Key Facts

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect, comprising four anatomical abnormalities that result from anterior malalignment of the infundibular septum.

Epidemiology

• Most common cyanotic CHD: ~10% of all congenital heart defects
• Incidence: ~3-5 per 10,000 live births
• Equal sex distribution

Aetiology

• Anterior malalignment of the infundibular (conal) septum — this single embryological defect produces all four features
• Genetic: 22q11.2 deletion (DiGeorge syndrome) in ~15%; Down syndrome; JAG1 mutations
• Environmental: maternal diabetes, phenylketonuria, rubella, fetal alcohol syndrome

Pathophysiology

• RVOT obstruction (infundibular muscular stenosis ± valvular PS) increases RV pressure
• Large non-restrictive VSD allows bidirectional shunting
• Direction of shunt depends on balance between systemic vascular resistance (SVR) and RVOT obstruction
• If RVOT obstruction is severe: right-to-left shunt → cyanosis (deoxygenated blood enters aorta)
• Degree of RVOT obstruction determines severity: mild = 'pink ToF' (acyanotic); severe = cyanotic
• RV hypertrophy develops secondary to pressure overload
• Tet spells: acute increase in RVOT obstruction (infundibular spasm) or decrease in SVR → sudden increase in right-to-left shunt → profound cyanosis

Neonatal/Infant Presentation

• Cyanosis: present from birth in severe cases; develops over first months in moderate
• 'Pink' ToF: mild RVOT obstruction, minimal or no cyanosis initially

Tet Spells (Hypercyanotic Episodes)

• Usually 2-6 months of age
• Sudden onset: deep cyanosis, agitation, rapid deep breathing (hyperpnoea), limpness
• Triggers: crying, feeding, defecation, fever, dehydration
• May lead to loss of consciousness, seizures, stroke, or death
• Squatting posture: older children squat to increase SVR (increases systemic resistance → reduces right-to-left shunt → improves pulmonary blood flow)

Examination Findings

• Central cyanosis (variable degree)
• Clubbing (older children with chronic cyanosis)
• Ejection systolic murmur at LUSE: due to RVOT obstruction (NOT the VSD — which is non-restrictive)
• Single S2 (soft/absent P2 due to reduced pulmonary flow)
• Softer murmur during tet spell (less flow through RVOT)
• No signs of heart failure (VSD is non-restrictive, ventricles equalise)

Red Flags

• Tet spell: medical emergency
• Progressive cyanosis
• Polycythaemia with hyperviscosity symptoms
• Brain abscess (paradoxical embolism)
• Stroke

Bedside

• Pulse oximetry: low SpO₂ (typically 75-90% in cyanotic ToF)
• ECG: RAD, RVH (tall R in V1, deep S in V6), right atrial enlargement
• CXR: boot-shaped heart (upturned apex from RVH with concave PA segment), oligaemic lung fields, right-sided aortic arch (~25%)

Bloods

• FBC: polycythaemia (secondary to chronic hypoxia)
• Blood gas: metabolic acidosis during tet spells
• Coagulation: may be deranged with severe polycythaemia
• Iron studies: iron deficiency worsens hyperviscosity risk in polycythaemia

Imaging

• Echocardiography: diagnostic — shows all four components; RVOT anatomy, VSD size, overriding aorta, coronary artery anatomy
• Cardiac MRI/CT: detailed RVOT anatomy, pulmonary artery anatomy, coronary anatomy (important pre-surgery)
• Cardiac catheterisation: rarely needed pre-operatively unless complex anatomy

Special Tests

• Genetic testing: 22q11.2 deletion (FISH or microarray) — especially if associated anomalies (cleft palate, immune deficiency, hypocalcaemia)
• Hyperoxia test: differentiates cardiac from respiratory cyanosis (minimal PaO₂ increase in cardiac causes)

Non-pharmacological

Tet spell management (emergency):

1. Knee-chest position (simulates squatting — increases SVR)
2. Calm the child (crying worsens spasm)
3. Oxygen (minimal effect but harmless)
4. IV morphine 0.1-0.2 mg/kg: reduces respiratory drive and relaxes infundibular spasm
5. IV fluid bolus: increases preload
6. IV phenylephrine 5-10 mcg/kg: alpha-agonist, increases SVR
7. IV propranolol: relaxes infundibular spasm
8. If refractory: emergency surgery

Pharmacological

• Propranolol 1-2 mg/kg TDS oral: prophylaxis against tet spells (relaxes infundibular muscle, reduces spasm)
• Iron supplementation: if iron-deficient (iron deficiency worsens hyperviscosity)
• Prostaglandin E1: in neonates with severe cyanosis (duct-dependent pulmonary blood flow)

Surgical/Interventional

• Complete intracardiac repair: definitive treatment
  • VSD patch closure + RVOT reconstruction (resection of muscle bundles ± transannular patch if needed)
  • Timing: electively at 3-6 months of age
  • Operative mortality: <2% in experienced centres
• Modified Blalock-Taussig (BT) shunt: palliative; systemic-to-PA shunt (subclavian to PA via Gore-Tex tube) for severely cyanotic neonates as bridge to definitive repair
• Balloon pulmonary valvuloplasty: palliative if predominant valvular stenosis
• Late pulmonary valve replacement (PVR): for severe PR following repair (timing guided by RV volumes on MRI)

Referral Criteria

• All cyanotic neonates: immediate neonatal/paediatric cardiology referral
• Tet spells: emergency management, expedite surgical repair
• Repaired ToF adults: lifelong GUCH follow-up

• Without surgery: only 50% survive to age 5; <5% survive to age 40
• Post-complete repair: 30-year survival >90%
• Operative mortality: <2% for uncomplicated ToF repair
• Most common late complication: pulmonary regurgitation → RV dilatation → RV failure/arrhythmias
• ~10-15% require PVR within 20 years of initial repair
• Late arrhythmias (VT, AF): occur in ~10-15%; leading cause of late death
• QRS duration >180 ms post-repair is a risk factor for sudden death
• Excellent quality of life with modern surgical techniques and follow-up

Four Components of Tetralogy of Fallot

Tet Spell Management Algorithm