5.2.4 Ventricular
Pre-excitation
Ventricular pre-excitation is an extremely common, although not
invariable, finding inPRKAG2cardiomyopathy, being reported in
77% of patients in a recent case series [67]. The underlying acces-
sory pathways are frequently multiple and with bidirectional con-
duction [36, 68]. Notably this finding of multiple patterns of
ventricular activation (consistent with several accessory pathways)
has also been observed in transgenic mouse models of the disease
[32]. Preclinical experiments have suggested ventricular
pre-excitation in the setting ofPRKAG2mutations to be linked
to disruption of the normal electrical insulation function of the
annulus fibrosus between the atria and the ventricles (Fig. 4)
[32]. Structural damage to the annulus due to glycogenosis has
been proposed to allow electrical conduction to bypass normal
conduction via the AV node. Several authors have reported acces-
sory pathways with atypical decremental conduction properties in
patients withPRKAG2mutations, with a prevalence of between
50 and 100% [12, 27]. The majority of patients with the
Arg302Gln mutation with ventricular pre-excitation who have
undergone invasive electrophysiological assessment have a
pre-excitation variant occurring over fasciculoventricular pathwaysFig. 11Schematic illustrating the course of different anatomical variants of ventricular pre-excitation. Note the
course and proximal ends of fasciculoventricular and nodoventricular pathways representing the substrate for
most ventricular pre-excitation associated withPRKAG2mutations (Reproduced from ref.69 with permission
from Blackwell Futura)
604 Arash Yavari et al.