Fibromuscular Dysplasia (FMD) Registry: Transforming Rare Disease Research with Data

On this episode of Inside the Texas Heart Studio, Dr. Stephanie Coulter sits down with Dr. Daniella Kadian-Dodov, a vascular medicine specialist at Mount Sinai, to discuss Fibromuscular Dysplasia (FMD).

The conversation dives deeper than the typical presentation of FMD, which is often characterized by the "string-of-beads" appearance on angiography. Dr. Kadian-Dodov sheds light on the evolving understanding of this condition, including:

• How the phenotype of FMD has broadened to encompass a wider range of presentations beyond young women with hypertension.
• The association of FMD with other vascular diseases like SCAD (spontaneous coronary artery dissection) and aneurysms.
• The importance of registries like the IRAD Registry and the FMD Registry at Mount Sinai in improving our understanding and treatment of FMD.
• The challenges of obtaining long-term prognostic data due to the relatively young age of most FMD patients.

For more information on the FMD Registry visit texasheart.org/fmd

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🔗 Watch Dr. Kadian-Dodov’s Grand Rounds 

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Chapters

• 0:20 FMD Awareness
• 1:06 Dr. Daniella Kadian-Dodov's Entry to Vascular Medicine
• 2:46 The Growing Understanding of FMD
• 4:47 Fibromuscular Dysplasia (FMD) Registry
• 8:20 FMD Symptoms

