Thoracic endovascular aortic repair (TEVAR) is an effective therapy for various thoracic aortic pathologies, including aortic aneurysm, aortic dissection, and traumatic aortic transection, particularly in patients with a high operative risk (1, 2, 3, 4, 5). TEVAR has a short procedure time, a low complication rate, and a low hospital mortality compared to open surgery for repair of the thoracic aorta (5, 6, 7, 8, 9). However, it is difficult to perform TEVAR in patients with a short proximal stent graft landing zone (10, 11). Most companies that fabricate thoracic aortic stent grafts recommend their use in patients with a proximal landing zone of > 15 mm. When patients have a short proximal landing zone near the aortic arch, there is an high risk of endoleak, migration of the stent graft due to angulation of the aortic arch, and high blood pressure in the aorta (6, 9, 12). Thirty to fifty percent of cases with aortic aneurysm, aortic dissection, and traumatic aortic transection involve the aortic arch (13 ,14, 15, 16). Several branched aortic stent grafts and fenestrated aortic stent grafts for aortic arch disease have been reported, but these products have also not been made commercially available because of various problems (17, 18, 19, 20). Here, we developed a convenient fenestrated aortic arch stent graft (FASG) with a preloaded catheter for the supraaortic arch vessels, and performed a preclinical study to evaluate this FASG in swine.

Eleven pigs were successfully implanted with FASGs. The mean procedure time for the one and two FASG groups was 30.2 (27.9-34.5) min and 43.1 (39.2-53.7) min, respectively. Additionally, the mean time for the selection of the carotid artery was 4.8 (4.2-5.5) min and 6.2 (4.6-9.4) min, respectively (Table 1). Major adverse events such as death, cerebral ischemia, limb ischemia, organ infarction, paraplegia, serious infection, and vascular complications were not observed in the 11 pigs. Ten of the pigs survived the 8-week observational period. However, 1 pig with a one FASG died at 4 weeks after the CT examination; the death was likely related to the high dose of ketamine used for the CT examination. Vascular damage to the iliac artery, aorta, and carotid artery was not detected in any of the 11 pigs during the procedure (Table 1). Moreover, none of the pigs showed migration of the FASG. We were able to select the carotid arteries easily in all 11 pigs using the preloaded catheter and had no instances of selection failure for these carotid arteries. The FASG moved easily after the partial deployment for fitting the fenestrated side holes into the carotid arteries.

For both the one and two FASG groups (n=6 and n=5, respectively), no endoleaks, no retrograde type A aortic dissection, no disconnection of the stent grafts, and no occlusion of the stent grafts for the carotid arteries were observed in the CT findings at 4 weeks (Fig. 5). Autopsy was performed on 1 pig at 4 weeks. The remaining 10 pigs were sacrificed at 8 weeks for autopsy. No disconnection or tearing of the stent grafts, no fractures in the stent grafts, no retrograde type A aortic dissection, and no occlusion of the stent grafts for the carotid arteries were found in the postmortem gross findings (Fig. 6).

A short landing zone for an aortic arch pathology can be problematic in performing TEVAR. In response to this particular issue, a few doctors have developed fenestrated or branched stent grafts for aortic arch disease. Inoue et al. (17) developed a branched aortic stent graft for aortic arch disease and attempted to use it in the treatment of 15 patients with thoracic aortic aneurysms and aortic dissections. Single-branched and triple-branched stent grafts were used in 14 patients and 1 patient, respectively. In 2 patients, the single-branched stent graft did not pass through the 22F sheath used. In 1 patient, the right external iliac artery ruptured during the procedure. However, complete thrombosis of the aneurysm was achieved in 11 patients (73%). In terms of complications, 4 persistent leaks and 1 minor leak occurred. Cerebral infarction occurred in 1 patient, and abdominal aortic aneurysm rupture was reported for 1 patient. The branched stent graft of Inoue has not become commercially available because the stent graft has the large profile of 22-24 French, a long procedure time, a complicated procedure method, and the requirement for surgical exposure of the carotid and subclavian arteries (17). The free end of traction wire attached to tip of the branched stent graft was caught and pulled back by a gooseneck snare wire through the left subclavian artery, carotid, and innominate arteries to deploy the folded branch stent graft. This complicated procedure method resulted in a long procedure time. Our FASG has a small size, a short procedure time, and a simple procedure method. Moreover, the FASG has a size of 18 French, which is comparable to the 7-mm diameter of the iliac artery. Of note, no iliac artery perforations were observed in our study. The mean procedure time was dramatically shortened because our FASG had a preloaded catheter with a diameter of 1.14 mm inside the main delivery system to select the carotid, innominate, and subclavian arteries. This system reduced the procedural time and made the procedure method easy. However, the selection of the carotid and subclavian arteries in the diseased aorta of humans will be difficult because of angulation of the diseased aortic arch and the variable location of the carotid and subclavian arteries. Hence, we prepared 0.035 inch, 0.018 inch shapeable guidewires to enable easier selection of the carotid and subclavian arteries. Sometimes, a gooseneck snare inserted through the left brachial artery can be used to catch the preloading wire in patients with an angulated aortic arch. As such, we do not recommend the FASG in patients with a severely angulated aortic arch.

