Definition and Pathology:
Tetralogy of Fallot (TOF) is a congenital cardiac anomaly consisting of the following four lesions:
- Large, high, mal-alignment, perimembranous, ventricular septal defect (VSD).
- Rightward shift of the aorta due to mal-development of the aorticopulmonary septum. The aorta is overriding the ventricular septum and receiving blood from both ventricles; i.e. there is bi-ventricular origin of the aorta.
- Pulmonary stenosis at different levels.
- Right ventricular hypertrophy (RVH).
The four components of TOF, and the commonly associated right aortic arch.
1. Ventricular septal defect (VSD) in TOF:
Embryologically, the bulbar cushions, which form the aorticopulmonary septum share, with the endocardial cushions, in the formation of the membranous ventricular septum, to close the interventricular foramen. Thus, the aorticopulmonary septum, is continuous with the ventricular septum.
Anatomically, the anterior wall of the aorta is normally continuous with the ventricular septum.
Normally, the anterior aortic wall is continuous with the ventricular septum (this continuity is lost in TOF). On the other hand, the posterior aortic wall is continuous with the anterior mitral leaflet (this continuity is maintained in TOF, but lost in double outlet right ventricle).
In TOF, the aorta is shifted rightwards, leading to mal-alignment between the aorticopulmonary & the ventricular septa. Thus, the continuity between the anterior aortic wall & ventricular septum is lost; a ventricular septal defect is created (mal-alignment VSD), usually sited high up in the membranous part of the septum beneath the aortic valve, such that the RV ejects directly into the aorta; not via the LV. The aorta is over-riding the ventricular septum, i.e. there is bi-ventricular origin of the aorta.
2. Over-riding of the aorta in TOF:
Normally, the aorta is only facing the left ventricle (no over-riding).
In TOF, usually two thirds of the aorta are facing the left ventricle and one third is facing the right ventricle.
Over-riding may, however, vary from milder to more severe degrees.
With increasing over-riding of the aorta over the right ventricle, more and more cyanosis occurs.
The normal fibrous continuity of the aorta with the anterior mitral leaflet is, however, maintained. This finding differentiates TOF from double-outlet right ventricle, in which this continuity is lost.
Uncommonly there is also fibrous continuity with the tricuspid septal leaflet.
3. Pulmonary stenosis (PS) in TOF:
Site of pulmonary stenosis (PS) in TOF:
- Infundibular PS in 50 % of cases.
- Infundibular plus valvular in 25 %.
- In the remaining 25%: isolated valvular or supra-valvular PS.
- TOF with absent pulmonary valve has also been reported.
PS in TOF may be severe to the extent of pulmonary atresia; a condition known as: pseudo truncus form of TOF.
Atresia may occur in the infundibulum, at the pulmonary valve or in the pulmonary trunk.
Pulmonary arteries in TOF:
- Pulmonary trunk is usually thin and narrow.
- Supra-valvular pulmonary stenosis or atresia may occur.
- One pulmonary artery may be absent.
- Anomalous origin of the right or left pulmonary arteries from the aorta may occur.
Coronary arteries in TOF:
Any of the following may occur:
- Normal coronary arteries in most cases; anomalies are present in only 3% of patients.
- Origin of the left anterior descending (LAD) artery from the right coronary artery (RCA).
- Origin of the left main coronary artery (LMCA) from RCA. In this case, LMCA passes leftwards infront of the pulmonary trunk.
- LMCA may arise normally, then pass rightwards between the aorta & pulmonary trunk, then leftwards infront of the pulmonary trunk.
- The infundibular branch of RCA is abnormally-large in almost all cases.
- Right aortic arch: in 30 %.
- Double aortic arch.
- Coronary arterial anomalies as mentioned.
- Pulmonary arterial anomalies as mentioned.
- Ductus Arteriosus may be left-sided, right-sided, bilateral, or absent.
- Persistent left superior vena cava (SVC).
- Mitral valve abnormalities.
- Tricuspid septal leaflet flap obstructing the VSD.
- Intracardiac defects:
- Multiple VSD’s, usually muscular.
- Atrioventricular septal defects (AVSD).
Complications of TOF:
- Hypoxic spills.
- Polycythemia, with increased blood viscosity, due to chronic hypoxia. This may result in intravascular thrombosis.
- Iron deficiency anemia.
- Cerebral abscess: thought to be due to iron deficiency, hypoxia and high hematocrit.
- Infective endocarditis: mainly after shunt operations.
- Pulmonary vascular obstructive disease (PVOD) may develop:
- after shunt operations,
- or in presence of big collaterals with excess pulmonary blood flow.
1. Cyanosis in TOF:
Cyanosis is favored by reduced pulmonary blood flow (QP), which occurs with:
- Severe PS.
- Increasing RV infundibular obstruction as occurs with:
- Use of inotropic drugs.
- Decreased RV filling, e.g. due to: Hypovolemia and/or Tachycardia.
- High pulmonary vascular resistance (RP) / systemic vascular resistance (RS) ratio.
