Het behandelen van kamerritmestoornissen bij patiënten met Tetralogie van Fallot, die een heroperatie ondergaan waarbij de pulmonalisklep wordt vervangen en die risicolopen op kamerritmestoornissen.

Background of the study:

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.



Objective of the study:

1) To evaluate the feasibility and the acute effect of intraoperative 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 reoperation and of patients who undergo first total correction.

3) To assess the long-term results of intraoperative cryoablation of the slow conducting anatomical isthmuses on recurrence and occurrence of monomorphic VT.



Study design:

A prospective duo-centre cohort study.



Study population:

Group A: Patients with repaired TOF and accepted for PVR from the age of eight years.

Group B: Patients with TOF who undergo first repair. This group serves only as a control group for the histology of the infundibular muscle which removal is part of the surgical repair.



Intervention:

Intraoperative cryoablation of the slow conducting anatomical isthmuses.

Primary study parameters/outcome of the study:

The main study parameters are: (1) prevalence and characteristics of slow conducting anatomical isthmuses, (2) inducibility of monomorphic isthmus related VT before intraoperative cryoablation, (3) histological and electrophysiological characteristics of the biopsies taken from slow conducting isthmuses (reoperation) and the infundibular muscle which is the most frequent location of a potential slow conducting isthmus later in life (initial repair). The main study endpoints are: (1) achievement of bidirectional conduction block after intraoperative cryoablation, (2) reinducibility of isthmus dependent monomorphic VT after intraoperative cryoablation and (3) occurrence and recurrence of VA during follow-up.

Improved understanding of slow conducting anatomical isthmuses in Tetralogy of Fallot and cryoablation of these slow conducting anatomical isthmuses during pulmonary valve replacement might prevent VT re- and occurrence.

1. Baseline evaluation (electrophysiologic study with right ventricular mapping and biopsies of slow conducting isthmuses and the infundibular muscle).

2. Follow-up: Primary endpoints.

The intervention is cryoablation of slow conducting anatomical isthmuses which (potentially) contain critical parts of the VT re-entry circuit.
The first two study endpoints (i, achievement of bidirectional conduction block after intraoperative cryoablation; ii, re-inducibility of isthmus dependent monomorphic VT after intraoperative cryoablation) will be checked during a post-operative electrophysiologic study with mapping of the right ventricle.
The third study endpoint (occurrence and recurrence of ventricular arrhythmias during follow-up) will be achieved by comparing the study cohort with a historical cohort operated/treated by the same team.