Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Massachusetts General Hospital, Boston, MA.
J Vasc Surg. 2023 Oct;78(4):929-935.e1. doi: 10.1016/j.jvs.2023.05.056. Epub 2023 Jun 15.
There is no proven therapy to reduce growth rates of small- to medium-sized abdominal aortic aneurysms (AAAs). Ex vivo and animal studies have demonstrated that a novel stabilizing agent, 1,2,3,4,6-pentagalloyl glucose (PGG), delivered locally to the aneurysm sac, can bind to elastin and collagen to re-establish strength and resist enzymatic degradation. We aimed to demonstrate that a one-time administration of PGG solution to the aneurysm wall is safe and potentially effective to slow the growth of small- to medium-sized AAAs.
Patients with small- to medium-sized infrarenal AAAs (maximum diameter <5.5 cm) were recruited. Via transfemoral access, a 14F or 16F dual-balloon delivery catheter was introduced into the aneurysm sac. A single, 3-minute, localized endoluminal infusion of PGG was delivered via a 'weeping' balloon to the aneurysm wall. Independent core laboratory measurements of maximum aneurysm sac diameter and sac volume measurements based on computed tomography angiography (CTA) were used for assessments at 1, 6, 12, 24, and 36 months. The primary endpoints were technical success and safety (major adverse events at 30 days). The secondary endpoint was growth stabilization, defined as freedom from aneurysm sac enlargement (diameter increase >5 mm per year or volume increase of >10% per year).
Twenty patients (19 male) were enrolled at five centers from May 2019 to June 2022 (mean age, 67.8 years; range, 50-87 years). All procedures were technically successful. The safety profile was consistent with standard interventional procedures. Four patients demonstrated transient elevations of liver enzymes levels that returned to normal by 30 days with no clinical symptoms. Through November 2022, follow-up CTA data is available on the first 11 patients. The average changes in maximum aneurysm diameter from baseline to 6, 12, 24, and 36 months were 0.2 mm, 1.1 mm, 1.2 mm, and 0.8 mm, respectively, and the average changes in volume were 2.0%, 9.6%, 18.1%, and 11.6%, respectively. At 12 months, none of the aneurysms showed growth >5.0 mm, and three had volume growth >10%.
The early results of this first-in-human, small cohort study demonstrated that a single, localized PGG administration to patients with small- to medium-sized infrarenal AAAs is safe. Longer term follow-up on all 20 treated patients is needed to better assess the potential impact on aneurysm growth.
目前尚无经证实的疗法可降低中小型腹主动脉瘤（AAA）的生长速度。离体和动物研究表明，一种新型稳定剂 1,2,3,4,6-五没食子酰葡萄糖（PGG）局部递送至动脉瘤囊内，可以与弹性蛋白和胶原蛋白结合，从而重新建立强度并抵抗酶降解。我们旨在证明单次给予 PGG 溶液至动脉瘤壁是安全的，并有可能减缓中小型 AAA 的生长。
招募患有中小型肾下 AAA（最大直径<5.5cm）的患者。通过经股动脉入路，将 14F 或 16F 双球囊输送导管引入动脉瘤囊内。通过“流泪”球囊将 PGG 单次、3 分钟的局部腔内输注递送至动脉瘤壁。使用独立的核心实验室测量最大动脉瘤囊直径和基于计算机断层血管造影（CTA）的囊体积测量值，分别在 1、6、12、24 和 36 个月时进行评估。主要终点是技术成功率和安全性（30 天内主要不良事件）。次要终点是生长稳定化，定义为无动脉瘤囊扩大（直径每年增加>5mm 或体积每年增加>10%）。
2019 年 5 月至 2022 年 6 月，在五个中心共纳入 20 名患者（19 名男性）（平均年龄 67.8 岁；范围 50-87 岁）。所有手术均技术成功。安全性与标准介入程序一致。四名患者的肝酶水平短暂升高，30 天内恢复正常，无临床症状。截至 2022 年 11 月，可获得前 11 名患者的首次 CTA 随访数据。从基线到 6、12、24 和 36 个月，最大动脉瘤直径的平均变化分别为 0.2mm、1.1mm、1.2mm 和 0.8mm，体积的平均变化分别为 2.0%、9.6%、18.1%和 11.6%。12 个月时，没有动脉瘤的生长超过 5.0mm，有三个动脉瘤的体积增长超过 10%。
这项首次人体、小队列研究的早期结果表明，单次局部给予 PGG 至患有中小型肾下 AAA 的患者是安全的。需要对所有 20 名接受治疗的患者进行更长时间的随访，以更好地评估其对动脉瘤生长的潜在影响。
