Research question:
How do structural, functional, electrical, and genetic markers of atrial cardiomyopathy (ACM) mediate the pathway from cardiovascular risk exposure to clinical outcomes such as atrial fibrillation (AF), stroke, heart failure, and mortality?
Objectives:
Phenotypic characterisation: Quantify left atrial structure and function from cardiac MRI and electrocardiographic indices to define multidimensional ACM subtypes.
Determinants and risk factors: Identify cardiometabolic, hemodynamic, inflammatory, and genetic determinants of ACM in the general population.
Clinical implications: Evaluate the prospective associations between ACM phenotypes and new-onset AF, stroke, and heart failure, determining whether ACM precedes these outcomes.
Causal inference and mechanisms: Use polygenic risk scores and Mendelian randomisation to test causal links between modifiable risk factors (e.g., blood pressure, obesity, inflammation) and atrial remodelling, and between atrial dysfunction and clinical events.
Translational modelling: Develop a simplified risk score integrating ECG, clinical, and genetic features to detect subclinical ACM in routine care.
Scientific rationale:
Atrial cardiomyopathy represents a unifying substrate underlying AF and cardioembolic stroke, yet its determinants and temporal evolution in the population remain unclear. UK Biobank offers an unprecedented multimodal platform-combining cardiac MRI, ECG, genotyping, and comprehensive phenotyping-to investigate ACM across structural, electrical, and molecular domains. By integrating imaging, epidemiology, and genetics, this project will clarify whether ACM acts as an intermediate phenotype linking common risk exposures to adverse cardiovascular outcomes. Findings will improve mechanistic understanding of atrial disease, identify novel prevention targets, and enable risk stratification before the onset of overt AF or stroke.
