💙 Tetralogy of Fallot (TOF)

1. Definition

Tetralogy of Fallot (TOF) is a cyanotic congenital heart disease characterized by a combination of four cardiac anomalies which are:
1. Pulmonary stenosis
2. Right ventricular hypertrophy
3. VSD
4. Overriding of aorta
Resulting in right-to-left shunting of blood and reduced oxygenation.
It is the most common cause of cyanotic heart disease beyond the neonatal period.

2. Causes

Embryologic maldevelopment of the conotruncal septum leading to misalignment of the aorticopulmonary septum
Often sporadic, but may be associated with:
- Chromosomal abnormalities (e.g., 22q11.2 deletion syndrome/DiGeorge)
- Genetic syndromes (Down syndrome, Alagille)
- Maternal diabetes or retinoic acid exposure

3. Risk Factors

Family history of congenital heart disease
Chromosomal disorders (e.g., 22q11 deletion, trisomies)
Maternal illnesses (e.g., diabetes, phenylketonuria)
Teratogenic exposures during pregnancy

4. Types

Type	Description
Classic TOF	All 4 components: VSD, RVOTO, overriding aorta, RVH
TOF with pulmonary atresia	More severe; complete RVOT obstruction
TOF with absent pulmonary valve	Rare; pulmonary regurgitation and airway compression
Pink TOF	Less severe RVOTO; minimal cyanosis

5. Pathogenesis

Right ventricular outflow tract obstruction (RVOTO) increases pressure in the right ventricle.
Blood is shunted right-to-left across the VSD due to increased RV pressure.
Deoxygenated blood enters the systemic circulation, leading to cyanosis.
Chronic hypoxemia → polycythemia, clubbing.
"Tet spells" occur due to sudden increase in right-to-left shunting (crying, feeding, exertion).

Where can RVOTO occur?

Location	Example
Subvalvular (infundibular)	Muscle narrowing below pulmonary valve
Valvular	Pulmonary valve stenosis
Supravalvular	Narrowing above the pulmonary valve
Combined	Seen in complex congenital heart disease

6. Clinical Presentation

Symptoms

Cyanosis (especially during crying/feeding)
Breathlessness, fatigue during feeding or exercise
"Tet spells" (sudden cyanosis, irritability, syncope)
Poor weight gain
Squatting posture in older children (increases SVR)

Signs

Central cyanosis
Clubbing of fingers and toes (long-standing cyanosis)
Harsh systolic ejection murmur (due to RVOTO)
Single second heart sound (A2 only)

Physical Examination

Systolic thrill at left upper sternal border
Cyanotic mucous membranes
Quiet precordium despite significant murmur
Normal or decreased peripheral pulses

7. Organ & System Complications

System	Complication
Cardiac	Right heart failure, arrhythmias, endocarditis
Respiratory	Hypoxic spells, polycythemia-induced thrombosis
Neurologic	Stroke, brain abscess, developmental delay
Hematologic	Polycythemia, iron deficiency
Growth & Nutrition	Failure to thrive

8. Diagnostic Investigations

Test	Reason
Chest X-ray	Boot-shaped heart (RVH), decreased pulmonary vascularity
ECG	Right axis deviation, right ventricular hypertrophy
Echocardiogram	Confirms all 4 components, assesses RVOTO and aortic override
Pulse oximetry	Persistent low saturations

9. Other Relevant Investigations

Test	Reason
Hb & HCT	Assess for polycythemia
Iron studies	Rule out iron deficiency in cyanotic child
Genetic testing	Screen for 22q11.2 deletion or other syndromes
Cardiac catheterization	Preoperative planning in complex or unclear anatomy

10. Treatment

Curative/Definitive

Total surgical repair (VSD closure + RVOT relief), usually done between 3–12 months of age

Empirical

Prostaglandin E1 in ductus-dependent neonates (to maintain PDA)
Beta-blockers (e.g. propranolol) for hypercyanotic ("tet") spells

Supportive

Knee-chest position for tet spells (increases SVR)
Oxygen and IV fluids during spells
Iron supplementation (if iron deficiency with polycythemia)
Nutritional support for failure to thrive

Palliative

Modified Blalock-Taussig (BT) shunt for high-risk neonates before complete repair

11. Long-Term Effects/Complications of Treatment

Treatment	Complication	Monitoring	Expected Results
Surgical repair	Pulmonary regurgitation, RV dilation	Annual echo, MRI	Stable RV size, preserved function
BT shunt (if done)	Shunt thrombosis, overcirculation	Clinical review, saturation checks	Adequate O2, weight gain
Polycythemia treatment	Iron deficiency	Iron studies, CBC	Normal HCT with adequate iron stores
Arrhythmias (post-repair)	Ventricular tachycardia	Holter ECG, clinical symptoms	Normal rhythm, no syncope

12. Surveillance for the Disease

Domain	Frequency	What to Monitor
Cardiac function	Yearly post-surgery	Echo, ECG, RV function, valve regurgitation
Growth & development	Every 3–6 months	Weight, height, developmental milestones
Hematology	Every 6–12 months	CBC, HCT, iron studies
Neurology	If concerns arise	Developmental assessment, neuroimaging if needed
Dental	Regular check-ups	Prevent endocarditis (good oral hygiene)

13. Malaysia Support Group for Parents

Support Group	Description	Contact/Link
MyHeart (Malaysia Congenital Heart Assoc.)	Parent-led group, emotional and educational support	Facebook: MyHeart Malaysia
Yayasan Jantung Malaysia (YJM)	Heart awareness and support programs	www.yjm.org.my
Hospital-based cardiac clinics	Follow-up with pediatric cardiology and surgery team	Available in IJN, HKL, HUSM, UMMC, Penang GH, etc.