Tetrology of Fallot (TOF) - A Review

2 5 - 0 8 - 2 0 1 5
Tetrology of Fallot

History
 Tetralogy of Fallot was first described by Niels Stenson in
1671, although its precise anatomical description was
elegantly illustrated by William Hunter at St Georges
Hospital Medical School in London in 1784.
 His description of a large outlet ventricular septal defect
together with subpulmonary and pulmonary valve stenosis,
and its resulting physiology, was refined by Etienne-
Louis Fallot in 1888 in his description of L’anatomie
pathologique de la maladie bleu, but the term
tetralogy of Fallot is attributed to Canadian Maude
Abbott in 1924.

Epidemiology
 About 3·5% of all infants born with a congenital heart
disease have tetralogy of Fallot, corresponding to one in
3600 or 0·28 every 1000 livebirths, with males and females
being affected equally.
 Its precise cause is unknown, as for most congenital heart
diseases.
 Most cases seem sporadic, although the risk of recurrence
in siblings is about 3% if there are no other affected first-
degree relatives.

Genetic factors
 Monogenic or polygenic mode of inheritance.
 Autosomal dominant mode of inheritance with reduced
penetrance,
 An autosomal recessive mode of inheritance,
 Multifactorial cause supporting the hypothesis that the
genetic cause of TOF is heterogeneous.
Environmental factors
 Maternal diabetes [threefold increased risk], Retinoic acids,
Maternal phenylketonuria (PKU), and Trimethadione

Syndromes and associations
 DiGeorge/Velocardiofacial syndrome, Down syndrome,
Alagille syndrome, Cat's-eye syndrome, recombinant
chromosome (or San Luis Valley) and Kabuki syndromes,
CHARGE and VATER/VACTERL associations, Poland
syndrome and Goldenhar’s syndrome(oculo-auriculo-
vertebral dysplasia).
Microdeletion on 22q11….seen in
 15–35% of TOF patients;
 45% of TOF + PA;
 65% of those with TOF + APV.

Embryology
 The aorta and pulmonary artery start as a single tube the
truncus arteriosus which is then divided by the spiral
septum.
 The spiral septum grows down to and attaches to the
ventricular septum which isolates the left and right
ventricles as well as isolating the aorta and pulmonary
artery.
 However, if the spiral septum is not in the midline,
but rather shifted over towards the right side of the
heart, then what would happen?
 The opening to the aorta would be large The opening to the
pulmonary would be small The spiral septum would “miss”
the ventricular septum.

 One abnormality results in 3 of the “defects” in TOF:
"overriding” aorta (it opens up to both the right and left
ventricles) pulmonary stenosis (the pulmonary artery is
small and narrowed) VSD (because the spiral and
ventricular septa do not line up and connect).
 The RV has to work extra hard to
pump blood into the pulmonary artery and therefore
hypertrophies to accommodate the extra work resulting
in RVH.
 The pulmonary stenosis (PS) determines the degree of
severity of this defect. Pulmonary perfusion depends on
the size of the PS.

Anatomy
 Anterior and cephalad deviation of the infundibular
septum.
 This results in a malaligned ventricular septal defect (VSD),
with the aortic root overriding the defect and leading to
subsequent right ventricular outflow obstruction.
 VSD is most commonly a single large malaligned subaortic
defect located in the perimembranous region of the septum.
 The VSD can extend into the muscular septum.
 There are rarely other muscular ventricular septal defects.

RVOT Obstruction
 The right ventricular outflow obstruction is often at multiple
levels.
 The anterior and cephalad deviation of the infundibular septum results in
subvalvar obstruction
 Hypertrophy of muscular bands in this region can further accentuate
subvalvar obstruction
 The pulmonary valve annulus is usually hypoplastic, although in some
instances it is of normal size
 The pulmonary valve itself is frequently bicuspid and stenotic
 It is not uncommon to identify an area of supravalvar
narrowing in the main pulmonary artery at the sinotubular
ridge.
 There may also be further obstruction at the branch
pulmonary arteries.
 These may be diffusely hypoplastic or have focal areas of
stenosis, most commonly at the proximal branch pulmonary
arteries.

Overriding aorta
 Aorta is displaced to the right over the VSD rather than the left
ventricle.
 This results in blood flow from both ventricles into the aorta.
 The degree of aortic override of the VSD can vary widely and is
one of the major factors used by some groups to differentiate
between TOF and DORV.
 If one defines double outlet right ventricle as the presence
of aortic/mitral valve fibrous continuity, then the degree of
override is not relevant to diagnosis.
 If, however, one defines double outlet right ventricle as a
condition with greater than 50 percent aortic override, then,
by definition, the degree of aortic override in TOF is limited.

