Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair

MA3RS Study Investigators, David Newby, Rachael Forsythe, Olivia McBride, Jennifer Robson, Alex Vesey, Roderick Chalmers, Paul Burns, O James Garden, Scott Semple, Marc Dweck, Calum Gray, Tom MacGillivray, Chengjia Wang, Yolanda Georgia Koutraki, Neil Mitchard, Annette Cooper, Edwin van Beek, Graham McKillop, Weiyang Ho, Liz Fraser, Hayley Cuthbert, Peter Hoskins, Barry Doyle, Noel Conlisk, Wesley Stuart, Colin Berry, Giles Roditi, Laura Murdoch, Richard Holdsworth, Emma Scott, Lynsey Milne, Fiona Strachan, Fiona Wee, Katherine Oatey, Catriona Graham, Gordon Murray, Garry Milne, Marise Bucukoglu, Kirsteen Goodman, Jakub Kaczynski, Anoop Shah, Andrew Tambyraja, Julie Brittenden, Graeme Houston, Robert Lambie, John Norrie, MA3RS Study Investigators, David Newby, Rachael Forsythe, Olivia McBride, Jennifer Robson, Alex Vesey, Roderick Chalmers, Paul Burns, O James Garden, Scott Semple, Marc Dweck, Calum Gray, Tom MacGillivray, Chengjia Wang, Yolanda Georgia Koutraki, Neil Mitchard, Annette Cooper, Edwin van Beek, Graham McKillop, Weiyang Ho, Liz Fraser, Hayley Cuthbert, Peter Hoskins, Barry Doyle, Noel Conlisk, Wesley Stuart, Colin Berry, Giles Roditi, Laura Murdoch, Richard Holdsworth, Emma Scott, Lynsey Milne, Fiona Strachan, Fiona Wee, Katherine Oatey, Catriona Graham, Gordon Murray, Garry Milne, Marise Bucukoglu, Kirsteen Goodman, Jakub Kaczynski, Anoop Shah, Andrew Tambyraja, Julie Brittenden, Graeme Houston, Robert Lambie, John Norrie

Abstract

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.

Keywords: MRI; abdominal aortic aneurysm; repair; rupture.

© 2017 The Authors.

Figures

Figure 1.
Figure 1.
MRI of abdominal aortic aneurysm.A, T2-weighted HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) sequence in the sagittal plane. B, Cross-sectional image (dashed line in A) using a T2-weighted fat-saturated sequence to highlight intraluminal thrombus (white) within the aneurysm. C, T2* map (blue) overlying the T2-weighted HASTE sequence (B), demonstrating enhancement of the posterior aneurysm wall with ultrasmall superparamagnetic particles of iron oxide (USPIO) (red).
Figure 2.
Figure 2.
Consolidated Standards of Reporting Trials (CONSORT) diagram of participant recruitment.
Figure 3.
Figure 3.
Major clinical events in the MA3RS study. Abdominal aortic aneurysm rupture or repair (primary end point) (A), all-cause mortality (B), and aneurysm-related mortality (C) in participants with (red) and without (blue) ultrasmall superparamagnetic particles of iron oxide (USPIO) enhancement of the aneurysm wall. Cross-hairs represent individual censoring.

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