Natural & modified history
of
Tetralogy of Fallot
27/10/2007
Background -
• TF is most commonly encountered CCHD
• TF is most common CCHD > 4 yr of age
• Clinical presentation & outcome - a spectrum
• Multiple variants with common developmental
basis
• Clinical, morphological & hemodynamic
variation determines the clinical course
• Intervention surgical or percutaneous modifies
the clinical course & outcome
• Knowledge of natural & modified history makes
us wiser with due respect to risks & benefits
Epidemiology –
• Prevalence –
– variably reported due to variable definitions
– 0.26 to 0.48 per 1000 live births
– Approx. 3.5 – 9 % of all CHD
– BWIS (1981-1989) – population based study
• Most common among CCHDs
• 6.8% (5.4% for TOF with PS) of all CHDs
• 0.33 (0.26 for TOF with PS) per 1000 live births
• Male preponderance ~ 56.4 % (statistically NS)
• No racial immunity to Tetralogy of Fallot
Epidemiology –
• Recurrence risk – mixed data ? Definition
– Sib affected (non syndromic)
• 2.5 % (2.2 – 3.1%) if single sib has TF
• 8 % if two or more
– Parents affected (non syndromic)
• 1.2 – 8.3 %
• 1.4 % if father has TF
• 2.6 % if mother has TF
# conotruncal anamolies have similar risk of
recurrence
# 20% if father is affected vs 10% if mother has CHD
Etiology – multifactorial
• Environmental –
– Teratogens
• Retinoic acid – most common CHD is TF
• Trimethadione
• Maternal PKU with poor control
• Maternal DM –
Three fold risk of TF/PS
Ten fold risk of TF/PA
Twenty fold risk of TF/PA if Insulin
dependent
Etiology – multifactorial
• Genetic –
– Syndromes associated are (OMIM 37/11/9)
• 22q11 deletion – Digeorge/ VCF syndrome
• Autosomal trisomies – 21> 18> 13
• Allaglle’s/ cat eye/ Kabuki syndrome
• Various associations – VATER/ VACTERL/ CHARGE
– Non syndromic genetic associations
• Transcription factor Nkx2.5 (or CSX)
• Missense mutation (G274D) in JAG1 – gene for
right heart development
# Syndromic association more in TF/PA
Etiology – multifactorial
BWIS cohort (pre 22q11 deletion detection)
TF/PS TF/PA
Syndrome 7.2% +2.1% 11.7%
Chromosomal abnormality 11.9% 8.3%
Single organ defects 11.4% 6.7%
Isolated heart disease 67.8% 73.3%
Digilo et al (phenogeno analysis of 22q11 deletion)
48 of 150 syndromic (17 CATCH 22 + 20 DS+ 11 others)
68% TF/PS had isolated CHD
# 8 – 23 % TF patients have 22q11 deletion
# mixed data for occurrence of 22q11 in TF/PS vs TF/PA
Tetralogy of Fallot -
• Four components –
Malaligned infundibular septum malaligned
VSD
Variable overriding of aorta
RVOT obstruction
RV hypertrophy
Embryology – exact
mechanism ?
• Faulty rotation & septation of conotruncus
– Most widely accepted
– Backed up by morphological studies
– Explains morphological features in great majority
• Hypoplasia of pulmonary infundibulum
– Proposed by Van Praagh
– Studies showed normal to longer than normal
Tetralogy of Fallot -
• Four components –
Malaligned infundibular septum malaligned VSD
Anterior, left & cephalad displacement of conal septum
attached to anterior limb of septal band
nonrestrictive VSD b/w anterior & posterior limbs of
trabecular septal band i.e. perimembranous (having
tricuspid – aorto- mitral continuity)
# VSD can be restrictive rarely –
de novo or secondary to TV leaflet prolapse
Faulty conotruncal rotation/septation
Faulty conotruncal rotation/septation
Tetralogy of Fallot -
• Four components –
Malaligned infundibular septum malaligned
VSD
Variable override (15-90%) & clockwise rotation of
aorta
no subaortic conus
maintains aortomitral continuity
makes RCC sit on VSD (normally on septum)
Tetralogy of Fallot -
• Four components –
Malaligned infundibular septum malaligned VSD
Variable (15 – 95%, usually < 50%) overriding of aorta
RVOT obstruction – infundibular/ valvar/ supravalvar
secondary to malaligned septum infundibular
PS
low antegrade flow variable degree
Valvar/
morphological PV anomaly supravalvar
dynamic (intra & inter patient variations)
due to relative flow in two outlets of RV, RVH
RVOT obstruction – valvar
Degree of valvar/ supravalvar obstruction inversely related to
antegrade flow
RVOT obstruction –
supravalvar
Degree of valvar/ supravalvar obstruction inversely related to
antegrade flow
RVOT obstruction –
Tetralogy of Fallot -
• Four components –
Malaligned infundibular septum malaligned VSD
Variable (15 – 95%, usually < 50%) overriding of aorta
RVOT obstruction – infundibular/ valvar/ supravalvar
RV hypertrophy –
pressure overload secondary to RVOTO
volume overload secondary to VSD
Major associated cardiac
anomalies–
Major associated cardiac
anomalies–
• Right aortic arch
25 % cases of TF/PS, 30 % of TF/PA
90 % have mirror image branching of arch vessels