Pathophysiology
 The VSD is almost always large and non-restrictive in TOF,
ensuring that the pressure is equal in the two ventricles.
 Consequently, the loud systolic murmur typical in affected
infants originates from the dynamic narrowing of RVOT.
 The direction and magnitude of flow through the defect
depends on the severity of the obstruction of RVOT.
 Most patients have adequate pulmonary blood flow at birth
but develop increasing cyanosis during the first few weeks
and months of life.

 One of the physiologic characteristics of TOF is that the RVOT
obstruction can fluctuate.
 An individual with minimal cyanosis can develop a dynamic
increase in right ventricular outflow tract obstruction with a
subsequent increase in right-to-left shunt and the development
of cyanosis.
 In the most dramatic situation, there can be near occlusion of the
right ventricular outflow tract with profound cyanosis.
 These episodes are often referred to as "tet spells" or
"hypercyanotic spells".

 Typical spell begins with progressive increase in rate and
depth of respiration and culminates in paroxysmal
hyperapnea, deepening cyanosis, limpiness, syncope and
occasionally in convulsions, CVA and death.
 Peak incidence in between second and sixth month of life.
 Spells typically initiated by stress of feeding, crying or a
bowel movement, particularly after awakening from deep
sleep.
 Mechanisms -
 Acceleration in heart rate
 Increase in C.O. and venous return
 Increase in R→L shunt
 Vulnerable respiratory centre
 Infundibular contraction

Complications
 Growth retardation
 Mental retardation
 Cerebral venous sinus thrombosis
 Nasal speech
 Brain abscess
 Cereberal embolism
 Infective endocarditis
 Coagulopathy
 Huperuricemia and Gout

Clinical features
 Wide due to variable severity of RV outflow obstruction
 USGfetal diagnosis
 Newborn & infants…cyanosis and systolic murmur.
 Acyanotic TOFmild pulmonary overcirculation rarely
CHF unless there is a large PDA or aortopulmonary
collateral arteries
 Pregnancy…poorly tolerated … gestational decrease in
SVR increases R-L shunt & the labile SVR during labor,
delivery leads to abrupt hypoxemia…..high fetal wastage /
dysmature offspring.

Examination
 Cyanosis, Clubbing
 JVP is normal
 Arterial pulses …normal in uncomplicated TOF
 Wide pulse pressure (arterial diastolic runoff)….
aortopulmonary collaterals, palliative surgical shunt or
PDA
 Accentuated precordial RV impulse
 LV impulse will not be hyperactive (normal cardiac output)
 S2 single& loud (anterior, dextroposed aorta)
 S3/S4 are unusual
 Aortic ejection click

 Systolic murmur…crescendo-decrescendo @ LUSB.
 The intensity of the murmur inversely parallels the degree
of pulmonic obstruction.
 Diastolic murmurs are unusual..Rarely AR murmur
 TOF with PA…..no harsh, obstructive precordial murmurs
 A harsh diastolic murmur, with a harsh murmur of PS,
[harsh sawing, to-and-fro murmur ] ……TOF and APV
syndrome
 Continuous murmurs….PDA, aortopulmonary collaterals,
may be best heard in the back.

Echocardiography
 2-D echocardiography provides the cornerstone for
noninvasive diagnosis of TOF.
 Doppler analysis provides further data regarding
hemodynamic characteristics.
 Study should be completed in a segmental and consistent
manner that allows complete definition of the desired
information.
 The coronary arteries are also readily apparent in PSAX view
slightly superiorly.
 The origin and course of the left and right coronary arteries
should be determined, paying special attention to whether any
vessels take an anterior course across the infundibulum.
 Correct definition of the coronary artery anatomy was possible
in most patients with a sensitivity of 82%, specificity of 99%,
and accuracy of 98.5% in a study by Need et al.

LAD
RCC
NCC
RCA
LCx
Pulm.
Valve
MPA
The anomalous LAD crossing the RVOT in TOF is identified when the transducer
is swept superiorly in the parasternal short -axis view .
This allows visualization of the anomalous LAD that is situated anterior to the
RVOT

Cardiac Catheterization
 With the evolution of noninvasive technology, the
indications for diagnostic cardiac catheterization have
diminished substantially.
 Nonetheless, invasive study to obtain both hemodynamic
and anatomic information is, on occasion, helpful prior to
deciding on surgical strategy.
 Foremost goal …. clarification or better definition of
anatomic characteristics, such as pulmonary arterial or
coronary arterial anatomy.
 Coronary artery anatomy … either by aortic root angio,
selective coronary artery injection, or a combination of
both.

A: An ascending aortogram in the LAO projection demonstrates a right anterior
descending coronary artery arising from the right coronary artery.
B: A selective left coronary injection shows filling of only the circumflex coronary artery.

