Page 163 - YORAM RUDY BOOK FINAL

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Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) 323

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important hereditary
cause of sudden death in young individuals, with an estimated prevalence as high as 1:1000 324,325 .
ARVC involves desmosomal mutations that cause decreased function of sodium channels and

gap junctions in cardiomyocytes 325,326 , and result in fibrofatty infiltration of the myocardium with
epicardial predominance. It was demonstrated that electrophysiological changes precede the
structural disease , implying that electrophysiological mapping of the epicardium can enhance
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earlier disease detection and diagnosis. We used ECGI together with advanced late gadolinium

enhanced (LGE) MRI to study the electric and structural substrates in ARVC patients . All 20
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patients were genotyped for desmosomal mutations.

Abnormal sinus rhythm activation and conduction were common in the ARVC patients.

We observed abnormal and varied epicardial breakthrough locations, regions of discontinuous
conduction, and fractionated EGMs. These characteristics are not present in the healthy heart.
Repolarization in ARVC was prolonged compared with control and this prolongation was often
spatially heterogeneous, although steep repolarization gradients were not observed. Importantly,

structural scar (from LGE MRI) co-localized with electrophysiological substrate abnormalities in
the LV (but not in the RV). The amount of scar within an LV anatomical segment correlated with
low-amplitude EGMs, increased fractionation, increased spatial gradients of activation times, and
increased ARI. Figure 5.24 presents activation patterns in one ARVC patient. Earliest epicardial

breakthrough was in the basal lateral LV. Low amplitude fractionated EGMs were present in both
RV and LV, and ARIs were prolonged relative to control.

Ventricular ectopy was common in the ARVC patients and occurred more frequently as

heart rate increased during and after exercise. We observed PVCs in 15 of 20 patients, with a total
of 41 distinct morphologies. The sites of earliest apicardial activation of the PVCs were spread
across both ventricles, with greater involvement of RV and basal locations. Figure 5.25 shows the
temporal occurrence and spatial location and propagation of PVCs in one patient.