Tetralogy of Fallot for Life

Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart defect consisting of
7-10% of all congenital heart disease with an estimated annual global incidence rate of
38,000. It is fatal if untreated; only 50% of patients are alive at 1 year of age. Surgery
has dramatically improved the survival so that >95% of repaired TOF children are alive by one
year. The initial justified enthusiasm for the benefit of surgical therapy are now tempered
by the findings of late sudden cardiac death secondary to right ventricular (RV) dysfunction.
The original trans-ventricular/trans-annular patching repair results in significant pulmonary
insufficiency which leads to RV dilation, subsequent functional tricuspid regurgitation,
atrial arrhythmias, and eventual RV failure and ventricular arrhythmias. In attempt to break
this cycle, an increasing number of patients are undergoing late pulmonary valve
implantation.

Recognizing that the RV adapts to stress signals has led to the idea that leaving mixed
residual stenosis and regurgitation may yield to an adaptive change that limits RV dilation
while still allowing for adequate cardiac output. Early attempts to limit pulmonary
insufficiency and RV damage involve minimal trans-annular patching or complete annulus
preservation (AP). Emerging data suggest that patients with a mixed lesion have improved
survival, so that 96.6% are alive at 25-years in comparison to 85-90% survival for the
conventional technique.

Preliminary Data: A review of data comparing AP to TAP repair at our institution (n=185, AP
repair=124, TAP=61) demonstrated that at 10-15 year follow-up those who received an AP repair
had smaller RV volumes and pulmonary regurgitant jet width. They were also seen to have
improved exercise capacity as measure by VO2 max tests. The AP technique also has been seen
to significantly decrease the risk of reoperation in comparison to TAP, 11% and 29%
respectively.

Current Problem: Although trans-ventricular VSD closure along with a TAP is known to result
in increased risk of long-term morbidity and mortality, it continues to be the predominant
repair strategy implemented globally according to STS/EACTS databases. Reasons for this are:

- Trans-ventricular/TAP approach is technically easier than annulus preservation, which
often requires multiple pump runs

- There is a fear of leaving too much obstruction

- High quality evidence supporting one approach over the other is lacking.

Gaps in Literature

1. Most data on the impact of surgical strategy emerge from single centre experiences that
are retrospective and based on small patient population. This makes the results
difficult to standardize to the general TOF population.

2. Retrospective registry data published by STS and EACTS omit many crucial surgical and
clinical variables that can potentially impact outcomes.

3. None of the current evidence are based on anatomically matched/adjusted patients

Inclusion Criteria:

- TOF with RVOT stenosis. TOF is defined as anterio-cephalad deviation of the
ventricular outlet septum with no more than 50% aortic override and a single outflow
VSD.

- TOF with pulmonary atresia and confluent pulmonary arteries.

- Admitted with intent to treat (i.e. patient planned to undergo a primary or staged
repair).

- Patients with coronary artery anomalies, right aortic arch, and 22q11 deletion may be
included

Exclusion Criteria:

- TOF with absent pulmonary valve

- Other major cardiac anomalies such as AVSD, multiple VSDs, right atrial isomerism, and
MAPCAs. In this instance, the definition of MAPCAs does not include dilated bronchial
collateral arteries.

- Unbalanced ventricles precluding biventricular repair

- Major genetic abnormalities/syndromes e.g. trisomy 13,18, and 21

- Major extra cardiac anomalies e.g. diaphragmatic hernia, omphalocele, absent sternum,
cerebral palsy

- Infective endocarditis as an indication for intra-cardiac repair

- Stroke in the last 30 days prior to palliation or intra-cardiac repair

- Known diagnosis of HIV or hepatitis B

- Any previous cardiac procedures

- Patient's circumstance that precludes completion of follow-up telephone call and/or
obtaining information from the 2-year cardiology follow-up