Linking Left Atrial Pressure and Flow Disturbance to Platelet Activation and Stroke Risk in Atrial Fibrillation (MatthewsG_U26FMH)
Key Details
- Application Deadline
- 31 March 2026 (midnight UK time)
- Location
- UEA
- Funding type
- Competition funded project (Home applicants only)
- Start date
- 1 October 2026
- Mode of study
- Full-time
- Programme type
- PhD
)
Welcome to Norwich
According to the Sunday Times, this city is one of the best places to live in the UK.
Project description
Primary supervisor - Dr Gareth Matthews
Background: Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting around 2 to 3% of the population and costing the NHS more than £2.2 billion per year. AF increases the risk of stroke and vascular dementia. Oral anticoagulation reduces stroke risk by around 63%, but it carries bleeding risk and does not explain why thrombus forms in some people but not others. Better ways to match prevention to the individual are needed.
This PhD addresses one defined question: why some people with AF develop left atrial thrombus and embolic events while others do not. The project will link atrial function and remodelling to platelet behaviour, aiming to find measurable markers that could improve risk stratification and point towards new prevention strategies. This multidisciplinary project is delivered in collaboration with the Earlham Institute, who bring molecular and platelet-focused expertise.
Overall aim: To identify and mechanistically validate physiological and blood-based markers linked to left atrial thrombogenicity in AF, supporting more personalised stroke prevention.
Project plan
Phase 1: Cohort discovery in PREFER-CMR (n ~2,000): Using the PREFER-CMR registry, we will relate advanced cardiac imaging measures of atrial and cardiac function to incident AF and thromboembolic outcomes. Multivariable models will test whether candidate measures add useful information beyond established clinical risk scores.
Phase 2: Linking clinical status to atrial electrical remodelling (n ~100): In a clinical ablation cohort, we will relate standard procedural measurements to mapping-defined atrial substrate, including low-voltage regions and conduction abnormalities. This phase connects patient physiology to atrial remodelling in the setting where AF is treated invasively.
Phase 3: Molecular profiling in a well-phenotyped subset (n ~50): We will perform targeted molecular profiling, with a focus on lipid pathways relevant to thrombosis and platelet biology. Molecular features will be integrated with clinical and imaging data to prioritise pathways for mechanistic testing.
Phase 4: Prospective platelet phenotyping in AF (n ~20): In a focused mechanistic study across AF patterns embedded within clinically indicated procedures, we will measure platelet activation and reactivity using established functional assays. Platelet phenotype will be related to rhythm status, clinical features, and the physiological context captured during the procedure.
Why it matters: By linking population-level evidence to patient-level mechanistic work, this project aims to move beyond a one-size-fits-all approach to anticoagulation. The goal is to pinpoint measurable signals of higher thromboembolic risk, and to identify biological processes that could be targeted in future studies to reduce stroke and vascular dementia in AF.
Entry requirements
The minimum entry requirement is 2:1 in Biological/Medical Sciences with previous training and exposure to biochemistry techniques. Quantitative skills with statistics or programming in R/python/MATLAB desirable.
Funding
This project is fully funded for 3 years. Funding includes tuition fees, an annual tax-free maintenance allowance and a research training support budget.
References
i) Kalaitzoglou M, Bertelsen L, Chambers B, Matthews G, Tsiverdis P, Tomoaia R, Anderton T, Diederichsen SZ, Svendsen JH, Garg P, Swoboda PP. Non-invasive cardiovascular magnetic resonance pulmonary capillary wedge pressure predicts future atrial fibrillation: a LOOP substudy. ESC Heart Fail. 2026 Feb 3;13(1):xvaf038. doi: 10.1093/eschf/xvaf038. PMID: 41711728.
ii) McDiarmid AK, Chambers BS, Broadbent DA, Patel R, Matthews G, Gonzalez-Fernandez O, Plein S, Garg P, Swoboda PP. Development and Validation of a Noninvasive Model of Mixed Venous Oxygen Saturation in Heart Failure. JACC Adv. 2026 Jan;5(1):102484. doi: 10.1016/j.jacadv.2025.102484. PMID: 41609283; PMCID: PMC12869880.
iii) Garg P, Grafton-Clarke C, Matthews G, Swoboda P, Zhong L, Aung N, Thomson R, Alabed S, Demirkiran A, Vassiliou VS, Swift AJ. Sex-specific cardiac magnetic resonance pulmonary capillary wedge pressure. Eur Heart J Open. 2024 May 15;4(3):oeae038. doi: 10.1093/ehjopen/oeae038. PMID: 38751456; PMCID: PMC11095051.
iv) Matthews G, Sawh C, Li R et al. Human pressure-volume loops from the impedance catheter: Development and validation of semi-automated beat-by-beat analysis [version 1; peer review: 2 approved with reservations]. Wellcome Open Res 2024, 9:723 (https://doi.org/10.12688/wellcomeopenres.23373.1)
v) Wojtowicz EE, Mistry JJ, Uzun V, Hellmich C, Scoones A, Chin DW, Kettyle LM, Grasso F, Lord AM, Wright DJ, Etherington GJ, Woll PS, Belderbos ME, Bowles KM, Nerlov C, Haerty W, Bystrykh LV, Jacobsen SEW, Rushworth SA, Macaulay IC. Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion. Genome Biol. 2023 Jun 27;24(1):152. doi: 10.1186/s13059-023-02976-z. PMID: 37370129; PMCID: PMC10294477.