When and How to Treat Patients With Genetic Aortic Disorders by Endovascular Aortic Techniques

(Leipzig, Germany) January 31, 2020 -- Tilo Kölbel, MD (German Aortic Centre, University Heart Centre Hamburg, Germany) questions the dogma that rejects the use of endovascular treatment of connective tissue disorders, during a session on the latest techniques for endovascular repair of thoracoabdominal aneurysms and the management of aortic ruptured or infected aneurysms.

Connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome and Loeys-Dietz syndrome are associated with aortic aneurysmal disease that often first manifests at a young age. Marfan syndrome, for example, comes with cardiovascular manifestations including progressive dilatation of the aortic root, as well as descending thoracic and abdominal aortic dilatation.¹

Dr Kölbel explained that the traditional mainstay of open surgical repair for patients with genetic syndromes leading to thoracoabdominal disease is gradually giving way to endovascular repair in well-selected patients managed at experienced centers.

The reasons underpinning this shift are several, he explained. “Open thoracoabdominal surgery is a very invasive procedure, which carries a significant morbidity and mortality and is usually only feasible in very young and fit patients. But fewer and fewer surgeons are able to do this.

“Another disadvantage besides its invasiveness is the cost of this procedure, which comes from the significant intensive care that is needed by these patients, even though the implant is cheaper compared to [those of] modern endovascular techniques. Patients are also more frequently discharged to nursing homes and have ongoing disabilities related to that kind of surgery. Endovascular repair is associated with much less trauma.”

It is within the context of this shift away from open repair that certain traditionally held views about patients with genetic aortic syndromes deserve equal questioning, explained Dr Kölbel.

One such view is that these patients do not react well to endovascular grafts, because of the nature of their native vessels being less resistant to the radial forces that form the mechanism by which grafts achieve sealing. However, Dr Kölbel noted that such an issue is complex: different genetic aortic syndromes are more or less vulnerable to this phenomenon; in addition, other factors play a role, such as the location of the graft’s landing zones.

Another misconception surrounds the notion that such patients are young and fit and able to tolerate open surgery: “I would call this a dogma,” said Dr Kölbel. “Today they get to much older ages. And they also require treatment of aortic disease in the stage and age when they are no longer fit for open surgery.”

He cited as further dogmas the notions that patients with genetic aortic syndrome patients do not tolerate stent grafts in native landing zones, and that endovascular therapy cannot offer good long-term results.

“That is what everybody has been thinking for a long time,” Dr Kölbel said. “And these ideas are built on the very early experience, in which first generation devices were used in patients with genetic aortic syndrome without good technique, without good knowledge – with catastrophic results.”

Further detailing the experience of patients with genetic aortic syndromes today, Dr Kölbel explained: “The reality is that these patients are frequently older, and they very frequently have had multiple previous operations. Many of them are cardiopulmonarily compromised. These are not the young, fit patients the cardiac surgeon sees for the first time. So they may also benefit from less invasive repair.

“Open thoracoabdominal repair is not well tolerated by these patients, and they are often turned down for open repair. Even the surgeons that advocate open repair turn down a significant number of them, because they say they are not fit enough.”

He added, “Patients with genetic aortic syndromes also request minimally invasive treatment, because they have frequently had difficult experiences with open surgery.

“Even the experts, when they report their results, show that it has a significant mortality. And this is something that is very hard to sell, even to genetic syndrome patients. If you know one in five doesn’t wake up, this is not really good enough. And these are the ones that they think can tolerate open surgery. Michael Jacobs – one of the titans of open thoracoabdominal surgery – says the thoracoabdominal surgery in genetic patients has a high risk of mortality and morbidity, but that there is no other option. The last part is what I would like to challenge, because there frequently is another option for those patients.”

Dr Kölbel noted that, in his experience, patients can tolerate stent grafts well, even in native landing zones, under certain circumstances. “The landing zones are not all the same,” he explained. “For instance, a landing zone in zone 2 of the aortic arch is frequently well tolerated. If the landing zone is in a straight segment, it is also well tolerated. And I have seen a significant number of patients with good long-term results with endovascular therapy.”

