Tetralogy of Fallot: Comprehensive Overview
Definition and Core Anatomic Features
Tetralogy of Fallot (TOF) is a congenital cyanotic heart malformation characterized by four mandatory anatomic components: anterosuperior deviation of the conal/outlet septum causing right ventricular outflow tract (RVOT) obstruction, a malalignment-type ventricular septal defect (VSD), biventricular origin of the aorta (aortic override), and right ventricular hypertrophy. 1
The fundamental pathophysiology stems from the anterosuperior deviation of the outlet septum, which creates the RVOT obstruction and malalignment VSD simultaneously. 1 This anatomic arrangement forces deoxygenated blood from the right ventricle to shunt across the VSD into the overriding aorta, producing cyanosis. 2, 3
Clinical Presentation and Physical Examination Findings
Unoperated/Pre-Repair Patients
Cyanosis severity inversely correlates with murmur intensity: Patients with severe RVOT obstruction have less flow across the outflow tract, producing a softer systolic ejection murmur but more profound cyanosis. 4
Loud precordial systolic ejection murmur from RVOT obstruction is the hallmark finding, often mistaken for an isolated small VSD. 4
"Pink tetralogy" (mild pulmonary obstruction) presents with minimal cyanosis and a loud precordial murmur, frequently misdiagnosed as isolated VSD. 4
Patients with severe obstruction and abundant aortopulmonary collaterals may have loud continuous murmurs over the thorax. 4
Clubbing and polycythemia develop in unrepaired cases due to chronic hypoxemia. 5
Post-Repair Patients
Absent P2 component of the second heart sound is the most consistent finding, reflecting pulmonary valve disruption or absence after repair. 4
Soft ejection systolic murmur from the RVOT is common. 4
Low-pitched, delayed diastolic murmur in the pulmonary area indicates pulmonary regurgitation, nearly universal after transannular patch repair. 4
Pansystolic murmur suggests residual VSD or VSD patch leak. 4
Diastolic murmur of aortic regurgitation may occur, particularly with aortic root dilation. 4
Diagnostic Approach
Initial Diagnosis
Echocardiography remains the primary diagnostic modality for identifying the four anatomic components, assessing severity of RVOT obstruction, and evaluating associated anomalies. 6, 7
Preoperative Imaging
Cardiac MRI is indicated prior to surgery to evaluate detailed anatomy, ventricular function, valve function, hemodynamics, and tissue characterization with late gadolinium enhancement for prognostication. 8 This is essential for surgical planning when echocardiography does not show primary indication for intervention or increased pressures. 8
CT plays an increasing role in assessing associated pulmonary arterial, aortic and coronary anomalies, as well as extra-cardiovascular structures, particularly helpful for delineating complex anatomy in TOF subtypes. 7
Fetal Diagnosis
Refinement of fetal screening and echocardiography has increased prenatal diagnosis rates. 6 Prenatal diagnosis, along with recognition of extracardiac anomalies and genetic abnormalities (including 22q11 deletion), establishes the framework for prenatal counseling and helps predict postnatal course. 6
Surgical Management
Timing and Approach
Complete surgical repair should be performed in infancy, typically between 3-6 months of age, with VSD closure and RVOT obstruction relief, achieving survival rates exceeding 98% and 30-year survival rates above 90%. 8, 3
The definitive repair consists of:
- VSD closure using a patch 8
- Relief of RVOT obstruction 8
- Pulmonary valve management 8
- Extracardiac conduit placement when necessary 8
Surgical Technique Options
Two main approaches exist for RVOT reconstruction: 8
Transannular patch repair: Most commonly used when valve preservation is not feasible, though this invariably results in severe pulmonary regurgitation and subsequent RV volume overload. 8
RV to pulmonary artery conduit: Alternative approach that may also result in pulmonary regurgitation and RV volume overload. 8
Contemporary Outcomes
Long-Term Complications and Surveillance
Nearly Universal Postoperative Complications
- Pulmonary regurgitation leading to RV volume overload 8
- RV systolic and diastolic dysfunction 8
- LV dysfunction 8
- Decreased exercise capacity 8
- Arrhythmias 8
- Residual or recurrent RVOT obstruction 8
- Tricuspid regurgitation 8
Lifelong Surveillance Requirements
All patients require lifelong annual follow-up with an adult congenital heart disease specialist, including: 8
- History and physical examination
- 12-lead ECG
- Comprehensive echocardiography
- Cardiac MRI for precise RV volume quantification and pulmonary regurgitation assessment
Reintervention Indications
Reoperation is indicated for: 8
- Symptomatic patients with severe pulmonary regurgitation
- Asymptomatic patients with severe pulmonary stenosis or pulmonary regurgitation plus progressive or severe RV enlargement or dysfunction
- Residual RVOT obstruction with RV/LV pressure ratio >0.7
Pulmonary valve replacement is the most common reintervention, with heterograft or homograft preferred. 8
Critical Clinical Pitfalls
Auscultation Limitations
The severity of pulmonary regurgitation is often underestimated by auscultation compared to Doppler echocardiography—absence of an audible diastolic murmur does NOT exclude significant pulmonary regurgitation. 4 Serial CMR imaging is required for accurate assessment. 8
Unexpected Findings
A loud P2 is NOT expected in repaired TOF and should prompt evaluation for pulmonary hypertension from alternative causes. 4
Surgical Considerations
Transannular patch repair inevitably causes severe pulmonary regurgitation—valve-sparing techniques should be employed when anatomically feasible to minimize long-term RV volume overload. 8
Delayed recognition of RV dysfunction is common, requiring proactive serial imaging rather than relying on clinical symptoms alone. 8
Natural History Without Repair
Patients with unoperated TOF rarely reach adulthood, and it is extremely rare to discover undiagnosed TOF in individuals over 60 years old. 5 Survival depends on the degree of RVOT obstruction, presence of aortopulmonary collaterals, and associated anomalies. 5
Associated Anomalies
TOF may be associated with: 6, 5
- Patent ductus arteriosus
- Multiple aortopulmonary collateral arteries
- Extracardiac abnormalities
- Genetic abnormalities including 22q11 deletion
These associated conditions significantly impact patient survival and surgical planning. 6