Tetralogy of Fallot (TOF)

The Four Cardinal Features

Classic TOF: deoxygenated blood shunts right-to-left through the VSD into the overriding aorta (Robbins & Kumar Basic Pathology)

Embryology

• The subpulmonic conus fails to expand normally
• This produces anterocephalad deviation of the outlet septum with hypertrophy of the septoparietal trabeculations
• The result is simultaneous subpulmonary stenosis, malalignment VSD, and an aorta that overrides the defect
• The RVH is entirely secondary - it is not a primary developmental defect
• The Developing Human (Moore), p. 4435-4447

Gross Morphology

• Heart is enlarged and "boot-shaped" (coeur en sabot) due to RVH with a concave main pulmonary artery segment
• Proximal aorta is dilated; pulmonary trunk is hypoplastic
• Left-sided chambers are normal in size
• RV wall can be as thick or thicker than the LV
• In severe cases (pulmonary atresia): a persistent PDA or bronchial collateral vessels are the only routes for pulmonary blood flow
• Robbins & Kumar Basic Pathology, p. 288-292

Hemodynamics

• Mild RVOT obstruction ("Pink Tet"): Left-sided pressure still dominates → left-to-right shunt → no cyanosis. Pink tets gradually become cyanotic by 1-3 years of age.
• Severe RVOT obstruction: Right-to-left shunting of deoxygenated blood → cyanosis from early infancy. Infants with severe obstruction may need PGE1 to maintain pulmonary flow via the PDA.

Blood shunting in TOF: severity of RVOT obstruction (OB) and systemic vascular resistance (SVR) determine the magnitude of right-to-left shunt (Rosen's Emergency Medicine)

Clinical Features

• Cyanosis (may deepen with crying, feeding, or exertion)
• Dyspnea on exertion
• Squatting posture in older children (increases SVR, reduces right-to-left shunt)
• Compensatory polycythemia
• Digital clubbing

• Varying cyanosis
• Systolic ejection murmur along the left sternal border (from RVOT obstruction - not from the VSD, which is typically silent)
• Single second heart sound (soft P2 due to low pulmonary pressure)
• RV heave

Tet Spells (Hypercyanotic / Hypoxic Spells)

↓ SVR  →  ↑ R→L shunt via VSD
→  ↓ PaO₂, ↑ PCO₂, ↓ pH (acidosis)
→  Hyperpnea → ↑ venous return to RV
→  More blood shunted R→L → ↑ hypoxia
→  Further ↓ SVR → worsening spell

Management of a Tet Spell (Rosen's Box 165.8)

1. Knee-to-chest position - compresses femoral arteries, raises SVR, reduces R-to-L shunt
2. Supplemental oxygen (limited benefit alone)
3. Morphine 0.1-0.2 mg/kg IV/IM (reduces hyperpnea, decreases sympathetic tone)
4. Fentanyl 1 µg/kg IV/IM (alternative to morphine); or 1.5-2 µg/kg intranasally
5. Midazolam 0.2-0.3 mg/kg intranasally
6. Sodium bicarbonate 1 mEq/kg IV if acidosis present
7. Ketamine 1-2 mg/kg IV or 3-5 mg/kg IM (raises SVR)
8. Propranolol 0.1-0.2 mg/kg (reduces infundibular spasm)
9. Phenylephrine 0.01-0.02 mg/kg IV (pure alpha agonist, raises SVR)

Associated Anomalies

• Right-sided aortic arch (~25%)
• Coronary artery anomalies - most commonly LAD originating from RCA, crossing the RVOT (surgical importance: may require RV-to-PA conduit instead of direct RVOT patch)
• ASD ("Pentalogy of Fallot" when ASD is present)
• AVSD (in Down syndrome)

Anatomic Variants

Surgical Management

• Blalock-Taussig-Thomas (BTT) shunt - subclavian artery to PA; increases pulmonary blood flow

• VSD closure with a patch
• RVOT reconstruction (infundibulectomy + patch, or transannular patch if annulus is small)
• Branch PA augmentation if hypoplastic

Left (A): Native TOF anatomy. Right (B): Post-repair anatomy with VSD patch and RVOT patch, and potential long-term complications (Braunwald's Heart Disease)

Long-term Complications After Repair

• Braunwald's Heart Disease, p. 2774-2808

Key Points Summary

• TOF = VSD + RVOT obstruction + overriding aorta + RVH - all from one embryologic defect (infundibular septum malalignment)
• Most common cyanotic CHD beyond infancy (~5% of all CHD)
• Clinical severity tracks with degree of RVOT obstruction
• Tet spells: manage with knee-chest position + morphine + bicarbonate ± phenylephrine
• Definitive treatment is surgical correction - primary repair in infancy is preferred
• Long-term: pulmonary regurgitation is the dominant post-repair problem, monitored with CMR; PVR when RV is significantly dilated
• Right aortic arch in 25%; coronary anomalies must be excluded before surgery

Tetralogy of Fallot - 1st Year MBBS

What is it?

