Measuring and Modeling Atrial Mechanics in Health and Heart Failure

2. Title: Measuring and modelling atrial mechanics in health and heart failure 3. ABSTRACT: Atrial contraction and relaxation are central to maintaining healthy human cardiac function. In humans, myocardium contractile Ca2+ signals and sarcomeric contraction kinetics are less well characterised in atria than ventricles, despite indications, from animal experiments, of differences that may underlie fundamental physiology. Differences are likely based on protein expression or regulation in atria and ventricle tissue and affect emergent muscle tension generation and contraction. Identifying the underlying causes and implications of these differences across scales and systems requires an integrative approach. Using measurement-based computational modelling, we will test four hypotheses: (1) Humans have differences in atrial/ventricular Ca2+ signals and sarcomere kinetics; (2) These differences impact whole-heart function. Additionally, animal experiments have observed changes in atrial properties during heart failure. We hypothesise that these changes (3) occur in both Ca2+ signalling and contraction mechanics in humans suffering from heart failure with reduced ejection fraction, and (4) compensate for decreased ventricular function. We will perform comprehensive observational studies of contraction in healthy and failing hearts, and quantitatively encode and investigate their cellular, tissue, and whole-heart physiological implications using biophysical models. These findings can ultimately guide patient diagnosis and inform treatment decisions.