Tetralogy of Fallot (TOF)

Josh Kailin, MD

 

Tetralogy of Fallot (TOF) is the most common form of congenital cyanotic heart disease (~8-10%)

Worldwide reported prevalence of TOF is 0.34 per 1,000 live births

 

TOF is a constellation of four findings:

• Pulmonary stenosis (PS)
  • The degree of pulmonary stenosis is variable.  Infundibular (subvalvar) stenosis is common and is often dynamic, but stenosis may also include hypoplasia and dysplasia of the pulmonary valve as well as main pulmonary artery hypoplasia (supravalvar).  Right ventricular outflow tract obstruction causes increased right ventricular pressure and can lead to right to left shunting across the VSD in addition to decreased pulmonary blood flow leading to cyanosis. In the setting of mild pulmonary stenosis, shunting across the VSD is predominantly left to right and patients are acyanotic. This is clinically referred to as a “pink Tet” 
• Ventricular septal defect (VSD)
  • The typical ventricular septal defect in TOF is a conoventricular septal defect with anterior malalignment, resulting in anterior, superior and leftward deviation of the infundibular septum causing narrowing of the right ventricular outflow tract. 
• Right ventricular hypertrophy (RVH)
  • Right ventricular hypertrophy component is the consequence of right ventricular pressure rather than a primary morphologic feature but adds to the right ventricular outflow obstruction
• Overriding Aorta
  • The aorta overrides the VSD and native ventricular septum
• Additional Findings
  • Right aortic arch (25%)
  • Clockwise rotation of the aortic root resultant rotation of the origin of the coronary arteries 
  • Coronary artery anomalies (~ 5%)
  • Left SVC to coronary sinus (~11%)
  • Atrioventricular septal defect (AVSD) (~5%)
  • Subtypes: TOF with atrioventricular septal defect, TOF with absent pulmonary valve

 

Fetal Imaging Pearls

Aortic Override

• Degree of aortic override best seen from fetal 5 chamber view
• Typically ~50% override of the native ventricular septum 
• Presence of mitral-aortic continuity (differentiates TOF from double outlet right ventricle where there is mitral-aortic discontinuity).

VSD

• Conoventricular VSD: Assess size and direction of shunting by 2D and color Doppler

Pulmonary Stenosis

• Degree of pulmonary valvar hypoplasia with pulmonary valve stenosis (2D, color and spectral Doppler, fetal z-scores)
• Degree of subvalvar stenosis (assess degree of anterior deviation of the infundibulum)
• Degree of supravalvar stenosis (main pulmonary artery size, fetal z-scores )
• Assess branch pulmonary arteries: Make sure pulmonary arteries appear confluent, size (fetal z-score)
• Findings consistent with severe pulmonary stenosis include retrograde aortic-to-pulmonary flow in PDA with severe pulmonary hypoplasia with flow turbulence or minimal flow across the pulmonary outflow

Patent Ductus Arteriosus

• Assess for presence of PDA: Small percentage of TOF patients will have absent PDA
• Assess flow pattern in PDA:  normally right to left shunting, however, retrograde aortic-to-pulmonary flow in PDA consistent with severe pulmonary stenosis and likely ductal dependency postnatally

Aortic Arch

• Assess aortic arch size, flow (2D, color spectral Doppler) and arch sidedness (~25% right aortic arch)

 

Genetic Considerations

Chromosome anomalies occur in ~25-30% of fetuses with TOF and include:

Most common:

Trisomy 21: Can be associated with a specific variant of TOF/AVSD

22q11 Deletion Syndrome (DiGeorge Syndrome):  ~10-15% of cases with increased risk in the setting of right aortic arch, hypoplastic thymus or extracardiac abnormalities

Other associated syndromes:

Alagille syndrome

Cat-eye syndrome

Aneuplodies: Trisomy 13,18

 

Fetal Surveillance

• Assess interval growth of right ventricular outflow tract, pulmonary valve and pulmonary artery and for any change in ductal flow pattern (flow reversal in PDA concerning for postnatal ductal dependent pulmonary blood flow).

 

Prostaglandins (PGE)  

• Variable.  
• Depends on severity of pulmonary stenosis. Patients with severe pulmonary stenosis/hypoplasia may require PGE following birth.

 

References:

Birth Prevalence of Congenital Heart Disease Worldwide: A Systemtic Review and Meta-Analysis. Linde DVD, Konings EM, Slager MA et al. J Am Coll Cardiol 2011; 58: 2241-2247

Lai WW, Mertens LL, Cohen MS et al. Echocardiography in pediatric and congental heart disease. Wiley-Blackwell 2009: 362-384

Delius RE, Kumar RV, Elliott MJ et al. Atriventricular septal defect and tetralogy of Fallot: a 15-year experience. Eur J Cardiothorac Surg 1977: 12: 171-176

Lakier JB, Stangr P, Heymann MA et al. Tetralogy of Fallot with absent pulmonary valve. Natural history and hemodynamic considerations. Circulation 1974; 50: 167-175

Craatz S, Kunzel E, Spanel-Borowski K. Right-sided aortic arch and tetralogy of Fallot in humans-a morphological study of 10 cases. Cardiovasc Pathol 2003; 12: 226-232

Need LR, Powell AJ, del Nido P, Geeva T. Coronary echocardiography in Tetralogy of Fallot: diagnostic accuracy, resource utilization and surgical implications over 13 years. J Am Coll Cardiol 2003; 36: 1371-1377

Abuhamad A, Chaoui R. A Practical Guide to Fetal Echocardiography: Normal and Abnormal Hearts. 2nd Edition. 2009.

Bader RS, Hornberger LK, Huhta JC. The Perinatal Cardiology Handbook. 2008.

• • Fetal Tetralogy of Fallot