INTERVENTIONS ‘CRUCIAL’ FOLLOWING RESCUE OF PRIOR EVAR WITH PMEG

The findings of a recent study on reinterventions and sac dynamics after fenestrated endovascular aneurysm repair (FEVAR) with a physician-modified endograft (PMEG) for index aneurysm repair and following prior EVAR led researchers to conclude that “vigilant” surveillance and a low threshold for further interventions are “crucial” following PMEG for rescue of prior EVAR with loss of proximal seal.

NICHOLAS J. SWERDLOW, MD, A vascular surgery fellow at Beth Israel Deaconess Medical Center in Boston, shared these findings during yesterday morning’s Plenary Session 4 on behalf of senior author Marc L. Schermerhorn, MD, chief of vascular and endovascular surgery at Beth Israel Deaconess Medical Center, and colleagues.

Swerdlow et al note in their study abstract that, while the high frequency of reinterventions after FEVAR with a PMEG has been well-studied, the impact of prior EVAR on reinterventions and sac behaviour following these procedures remains unknown. In the present study, therefore, the researchers analyzed three-year rates of reinterventions and sac dynamics following PMEG for index

Patient Safety

aneurysm repair compared with PMEG for prior EVAR with loss of proximal seal.

The investigators analyzed 122 consecutive FEVARs with PMEGs at a tertiary care center that was submitted to the Food and Drug Administration (FDA) in support of an investigational device exemption (IDE) trial. They excluded patients with aortic dissection, type I–III thoracoabdominal aneurysms, non-elective procedures and prior aortic surgery other than EVAR, for a final cohort of 92 patients.

Patients were divided into those who underwent PMEG for index aneurysm repair (index-PMEG) and those who underwent PMEG for rescue of prior EVAR with loss of proximal seal (rescue-PMEG).

Novel drug candidate for slowing AAA growth demonstrates safety in humans

The local delivery of a glucose-derived compound in small- and medium-sized abdominal aortic aneurysms (AAAs) has been deemed safe, with “promising” early efficacy data indicating its potential in stabilising or slowing AAA sac growth.

According to Stephen Cheng, MBBS, MS, chair of the Department of Surgery at the University of Hong Kong, these first-inhuman study findings—which he will present today at VAM 2023 during Plenary session 6 (10–11 a.m.) in Potomac A/B—merit further evaluations within randomized controlled trials.

Swerdlow shared with the audience that, of the 92 patients included in the analysis, 55 (60%) underwent index-PMEG and 37 (40%) underwent rescue-PMEG. He added that rescue-PMEG patients were older—78 years (interquartile range [IQR] 75–83) vs. 73 years (69–78), p<0.001. Otherwise, there were no statistically significant differences in baseline demographics and procedural characteristics.

The presenter reported that perioperative mortality was 1.8% for index-PMEG and 2.7% for rescue-PMEG (p=0.8) and that, at three years, overall survival was 83% for index-PMEG and 72% for rescue-PMEG (p=0.08).

In addition, he noted that freedom from reintervention was significantly higher for index-PMEG than rescue-PMEG, specifically 79% vs. 45% at three years (p<0.001).

Swerdlow then shared sac dynamic findings. He revealed that, at three years following index-PMEG, aneurysm diameter was stable in 58% of patients and decreased in 42% of patients, with no cases of sac expansion.

At three years following rescue-PMEG, however, he noted that aneurysm diameter was stable in 31% of patients, decreased in 31% of patients and increased in 38% of patients (p=0.05).

The presenter stated in his conclusion that FEVAR with PMEGs for index aortic repair and rescue of prior EVAR with loss of proximal seal are “two distinctly different entities.” He summarized that, following FEVAR with a PMEG for index aneurysm repair, less than a quarter of patients had undergone reintervention at three years and sac expansion was “rare.”

“THE MAIN MESSAGE IS THAT THIS IS A GROUP of patients where, currently, there are no effective treatments to slow the growth of [abdominal aortic] aneurysms,” Cheng tells VS@VAM. “And, therefore, the idea of using a drug that is delivered only once inside the aneurysm sac sounds attractive— especially if it leaves nothing behind and all the future treatment options are left open.”

The multicenter study in question saw patients with an AAA (diameter <5.5cm) recruited to receive a one-time, local administration of 25ml of 1,2,3,4,6-pentagalloyl glucose (PGG) solution via transfemoral access. The study’s primary endpoints were technical success and safety—determined by the occurrence of major adverse events at 30 days. Cheng et al have reported a 100% rate of technical success, and found that the only safety-related concern was that four of the 21 enrolled patients showed a transient elevation of liver enzyme levels. However, these levels returned to normal within 30 days and triggered no clinical symptoms.

“When we talked to the pharma scientists, who are really looking at the molecular aspects of why these drugs work, the answer was that PGG is largely metabolized in the liver,” Cheng adds. “This is a way that the liver responds to any [raised level] of glucose in the metabolism pathway. That is the explanation that has been given to us, but we have seen no adverse effects in the patients. It will certainly be an area we will be closely monitoring as to how patients behave afterwards but, so far, they are all

At three years following PMEG rescue of prior EVAR with loss of proximal seal, however, it was observed that over half of patients had undergone reintervention and over a third had ongoing sac expansion, which led Swerdlow to underscore the importance of “vigilant” surveillance and a low threshold for further interventions in this group of patients.

Ahead of Swerdlow’s presentation, Schermerhorn shared some thoughts on the study findings with VS@VAM: “I have changed my practice now to reline the entire graft whenever I do a rescue PMEG. I believe that many of these patients have undetected type 3 endoleaks that lead to sac expansion and subsequent loss of the proximal seal.

“Extending the seal proximally fixes the 1a leak but does not address the original cause of sac expansion for the subgroup that had original expansion due to type 2 or 3 endoleak and we need to be alert to this possibility. I have now performed sacotomy on four patients for presumed type 2 endoleak with sac expansion (two of whom had prior rescue PMEG) and found fabric tears that were not detected by [computed tomography angiography], duplex, or angiography.” fine and the one patient who did have a very high enzyme level returned to normal in about a month’s time.”

With this being a first-in-human study, Cheng is quick to point out that any conclusions drawn from the results regarding efficacy of the PGG solution in slowing AAA growth are preliminary.

Nevertheless, as per their secondary endpoint of freedom from aneurysm sac enlargement, the researchers report average AAA diameter changes from baseline of 0.2mm, 1.1mm, 2mm and 0.8mm at six, 12, 24 and 36 months, respectively. Follow-up computed tomography angiography (CTA) data further indicated average volume changes of 2.5%, 9.6%, 24.3%, and 11.6%, respectively—and, at 12 months, none of the aneurysms had grown by more than 5mm in diameter, while only three had a volume growth >10%.

Prior studies have indicated that the average rate of AAA sac growth is around 3–3.5mm per year, according to Cheng. He states that this figure was used as a target in the present study, adding that the treatment threshold in Caucasians is an aneurysm diameter of 5.5cm and, “if we can slow the growth by 50% [to about 1.7mm], then we can push back the threshold for intervention from five years to 10 years, and that would bring expected benefits”.

“But, I must reiterate that this is a first-in-human study of a relatively small number of patients,” he adds. “The main focus was on patient safety rather than long-term aneurysm sac [growth].”