Wei et al. (20) developed a 3-part modular branched aortic stent graft and implanted it in canine models. However, this stent graft has not undergone a clinical study because of the long procedure time (320 min), complicated procedure method, and the need to surgically expose the carotid and subclavian arteries. Meanwhile, Yokoi et al. (21) developed a precurved fenestrated stent graft for aortic arch aneurysm and aortic dissection. This device made the fenestration site for the carotid artery subclavian artery in advance using 3D computed tomography. Yokoi et al. reported that 383 patients who required a stent graft in the aortic arch were treated with this precurved fenestrated stent graft. Technical and initial successes were achieved in 380 and 364 cases, respectively. The mean operative time was 161±76 min, and the mortality rate was 1.6% (21). However, this type of fenestrated stent graft has the risks of inaccurate deployment and stent graft migration, and the fenestrated site may be difficult to fit into the carotid artery accurately. Our FASG has a preloaded catheter, and the 0.035-inch guidewire can be placed into the carotid and subclavian arteries in advance. This wire can prevent migration of the FASG during deployment and can fit the branch of stent grafts to the carotid and subclavian arteries accurately. Further, the delivery sheath of the FASG was removed from the aorta, with the guidewires for the carotid arteries maintained in place, and the advanced branch of stent grafts were fit to the carotid and subclavian arteries respectively. We considered that a weak portion of the FASG might be connections of the main stent graft and the branch of stent grafts. The small gap between the 2 stent grafts could make an endoleak. Hence, the FASG was made with a side hole, 8 mm in diameter, and with a branch of stent graft oversized at 10 mm in diameter. Additionally, percutaneous transluminal balloons were inflated to create good connections between the main FASG and the stent grafts for the carotid arteries. No endoleaks were observed in the animal study. In the postmortem gross findings, the main body of the FASG and stent grafts for the carotid arteries adhered to the aorta and carotid arteries tightly.

Based on our findings, we have submitted an application for a Phase I clinical study to the Korea Food and Drug Administration, and we will perform a clinical study in the near future.

Our animal study has a few study limitations. In our animal study, we were unable to develop an aortic arch aneurysm model. To our knowledge, the development of this type of model is not possible. Hence, it was difficult to estimate precisely the occurrence of endoleaks for the connecting portion between the main stent graft and the branch of stent grafts. However, we did not detect any significant endoleaks.

Humans are anatomically different from pigs in several respects relevant to this study. Although pigs possess 2 carotid arteries that are uniform in size and located at regular intervals, the innominate, carotid, and left subclavian arteries are anatomically variable in humans. Therefore, we will be fabricating the FASG following a CT analysis of each patient. Moreover, the angulation of the aortic arch in pigs is different from that in humans. Hence, we prepared 0.035 inch, 0.018 inch shapeable guidewires to enable easier selection of the carotid and subclavian arteries. As such, we do not recommend the FASG in patients with a severely angulated aortic arch.

The FASG with the preloaded catheter for the carotid and subclavian arteries was developed for patients in whom the aortic pathology involves the aortic arch and only a short proximal landing zone is thereby available for the stent graft. In this study, we performed a preclinical study with this device in swine. The procedure with the FASG could be performed safely, had a short procedure time, and involved an easily performed technique. No endoleaks, no aortic dissections, and no disconnection, occlusion, or tearing of the stent grafts were found in the CT and postmortem gross findings. In conclusion, The FASG with the preloaded catheter developed here is comparatively safe and convenient in this preclinical study in swine.