Myocardial adaptation and reverse remodelling in aortic regurgitation: Integrating invasive and non-invasive phenotyping by CMR and biopsy (Dr George Thornton)

Current guidelines for the management of severe chronic aortic regurgitation (AR) advocate surgical aortic valve replacement (SAVR) when the heart dilates, becomes impaired or when symptoms start. But this is too late and much heart damage is irreversible.

Cardiac magnetic resonance (CMR) techniques, validated using biopsy and outcomes, can measure myocardial remodelling, perfusion, fibrosis and haemodynamics. These, including key outputs from our group, are changing the timing of surgical intervention for aortic stenosis. We want to do the same for AR.

Hypotheses: Pathophysiological changes in severe, chronic AR (structure/function, ischaemia, fibrosis) quantified by CMR and myocardial histology predict reverse remodelling and functional recovery after surgical AVR.

Methods: 80 patients with severe, chronic AR will undergo deep-phenotyping CMR (volumes/function, stress perfusion, scar, 4D flow) and cardiopulmonary exercise testing (CPEX) pre-SAVR and intra-operative myocardial biopsy (cell hypertrophy, capillary rarefaction, fibrosis). Reverse cardiac remodelling and functional recovery will be assessed at 6 months post-AVR.

Expected Results: I want to enhance our understanding of the myocardial response to AR, tying together the cascade of remodelling, reduction in MBF and fibrosis.

Ultimately, I want to improve the timing of AVR in AR, especially in asymptomatic patients to reduce heart failure and mortality.