Melanie Cole, MS (Host): Welcome to UF Health Med EdCast with UF Health Shands Hospital. I'm Melanie Cole and today we have a panel for you with two physicians from the University of Florida College of Medicine. Today's discussion focuses on how the historical norms are being challenged for connective tissue disease patients in endovascular repair. Is it time to change the guidelines? In what circumstance is endovascular repair indicated?

 Joining me is Dr. Salvatore Scali. He's a Professor of Surgery in the Division of Vascular Surgery and Endovascular Therapy, and he's the Program Director of the Vascular Surgery Fellowship. And Dr. John Spratt, he's an Assistant Professor of Thoracic and Cardiovascular Surgery.

Doctors, thank you so much for joining us today. And Dr. Scali, I'd like to start with you. Can you just kind of set the stage for us and tell us the prevalence of patients with mixed connective tissue disease? What's going on? What have you seen in the trends?

Salvatore Scali, MD: Yeah, this is a great question just to sort of get everybody oriented to this problem. If you look at it a population base, it's quite rare. Marfan syndrome being, the most sort of common, genetic disorder that we often see treated. These patients has a population based prevalence of about one in 5,000 to one in 10,000 individuals, with the other disorders that we often see like vascular Ehlers Danlos syndrome or Lloyd's Dietz syndrome and other variants that we see are familial inherited thoracic aortopathies.

 They all have even more rare presentation. That being said, that's at a general population level. At aortic centers, because of the referral bias that you see, it's a higher proportion of patients that are seen in referral. And certainly for patients who present with dissection and or aneurysm, depending on certain risk factors and age, it's presentation, that prevalence can increase by certain patient subgroups, but overall, they are rare disorders.

Host: Well, thank you for that, Dr. Scali. So Dr. Spratt, current guidelines for treating aortic disease in patients with mixed connective tissue disease. How does that impact the choice of endovascular versus open repair? And do you believe the current guidelines are outdated? If so, tell us if you have evidence that supports a shift towards including endovascular repair as more of a standard option.

John R. Spratt, MD: Sure. So for years and years, the best way that we had to make decisions about who needed, aortic surgery was primarily based on the diameter of the aorta in patients with aortic aneurysms. And for a long time, that threshold diameter was about five and a half centimeters, especially in the aortic root in the ascending.

And in the descending aorta, that descending thoracoabdominal aorta, that number has actually been a little bit higher over time. However, as I think we as a field on both the cardiac and the vascular side have gotten better at taking care of these patients, and we've identified that many of these folks have issues at lower diameters than that, particularly aortic dissection, that threshold diameter has come down, and in the most recent guidelines for non connective tissue disease patients, that diameter is anywhere between 5 and 5.2 centimeters in size. And so for patients with connective tissue disease, usually a diameter of about 4 or 4.5 centimeters is used. And so, however, you know, the connective tissue disease patients tend to be younger and tend to overall be pretty good candidates for open surgery compared to many older people that have non connective tissue disease forms of aortic disease.

And so, because patients with connective tissue disease are thought to have subjectively worse sort of tissue quality from a handling perspective, and are more likely to have difficulty with things like retrograde type A dissection and maladaptive interactions between the endovascular devices and the dysmorphic tissue; it's thought that these patients benefit more from open surgery compared to endovascular approaches. However, we especially at UF, deal with a large population of patients with complex aortic disease and so many of these patients come back to us having had prior aortic surgery or otherwise present in such a way that they're not necessarily great candidates for open surgery, be it either for because they present as an emergent situation and maybe don't have time to do all the setup that would be required for a complex, say, thoracobdominal aneurysm repair, or if they've had, as I mentioned before, prior aortic intervention that can complicate an open procedure.

And so guidelines tend to be sort of a lagging indicator of the state of a field or a specialty. And guidelines, more importantly, are developed based on previously reported data and experience and so that necessarily means that before a new guideline document is issued, oftentimes that sort of non guideline therapy is being performed and new data is being generated.

And so, I don't know that it's necessarily the case that endovascular therapy should become guideline specified, first line therapy for connective tissue disease patients, but I certainly think it has an important role in the day to day care of these patients as we encounter them.

Host: Dr. Scali, as we're talking about the risks and the complications of endovascular repair compared to open surgical, where does the experience of the surgeon play into this? Because you and I had a discussion about students learning open versus endo, and Dr. Spratt just mentioned whether it was an emergent situation might change that discussion.