He added that, in some patients where adequate landing zones are absent, additional surgical work can be necessary, such as debranching: “The reason we do this in the endovascular procedure is that we would otherwise need to land with the stent graft in a native vessel – but because we don’t like to do this in a patient with genetic aortic syndrome, we replace this vessel first with a surgical graft, and then we land in the replaced vessel. In that way, we can mitigate the risk of landing in native vessel.

Early data on the endovascular treatment of patients with genetic aortic syndromes was collectively analysed as part of a systematic review by Böckler et al (2017).² These data were based largely on patients who were treated before receiving their diagnosis of connective tissue disorder, as well as patients unfit for open repair. In Böckler et al (2017), the authors conclude that conservative therapy, monitoring and possibly also conventional surgical treatment should be considered standard in the management of these patients.² “In their meta-analysis, they found that the majority of patients needed conversion or died after endovascular repair,” commented Dr Kölbel. “One of the conclusions of the study is that they should not be treated endovascularly.

“But there are also publications that show good results of endovascular repair in genetic aortic syndrome patients. As such, we should not throw out the baby with the bathwater for these patients.”

Indeed, Clough et al (2017) report a retrospective study of patients with connective tissue disease who underwent thoracoabdominal or arch aneurysm repair using a fenestrated and/or branched endograft in a single, high-volume centre between 2004 and 2015. No early mortality or stroke occurred in this cohort, and mid-term follow up of a mean of 3.4 years was deemed favorable.³

Dr Kölbel also discussed data from his center in Hamburg, reported by Tsilimparis et al (2019). In this cohort of 54 patients who underwent branched arch procedures, five had connective tissue disorders. Within this subset, no deaths occurred (while overall in the cohort of 54 patients mortality was 6% [n=3]) and one patient had a stroke (in the overall cohort the stroke rate was 11% [n=6]) within 30 days.⁴

More recently acquired data is in preparation for publication, Dr Kölbel noted, of 30 patients treated endovascular in Hamburg over an eight-year period (2010–2018). The majority of these patients had Marfan syndrome (n=23), while others had Loeys-Dietz syndrome (n=5) or Ehlers-Danlos syndrome (n=2). “I don’t think anything like this has been reported, because we also did six complex procedures in those patients,” commented Dr Kölbel. “The types of disease treated where aneurysms and dissections, and a significant proportion of those were urgent treatments for rupture or symptoms.”

Summarizing the treatment strategy adopted in Hamburg, he continued, “We consider endovascular treatment as a first option in all genetic patients if it can be done without significant risks. We prefer endovascular treatment in all genetic patients when EVAR can be done by bridging graft-replaced aortic segments (landing with an endovascular graft in previously-grafted aorta is a safe thing to do, and the genetic patient is no different to any other patient in this case).

“Another conclusion is that zone 2 in the aortic arch, in my experience, seems to be a relatively stable landing zone in genetic patients, as we have not seen significant problems as long as we use non-bare stent devices. In contrast to other patients, the oversizing should probably be somewhat lower, and we should take even more care to land in straight aortic segments, because landing in curvature is dangerous due to the excessive forces in the outer curvature."

An important part of the recipe of successful endovascular treatment in genetic syndromes, he stressed, is a good patient selection, as well as knowing which devices work and do not work. He further emphasized that treatments of genetic aortic syndromes should be centralized to aortic centers that can offer these treatment options: “There is some necessary experience with these techniques too, and there are not too many centers that can offer that.”

He concluded: “There is no place for dogma in aortic surgery. Patients with genetic aortic syndromes should be offered contemporary, minimally invasive techniques when justifiable.”

References

1.         Cury M, Zeidan F, Lobato AC. Aortic disease in the young: genetic aneurysm syndromes, connective tissue disorders, and familial aortic aneurysms and dissections. Int J Vasc Med. 2013;2013:267215.

2.         Böckler D, Meisenbacher K, Peters AS, et al. Endovascular treatment of genetically linked aortic diseases. Gefasschirurgie. 2017;22(Suppl 1):1–7.

3.         Clough RE, Martin-Gonzalez T, Van Calster K, et al. Endovascular Repair of Thoracoabdominal and Arch Aneurysms in Patients with Connective Tissue Disease Using Branched and Fenestrated Devices. Ann Vasc Surg. 2017;44:158–63.

4.         Tsilimparis N, Detter C, Law Y, et al. Single-center experience with an inner branched arch endograft. J Vasc Surg. 2019;69(4):977–985.e1.