DESCRIPTION

The exact embryologic abnormality that results in tetralogy of Fallot (TOF) is unknown. Primary morphologic abnormality is anterior and cephalad deviation of the infundibular (outlet) septum. It is characterized by the following:

• A large and unrestrictive, misaligned ventricular septal defect (VSD)
• Overriding aorta: Aortic root overrides the VSD.
• Right ventricular outflow tract (RVOT) obstruction (RVOTO): multilevel obstruction across the RVOT
• Right ventricular hypertrophy (RVH) in response to the large VSD and RVOTO causing systemic right ventricular (RV) pressure.

EPIDEMIOLOGY

• The most common cyanotic congenital heart disease
• Prevalence of TOF is 4 to 5 per 10,000 live births in the United States.
• Nearly equal sex distribution

RISK FACTORS

PATHOPHYSIOLOGY

• The clinical signs and symptoms are dependent on the degree of RVOTO.
• Patients with higher degree of RVOTO have decreased pulmonary blood flow and right-to-left shunting at the level of VSD, which results in large volume of desaturated blood entering the systemic circulation causing cyanosis.
• Patients with minimal RVOTO have left-to-right shunting at the VSD and are acyanotic. These patients may develop pulmonary over circulation leading to symptoms of heart failure.
• Patients with minimal or no cyanosis may develop dynamic increase in RVOTO over time and right-to-left shunt across the VSD leading to cyanosis.
• In extreme cases, patient may present with a “tet spell” or hypercyanotic spell.

COMMONLY ASSOCIATED CONDITIONS

• TOF with pulmonary atresia
  • Most extreme form of RVOTO
  • Also known as pulmonary atresia with VSD (PA-VSD)
• TOF with absent pulmonary valve
  • 3–6% patients with TOF, pulmonary valve leaflets are absent, or there is a rudimentary ridge of tissue
  • Results in significant stenosis and regurgitation and resultant aneurysmal dilation of branch pulmonary arteries, which causes respiratory distress in neonatal period due to compression of bronchi
• TOF with atrioventricular septal defect (AVSD)
  • 2% patients with TOF have an associated AVSD.
  • Trisomy 21 may be associated with this entity.

HISTORY

• Varying degree of cyanosis, especially when crying or during and after physical activity
• “Blue tets”
  • Present with cyanosis at or shortly after birth
• “Pink tets”
  • May not present until 4 to 6 weeks of age (once pulmonary vascular resistance drops)
  • May present with signs of pulmonary over circulation and heart failure (failure to thrive, diaphoresis with feeds, increased work of breathing)

PHYSICAL EXAM

• Cyanosis may be present at birth or may appear later during infancy or childhood because of progressive RVOTO.
• Normal S₁ and loud S₂ secondary to a more anteriorly located aorta
• Systolic ejection murmur at the left lower sternal border that radiates to the back, secondary to RVOTO.
• Loudness of the murmur is proportional to the degree of RVOTO.
• Length of the murmur is inversely proportional to the degree of RVOTO.
• Patients with severe RVOTO or those having a “tet spell,” murmur may be short and soft or inaudible as there is minimal or no flow across the RVOT during the spell

DIFFERENTIAL DIAGNOSIS

• TOF should be considered in all infants with a heart murmur and cyanosis as well as acyanotic infants or children with a history of hypercyanotic episodes.
• Other forms of cyanotic congenital heart disease should be considered, including the following:
  • Double outlet right ventricle (DORV)
  • Transposition of the great arteries (TGA)
  • PA-VSD

DIAGNOSTIC TESTS & INTERPRETATION

• Electrocardiography (ECG)
  • Normal or rightward axis deviation (+90 to +180 degrees); TOF with AVSD may have left axis deviation.
  • RVH (Prominent RV forces is normal in neonatal ECG.)
  • ECG in repaired TOF patients shows right bundle branch block (RBBB) with prolonged QRS duration from TOF repair.
• Chest radiograph
  • Normal cardiac size and upturned apex “boot-shaped heart” due to RVH and concave main pulmonary artery segment
  • Decreased pulmonary vascular markings in “blue tets” (may be increased markings in “pink tets” after pulmonary vascular resistance drops)
  • Right aortic arch: absence of usual left-sided aortic knuckle and a bulge to the right of the upper mediastinum. ~25% patients with TOF have right aortic arch.
• Echocardiogram
  • Anterior malalignment VSD
  • Degree and level of RVOTO: subvalvar, valvar, and supravalvar
  • Pulmonary valve anatomy: size and degree of valvar pulmonary stenosis
  • Main and branch pulmonary artery size and stenosis
  • Overriding aorta and aortic valve function
  • Aortic arch sidedness and branching
  • Coronary artery anatomy (most common anomaly is left anterior descending coronary artery [LAD] originating from the right coronary artery, seen in 4% of patients). Dual LAD is another abnormality seen in TOF. It is extremely important to evaluate the coronary artery origins on preoperative echocardiogram due to increased risk of coronary artery injury during surgery.
• Cardiac catheterization
  • Generally, not indicated in infants unless there is concern regarding the branch pulmonary artery anatomy or coronary anatomy
  • Patients with repaired TOF need catheterization for pulmonary valve replacement, and intervention on branch pulmonary arteries.
• Cardiac magnetic resonance imaging (MRI) and cardiac computed tomography (CT) scan
  • Rarely needed in infants to evaluate pulmonary artery anatomy
  • Routinely done in adults to assess RV size, function, pulmonary valve size, regurgitation, and branch pulmonary arteries for follow-up, for timing and planning for pulmonary valve replacement, and intervention on branch pulmonary arteries

