  Atrial fibrillation (AF) increases the risk of stroke by a factor of four to
five and is the most common abnormal heart rhythm. The progression of AF with
age, from short self-terminating episodes to persistence, varies between
individuals and is poorly understood. An inability to understand and predict
variation in AF progression has resulted in less patient-specific therapy.
Likewise, it has been a challenge to relate the microstructural features of
heart muscle tissue (myocardial architecture) with the emergent temporal
clinical patterns of AF. We use a simple model of activation wavefront
propagation on an anisotropic structure, mimicking heart muscle tissue, to show
how variation in AF behaviour arises naturally from microstructural differences
between individuals. We show that the stochastic nature of progressive
transversal uncoupling of muscle strands (e.g., due to fibrosis or gap
junctional remodelling), as occurs with age, results in variability in AF
episode onset time, frequency, duration, burden and progression between
individuals. This is consistent with clinical observations. The uncoupling of
muscle strands can cause critical architectural patterns in the myocardium.
These critical patterns anchor micro-re-entrant wavefronts and thereby trigger
AF. It is the number of local critical patterns of uncoupling as opposed to
global uncoupling that determines AF progression. This insight may eventually
lead to patient specific therapy when it becomes possible to observe the
cellular structure of a patient's heart.
