[69–71], although nodoventricular fibers have also been reported
(Fig.11)[ 28]. Fasciculoventricular fibers are not a substrate for
reentrant tachycardia, and due to the small incidence of a truly
atrioventricular accessory pathway, circus movement tachycardia is
rarely reported. If catheter ablation is attempted in this setting, it is
very important to correctly identify the type of accessory pathway in
order to avoid iatrogenic damage to the conduction system axis, as
can occur if a fasciculoventricular pathway is not distinguished from
a superior paraseptal accessory pathway [57, 69–71]. An isolated
short PR interval in the absence of a delta wave (abnormal slurred
initial QRS vector) or QRS prolongation (i.e., without the Wolff-
Parkinson-White ECG pattern and with exclusion of rarer variants
of accessory pathway at EPS in some) has also been reported
[27, 65, 67].5.3 Heart Failure Symptoms of heart failure can occur in the setting of preserved
ventricular systolic function, usually in the presence of severe LVH
(suggesting significant diastolic dysfunction) as in the case of a
Turkish family carrying the Glu506Lys mutation [72]. This may
be associated with biochemical evidence supporting a diagnosis of
heart failure, as in the case of the 19-year-old proband with the
latter mutation who exhibited severe biventricular hypertrophy and
a profound elevation in plasma N-terminal pro-B-type natriuretic
peptide to 32,822 pg/ml (normal range in the non-acute setting
<125 pg/ml) [72, 73]. Progression to frank systolic heart failure
appears to be more frequent in the setting of aPRKAG2mutation
than that encountered in classical sarcomeric HCM, being reported
in the former in ~12% of all patients [17] and even higher (up to
25%) in some cohorts [67]. When considering the incidence of
progression to ventricular dilatation with severe systolic dysfunc-
tion and potential requirement for cardiac transplantation, pub-
lished reports suggest the existence of genotype-phenotype
correlations. Thus, progression from HCM to end-stage cardiac
failure has been described in three carriers of the Val336Ala variant
from a single family [67], while a de novo Lys485Glu mutation was
identified in a single patient diagnosed with HCM and WPW at age
15 years who subsequently progressed to severe cardiac enlarge-
ment and symptomatic heart failure by his early 20s [74]. Marked
propensity toward early transition to cardiac dilatation with systolic
failure has been noted in patients harboring other mutations, such
as His383Arg [10], His530Arg [67, 75], and Arg350_Glu351in-
sLeu [10], with individuals undergoing cardiac transplantation
between 19 and 42 years of age. Fulminant onset of ultimately
fatal infantile heart failure in the setting of severe HCM has been
reported with de novo Arg531Gln mutations, mirroring the pro-
found biochemical impact of this mutation on adenine nucleotide
binding and basal activation of AMPK [26]. In contrast to these
variants, the frequency of progression of hypertrophy to a dilated
PRKAG2 syndrome 605