Tetralogy of Fallot

Overview

Definition

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease and has the following 4 (tetra) features:

• Right ventricular outflow obstruction (pulmonary stenosis (PS))
• Interventricular communication (ventricular septal defect (VSD))
• Concentric right ventricular hypertrophy (RVH)
• Overriding aorta (over the VSD)

Epidemiology

• 7%–10% of congenital heart defects
• Most common cyanotic congenital heart disease
• Prevalence: 4–5 per 10,000 live births
• Boys = girls
• Reduced life expectancy if untreated, 90% mortality rate in < 20 years of age

Etiology

• Deviation of the infundibular septum during fetal development results in:
  • Large malaligned VSD (sometimes extends into muscular septum)
  • Aorta displaced to the right
  • Right ventricular outflow tract (RVOT) obstruction at multiple levels:
    • Subvalvular (septal deviation + muscular hypertrophy)
    • Hypoplastic/stenotic valve
    • Stenotic pulmonary artery
• Most cases are sporadic, but a genetic component is likely.
• 15% have a syndromic association:
  • DiGeorge syndrome
  • Down’s syndrome
  • Alagille syndrome
• Non-genetic risk factors:
  • Rubella infection during pregnancy
  • Maternal use of alcohol
  • Maternal age > 40

Mnemonics

DROP:

• Displaced aorta
• Right ventricular hypertrophy
• Opening in the septum
• Pulmonary stenosis

PROVe:

• Pulmonary stenosis
• Right ventricular hypertrophy
• Overriding aorta
• VSD

Pathophysiology

• VSD is large and unrestrictive.
• Pressure in left and right ventricles is essentially equal.
• The direction of blood flow depends on the degree of RVOT obstruction:
  • Acyanotic presentation:
    • RVOT resistance < aortic resistance
    • Left-to-right shunting
  • Cyanotic presentation:
    • RVOT resistance (significant RVOT obstruction) > aortic resistance
    • Right-to-left shunting
  • Shunting can fluctuate:
    • Dynamic increase in RVOT resistance
    • Sudden cyanotic (“tet”) spells
• TOF may be associated with other cardiac defects:
  • Right aortic arch (25% of cases)
  • Abnormalities of coronary arteries
  • Multiple VSDs
  • Complete atrio-ventricular septal defects
  • Patent ductus arteriosus

Clinical Presentation

Age of presentation is inversely proportional to the degree of RVOT obstruction.

Severe RVOT obstruction

• Presents in newborns
• Profound cyanosis
• Lethargy
• Poor feeding

Mild-to-moderate RVOT obstruction

• Usually within 6 weeks of birth
• Murmur picked up on physical exam
• Progressive increase in RVOT obstruction → cyanosis
• Failure to thrive
• Tet spells:
  • Worsening cyanosis
  • Hyperpnea (rapid, shallow breaths)
  • Irritability
  • Precipitated by rapid increase in RVOT resistance:
    • Pain, crying
    • Feeding
    • Bowel movement
    • Agitation
    • Fever

Minimal RVOT obstruction

• Initially asymptomatic
• Develop pulmonary overcirculation in first 4–6 weeks
• Heart failure: dyspnea, tachypnea

Diagnosis

Physical examination

• Patients with mild forms appear to be in no distress except for tet spells.
• Blue lips or nail beds if cyanosis is present
• Failed pulse oximetry with oxygen saturation < 92%
• Auscultation: 
  •  Pulmonic stenosis murmur: 
    • Systolic, crescendo-decrescendo, harsh ejection–like 
    • Heard at the left upper sternal border, radiating to the back
  • Single S2 (no pulmonic component)
  • Early systolic click
  • A systolic thrill in the 3rd and 4th intercostal spaces

