Spinal cord ischemia (SCI) is one of the most devastating complications following surgical or interventional treatment of thoracoabdominal aortic aneurysms (TAAA). It can occur immediately or delayed and it depends strongly on the extent of the TAAA that is being treated, with reports of up to 22% of patients with Crawford type II aneurysms being affected (1-4). A variety of—in some instances counterintuitive or even seemingly contradictory—concepts have been described to prevent SCI including intra- and perioperative cerebrospinal fluid drainage, preservation of an adequate mean arterial pressure, especially in relation to the patient’s preoperative arterial pressure, as well as generous systematic sacrifice and reimplantation of intercostal and lumbar arteries without motor evoked potential (MEP) or somatosensory evoked potential (SSEP) monitoring during surgical repair (3,5). It is well known that a staged repair significantly reduces SCI in TAAA repair (6,7).
Following extensive translational research on preventing SCI in the large animal lab by Dr. Griepp’s group under the lead of Dr. Etz in the late 2000s, the collateral network concept of spinal cord perfusion has been thoroughly investigated (8-12). This culminated in the introduction of the technique of Minimally Invasive Staged Segmental Artery Coil Embolization (MIS2ACE) to combine the advantages of an individualized, selective, staged approached with modern endovascular technologies (13). This Keynote Lecture presents the rationale of the PapaArtis trial (Paraplegia Prevention in Aortic Aneurysm Repair) by MIS2ACE. It is the largest publicly funded randomized controlled international multicenter trial in aortic aneurysm repair so far (14).
SCI in thoracoabdominal aortic repair
In 1986, Dr. Crawford introduced a classification, in which TAAA are divided into four groups depending on the extent of the aneurysm (1). This classification was modified by Dr. Safi in 1998 with an additional fifth group (2). It is well known that patients undergoing surgical repair for TAAA have significantly better survival compared to patients who are not treated surgically (15). Endovascular and open repair techniques show similar survival and rates of SCI; however, the choice of technique may depend on patients’ age and comorbidities (3). With either technique, SCI remains as the major concern. Pathophysiologically, an increase in intracranial pressure leads to decreased spinal cord perfusion pressure, resulting in SCI (5). As SCI does not only occur immediately after the intervention, but also in a delayed manner, a dynamic aspect in spinal cord perfusion can be assumed (16). In addition, it is well known that a staged approach reduces the risk of SCI significantly (6,7). This is based on improved arterial blood supply by a sophistically primed spinal cord collateral network, which—according to current concepts—can be ‘primed’ by arteriogenesis with the development of new arteries, transferring arterial blood from three major inflow sources to the paraspinal (and spinal) microcirculation. The presence of this collateral network led to the concept that a staged approach by preemptive segmental artery coil embolization may prevent SCI (11,12) through priming of the collateral network (by arteriogenesis).
The technique of MIS2ACE is described in another paper in this special issue of the Annals of Cardiothoracic Surgery. In brief, MIS2ACE is performed under local anesthesia with percutaneous access. Up to seven segmental artery pairs are occluded within one session, depending on the clinical symptoms of the patient during coil embolization. These symptoms may occur as transient back pain. Depending on the number of segmental arteries that need to be occluded, the coil embolization is repeated, with at least five days and a recommended three-week interval between sessions. Patient are closely monitored for the first 72 hours after the intervention to ensure they are maintaining an adequate blood pressure, which needs to be correlated with the preexisting blood pressure.
The “first in man” endovascular preconditioning of the spinal cord collateral network was performed in 2015 (17), followed by the first series of ischemic priming in patients undergoing endovascular TAAA repair (18).
As the MIS2ACE concept showed promising results, the PapaArtis trial was initiated, striving for ‘Level A’ evidence. The trial received funding from the European Union’s (EU) Horizon 2020 research and innovation programme under grant agreement No. 733203 and from the German Research Foundation under grant agreement ET 127/2-1. Until now, it is the largest publicly funded randomized controlled trial in aortic surgery. The trial has been registered with clincaltrials.gov (NCT03434314) and a detailed trial protocol was published in 2019 (14). Trial duration was initially set for five years with 500 participants and 31 recruiting centers in nine countries across Europe and the United States (Figure 1). The coronavirus disease (COVID) pandemic, however, led to a dramatic shortage in intensive care unit (ICU) capacity throughout Europe basically putting all major surgical trials on hold for two years. Following expert reviewer’s advice, the trial duration was therefore recently officially extended by the EU and the German Research Foundation. The trial pathway is depicted in Figure 2.
Patient preoperative data showed excellent representation of “real world” aneurysm extent data with 55% and 50% of stage II TAAA in the surgical and control arm, respectively. So far, no SCI has been reported during MIS2ACE procedures performed in this trial. Patients are assessed with detailed neurological investigations including the modified Rankin Scale-9Q (19), the Montreal Cognitive Assessment (MoCA) (20) and Barthel-Index (21). A first interim analysis is expected in the fourth quarter of 2023.
The PAPAartis trial is a prospective, randomized, multicenter international trial to assess the outcome of selective staged segmental artery coil embolization prior to open and endovascular TAAA repair to prevent SCI and ultimately permanent paraplegia. Initial results and experimental studies are promising and strongly suggest that with this concept, SCI can be significantly reduced in patients undergoing open or endovascular treatment for various thoracoabdominal aortic pathologies.
Conflicts of Interest: The authors have no conflicts of interest to declare.
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