So tell us a little bit about the experience of the surgeon and where you see that playing a role in all of this discussion.

Salvatore Scali, MD: I couldn't emphasize how important it is to have a multidisciplinary approach both, with experienced providers who are well versed in the management of these patients. These are a heterogeneous, very complicated group of patients that present In a variety of different ways, whether it be elective or non elective, more often than not, there are referrals to the University of Florida as a major aortic center in the southeastern United States, and as Dr. Spratt well knows, we have a really, really wonderful collaboration between the vascular division and the thoracic and cardiovascular divisions where we use a shared decision making model and use the collective wisdom of the group that we've accumulated over many, many years of managing these patients.

We're all good stewards of the evidence base that's out there. And as Dr. Spratt highlighted, there's a really a paucity of evidence to suggest what is appropriate use for endovascular therapy. It's only more contemporaneously that we've sort of evolved, that literature base and Dr. Spratt's efforts with his primary research focus has really, really been on the forefront of this and sort of saying, when is it reasonable to consider these options in these high risk patients?

Because we know that endoluminal therapies have inherent risks, whether it be, how you access the vessels causing retrograde dissection, further aneurysmal degeneration that can occur. We know that distal stent graft reentry, tears can occur with patients with dissection pathology, particularly in those with fragile aortas like our CTD patients.

And so, it does require a lot of experience and wisdom and probably more than a single, individual provider to be able to come to a consensus decision because as is often the case in these emergent scenarios or redo operation scenarios, end of luminal therapies are increasingly being used certainly in our own practice here at UF, as either bridging strategies or strategies whereby we're trying to get patients past their acute episodes of pathology and maybe reduce the subsequent complexity of any proposed open operation. So making those decisions often requires differential skill sets. if I say I want to put in a stent, well, Dr. Spratt may have to deal with the downstream complications that I induce by that stent. So, we often need to consider these options together, knowing that what are the risks and benefits. And so it's a great question. And I think that's why I think most people would agree that these patients absolutely, when possible, should be managed at centers that are seeing these patients both electively and non electively in a more routine basis.

Host: Dr. Spratt, Dr. Scali just mentioned your research. So why don't you tell us about any recent studies on the outcomes of endovascular graft repair in this patient population. But while you're telling us that, speak a little bit about how that type of repair impacts patients' recovery times, quality of life, and overall satisfaction compared to open repair as you're telling us about these outcomes.

John R. Spratt, MD: So, we actually just had a paper accepted in the last couple of days to the journal Innovations, looking historically at our experience with endovascular repair in these connective tissue disease patients. And the series out there about this particular topic are not very large and our series was about 45 patients over the course of several years. And, the reasons why we looked at doing endovascular therapy in these folks, the most common reasons were either previous, them having undergone previous procedures or an urgent or emergent presentation, and those are two of the things that Dr. Scali had alluded to just a moment ago. And overall, the results were pretty good. We were able to see that the patients had a more than 80 or 85 percent freedom from what we call aorta related mortality in the near to intermediate term, about one to three years, post procedurally.

There was a fairly high rate of need for additional intervention later on, and that goes again with what both of us were saying earlier, about the interaction between the stents and the dysmorphic aortic tissue. Almost half of the patients required some kind of intervention, in the median time to that new intervention was about six months, which means sometimes it's shorter and sometimes it can be longer.

But overall, I think the most important role of these endovascular procedures is to help sort of get patients out of a pretty difficult situation that they may sometimes present in. Even if it just means getting a stent graft deployed quickly to treat an acute issue only to, have them come back later on, and then we can do a more formal repair in an elective planned fashion later, which would set them up better for the future.

But as far as recovery goes, open, especially surgery on the descending and thoracobdominal aorta is a very morbid procedure to undergo. It requires a large and fairly high left thoracotomy, which is a very painful incision because of the irritation to the intercostal nerves. It can also have lots of issues with pulmonary complications after surgery.

And then, there's difficulty in patients that have thoracoabdominal pathology, that incision has to be extended onto the abdomen, which also creates its own set of issues and, can be a lot for some patients to recover from. We've been fortunate because the connective tissue disease population, as I mentioned earlier, tends to be younger and usually a bit more fit for big operations like that, but still, it's nice not to have to expose patients to that level of morbidity if we're able to avoid it.