Imaging

• Chest X ray:
  • “Boot-shaped” heart (upturned apex, concave main pulmonary artery)
  • Right aortic arch when present
• Echocardiogram:
  • Main confirmatory test
  • Can also be used for prenatal diagnosis
  • Evaluates:
    • Location and number of VSDs
    • Anatomy and severity of RVOT obstruction
    • Aortic arch anatomy
    • Coronary arteries
    • Associated anomalies

Other tests

• Electrocardiogram (ECG; signs of right ventricular hypertrophy):
  • Right axis deviation
  • Prominent R waves anteriorly
  • Prominent S waves posteriorly
  • Upright T wave in V1
• Cardiac catheterization:
  • To further delineate anatomy in addition to echocardiogram
  • Will show equal systemic left and right ventricular pressures
  • Normal or low pulmonary artery pressures
  • Can be therapeutic: balloon valvuloplasty of the pulmonary valve

Management

Medical management

• Neonates with severe form: intravenous prostaglandins to maintain ductus arteriosus patency
• Tet spells:
  • The rationale is to increase pulmonary blood flow.
  • Knee-chest position (squat for older children): increases systemic vascular resistance
  • Oxygen: vasodilator for pulmonary artery
  • IV fluids: improves right atrium filling volume
  • Morphine: mechanism unclear
  • Beta-blockers: RVOT relaxation
  • Phenylephrine: increases systemic afterload
• Heart failure:
  • Digoxin
  • Loop diuretics
  • Angiotensin-converting enzyme (ACE) inhibitors and receptor blockers should not be used.
• All cases: prophylactic antibiotics to prevent endocarditis until surgical repair

Surgical repair

Definitive:

• Always required for normal functioning/lifespan
• Preferred initial approach when feasible
• Usually performed within the first 6 months of life
• Procedure involves:
  • Repair of VSD
  • Enlargement of RVOT
  • Preservation of functional pulmonic valve if possible

Palliative:

• Indicated for:
  • Severe RVOT
  • Preterm infants (too small for definitive repair)
  • Refractory tet spell
  • Coronary artery abnormalities
  • Pulmonary artery hypoplasia
• Procedures:
  • Ductus arteriosus or RVOT stents
  • Shunts:
    • Modified Blalock-Taussig shunt (subclavian artery to pulmonary artery)
    • Central shunts

Prognosis

• Untreated: 
  • 50% mortality within 1st few years of life
  • Up to 90% by 18 years
• Repaired TOF patients may have a normal life expectancy.
• High cardiovascular morbidity; yearly monitoring required
• Higher morbidity with residual neurodevelopmental delay, even in treated infants
• Post-surgical complications are frequent:
  • Recurrence of RVOT requiring reoperation
  • Pulmonary valve insufficiency post-repair of the stenosis
  • Arrhythmias that may cause sudden cardiac death
  • Higher risk for bacterial endocarditis

Differential Diagnosis

• Tricuspid atresia: congenital heart disease characterized by the lack of development of the tricuspid valve. Presents with cyanosis, labored breathing, hypoxic spells. Holosystolic murmur and single S2 are present on exam. Diagnosis is made by echocardiogram and ECG.
• Transposition of the great vessels: congenital heart defect characterized by the switching of the great vessels so that the aorta originates from the right ventricle and the pulmonary artery from the left. Presents with cyanosis, tachypnea, heart failure, and hypoxemia unresponsive to supplemental oxygen.
• Truncus arteriosus: emergence of the aorta and pulmonary artery from a common trunk overriding a VSD. Symptomatic from the 1st days of life, including cyanosis, respiratory distress, heart failure, poor feeding, and excessive sweating. Diagnosed by echocardiogram.
• Total anomalous pulmonary venous return: rare congenital cardiopathy in which pulmonary veins drain to sites other than the left atrium. Presents with cyanosis from birth, heart failure, and respiratory distress. Characterized by wide-split S2.
• Ebstein anomaly: congenital heart defect in which there is downward displacement of the tricuspid valve leaflets causing RVOT obstruction. Presents with cyanosis, arrhythmias, and failure to thrive. Diagnosed by echocardiogram.