GENERAL MEASURES

• Earlier diagnosis and corrective surgery have decreased the need for medical management.
• Neonates with severe RVOTO who present with severe cyanosis at birth need prostaglandin therapy to keep the patent ductus arteriosus open and maintain adequate pulmonary blood flow before a transcatheter or surgical intervention.
• Hypercyanotic episodes “tet spells”: decreased pulmonary blood flow due to increased pulmonary vascular resistance usually provoked or worsened by crying or physical activity
  • The goal of treatment is to increase RV preload, promote pulmonary blood flow, and decrease right-to-left shunting at the VSD.
  • Knee-chest position increases systemic vascular resistance.
  • Oxygen decreases pulmonary vascular resistance and increases pulmonary blood flow.
  • Intravenous fluid bolus increases RV filling and pulmonary blood flow.
  • Intravenous sodium bicarbonate (NaHCO₃) improves acidosis and decreases oxygen demand.
  • Morphine sulfate alleviates pain and anxiety and lowers the heart rate and respiratory rate.
  • β-Blocker (IV esmolol bolus followed by infusion for immediate therapy, oral propranolol for long-term prophylaxis) lowers heart rate and improves ventricular filling time.
  • Phenylephrine increases systemic vascular resistance.
  • Intubation and mechanical ventilation if there is no response
  • Emergent surgical intervention or mechanical circulatory support for a life-threatening spell
• Subacute bacterial endocarditis (SBE) prophylaxis
  • Cyanotic patients should receive SBE prophylaxis prior to dental procedures.
  • All patients should receive SBE prophylaxis for 6 months after surgery.
  • Patients with prosthetic valves or residual defects should receive SBE prophylaxis prior to dental procedures for life.

SURGERY/OTHER PROCEDURES

• Transcatheter palliation: reserved for a small or premature infants with increased risk of surgical mortality and morbidity
  • Percutaneous stent placement across the RVOT
  • Stent placement in the ductus arteriosus
• Palliative surgery:
  • Blalock-Thomas-Taussig shunt: systemic-to-pulmonary artery shunt
• Corrective surgery: usually done between 3 and 6 months
  • VSD patch closure and RVOT reconstruction (transannular and non-transannular patch)
  • VSD patch closure and right ventricle to pulmonary artery conduit placement
• Transcatheter or surgical pulmonary valve replacement in patients with repaired TOF.

PROGNOSIS

• Survival rate in patients with unrepaired TOF is 66% at 1 year of age and ~3% at 40 years.
• Surgical mortality is low ~2%.
• 90% patients with repaired TOF are expected to survive to adulthood.
• 35-year survival is ~85% in repaired TOF patients.
• Higher risk of adverse outcomes in patients who get repaired later
• Residual hemodynamic abnormalities that require percutaneous or surgical interventions:
  • Pulmonary insufficiency (transannular patch repair)
  • RV dilation and dysfunction due to chronic volume overload from pulmonary insufficiency.
  • Residual RVOTO
  • Branch pulmonary artery stenosis
  • Residual VSD
  • Aortic root dilation and aortic valve insufficiency
• Conduction abnormalities (atrial, ventricular tachyarrhythmias, and heart block)
  • Incidence of sudden death is generally attributed to ventricular arrhythmias.
• Pulmonary valve replacement after the 2nd decade of life due to RV dilation resulting from pulmonary valve insufficiency.

COMPLICATIONS

• Preoperatively
  • Hypercyanotic episodes (a.k.a. “tet spells”)
  • Bacterial endocarditis
  • Cerebrovascular accident secondary to cyanosis and polycythemia
• Postoperatively
  • Pulmonary insufficiency
  • Residual lesions requiring multiple interventions
  • Progressive RV dilation and dysfunction
  • Ventricular or atrial arrhythmias
  • Sudden death (ventricular arrhythmias)

ICD 10

Q21.3 Tetralogy of Fallot