Design, development and evaluation of a novel percutaneous Ascending Thoracic Aortic Graft (ATAG.
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There is a huge unmet clinical need for a new, safe and effective minimally invasive treatment for Acute Ascending Aortic Dissection (AAAD) (1). In 2012 AAAD has a mortality rate of 1-2% per hour within the first 24 hours, and even with contemporary surgical techniques, advanced intensive and post operative care, the mortality from AAAD following surgery in most series remains in the unacceptable range of 10-30% at 30 days (2;3). 28% of patients presenting with AAAD are denied life saving surgery often because of age or co-morbidity - medical therapy alone associated with an in hospital mortality rate in excess of 50% (2;4-6). Currently available endovascular stent grafts used in the descending thoracic and abdominal aorta are not adequately designed to be utilised within the ascending aorta. They have a large stowed diameter 22-25 French (F), with a rigid covering of either Dacron or ePTFE, and a stiff inflexible delivery system unlikely to traverse the aortic arch without complication. While the contemporary results of elective surgery for ascending thoracic aortic aneurysm (ATAA) are good, with an elective mortality of <5%, surgical results for AAAD have improved little over the last 20 years, with a 30 day mortality rate between 10-30% (3;7). With the emerging role of endovascular stent grafts in the treatment of thoracic aneurysm and dissection, with shorter hospital stays and improved outcomes I believe now is the time for the development of a percutaneous solution for AAAD. Potential ascending thoracic aortic graft (ATAG) designs must take into account the very close proximity of intimal tear to both the coronary arteries and aortic valve, allowing a 4 good proximal graft seal without compromising coronary flow or aortic valve competence. ATAG should have a low profile, with a thin non porous covering and a flexible delivery sheath with accurate and precise deployment characteristics. Following a literature review and novel anatomical data collection from computerised tomography (CT) and magnetic resonance imaging (MRI) scans of AAAD and ATAA patient cohorts, it seems that 3 embodiments of ATAG should be designed and developed, all sharing advanced core technologies including a laser-cut nitinol stent frame, thin polyurethane (PU) material covering and accurate and precise deployment mechanisms: 1) The “supra-coronary tubular ATAG”, for treating AAAD with an intimal tear in the ascending aorta, no coronary or aortic valve involvement and adequate landing zones above the coronary arteries and before the right brachiocephalic trunk (RBCT). It is likely that this graft will be capable of treating at least a third of all patients with AAAD (8). 2) The “inverted t-shirt ATAG” to proactively protect coronary artery flow and achieve proximal seal within the sinuses in patients with an intimal tear in close association or involving the coronary arteries. 3) The “valved ATAG” to treat patients who have significant aortic regurgitation (AR), to achieve a proximal seal at the annulus when anatomy suggests it would be difficult to achieve with embodiment 1) or 2), and in those patients who have a hugely dilated aortic root, so that the ATAG can seal proximally at a relatively normal annulus size, and seal distally at a normal ascending aorta diameter 5 proximal to the RBCT. This could be the treatment option for the 25-35% of AAAD patients who currently require aortic valve repair or replacement (9). The most complex of the 3 devices above is embodiment 2), the “inverted t-shirt ATAG”, as it must ensure proximal aortic seal within an often dilated sinus, without compromise to aortic valve and proactively protect both coronary arteries with 2 coronary sleeves. Basic proof of concept (PoC) of this embodiment has been demonstrated in vitro within a normal sized aortic glass model, with some important study limitations, nevertheless it does demonstrate that tracking an ATAG branched graft with 2 coronary sleeves is possible over 3 guidewires and deploying accurately within the aortic root under both direct vision and fluoroscopy. Following successful PoC deployment I then specified and had manufactured a 2nd Generation ATAG (2G ATAG), with a laser-cut nitinol frame, longitudinal tie bars, and a novel thin PU graft covering material. The 2G ATAG has been shown to have adequate radial strength when compared to competitor devices, and can be stowed to 28 F for deployment. During ATAG development 2 patents have been filed, and I wrote with Professor Rothman a successful NIHR I4I grant for £743,000 to take ATAG from the current 28 F 2G device, towards the goal of an 18 F device with bench testing, in vitro flow rig and deployment analysis, and in collaboration with the Royal Veterinary College (RVC) into an animal model over the next 3 years (beyond the scope of this thesis). I hope that within this next development cycle ATAG can be iterated into a device that might be ready to embark on a first in man (FIM) trial to offer the AAAD population an effective and less invasive treatment strategy.
AuthorsKeeble, Thomas Roger
- Theses