Vascular Surgery (Tsilimparis 2) 

Project description

Study rationale: Penetrating Aortic Ulcers (PAU) are typical focal lesions of the atherosclerotic aorta characterized by the erosion of the intima and elastic lamina with an outpouching shape. ^1,2 They are classified together with aortic dissections and intramural hematoma as acute aortic dissections, but differ from other conditions for the typical isolated pattern, specific complications and indication for treatment.^3,4 PAU are very often reported in the aortic arch and descending thoracic aorta, whereas the localization in the abdominal aorta is up to 30% and little is known on their natural history, treatment options and outcomes.^4,5

Study objectives: Indication and technique of treatment and outcome of infrarenal penetrating aortic ulcer (iPAU) is not frequently reported. Performing a multi-center single-arm pilot study with homogenous selection criteria and treatment protocols, with pooled-data collected, may lead to a better understanding of the indication and treatment options used for infrarenal penetrating aortic ulcers.

Study design and plan: The study will be a multi-centered, multi-national/national study conducted at seventeen investigational centers. The involved centers will provide their data collected on treatment of iPAU. This includes retrospective data collected since January 2018 until December 2022. The intended sample size is 300 patients, considering to equalize the most significant available number of includable patients published up to date in a retrospective analysis over three years, and estimating a mean number of 20 to 30 patients treated in each large vascular center. However, if more patients are available from the centers, we will include all available patients to increase precision.

Study participants: In this study all consecutive patients who underwent open or endovascular repair for infrarenal PAU will be included. The treatment options of interest are open surgical repair (OSR), endovascular repair with balloon expandable aortic stent-graft system (BeGraft Aortic Stent-Graft System/Bentley), covered endovascular reconstruction of aortic bifurcation (CERAB) and endovascular aortic repair (EVAR).

Primary endpoints: The primary combined endpoint is 1) Technical success: Technical success in endovascular treatment is defined as: Successful endovascular access and stent-graft deployment of all aorto-iliacal devices. No type I or III endoleak or target vessel occlusion/stenosis persistent at first control CT-angiography and/or contrast enhanced ultra-sound. Technical success in Open repair is defined as: Successful performance of planned proximal and distal anastomosis with exclusion of PAU. And 2) Safety: 30 day all-cause and aorta-related mortality, all cause and aorta-related re-intervention. 30 day major adverse events including myocardial infarction, renal failure, TIA/stroke, paraplegia.

Secondary endpoints: Follow-up all-cause and aorta-related mortality, all cause and aorta-related re-intervention.

Additional variables:

• Mesenteric events
• Respiratory events
• Other secondary outcomes: endo-procedural outcomes (duration of the procedure, total radiation used, contrast use, and fluoroscopy time); open repair outcomes (duration of operation, blood loss, autologeous re-transfusion, blood products); device failure
• iPAU evolution (evidence of shrinking (5mm), stabilization or progression (5mm))
• Endoleaks (at 30 days (first CTA) and during follow-up)
• Post-operative ruptures (30-day and during follow up)
• Endograft instability including: patency (primary, assisted, and secondary); device integrity; migration; vessel complications; disconnection/fracture
• Iliac artery patency
• Frequency of device deficiencies
• Access vessel complications
• Anastomotic and pseudo- aneurysm

• Incisional hernia

Data collection: This project is conducted as a retrospective observational study. Pre-, postoperative, procedural and follow up data will be collected, analyzed, and compared. All patients with an infrarenal penetrating aortic ulcer (PAU) are included in the study. All patients that underwent open or endovascular treatment due to an infrarenal PAU in the time between January 2018 and now that are treated, will be included in the study retrospectively and fully anonymized. No further information will be obtained other than the data in the patients’ records.

Statistics: The data will be analyzed and processed using SPSS version 26.0 (IBM Corp, Armonk, NY) for Mac Os. We will perform descriptive statistics as well as comparative analysis using univariate tests, such as Chi2 (Fisher’s exact test when appropriate) and student-t test (Mann-Whitney test when appropriate), and multivariate analysis using linear and logistic regressions, when appropriate to adjust for confounders. Time-to-event outcomes will be analyzed using Kaplan-Meyer curves and Log-Rank test, and cox-regression analysis will be used for multivariate analysis.Further subgroup/sensitivity analysis will be performed with the available data if appropriate and agreed upon between all centers.

Literature:

1. Oderich GS, Kärkkäinen JM, Reed NR, Tenorio ER, Sandri GA. Penetrating Aortic Ulcer and Intramural Hematoma. CardioVascular and Interventional Radiology 2019;42(3). Doi: 10.1007/s00270-018-2114-x.

2. Salim S, Locci R, Martin G, Gibbs R, Jenkins M, Hamady M, et al. Short- and long-term outcomes in isolated penetrating aortic ulcer disease. Journal of Vascular Surgery 2020;72(1). Doi: 10.1016/j.jvs.2019.09.039.

3. Ganaha F, Miller DC, Sugimoto K, Do YS, Minamiguchi H, Saito H, et al. Prognosis of Aortic Intramural Hematoma With and Without Penetrating Atherosclerotic Ulcer. Circulation 2002;106(3). Doi: 10.1161/01.CIR.0000022164.26075.5A.

4. Nathan DP, Boonn W, Lai E, Wang GJ, Desai N, Woo EY, et al. Presentation, complications, and natural history of penetrating atherosclerotic ulcer disease. Journal of Vascular Surgery 2012;55(1). Doi: 10.1016/j.jvs.2011.08.005.

5. Patel HJ, Williams DM, Upchurch GR, Dasika NL, Deeb GM. The challenge of associated intramural hematoma with endovascular repair for penetrating ulcers of the descending thoracic aorta. Journal of Vascular Surgery 2010;51(4). Doi: 10.1016/j.jvs.2009.11.050.