Ablation of slow conducting anatomical isthmuses in patients with repaired Tetralogy of Fallot, who undergo reoperation for pulmonary valve replacement and who are at risk for isthmus related ventricular arrhythmias.

Tetralogy of Fallot (TOF) is the most common severe congenital heart disease
and is associated with late morbidity and mortality due to ventricular
arrhythmias (VA). Patients with documented or suspected VA usually receive
implantable cardioverter defibrillators (ICDs). However, not all VA are
life-threatening although an important source of morbidity. In addition, ICDs
do not prevent VA therefore additional and/or alternative treatment options are
required. Of importance, the majority of VA associated with TOF are monomorphic
ventricular tachycardias (VT). We recently could demonstrate that the substrate
for the majority of these monomorphic VTs are slow conducting anatomical
isthmuses bordered by unexcitable tissue. These slow conducting isthmuses may
be the consequence of the initial repair in childhood but may also be due to
the abnormal myocardium of the malformation itself. Targeting these isthmuses
by catheter ablation has been shown to prevent VT recurrence and is the
accepted current approach in clinical practice. Patients after initial total
repair of TOF may require a reoperation for pulmonary valve regurgitation.
However, simply replacing the valve does not affect the risk for VT. During
reoperation potential slow conducting isthmuses can be ablated with the
potential to prevent VT recurrence but also VT occurrence and thereby *curing*
the isthmus dependent monomorphic VT provided that isthmus block is achieved.
Preventive ablation of the slow conducting isthmuses during surgery becomes
particular important if pulmonary valve replacement (PVR) by a homograft is
performed. In this case, the homograft may cover important parts of the slow
conducting isthmus which makes catheter ablation at a later stage impossible
and is the most important reason for ablation failure in patients that present
with VT after PVR.

1) To evaluate the feasibility and the acute effect of intra-operative
cryoablation of the slow conducting anatomical isthmuses (endpoint
bidirectional conduction block) and on the re-inducibility of monomorphic
isthmus dependent VT.
2) To study the pathomechanism of slow conduction within these isthmuses by
comparing histological and electrophysiological characteristics of biopsies in
patients after repair of TOF who undergo re-operation and of patients who
undergo first total correction.
3) To assess the long-term results of intra-operative cryoablation of the slow
conducting anatomical isthmuses on recurrence and occurrence of monomorphic VT.

A prospective duo-centre cohort study.

Intra-operative cryoablation of the slow conducting anatomical isthmuses.

Group A: All patients with repaired TOF who are accepted for PVR will undergo
electrophysiologic evaluation consisting of programmed electrical stimulation
(PES) and right ventricular electro-anatomical mapping (EAM) before operation.
Only EAM is part of the research protocol, except for patients who previously
experienced an episode of spontaneous VA. Right ventricular mapping is
performed through the same venous access already obtained for PES and performed
using a standard non-fluoroscopic 3D mapping system (CARTO 3). EAM takes
additional 10-15min procedure time and has no specific additional risks. During
operation, a biopsy will be taken from the infundibular septum in all patients
which is the most frequent location of slow conducting myocardium. The
intra-operative biopsy is a study procedure, which is associated with minimal
risks and taken from an already diseased area. Furthermore, intra-operative
cryoablation will be performed in patients with slow conducting anatomical
isthmuses and/or VA. The intra-operative cryoablation is part of the
investigational treatment in patients with slow conducting anatomical isthmuses
but without documented or induced VA. However, these patients are still at high
risk to develop arrhythmias from these areas after re-operation. Of importance,
these specific areas are difficult to target or impossible to target by
catheter ablation after valve replacement as the homograft covers important
parts. Cryoablation is associated with minor risks and the standard
intra-operative treatment for other arrhythmias. In patients inducible for VA
and/or patients with slow conducting anatomical isthmuses postoperative EP
study and EAM will be performed to evaluate the results of surgical
cryoablation. For patients with a slow conducting isthmus only as potential
substrate for future VTs, EPS and EAM is part of the research protocol. The
specific risks of the tests are described in detail in the protocol.
Group B: The tissue that will be investigated regarding histological and
electrophysiological characteristics is tissue that will be removed as part of
the repair operation, therefore there is no additional risk.