And so, just for comparison, a person that has an open descending or thoracoabdominal aortic repair typically will spend a minimum 5 or 6 days in the ICU and probably 10 days to 2 weeks in the hospital, assuming that everything goes perfectly. During that time, they have multiple chest tubes and central lines and things like that.

 They require a high degree of nursing care early on. Whereas a person that has, a straightforward endovascular repair, will have considerably fewer, I think, needs early on after surgery, tend to have less pain, they typically spend less time on the ventilator, and they're able to be up and moving around usually a bit sooner than the patients undergoing open procedures are as well.

And as far as the satisfaction part goes, you know, certainly I think patients are not interested in having big open operations if they're able to avoid it. And if they're able to get, a good result or at least one that will get them set up for better therapy in the future without having a big incision on their chest and abdomen. They're very happy to do so and we are obviously happy to provide that when possible.

Host: This is really an enlightening conversation, and I'd like to give you each a chance for a final thought here. And Dr. Scali, as we think about recent advancements in endovascular graft technology, how do you see that improving in the future? And how has that improved outcomes for this challenging population. What do you see happening as we go forward?

Salvatore Scali, MD: Obviously we have to work with our industry partners as well as our basic and translational researchers to better understand, because there's a lot of variation amongst the patients. And so I don't know that we'll have a one size fits all decision algorithm or necessarily a one size fits all endoluminal stent for that matter; that works for every patient with any given connective tissue disorder. We know that Marfan's patients are different than vascular Ehlers Danlos, for example. And so I don't know if we're going to have to have differential endographs that have differential properties to try to accommodate the different fragilities of the aorta.

That being said, we're going to have to develop smart graft technology because one of the things that's critical is getting feedback about the performance in vivo of the graft in real time and how it's behaving and interfacing with the patient's tissues. And so this will be on the forefront, not just for the CTD patients that we treat, but also all patients who get endoluminal strategies for aortopathies.

And so, this will sort of have to be at the forefront, the merger, if you will, between the genetics and the pathophysiology of the underlying disease and trying to merge that with the actual construct of the endoluminal graft so that they can be merged and married better.

Host: Dr. Spratt, last word to you. What are some of the key unanswered questions or areas? You do research and studies and you've spoken about those here with us today. What would you like the key takeaways to be for other providers today on the future regarding the use of endovascular graft repair in heritable aortic disease?

John R. Spratt, MD: I think the future isn't so much related to the development of new stent grafts with key properties. Although I do think that will be an important thing as time goes on, but I think the most important element in taking care of these patients, as Dr. Scali alluded to earlier, is a team based approach to how we take care of them.

One thing that certainly increases the utility and possibility of patients getting endovascular repair in the future, is if they have been set up in such a way by previous procedures. And so very commonly, the first aortic operation that a connective tissue disease patient will undergo is a procedure on the aortic root or replacement of the ascending aorta.

And during that time, when the chest is open and the patient is in a place to have a more advanced arch procedure done, we've become very aggressive about doing what's called arch debranching procedures, which allows us to essentially reconfigure the anatomy of the blood vessels coming off the top of the aortic arch, which feed the head and the arms, and reconnect them in such a way that it creates a long proximal landing zone for deployment of endovascular stents.

And so, if we have a patient referred to us, for instance, who has large root aneurysm and aortic valve disease, not only would we do something to address their aortic root, we can also debranch the arch at the same operation. And, as we create this long proximal landing zone for them, which should theoretically eliminate the risk of retrograde dissection; as technology improves regarding fenestrated endografts and branch devices, it may be possible that that open operation that the patients get first is the only open aortic operation that they have to have because the stent technology will continue to improve. And so I think the takeaway is that if folks are operating on connective tissue disease patients, especially, through the mediastinum, then I think one of the most important things to be thinking about is setting the patient up for the future, whether it's doing a full arch replacement or just debranching even one or two arch vessels to try and facilitate an endovascular approach later on.

Host: Thank you both so much for joining us today and sharing your incredible expertise for other providers. To learn more about this and other healthcare topics at UF Health Shands Hospital, please visit innovation.ufhealth.org. And to listen to more podcasts from our experts, you can always visit ufhealth.org/medmatters. That concludes today's episode of UF Health Med Ed Cast with UF Health Shands Hospital. I'm Melanie Cole. Thanks so much for joining us today.