Successful redo open thoracoabdominal aortic aneurysm surgery in a patient with vascular Ehlers–Danlos syndrome: A case report

Abstract

We report a case of a 63-year-old woman diagnosed with vascular Ehlers–Danlos syndrome (vEDS) who survived two prophylactic surgeries for the dilatation of a thoracoabdominal aortic aneurysm. She initially developed acute type B aortic dissection at the age of 44 years. Five years later, her dissected descending aorta was enlarged to 54 mm; thus, the descending aorta was replaced as the first surgery. Fortunately, the intra- and post-operative courses were uneventful. Fourteen years post her first surgery, the dissected thoracoabdominal aorta distal to the graft expanded to 53 mm; however, no anastomotic leakage was observed. Genetic testing revealed a COL3A1 abnormality, confirming the diagnosis of vEDS. Thoracoabdominal aorta replacement using deep hypothermia circulatory arrest was performed because of the high risk of aortic aneurysm rupture. The second surgery was performed without complications, and no complications were observed 13 months post-surgery. The major reason for a successful surgery in this patient was the relatively low vascular fragility associated with vEDS. This case demonstrates that there may be considerable individual differences in vascular fragility in patients with vEDS. Thus, surgical repair, along with endovascular therapy, might still be a beneficial option for patients with vEDS having large aortic aneurysms and a high risk of rupture.

Learning objective

Prophylactic surgery for vascular lesions in Ehlers–Danlos syndrome (vEDS) is generally not recommended because of its high vascular fragility. However, if a patient with vEDS has an aortic aneurysm that is at a very high risk of rupture, aggressive treatment is a plausible option as there may be considerable individual differences in vascular fragility among patients with vEDS.

Introduction

Vascular Ehlers–Danlos syndrome (vEDS) is one of the 13 types of EDS. It is a rare disease caused primarily by COL3A1 mutations. vEDS is often complicated by vascular, uterine, and gastrointestinal tract lesions, of which vascular lesions are prognostic determinants of vEDS [1]. However, prophylactic surgery for vascular lesions in vEDS is generally not recommended because of high vascular fragility in patients with vEDS [2].

Here, we report the case of a patient with vEDS and a missense COL3A1 mutation who successfully underwent prophylactic surgery for thoracoabdominal aortic aneurysm.

Case report

A 63-year-old woman was admitted to our hospital for a thoracoabdominal aortic replacement. She had a history of two cesarian sections without complications and her son experienced a type A acute aortic dissection at the age of 34 years and died during the perioperative period. She developed an acute type B aortic dissection at the age of 44 years, which was managed at another hospital. Five years later, she was referred to our outpatient clinic for a dilated, dissected aortic aneurysm. Computed tomography (CT) showed that the diameter of the dissected descending thoracic aorta had expanded to 54 mm (Fig. 1A-1) and that the base of the superior mesenteric artery (SMA) was occluded because of an aortic dissection with a well-developed collateral arcade from the celiac artery (Fig. 1A-2).

Fig. 1.

(A-1) Computed tomography (CT) scan at the time of referral, 5 years after the development of type B aortic dissection, shows that the dissected descending thoracic aorta had expanded to 54 mm. (A-2) CT scan at the time of referral shows that the superior mesenteric artery base (triangle) had occluded owing to the aortic dissection with well-developed collateral arcade from the celiac artery. (B) Fourteen years post her first surgery, the dissected area distal to the graft had expanded to 53 mm. However, no anastomotic leakage was found. (C) Follow-up CT performed 14 days after the thoracoabdominal aorta replacement showed no complications. (D) Follow-up CT performed 13 months after the thoracoabdominal aorta replacement showed no anastomotic leakage.

When she was referred to our outpatient clinic, the doctors in charge did not strongly suspect connective tissue disorders and did not perform genetic testing for a definitive diagnosis. Therefore, the patient underwent descending thoracic aortic replacement with a 24-mm Haemashield graft (Maquet, Rastatt, Germany). Fortunately, the intra- and post-operative courses were uneventful (Table 1, left). After discharge, the patient was followed up at the outpatient clinic. During follow-up, her systolic blood pressure was well controlled at around 120 mmHg while taking 5 mg of amlodipine. CT scans were performed annually, revealing a gradual expansion of the dissected thoracoabdominal aorta distal to the graft. Fourteen years post-surgery, this segment had expanded to 53 mm; however, no anastomotic leakage was observed (Fig. 1B).

Table 1.

Details of surgical repair.

	1st surgery, 2008: Descending thoracic aorta replacement	2nd surgery, 2022: Re-do thoracoabdominal aorta replacement
Extracorporeal circulation method	Left heart bypass	Deep hypothermic circulatory arrest
Operation time (min)	296	629
Extracorporeal circulation time (min)	92	219
Aortic cross clamp time (min)	89	155
Circulatory arrest time (min)	0	26
Blood loss (mL)	1070	4033
Transfusion (mL)	1680	5600

When we first met her as an outpatient, we considered that she might have had a connective tissue disorder and performed genetic testing at another institute before the second surgery. Missense mutations in the COL3A1 gene (c.1826G > T, p.Gly609Val) were identified as pathogenic mutations, and the diagnosis of vEDS was confirmed. We explained to her and her family that an aortic aneurysm in a patient with vEDS has a much higher risk of rupture than that in patients without a genetic disorder, while the surgical repair for patients with vEDS generally poses high risk because blood vessels are too fragile for vascular suture. We added another explanation that the first surgery was performed without any complications. After obtaining consent for the surgery, we performed a repeat open thoracoabdominal aortic repair.

