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

The 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; Lyndsey Milne; Fiona Strachan; Fiona Wee; Katerine Oatey; Catriona Graham; Gordon Murray; Garry Milne; Marise Bucukoglu; Kirsteen Goodman; Jakub Kaczynski; Anoop S V Shah; Andrew Tambyraja; Julie Brittenden; Robert Lambie; John Norrie

doi:10.1161/CIRCULATIONAHA.117.028433

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

The 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 HoLiz Fraser, Hayley Cuthbert, Peter Hoskins, Barry Doyle, Noel Conlisk, Wesley Stuart, Colin Berry, Giles Roditi, Laura Murdoch, Richard Holdsworth, Emma Scott, Lyndsey Milne, Fiona Strachan, Fiona Wee, Katerine Oatey, Catriona Graham, Gordon Murray, Garry Milne, Marise Bucukoglu, Kirsteen Goodman, Jakub Kaczynski, Anoop S V Shah, Andrew Tambyraja, Julie Brittenden, Robert Lambie, John Norrie

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	787–797
Number of pages	11
Journal	Circulation
Volume	136
Issue number	9
Early online date	18 Jul 2017
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.117.028433
Publication status	Published - 29 Aug 2017

Keywords / Materials (for Non-textual outputs)

Aged
Aorta
Aortic Aneurysm, Abdominal
Aortic Rupture
Blood Pressure
Contrast Media
Dextrans
Disease-Free Survival
Female
Humans
Inflammation
Magnetic Resonance Imaging
Magnetite Nanoparticles
Male
Middle Aged
Proportional Hazards Models
Prospective Studies
Sex Factors
Smoking
Survival Rate
Journal Article

Access to Document

10.1161/CIRCULATIONAHA.117.028433

MA3RS - final publicationFinal published version, 635 KBLicence: Creative Commons: Attribution (CC-BY)

The BHF Chair of Cardiology
Newby, D.
UK-based charities
1/08/16 → 31/03/24
Project: Research
Identification and prediction of coronary artery plaque rupture using 18F-fluoride positron emission tomography
Newby, D.
UK-based charities
1/01/15 → 30/06/22
Project: Research
BHF Research Excellence Award (2) (renewal) grant 6
Mullins, J.
1/04/14 → 31/03/19
Project: Research

Marc Dweck
- mdweckstaffmail.ed.acuk
- Deanery of Clinical Sciences - Personal Chair of Clinical Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active (Research Assistant)
David Newby
- d.e.newbyed.acuk
- Deanery of Clinical Sciences - BHF Duke of Edinburgh Chair of Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active

Cite this

The MA3RS Study Investigators , Newby, D., Forsythe, R., McBride, O., Robson, J., Vesey, A., Chalmers, R., Burns, P., Garden, O. J., Semple, S., Dweck, M., Gray, C., MacGillivray, T., Wang, C., Koutraki, Y. G., Mitchard, N., Cooper, A., van Beek, E., McKillop, G., ... Norrie, J. (2017). Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair. Circulation, 136(9), 787–797. https://doi.org/10.1161/CIRCULATIONAHA.117.028433

@article{ce985bb7faf04eba8f4707314edce8ba,

title = "Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.",

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 = "Aged, Aorta, Aortic Aneurysm, Abdominal, Aortic Rupture, Blood Pressure, Contrast Media, Dextrans, Disease-Free Survival, Female, Humans, Inflammation, Magnetic Resonance Imaging, Magnetite Nanoparticles, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Sex Factors, Smoking, Survival Rate, Journal Article",

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

note = "{\textcopyright} 2017 The Authors.",

year = "2017",

month = aug,

day = "29",

doi = "10.1161/CIRCULATIONAHA.117.028433",

language = "English",

volume = "136",

pages = "787–797",

journal = "Circulation",

issn = "0009-7322",

publisher = "AMER HEART ASSOC",

number = "9",

}

The MA3RS Study Investigators , Newby, D, Forsythe, R, McBride, O, Robson, J, Vesey, A, Chalmers, R, Burns, P, Garden, OJ , Semple, S , Dweck, M , Gray, C , MacGillivray, T, Wang, C, Koutraki, YG, Mitchard, N, Cooper, A, van Beek, E, McKillop, G, Ho, W, Fraser, L, Cuthbert, H, Hoskins, P, Doyle, B, Conlisk, N, Stuart, W, Berry, C, Roditi, G, Murdoch, L, Holdsworth, R, Scott, E, Milne, L, Strachan, F , Wee, F , Oatey, K , Graham, C , Murray, G , Milne, G, Bucukoglu, M, Goodman, K, Kaczynski, J, Shah, ASV, Tambyraja, A, Brittenden, J, Lambie, R & Norrie, J 2017, 'Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.', Circulation, vol. 136, no. 9, pp. 787–797. https://doi.org/10.1161/CIRCULATIONAHA.117.028433

TY - JOUR

T1 - Aortic Wall Inflammation Predicts Abdominal Aortic Aneurysm Expansion, Rupture, and Need for Surgical Repair.

AU - The MA3RS Study Investigators

AU - Newby, David

AU - Forsythe, Rachael

AU - McBride, Olivia

AU - Robson, Jennifer

AU - Vesey, Alex

AU - Chalmers, Roderick

AU - Burns, Paul

AU - Garden, O James

AU - Semple, Scott

AU - Dweck, Marc

AU - Gray, Calum

AU - MacGillivray, Tom

AU - Wang, Chengjia

AU - Koutraki, Yolanda Georgia

AU - Mitchard, Neil

AU - Cooper, Annette

AU - van Beek, Edwin

AU - McKillop, Graham

AU - Ho, Weiyang

AU - Fraser, Liz

AU - Cuthbert, Hayley

AU - Hoskins, Peter

AU - Doyle, Barry

AU - Conlisk, Noel

AU - Stuart, Wesley

AU - Berry, Colin

AU - Roditi, Giles

AU - Murdoch, Laura

AU - Holdsworth, Richard

AU - Scott, Emma

AU - Milne, Lyndsey

AU - Strachan, Fiona

AU - Wee, Fiona

AU - Oatey, Katerine

AU - Graham, Catriona

AU - Murray, Gordon

AU - Milne, Garry

AU - Bucukoglu, Marise

AU - Goodman, Kirsteen

AU - Kaczynski, Jakub

AU - Shah, Anoop S V

AU - Tambyraja, Andrew

AU - Brittenden, Julie

AU - Lambie, Robert

AU - Norrie, John

PY - 2017/8/29

Y1 - 2017/8/29

N2 - 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.

AB - 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.

KW - Aged

KW - Aorta

KW - Aortic Aneurysm, Abdominal

KW - Aortic Rupture

KW - Blood Pressure

KW - Contrast Media

KW - Dextrans

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Inflammation

KW - Magnetic Resonance Imaging

KW - Magnetite Nanoparticles

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Sex Factors

KW - Smoking

KW - Survival Rate

KW - Journal Article

U2 - 10.1161/CIRCULATIONAHA.117.028433

DO - 10.1161/CIRCULATIONAHA.117.028433

M3 - Article

C2 - 28720724

SN - 0009-7322

VL - 136

SP - 787

EP - 797

JO - Circulation

JF - Circulation

IS - 9

ER -

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

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Keywords / Materials (for Non-textual outputs)

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Projects

The BHF Chair of Cardiology

Identification and prediction of coronary artery plaque rupture using 18F-fluoride positron emission tomography

BHF Research Excellence Award (2) (renewal) grant 6

Profiles

Marc Dweck

David Newby

Cite this