Transcript

0:00

Good afternoon. I'm Stephanie Coulter from the Texas Heart Institute here to welcome Daniella Kadian Dodo, who is our grand round speaker today. Flew in from Mount Sinai, New York and gave us a lovely talk on fibromuscular dysplasia. And it's a topic that we here in the med center very interested in. And, um, I think that people think they're not gonna see patients with FMD and they will Absolutely. It's part of cardiology clinic today. I think that the awareness really because of people like you and your mentors have shined a light on a problem that's been with us really since the inception. But because it's primarily a disease of females, it's unfortunately been misunderstood at best and ignored at worst. And I'd like to know what made you interested in it and why were you interested in vascular medicine? Yeah, thank you for that. So I really fell into vascular medicine. I mean, there are not many centers that have a dedicated vascular medicine, um, person available to them. Um, when I was a resident, I came across, um, Dr. Jonathan Halperin as a, um, teaching attending, and he's vascular medicine trained prior to his cardiology training. Um, and he really took me in under his wing and then introduced me to my mentor and now senior partner Jeffrey Olin. Um, and so my initial plan was to do cardiology fellowship, um, with vascular medicine training beforehand. But I, I fell in love with vascular. I realized that this was a group of patients that were, um, in need. The area was not saturated, it was under saturated. Um, there was incredible opportunities for science and to make an impact. Um, and, uh, I wanted to be a part of that and there was enough cardiology involved with it that it kind of satisfied that piece for me. Um, and so it's been a great journey. It's been a Really cool journey. Well, we're so glad to have you here because, you know, we have a lot to learn and there's so many things that we don't know. In fact, I loved your slide because today I didn't realize that, you know, people that have, I knew it because I see it, but like that people with splenic artery aneurysms isolated, they have FMD, you know? Yeah. And when did, when has that changed? Because I don't think that that message is, is very well, you know, distributed. Yeah. Because, you know, I look for people with that. I look for median arcu at ligament syndrome and, um, and then I look for other evidence of FMD. Would you recommend anything else? Yeah, so I mean, I think the, the phenotype has really, the understanding of the phenotype has really expanded, right? So first we thought this was a disease of, you know, young women and it caused hypertension only. And then we realized, well, maybe, no, maybe it's also affecting the, the carotid arteries. And then, oh, look, there's this SCAD association with fibromuscular dysplasia, and now we're starting to pick up more of these patients as we go looking who perhaps don't have the characteristic multifocal or focal FMD lesions, but just have an aneurysm or just have a dissection. Mm-Hmm. Um, the way that I have started identifying them as possibly being on the spectrum mm-hmm, of FMD is either a family history of someone with FMD or aneurysms, dissections. They have to have negative genetic testing for any other cause of aneurysm or dissections. Um, but it's really in that way, on paper, they look like an FMD patient Mm-Hmm. In, in every other aspect. Right. And would you say that the pers the epidemiology of this, I mean, obviously we don't know what the true prevalence is Mm-hmm. Right. Um, but tell me how you guys came up with the registry and how is that impacting what we're now what we're learning? Yeah, so I have to, that goes credit goes to, um, my mentor and senior partner, Dr. Jeffrey Oland and his work with Pam Mace, who's the, the head Michigan founder of F-M-D-S-A. And Heather Gonick was heavily involved with that as well. Um, but I think they realized that in order to make strides in this as a quote unquote rare disease, um, registry type, uh, research is really great for that in terms of pooling data from multiple different areas so you can start to see associations. And so I think because of the IRAD registry being in Michigan, um, they looked to EMCOR for the FMD registry and true enough, we've learned a lot. We Have A lot about these patients. And really, how long has it been since the registry was established? It's Less 2007, 2008 was when it started. So We're at 15 years. Yeah. And you get a lot of attention because anybody that receives a diagnosis that's rare, FMD or scad, they end up on your website. Yep. And in fact, there's a Facebook, um, page where in fact that's where pri predominantly I was getting referrals and I had no idea. I mean, I asked people, how did you find out? Yeah.'cause yeah, I know something about it, but like what we all know is lacking. Yep. And what we are really lacking is prognostic data. Yeah, absolutely. And I think that's hopefully the next piece of data that's gonna come out of the registry now that it's been going for a number of years. But you're absolutely right. I mean, You need 30 years follow up. Totally. 'cause these, these people are in their forties, fifties, and you wanna follow them for the rest of their life so that you'll know what the true recurrent rates are. Yeah. But these people that are involved in the registry, they're very motivated. Yes. So there's some very good opportunities, so to speak. So tell me about the research that you were involved that you are now involved in at Mount Sinai. That's outside of the registry. Yeah, because I'm interested in that. Sure. So we're doing a clinical trial called the Define FMD trial. Um, this was funded by philanthropy, it's an investigator initiated. Um, we're the only site that's enrolling for this one. And we're recruiting patients with FMD patients with cervical artery dissection. Mm-Hmm. Patients with scad and then healthy controls that are age sex matched, race matched, Mm-Hmm. BMI and blood pressure medications, as well as the other number of blood pressure medications. Um, and from those participants we get a, um, punch skin biopsy where we can get skin fibroblasts Mm-Hmm. To get, um, RNA information as well as protein, um, signaling information and then blood for DNA. Um, and the goal is to try to identify differentially expressed genes, proteins, proteins, RNA, um, in these different groups, look for overlap Mm-Hmm. Since we know that there's definitely some clinical and genetic overlap between FMD, cervical artery Absolutely. Intersection and scad. Um, and hopefully identify the key drivers behind this disease. It's not gonna be one gene, it's definitely polygenic. Um, but figuring out that kind of hierarchy and, and what's at play to create a different experience for a different person, um, is ultimately what we hope to learn. And I'm assuming you're gonna follow them longitudinally. Yeah. Because then you'll have the DNA basis and then you'll have the clinical Yeah. And then you could look at predictors of Right. Recurrent events from that data. All of the FMD patients are also in the US registry. Perfect. So we are following, following them all prospectively, all the SCAD patients are also in the i a registry. Perfect. Um, so yeah, Definitely. How many are you looking to enroll Total? 