The Four Defects (Must Memorize)

Mnemonic: PROVE - Pulmonary stenosis, RVH, Overriding aorta, VSD

Classic TOF: Note the enlarged RV (blue/mixed blood), small PT (pulmonary trunk), and the large Ao sitting over both ventricles - Robbins & Kumar Basic Pathology

Embryology (Most Important for 1st Year)

Normal Development (Quick Recap)

• The primitive heart tube has a single outflow channel called the truncus arteriosus
• The truncus arteriosus is divided into the aorta and pulmonary trunk by a spiraling septum called the aorticopulmonary septum
• At the same time, the interventricular septum grows upward to close the gap between the two ventricles
• The infundibular (outlet) septum separates the outflows of the two ventricles

What Goes Wrong in TOF

Anterosuperior displacement of the infundibular septum during development

Infundibular septum displaced anterosuperiorly
              ↓
    ┌─────────────────────────────────┐
    │  Unequal division of truncus    │
    │  arteriosus                     │
    └──────────┬──────────────────────┘
               │
    ┌──────────▼──────────────────────┐
    │  Pulmonary trunk → too SMALL    │  → Pulmonary stenosis (#1)
    │  Aorta → too BIG (dilated)      │
    └──────────┬──────────────────────┘
               │
    ┌──────────▼──────────────────────┐
    │  Interventricular septum        │
    │  cannot close properly          │  → VSD (#2)
    └──────────┬──────────────────────┘
               │
    ┌──────────▼──────────────────────┐
    │  Large aorta shifts to sit      │
    │  over the VSD                   │  → Overriding aorta (#3)
    └──────────┬──────────────────────┘
               │
    ┌──────────▼──────────────────────┐
    │  RV pumps against obstruction   │
    │  → wall thickens                │  → RVH (#4)
    └─────────────────────────────────┘

• Note: RVH is secondary - it is not a primary developmental defect. It develops after birth as the RV works against the RVOT obstruction.
• Extreme form: Pulmonary atresia with VSD - the pulmonary trunk is completely blocked; all blood exits through the aorta. Lungs get blood only via a Patent Ductus Arteriosus (PDA) or bronchial collaterals.

Anatomy of the Defects

1. The Heart's Shape

• The heart looks "boot-shaped" (coeur en sabot) on X-ray
• This is because the RV is massively enlarged and the pulmonary trunk segment is concave (small)

2. VSD Location

• Usually large and perimembranous (near the membranous part of the interventricular septum)
• Located just below the overriding aortic valve

3. Pulmonary Stenosis

• Most commonly infundibular (subpulmonic) - the narrowing is in the muscular outflow channel below the pulmonary valve
• Can also involve the pulmonary valve itself
• In extreme cases: pulmonary atresia (complete blockage)

4. Overriding Aorta

• The aortic root is displaced to the right and sits directly above the VSD
• It receives blood from BOTH the left and right ventricles

5. Right Ventricular Hypertrophy

• The RV wall becomes as thick or thicker than the LV
• This is a compensatory change, not a primary structural defect

Physiology - Why Cyanosis Occurs

Normal Blood Flow (for comparison):

Deoxygenated blood → RV → Pulmonary artery → Lungs → Oxygenated

In TOF:

Deoxygenated blood in RV
        ↓
Pulmonary artery is NARROW (stenosis)
        ↓
Blood cannot easily go to lungs
        ↓
Takes the easier path → Through the VSD into LV
        ↓
Mixes with oxygenated blood from lungs
        ↓
Exits through the OVERRIDING AORTA
        ↓
Deoxygenated (mixed) blood goes to body
        ↓
CYANOSIS (blue baby)

The Severity Depends on How Narrow the Pulmonary Stenosis Is:

• In "Pink Tets," cyanosis may not be present at birth but gradually develops by 1-3 years of age as the infundibular obstruction worsens

Simple Clinical Points (1st Year Level)

Summary Box for Exam