The surgical procedure is illustrated in Fig. 2. The patient underwent left eighth intercostal thoracotomy. Cardiopulmonary bypass was performed by arterial cannulation via the descending native aorta and venous drainage via the left femoral vein. The core temperature was cooled to 20 °C for a deep hypothermic circulatory arrest. The previous graft could not be clamped because of strong adhesions surrounding it. We then clamped the native descending aorta proximal to the cannulation site to the visceral and lower extremities, and retrograde cerebral circulation was initiated. The previous graft was trimmed and open proximal anastomosis was performed using a branched 22-mm Triplex (Terumo, Tokyo, Japan) graft (Fig. 2A). After the anastomosis, distal site of anastomosed Triplex was clamped, meaning that proximal perfusion was switched through the side branches of the Triplex graft. After stopping distal perfusion, the celiac trunk was perfused and the renal arteries were cooled. The SMA was occluded (as shown on the Fig. 1A-2). In a short open distal time, distal anastomosis of a four-branched 22-mm Gelweave (Terumo) graft to the abdominal aorta was performed using 4–0 polypropylene continuous sutures reinforced by interrupted horizontal mattress sutures with felt pledgets and fenestration on the intimal flap (Fig. 2B), which was our ordinary method and was used in the first surgery. Distal perfusion was restarted with the side branch of the Gelweave graft. Visceral arteries were button trimmed and connected to each of the branches of the Gelweave graft. Finally, the Triplex and Gelweave grafts were anastomosed (Fig. 2C). The aortic tissue was fragile and required much time to achieve hemostasis; however, we were able to complete the surgery without serious complications. The details of the second surgery are presented in Table 1 (right). Unfortunately, we could not obtain pathological specimens.

Fig. 2.

Surgical procedures in the second surgery – thoracoabdominal replacement. Anastomosis sites are A–C.

FV, femoral vein; CPB, cardiopulmonary bypass; SMA, superior mesenteric artery.

The patient was extubated on post-operative day (POD) 3, transferred from the intensive care unit to the general ward on POD 10, and discharged on POD 29. Although the evidence is insufficient, treatment with celiprolol, which has been shown to be effective for aortic events in vEDS [3], was initiated after the second surgery. Follow-up CT performed 14 days (Fig. 1C) and 13 months (Fig. 1D) after thoracoabdominal aortic replacement showed no complications such as anastomotic leakage.

Discussion

vEDS is a well-known hereditary connective tissue disorder, and vascular lesions are its prognostic determinants [1]. However, invasive therapy for vascular lesions in vEDS is generally not recommended because of high vascular fragility [2].

The Japanese Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection has no standard for preventive aortic surgery [4]. Previously, the prophylactic invasive treatment of vascular lesions in vEDS was avoided. However, this approach is gradually changing over time. Regarding open surgery, a successful series of surgical repairs for vascular lesions in vEDS has been reported [5,6]. In contrast, endovascular therapy is noninvasive and appears to be suitable for aortic and arterial lesions in vEDS. However, because of the fragility of the vessels, there is a risk of vascular injury caused by stent–grafts, and the accumulation of evidence for endovascular therapy is still insufficient compared to that for open surgery. There are both favorable [7] and unfavorable [8] opinions regarding the use of stent–grafts, which are currently under discussion. With advances in stent–grafts, their use in vEDS may increase even more.

In our case, prophylactic surgery prior to arterial rupture [6] and identification of the COL3A1 mutation prior to the second surgery [9] may have contributed to the successful surgical repair. Although there is a recommended method for vascular anastomosis in vEDS [10], we used the usual anastomosis method in the second surgery as well as in the first surgery. As in the first surgery, we used 4–0 polypropylene continuous sutures reinforced by interrupted horizontal mattress sutures with felt pledgets, resulting in no complications. Therefore, blood vessel anastomosis should not be considered a contributing factor to the success of our surgery. Finally, the most important reason for successful surgery was the relatively low vascular fragility of vEDS, which was proven by two open lateral thoracotomy surgeries without complications.

Vascular fragility generally depends on COL3A1 mutation patterns. Three patterns of COL3A1 mutations are known in patients with vEDS: nonsense, missense, and frameshift mutations. Nonsense mutations cause haploinsufficiency, resulting in the production of 50 % of normal type III procollagen. In contrast, missense and frameshift mutations result in the production of 10–15 % of normal type III procollagen, causing vascular fragility. The post-operative outcome of patients with nonsense mutations is known to be better than that of patients with missense mutations [9].

In this case, the patient's mutation pattern was missense, not nonsense. However, our results demonstrate that there may be considerable individual differences in patients with missense COL3A1 mutations. Her son developed type A acute aortic dissection at the age of 34 years, which was much younger than her age of onset, and his operation resulted in perioperative death. Thus, vascular fragility varies among individuals harboring the same genetic mutations. We conclude that surgical repair is not always impossible in all patients with vEDS.

If a patient with vEDS has a large thoracoabdominal aortic aneurysm with a very high risk of rupture, it would be difficult to save their life after aneurysm rupture, and surgical repair could be one of the options for treatment. In this case, we believe that a second surgery could be safely performed because the clinical course after the first surgery was very good.

Conclusion

This case demonstrates that there may be considerable individual differences in vascular fragility in patients with vEDS. Information on the genetic mutation type is a good predictor of vascular fragility but may not necessarily be correct. Therefore, if patients with vEDS have a large aortic aneurysm with a high risk of rupture, surgical repair along with endovascular therapy may be a beneficial option.

Consent statement

Written informed consent was obtained from the patient for the publication of this case report, including accompanying images.

Declaration of competing interest

The authors declare that there is no conflict of interest.