600. Oh, that's huge. Yeah. We have actually 439 total involved. About two 60 or so, or FMD, scs, cervical artery dissection. The rest are controls. So if we find somebody we can send them to you. Absolutely. Okay. Cool. That's something we could do. Absolutely. That would be helpful. People love to participate. Yeah. This group is very motivated. They are, theyre Smart. I was just gonna say, you know, and I think some of it has to do with the fact of what you were alluding to before, that, you know, some of their symptoms can be very subtle or maybe not that impressive. Like postal tinnitus that they're told is no big deal for many years. Mm-Hmm. And there's often a delay to diagnosis. And so Mm-Hmm. Frequently they're very motivated to seek answers on their own. They go through the Facebook groups to identify centers of excellence. Um, so they are a very motivated group. So for a patient that may present with pulsatile, tinnitus, they, sometimes they will get to someone like you or me, but many times they, they seek help through their ENT. Yeah. And what's your experience been with that kind of an approach? Yeah, so that's tricky'cause they'll do the whole audiology workup and try to figure out if there's something going on in the inner ear. Um, the savvy ENT, we'll send them for carotid artery duplex. That's What I was ask, But that doesn't always happen. Right? It should. Yes. So for somebody that's had I, I saw a recent patient, um, actually kind of a friend who had, you know, symptoms of newish onset pulsitile tinnitus. And I scanned her CTA, you know, really above the, above the chest. And I got an echo. Yeah. Um, and was totally normal. And she'd really just recently started on a lot of magnesium. And maybe she was vasodilating and had an, I mean, I couldn't come up with another reason, but I, I just reassured her that at this point I, I can find nothing vascular. Yeah. And other, like, otherwise she was Well do you see people like That? Yeah, totally. It happens. And actually I experienced that Myself. Okay. I said to her, I've had it myself as well. Yeah. So if you get really dehydrated Yeah. And your heart's and you've, yeah. Okay. Cool. Okay. That makes me feel much more secure. Yeah. Thank you for that. And I did screen myself And I don't know, I did not, I did not, but, but I, because I figured I, I I feel fine. Yeah. Okay. I don't have a brewery. Um, and as a center of excellence,'cause clearly you're the center of excellence for which we will all be compared. Um, how busy is it for a clinic? I mean, how many patients a week do you see? We see a lot of FMD and dissections. Um, I would say that, and, and Dr. Oland's practice is almost exclusively dissection and FMD now I, I still see quite a bit of, you know, typical PAD and venous thromboembolism and vasculitis as well as FMD and dissection. Um, but I would say that we're probably seeing, um, I don't know, 20 patients a week if not more, with FMD and dissection and maybe about five to six of those or new patients. Mm-Hmm. Coming in to be screened Takes a lot of time. It's a lot. It's a lot. It's a lot. And yeah. And do you have the patients bring their imaging studies with them? We try. It's mandatory. Right. We tell them to send it ahead of time. Yeah. That's what we're trying to do as well. They don't always do that, but it's not always perfect. No, they don't always do that. So if they show up with imaging in hand or they don't have it, then we'll end up doing a telehealth follow up after we've had a chance to review The imaging. Okay. That's a really great idea. Yeah, I like that. Yeah. Okay. I wanna move on to, I'm gonna pick your brain. Okay. So as a vascular specialist, um, what do you think about tatsuo and what should we be doing as a research community for follow up on tatsuo? Because at the present time we are like, well, you had this kind of rare problem and you've healed, but people have recurrent Tao Mm-Hmm. Um, do we think it's related to anything in your spectrum? It Definitely could be. Could be. I mean, first thing I would be worried about is a missed dissection in a, particularly a wraparound LAD mm-Hmm. So I would go back and look really closely at the Imaging, at this imaging. Right. I'd look to see if there's any coronary, um, tortuosity Mm-Hmm. Because we tend to see that more often in dissection. It can be subtle. Um, the dissection can be subtle. Um, I would look for other signs and symptoms of FMD. Right. So pulse, tinnitus, migraine headaches. Mm-Hmm. Hypertension and family history. Mm-Hmm. Um, and, and look for a reason to screen that patient. Right. Basically. Cool. I'm wor I'm worried. Yeah. Because obviously, you know, it's in our wheelhouse for rare female diseases and um, and I don't, I don't wanna miss the opportunity, you know, to screen them, but you're not screening them head to toe for CTAs. We're not either. No, it's not indicated. No. It's a lot of Radiation not for everybody. Yeah, Exactly. And I love it that you have come to the conclusion that if on the onset of your diagnosis, if you are screened CTA head to toe and you don't have evidence of abnormality in your vasculature at the onset of ground zero for you Mm-Hmm. That, that you probably won't develop it. So then you do have some prognostic information to these people to give to people that these arteries look pretty good. Yeah. And we don't keep rescreening those arties sections. Yes. Yeah. So for the FMD patient, That's a big deal. Totally. Totally. I'm not sure that doctors out there know that and they, they're, you know, they're ordering tests that are unnecessary. Yeah. Yeah. I mean for the FMD patient, once they get a, that initial screening, we see where the disease is, if they have an aneurysm or dissection. Um, I, the experience has been that they don't develop new beads and new arteries over time. Mm-Hmm. Um, which is always a big question the patient has. Absolutely. Is this going to just Ert go everywhere to go Everywhere? Right. Totally repeat dissection is the main thing we worry about.'cause that can happen suddenly. And so that's why most of the lifestyle modification is focused on reducing stress on the arteries. Right. Any way we can, the one caveat to all that is when family, when they would like their children to be screened. Yes. And so we do do that sometimes even in absence of symptoms. But what I tell them is, you know, we don't know the mean age of diagnosis is 54, so if I screen your 18-year-old now and it's normal, doesn't mean it don't what that means. Right. So, Right. Do you think there's anything else that we should be telling patients that are at risk that they, do you think that they should be seen in the center of excellence? I think so. Yeah. I think if you are able to get there that there's definite benefit to it. I mean, you're gonna be seeing a group of physicians that are seeing higher than normal volume Right. Of these type of patients, um, that are equipped to provide you with very practical recommendations. Right. Of things you can avoid day to day to keep yourself healthy. Um, and that are gonna give you guideline directed and expert consensus kind of information on how to manage your disease. Plus you get to help move the field forward by participating in research. Yeah. I'm a big fan Of that. So I think it's a win all around. And even if it's to contact a center of excellence, send your data through and do a zoom Right. Or a teleconference. I'm good with that. Are you good with that? I am, yes. I'm good with with that. We can, if we can do it. Absolutely. Okay. Good. Daniella, thank you so much for coming to the Texas Heart Institute and we're so pleased that you could travel before Christmas to come and enlighten us all, but we were thrilled to have you and you guys all have a Merry Christmas and Happy New Year.