Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically
determined cardiomyopathy characterized by ventricular arrhythmias (VA)
of predominant right ventricular (RV) origin and, pathologically, by a
loss of cardiomyocytes with fibrofatty replacement that typically
progresses from the subepicardial RV layers to the midmyocardium and
subendocardium.1 Frequent premature ventricular
contractions (PVCs) are a common clinical manifestation of the disease,
and represent one of its diagnostic criteria.2 A high
PVC burden has also been independently correlated with long-term risk of
life-threatening VA in patients with a definite diagnosis of ARVC and no
previous history of sustained VA/sudden cardiac death (SCD) and,
recently, included in a multiparametric longitudinal SCD risk prediction
model.3 4
Surprisingly, there is a paucity of published studies focusing on
different management strategies for PVCs in patients with ARVC. Multiple
prior studies have documented a substantial benefit of catheter ablation
(CA) to achieve suppression of sustained VT, mostly after failure of
antiarrhythmic drug (AAD) therapy .56 7 Owing to the more extensive
epicardial pathological substrate, endocardial only approaches have led
to suboptimal results,8 910 and a combined endocardial and epicardial approach
has been shown to provide good long-term outcomes with an overall
VT-free survival ranging from 45% to 91% (average follow-up 41 months,
range 11 to 88 months) (Table ).56 11 1213 The extent to which these results can be
extrapolated to the treatment of PVCs warrants adequate investigation.
In this issue of the Journal of Cardiovascular Electrophysiology ,
Assis et al. report novel and important information on the efficacy of
CA for symptomatic PVCs in patients with ARVC. The authors
retrospectively analyzed eight ARVC patients with a moderate-to-high
burden of symptomatic PVCs (range 5%-25% within 24-h) who underwent CA
at their institution. Most patients (62.5%) had previously failed AAD
therapy (class I or III agents, none treated with amiodarone), and
presented an average of 2.7±1 distinct PVC morphologies, all with a left
bundle branch block configuration (87.5% with an inferior axis). Acute
procedural success was achieved in 50%, whereas complete long-term
success (defined as >80% reduction in the PVCs burden at
follow-up monitoring) in 2 (25%) at a median follow-up of 345 days; of
these, only 1 patient was maintained off AAD therapy.
Overall, the results of this study are compelling: CA of PVCs was not
associated with a clinical benefit in the large majority of patients
included in this series. The authors concluded that CA pf PVCs should be
reserved only for highly symptomatic ARVC patients who have failed AAD
therapy. From a mechanistic perspective, the study by Assis et al.
provides several intriguing insights. For instance, it is notable that
the PVCs were all localized within areas of abnormal substrate, and no
patient had concomitant idiopathic PVCs from areas of normal voltage
and/or intracavitary structures. With this in mind, a substrate-based
ablation approach should have been effective in eliminating the PVCs
similarly to what has been reported for reentrant VTs. On the other
hand, an extensive endo-epicardial substrate-based ablation approach may
not be appropriate for patients presenting only with symptomatic PVCs
and no documentation of VT and may also be associated with
pro-arrhythmia. Notably, two patients that presented with multiple
distinct PVC morphologies and extensive endo-epicardial abnormal
substrates were treated with supplemental substrate modification at the
time of the index procedure and developed new VT during follow-up.
In the presence of a mappable arrhythmia, most operators would opt for a
more targeted approach focused on the site of origin of the VA detected
with detailed activation mapping and pace mapping. However, these
techniques may have limitations in the context of focal PVCs arising
from areas of abnormal substrate. For instance, prior investigations
have documented that the spatial resolution of pace mapping within the
abnormal substrate, defined as the area subtending sites with matching
12-lead ECG pace maps, averages 3.6-3.8
cm2.14 15 In
addition, multiple distinct QRS morphologies may also be observed from
the same pacing site within the scar due to the presence of multiple
exit sites and/or preferential conduction routes that may be dependent
on different pacing rates/coupling intervals.16Activation mapping is without doubt the most reliable approach to
identify the site of origin of focal PVCs, but requires a high
intraprocedural ectopic burden, and the depth of anesthesia may affect
the frequency of PVCs available to map. In the study by Assis et al.
epicardial mapping and ablation were performed in 88% of cases (7 out
of 8 patients); as the authors also point out, the use of general
anesthesia to facilitate epicardial access and increase patient’s
comfort during epicardial mapping and ablation may have greatly
influenced the ability to perform a detailed activation map in the
epicardium and ultimately impact the procedural success. Of note, the
same group of investigators has previously reported excellent results
with catheter ablation of focal sustained VTs in a series of patients
with ARVC, with a cumulative freedom from recurrent VT of 85% at 1 year
and 75% ay 2 years.3 As the procedural approach to
focal sustained VT and PVCs is the same, the discrepancy in the observed
outcomes may reflect unique mapping challenges that prevented an
adequate PVC localization in the present study.
In summary, the study by Assis et al. adds novel and clinically relevant
data. This is the first study to systematically evaluate the role of CA
to treat PVCs in ARVC and the results do not appear to support the
widespread use of CA for the treatment of symptomatic PVCs in patients
with ARVC. Additional investigations are needed to better comprehend the
reasons for the poor outcomes described in this study and to reconcile
these findings with prior reports documenting good results with CA of
reentrant and focal VT in ARVC.