Right sided ductus, aberrant LSCA common
• Absent ductus arteriosus
Approx. 30 % cases
More associated if right arch
# severe LVOTO & CoA are rare
Major associated cardiac
anomalies–
• Coronary anatomy –
– Surgically important
– May prohibit ICR
– Might require conduit
# Infundibuloarterial inversion –
RCA around RVOT
Minor associated cardiac
anomalies –
Clinical profile -
• Represents spectrum
– Severity of RVOTO - progressive
– Net pulmonary blood flow (PV + DA + MAPCAs)
– Associated pulmonary vasculature anomaly
Oligemic lungs to heart failure
Acyanotic cyanosis on crying resting cyanosis
Resting cyanosis cyanotic spells
Decreased exercise tolerance, effort dyspnea
Clinical profile - cyanosis
67% were acyanotic at birth
Cyanosis mean age 6.1 mo (1 wk -
2 yr)
All TOF with [Link] cyanosed by 5-8 yr
Clinical profile -
Clinical profile – cyanotic spells
• Pediatric cardiology emergency
– Peaks at 2 mo – 6 months of age
– Uncommon beyond 2 yrs
– Multiple mechanisms – relative syst./ pulm. resistance
Tachycardia
Decreased systemic resistance
Increased cardiac output/ venous return
Vulnerable respiratory centers – morning occurrance
Dynamic infundibular obstruction
# may be first presentation of cyanosis
# more common with less cyanosis (?) / iron deficiency
Clinical profile – squatting
• Adaptive postural mechanism for effort dyspnea
– High specificity for Tetralogy of Fallot
– Multiple ways of benefits
# orthostatic hypotension
# deoxygeneted blood of lower limbs
# increase SVR Peaks at 2 mo – 6 months of
age
promotes Left to Right shunt, antegrade flow
# respiratory stimulus for hyperventilation
Clinical profile – polycythemia….
• An adaptive mechanism – increase O2 carrying
– Double edged, simultaneous ill effects common
• Chronic as well as acute complications common
• Hct > 65 % viscosity rises exponentially - hyperviscosity
• Chronic effects
Relative anemia, iron deficiency
Sluggish circln – TIA/ CVA/ CVT/ brain abscess Low
MR, grade DIC (consumption coagulopathy)
velopharyngeal
Hemoptysis – infarct/ thrombosis/ rupture
insuff
Hyperuricemia
Arthritis
Clinical profile – Heart failure
• An uncommon entity theoretically
– Upto 10 % may have in early infancy (mild PS)
– Associated conditions makes it possible
Anemia
Restrictive VSD
Large collateral flow (specially in TF/PA)
Infection/ infective endocarditis
Systemic hypertension/ LVOTO
Aortic regurgitation – uncommon (<1.0 %)
Myocardial diseases
Progressive RV/ LV dysfunction (ongoing fibrosis)
Clinical profile – others
• Infective endocarditis
– Regurgitant/ bicuspid aortic valve
– Stenotic/ deformed pulmonary valve
• Systemic infections
– Chronic hypoxia
– Hypoplastic lung alveolar & vasculature (mainly TF/PA)
– Associated genetic disorders with immunodeficiency
• Poor effort tolerance
– Chronic hypoxia, poor respiratory reserve
• Late onset VT & SCD (uncommon, upto 12 %)
– Secondary to ongoing fibrosis, increases with age
• Pregnancy – poorly tolerated, high fetal wastage
Clinical profile – survival
Clinical profile – survival
Modes of death
When to intervene – optimum
age ?
• Symptomatic child – single stage preferred
Severe cyanosis SpO2 < 70%
Recurrent spells even on beta blocker
Polycythemia Hb > 18 gm% / Hct > 60 %
• Usual optimum age – 3 to 12 mo
• Contraindications to ICR – mandates two stage
– Hypoplastic pulmonary vasculature
– Major coronary artery/ branch crossing RVOT
# Multiple VSDs needs modification – usually 2
staged
Palliation -
a. Blalock Taussig classic
b. Blalock Taussig modified
c. Blalock Taussig modified
d. Central shunt
e. Pott’s shunt – LPD
f. Waterson’s shunt – RAW
g. Percutaneous PV valvloplasty
How to intervene – complete
repair
• Early complete repair –
– Advantages
eliminates hypoxia cognitive deficits
Avoid R L shunt causing cerebral emboli
Avoid progressive RVH, allows proper PA & alveolar growth
Prevent MAPCA related PVOD, shunt related complications
Smaller Ventriculotomies
– Disadvantages
not for coronary across RVOT/ multiple VSD/ small PA
more chances of using TAP Pulmonary regurg
# Iatrogenic pulmonary artery problems (rare)
# Pulmonary vascular disease (>5 years)
# Unknown attrition rate (up to 7%)
# Development of subendocardial fibrosis in infundibulum
How to intervene – complete
repair
• Approach –
– Atrial/ ventricular/ PA/ combined
– Based on need of patch closure/ TAP
– Atrial is preferred – no RBBB/ VTs
• TAP required –
– Hypoplastic PAs
Z score of RV – PA trunk junction
MaGoon index LPA + RPA /DTA < 1.3 (n = 2)
Nakata index ALPA + ARPA/BSA < 150 mm2/m2
– Intraoperative PRV/LV > 0.7
How to intervene – complete
repair
How to intervene – complete
repair