Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair
Authors:   The MARS Study Investigators, Newby David , Forsythe Rachael , McBride Olivia , Robson Jennifer , Vesey Alex , Chalmers Roderick , Burns Paul , Garden O James , Semple Scott , Dweck Marc , Gray Calum , MacGillivray Tom , Wang Chengjia , Koutraki Yolanda Georgia , Mitchard Neil , Cooper Annette , van Beek Edwin , McKillop Graham , Ho Weiyang , Fraser Liz , Cuthbert Hayley , Hoskins Peter , Doyle Barry , Conlisk Noel , Stuart Wesley , Berry Colin , Roditi Giles , Murdoch Laura , Holdsworth Richard , Scott Emma , Milne Lynsey , Strachan Fiona , Wee Fiona , Oatey Katherine , Graham Catriona , Murray Gordon , Milne Garry , Bucukoglu Marise , Goodman Kirsteen , Kaczynski Jakub , Shah Anoop , Tambyraja Andrew , Brittenden Julie , Houston Graeme , Lambie Robert , Norrie John 
Published: July 2017

Background:
Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes.

Methods
In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair.

Results

Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year,
P
=0.0424), although this was not independent of current smoking habit (
P
=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1–22.2;
P
=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%,
P
=0.1857) or repair (41.8% versus 32.5%,
P
=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (
P
=0.0275), all-cause mortality (
P
=0.0635), and aneurysm-related mortality (
P
=0.0590). Baseline abdominal aortic aneurysm diameter (
P
<0.0001) and current smoking habit (
P
=0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic, 0.7935–0.7936).

Conclusions
USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with abdominal aortic aneurysms and predicts the rate of aneurysm growth and clinical outcome. However, it does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors.

Clinical Trial Registration:

URL:
http://www.isrctn.com
. Unique identifier: ISRCTN76413758.