Figure 8.

Development of arrhythmia resulting from a combination of Nav1.5 haploinsufficiency and structural change in progressive cardiac conduction defect (PCCD) and Brugada syndrome (BrS). Nav1.5 haploinsufficiency produces a background electrophysiological defect in conduction. This results in arrhythmic substrate typically unmasked by flecainide or ajmaline challenge. Cardiac fibrotic changes occur with age, particularly in males. This further compromises action potential propagation. Superimposition of the two factors sufficiently compromises conduction, thereby accentuating arrhythmic substrate to lead to arrhythmic events. There is thus a combination of biophysical and structural change with age, particularly in males, that results in arrhythmia. [From Jeevaratnam et al. (500).]