Tetralogy of Fallot

Definition and Anatomy

Most common cyanotic congenital heart disease.
Primary embryonic defect: Anterior and cephalad deviation of infundibular (conal) septum.
Four classic anatomic components:
- Right ventricular outflow tract (RVOT) obstruction (infundibular, valvar, or supravalvar pulmonary stenosis).
- Malalignment ventricular septal defect (VSD).
- Dextroposition/overriding aorta.
- Right ventricular hypertrophy (RVH).

Unrestrictive VSD permitting equalized systolic pressures between right and left ventricles.
Shunt direction and cyanosis severity dictated by RVOT obstruction severity.
Mild RVOT obstruction: Balanced or left-to-right shunting, minimal cyanosis ("Pink TOF").
Severe RVOT obstruction: Right-to-left shunting, systemic hypoxemia, overt clinical cyanosis.
Pulmonary blood flow inversely proportional to RVOT obstruction severity.
Extreme obstruction: Ductus arteriosus patency critical for neonatal pulmonary blood flow.

Incidence: 25 to 40 per 100,000 live births.
Accounts for 5% to 10% of all congenital heart defects.
Genetic association: 22q11. 2 microdeletion (DiGeorge/Velocardiofacial syndrome) in approximately 13% to 40% of cases.
Additional syndromic associations: Trisomy 21 (commonly with associated atrioventricular canal defects), Alagille syndrome, VACTERL association.
Maternal risk factors: Untreated phenylketonuria, pregestational diabetes, retinoic acid exposure.

Cyanosis present from 6 week of life or appearing in early infancy (worsens with ductal closure).
Severity of cyanosis inversely related to systolic murmur intensity.
Effort intolerance and exertional dyspnea.
Squatting behavior in older children (increases systemic vascular resistance, augmenting pulmonary blood flow).
Delayed growth and puberty in unoperated patients.
Digital clubbing in older, chronically hypoxemic patients.

Normal peripheral pulses and central venous pressures.
Prominent left parasternal heave or right ventricular impulse.
Palpable systolic thrill at mid/upper left sternal border.
Normal first heart sound (S1).
Single second heart sound (S2) or soft, delayed pulmonary component.
Harsh, crescendo-decrescendo ejection systolic murmur at mid/upper left sternal border (originating from RVOT turbulence, not VSD).
Murmur shortens and softens with progressive RVOT obstruction.

Right aortic arch (20% to 25% of cases).
Coronary artery anomalies (e. g. , Left anterior descending artery originating from right coronary artery in 5% to 10% of cases).
Patent ductus arteriosus (PDA).
Multiple VSDs.
Atrioventricular septal defect (AVSD).
Absent pulmonary valve syndrome.
Major aortopulmonary collateral arteries (MAPCAs) (in pulmonary atresia variants).

Modality	Key Findings
Electrocardiogram (ECG)	Right axis deviation (RAD). Right ventricular hypertrophy (RVH) (tall R wave in V1, deep S wave in V6). Upright T wave in V1. Right atrial enlargement (peaked P waves).
Chest Radiograph (CXR)	Normal overall cardiac size. "Boot-shaped" cardiac silhouette (Coeur en Sabot) due to upturned RV apex. Concave main pulmonary artery segment ("pulmonary bay"). Oligemic (decreased) pulmonary vascular markings. Right-sided aortic arch (indentation on right side of trachea).
Echocardiography	Diagnostic modality of choice. Anterior malalignment of conal septum. Overriding aorta with mitral-aortic fibrous continuity. Large malalignment VSD. Multilevel RVOT obstruction evaluation via continuous/pulsed wave Doppler. Assessment of pulmonary valve annulus and branch pulmonary arteries.
Cardiac CT / MRI / Angiography	Indicated for complex pulmonary artery anatomy evaluation. Delineation of coronary artery anomalies (LAD from RCA) crossing RVOT. Post-repair quantification of RV volumes, ejection fraction, and pulmonary regurgitation.

Intravenous Prostaglandin E1 (PGE1) infusion (0. 01 - 0. 1 mcg/kg/min) for severe neonatal RVOT obstruction (maintains ductal patency for pulmonary blood flow).
Iron supplementation for optimal oxygen-carrying capacity (treatment/prevention of relative anemia in polycythemic patients).
Intravenous hydration to prevent hyperviscosity complications.

Indicated for premature, low-birth-weight infants, or patients with unfavorable anatomy (e. g. , severe pulmonary artery hypoplasia, complex coronary crossing RVOT).
Modified Blalock-Taussig-Thomas (mBTT) shunt: Polytetrafluoroethylene (PTFE) tube graft anastomosis between subclavian artery and ipsilateral branch pulmonary artery.
Transcatheter alternatives: RVOT stenting, balloon pulmonary valvuloplasty, or ductal stenting.

Elective timing typically between 3 and 12 months of age (commonly 4-6 months).
Cardiopulmonary bypass utilization.
Transatrial-transpulmonary approach preferred (avoids large right ventriculotomy).
VSD patch closure.
RVOT obstruction relief (infundibular muscle resection, pulmonary valvotomy).
Transannular patch placement for hypoplastic pulmonary valve annulus.
"Valve-sparing" strategies increasingly preferred to mitigate long-term pulmonary regurgitation.

Preoperative Complications	Postoperative Complications
Polycythemia and hyperviscosity syndrome	Pulmonary valve regurgitation (common post-transannular patch)
Cerebral thrombosis/stroke (exacerbated by dehydration and iron deficiency)	Right ventricular dilation and systolic/diastolic dysfunction
Brain abscess	Ventricular arrhythmias and sudden cardiac death
Infective endocarditis / endarteritis,	Right bundle branch block (RBBB),
Delayed puberty and growth failure	Residual RVOT obstruction or branch pulmonary artery stenosis
Congestive heart failure (rare, seen in "pink" TOF with large left-to-right shunt),	Atrial arrhythmias (e. g. , atrial flutter, atrial fibrillation)
	Aortic root dilation and progressive aortic regurgitation