 The goal of management of TOF patients is to allow total surgical
correction with minimal mortality and morbidity and to prevent
or treat complications.
 Most newborns with TOF do not have ductal-dependent
pulmonary blood flow and may be followed without specific early
intervention.
 Depending of the severity of obstruction within the RV outflow
tract, an infusion of prostaglandin may be initiated to preserve
ductal patency, and provide a stable source of flow of blood to the
lungs.
 IE Prophylaxis as per recommendations.

Hypercyanotic spells
Treatment aims @ lowering impedance to pulmonary flow and
further increasing systemic vascular resistance.
Rx…..Oxygen, Volume expansion, Sedation with morphine or
ketamine, and, if needed, vasopressors[phenylephrine]
Refractory to above …..
 Transfusion of whole blood/red cells
 Balloon angioplasty of pulmonary annulus
 Emergent surgical palliation or repair
Propranolol …having some efficacy in minimizing or
extinguishing the occurrence of spells. It may be used for patients
who are awaiting surgical intervention or who have a medical
contraindication to either complete repair or aortopulmonary
shunt.

Timing of Surgery
 Palliative shunts were initially reserved for infants, and
intracardiac repair for children, but the excellent results of
intracardiac repair for neonates and infants have made it
the current treatment of choice for all patients with TOF in
most centers.
 Surgery is usually performed electively in the first year of
life and can be performed in the first three months, if
necessary.
 Intracardiac repair is also performed in asymptomatic
acyanotic infants (pink variant) with a low morbidity and
mortality; this approach may allow normal growth of the
RVOT and pulmonary annulus.

Contraindications for repair in early infancy 
Palliation initially
 LAD from RCA crossing infundibulum
 Severely hypoplastic PAs
 Pulmonary atresia

Aim of surgery
 Relieving all possible sources of RVOTO.
 If possible, pulmonary valve function is preserved by avoiding
a transannular patch.
 Closure of VSD (dacron patch)
 To relieve RVOTOpulmonary valvotomy, the insertion of an
outflow tract patch or a transannular patch are often required.
 Surgery during early infancy, when the pulmonary annulus is
markedly stenotic, frequently requires the insertion of a long
and wide transannular patch.
 Consequently, most patients acquire PR as a result of the
repair. PR may be well tolerated by many in the early
postoperative years, but in the long term chronic PR is
associated with reduced exercise capacity, RV dilatation,
ventricular arrhythmias, and sudden death.

PA anatomy assessment
1) McGoon ratio: (Diameter of RPA/DAo + Diameter of LPA/DAo)
 Normal 2.1
 Adequate for VSD closure 1.2
 Inadequate <0.8 for VSD closure
2) Nakata Index:(CSA of RPA + CSA of LPA)/BSA
 Normal value > 200 mm2/m2
> 150 mm2/m2 is adequate.
(Not usable preoperatively when MAPCAs are the major source of PBF & one-
stage unifocalization + full repair is planned).
3) Total Neo-Pulmonary Artery Index (TNPAI) = APC index + Nakata Index
 APC index is the sum of CSA of all usable APCs/BSA
>250 - suitable for one-stage repair including VSD closure (These pts. have low
RV/LV pressure ratio postoperatively).
4) Z- score – no’s of SD PA size is away from the mean for children of same age and
sex.
 Neaton’s number, Natio index, Blackstone index and Kugelberg angiographic
classification.

Post Repair for TOF
 Current surgical survival, even for symptomatic infants <3
months of age, is excellent.
 Hospital and 1-month survival rates of 100% have been
reported.
 Earlier age at repair (<1 year of age) did not adversely affect
the rate of reintervention; so primary repair should be
regarded as the preferred management strategy.
 Twenty-year survival for hospital survivors, irrespective of
management strategy, was 98% for patients who have TOF
with PS and slightly lower for patients with PA, reflecting
the overall excellent long-term survival of these patients.

Complications
 Residual VSD
 Pulmonary regurgitation
 Residual RVOT obstruction
 RV wall motion abnormalities
 RV dysfunction and RHF
 Atrial tachycardia
 Ventricular tachycardia (VT)

Conclusions
 Tetralogy of Fallot is the most common form of cyanotic
congenital heart disease, and one of the first to be
successfully repaired by congenital heart surgeons.
 Since the first procedures in the 1950s, advances in the
diagnosis, perioperative and surgical treatment, and
postoperative care have been such that almost all those
born with tetralogy of Fallot can now expect to survive to
adulthood.
 The care of children with tetralogy of Fallot and their
transition to adult life has been a success of modern
medicine.
 Most of them now survive early repair and have an
essentially normal childhood.

Tetrology of Fallot (TOF) - A Review

In this document