutic trials were ultimately inconclusive because they were treating patients that were across this broad spectrum. But of those that actually have the profile that would benefit from that intervention. Yeah, super interesting. Like kind of stealing the, from the topic of women's health and how we use like pet imaging with, you know, micro-askar dysfunction or whatnot. You know, what have, do we know there's like development and understanding the different micro-askar dysfunction, for example, as it applies to cardiac amyloid doses. Like a lot of times I find like, you know, our patients come and we're like thinking, oh, you know, they're women, they have micro-askar dysfunction. Ultimately, you end up finding that the micro-askar dysfunction was not really just from like the traditional risk factors, but they have infiltrative heart disease. I don't know if you guys have, you know, experiencing both in the research or clinical realm to notice this changes because I often wonder to what extent the current treatments would affect or alter, you know, those parameters or the cause, the root cause of this micro-askar dysfunction and amyloid doses. You're absolutely right. We see micro-askar dysfunction also in other things such as hypertrophic cardiomyopathy. There's an association also with, you know, non-obstructural coronary artery disease. So you see it in a whole host of other diagnoses that now we're beginning to associate with it. Also, I know about itself, there are so many sub-tites, right? We want to look into things like tachysobo, CMD. So it's a very interesting evolving field. And I think as new tracers start to develop and start seeing wider spread application, when they touch a broader range of cardiovascular conditions and even outside of the cardiovascular space, the regulation of those compounds, the availability of those compounds changes, gets wider applicability, and that gives us the opportunity to explore it a little bit more effectively. So kind of ubiquitous markers, like inflammation, fibroblast activation have real potential to make inroads in cardiovascular disease because of their success in cancer imaging and to a lesser extent in other organs, which I think is really intriguing and provides us with also the possibility to look at how cardiovascular disease influences other organs. Certainly, crosstalk between heart and brain has been a focus of some of our research, but also into the kidney and into the liver, where being able to look outside of just the heart, there's also those opportunities. And having that kind of marker that is responding to multiple drugs or responding to multiple new therapeutics, even if it's not identical to the target of the therapeutic, I think you have a really meaningful outcome measure or response measure that you can then use to as a baseline to evaluate whether you're actually getting a efficacious response to the treatment. That I think it's just incredibly exciting where we've been, you know, I remember graduating from fellowship like six years ago and it's been like just this huge shift of how imaging has become important again, I think, in cardiology for all of those reasons. Actually, like no discussion about the cardiovascular system in advanced imaging right now would be incomplete without mentioning fluid period as because I think that's probably one of the most exciting frontiers, especially in nuclear medicine for us. Things that I'm looking forward to is increased access and more availability across the country. Fluid period as will let us do also potentially exercise and doing cardiac intensively because before we were on a limited to pharmacologic evaluation. What are your guys thoughts? Well, we at Yale recently started the flu period as program so everyone is incredibly excited and like the quality of imaging has been great. I think there's still, you know, things to get used to it, but I still remember when we started also our pet program years ago, it was kind of the same, I think just I think I echo your comment about availability even within our system. You know, it's not that pet is widely available. But sure, probably Europe is ahead of us and that. Yes, so we've been doing for piercers now for the last year or so and the image quality is really exquisite. Gives us a lot of opportunity to investigate mortar, more localized areas within the myocardium. And since the end of last year when we installed our total body camera in Hanover, we're also starting to look at how the cardiovascular or the cardiac perfusion relates to fufusion outside of the myocardium, which is very preliminary data at this point. But the stress response is as UC Davis is shown as well or not restricted to the myocardium obviously and seeing what changes in a cold press or test or in a pharmacological or exercise stress. I think it's going to be a really interesting, really interesting moving forward and certainly with flirpire desda makes that that easier. On a side note, we're also trying to implement it in mice, but that is a that is another interesting approach that is going to take a little bit of time to figure out some kinetics, but also very exciting. Yeah, I think my buddies at white trick here, Stephanie Thorn and Alzenooses are also looking into what interesting stuff they can find with the tracers. Well, I think we scratched the surface a little bit today about the prospects in cardiovascular imaging, how it crosses boundaries in terms of tracers and ideas that come out of oncology, out of brain and out of other areas. And really, I think what we've established is just how exciting the very near future should be with cardiac imaging and closing remarks. Ren, Cizia. Like you said, the future is bright. Hopefully we get to do justice to the women with advanced cardiac imaging. And I look forward to what the future brings. I think I echo your remarks. I think it's really truly exciting to be where we're at, particularly, you know, I find a lot of excitement in what we do in cardiac amylidosis specifically, but just in general. I think we probably deserve a second part of this podcast to continue chatting about all these advances and how they're expanding our understanding of diseases and our availability to provide, you know, different treatments and more personalized approach to patients. Absolutely. So, thank you both for being part of this and thank you to our listeners.