Novel imaging and blood biomarkers in acute aortic syndrome

BACKGROUND: Acute aortic syndrome is an unpredictable and catastrophic condition. It is characterised by medial degeneration which is beyond the resolution of conventional anatomical imaging. Here, we investigate 18F-sodium fluoride positron emission tomography and computed tomography (PET/CT) and circulating biomarkers in patients with acute aortic syndrome. METHODS: We performed 18F-sodium fluoride PET/CT in 56 patients with aortic dissection, intramural haematoma or penetrating aortic ulcers and 20 healthy controls. First, we characterised radiotracer uptake in relation to demographic and clinical factors (Chapter 3). Next, we investigated the role of 18F-sodium fluoride PET/CT and disease progression in patients with aortic dissection or intramural haematomas (Chapter 4). In a sub-study, we measured plasma desmosine concentration in patients with acute aortic syndrome and investigated these in relation to aortic expansion (Chapter 5). Finally, we identified candidate miRNAs and measured their circulating expression in patients with acute aortic syndrome. Again, we related these to disease characteristics and progression (Chapter 6). Patients with acute aortic syndrome had increased 18F-sodium fluoride PET/CT signal compared to healthy controls (tissue-to-background ratio 2.08±0.45 vs 1.36 ±0.39, p<0.001). 18F-Sodium fluoride uptake concentrated at the site of intimal disruption (+32.5%, p<0.001). Radiotracer uptake in the false lumen was associated with aortic expansion independent of aortic diameter (+7.1 mm/yr, p=0.011). Peak 18F-sodium fluoride uptake was independently associated with aortic rupture, repair or aorta-related death (hazard ratio 8.6 [95% CI, 1.1-68.1], p=0.041). Plasma desmosine concentrations were also elevated in patients (0.58±0.26 vs 0.27±0.07 ng/mL, p<0.001) and peaked at presentation (0.82±0.17 ng/mL, p<0.001). Plasma desmosine concentration was associated with aortic expansion, again, independent of aortic diameter (𝛽=+2mm/yr, p<0.001). We identified 16 candidate circulating miRNA, several of which were associated with aortic diameter, expansion and 18F-sodium fluoride uptake. miRNA expression was independently associated with major adverse aortic events (hazard ratio 3.32 (1.71-6.46), p<0.001). CONCLUSION: This is the largest PET study in patients with acute aortic syndrome and the first to use 18F-sodium fluoride PET/CT. In this proof-of-concept study, we demonstrate the potential for 18F-sodium fluoride PET/CT to detect acute aortic syndrome and improve risk stratification. Desmosine is a promising circulating biomarker in this condition and may play a role in diagnosis. Finally, we identified a miRNA signature associated with major adverse aortic events following acute aortic syndrome.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2022

Author dc:creator

• Syed, Maaz Bin Junaid

Advisors dc:contributor.advisor

• Newby, David
• Dweck, Marc

• acute aortic syndrome
• 18F-sodium fluoride
• PET
• aortic dissection
• intramural haematoma
• penetrating aortic ulcer
• micro-RNA
• desmosine

Language dc:language.iso

en

Identifier URI

http://dx.doi.org/10.7488/era/2492

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/39241