Appearance of cyanosis may be delayed in patients with TOF due to:
- Compensation by a patent ductus arteriosus, which increases the pulmonary blood flow. When the ductus closes, cyanosis appears.
- Limited activity in infancy. Cyanosis appears with increasing activity and increasing tissue O2 requirements.
- Infundibular hypertrophy may be mild at the start, then progresses gradually.
Absence of cyanosis in patients with TOF may be due to:
- Delayed cyanosis.
- Very mild PS, with normal or even excess pulmonary blood flow.
Hyperpnea encourages venous return, which in patients with TOF augments the right-to-left shunt and intensifies cyanosis. The presence of PS prevents any increase in pulmonary blood flow.
In normal subjects, however, hyperpnea increases pulmonary blood flow and increases O2 delivery to various tissues.
Mechanisms of cyanotic spills:
- Increased activity.
- Infundibular spasm is suggested.
- Sudden drop of systemic vascular resistance augments the right-to-left shunt (increased RP/RS ratio), e.g. during exercise, vasodilators...etc.
- Metabolic acidosis.
Squatting and knee-chest position:
Squatting and knee-chest position are known to improve cyanosis in patients with TOF. This is most probably due to:
- Decreased venous return of the markedly unsaturated blood from the legs.
- Increased peripheral vascular resistance (decreased RP/RS ratio), reducing the right-to-left shunt.
Polycythemia occurs in patients with TOF as an adaptive mechanism in response to chronic hypoxia.
It may cause intravascular thrombosis & decreased blood flow especially in the pulmonary and the cerebral vessels.
2. Heart failure in TOF:
In TOF; heart failure is so rare because no extra work is done by the heart.
Although there is RV outflow obstruction, VSD is non-restrictive, both RV & LV pressures are equal, and RV output is delivered to both PA & AO. The total cardiac work is not usually increased.
1. Cyanosis and cyanotic spills:
Cyanosis appears at age 6 months in the majority.
Cyanotic spills are common at age 2 months-2 years.
Factors precipitating cyanotic spills include: Exertion: e.g. Crying, feeding, bowel habit…etc. as well as Infection & Hot weather.
Pulmonary blood flow markedly decreases during cyanotic spills with diminished or absent systolic murmur.
Cyanotic spills may cause: Syncope, Seizures, or even death.
2. Shortness of breath (SOB) on effort is common, due to hypoxia, although CHF is rare.
3. Squatting is common at age 1.5-10 years. It is almost pathognomonic but not diagnostic of TOF.
Hemoptysis occasionally occurs: due to rupture of collateral vessels and/or Coagulation defects.
- General examination:
- Growth is usually normal.
- Cyanosis; usually at 6 months.
- Clubbing; not before 3 months.
- Local cardiac examination:
- Single second sound, due to absence of the pulmonary component (P2).
- Ejection systolic thrill & murmur of PS, which is shorter with severer cases. In isolated PS, on the other hand; with severer case, the RV ejection time & the duration of the murmur are increased.
- Continuous murmur due to flow in collateral vessels or associated PDA.
- Ejection systolic aortic click is common.
- Heart size is usually normal.
- RV hypertrophy causes elevation of the cardiac apex above the left cupola of the diaphragm in PA view, often described as: Coeur en sabot or boot-shaped heart.
- Right aortic arch in 30 % of cases.
- Pulmonary oligemia is often present.
- Enlarged ascending aorta & aortic knuckle.
Postero-anterior (PA) view in a patient with TOF shwing
Coeur en sabot (boot-shaped heart) due to elevation of the cardiac apex above the left cupola of diaphragm, with acute cardio-phrenic angle.
Tetralogy of Fallot in an infant. A frontal radiograph of the chest shows a mildly enlarged heart and decreased pulmonary vascularity.
- Right axis deviation in most cases.
- RV hypertrophy (RVH) in most cases.
- RA enlargement (RAE) in a few.
- Left axis deviation suggests:
- Atrioventricular septal defect (AVSD).
- Single ventricle.
- Biventricular enlargement occurs in acyanotic cases, and then changes to isolated RVH when cyanosis develops.
Right ventricular hypertrophy with right axis deviation.
Over-riding of the aorta seen in parasternal long-axis (LAX) view is usually the first finding that directs the attention to the diagnosis of TOF. However, false overriding may be created by too high transducer position on the anterior chest wall.
Over-riding of the aorta is seen in other anomalies including:
- Pulmonary atresia with VSD: RV outflow tract ends blindly & no pulmonary valve is recorded.
- Double-outlet RV (DORV): both AO & PA arise totally from the anatomical RV. A characteristic feature of DORV is that the continuity between the aorta & mitral valve is lost.
- Persistent truncus arteriosus (PTA): one large artery arises from the heart, and the PA origin differs according to the type of PTA.
Echocardiography. Long-axis view in Tetralogy of Fallot, revealing a large ventricular septal defect (VSD) (arrow) and overriding aorta.
- On detection of over-riding of the aorta in the parasternal long-axis view, the continuity between posterior aortic wall & anterior mitral leaflet is noticed;
- If no continuity; the case is DORV. Search for PA origin is then needed.
- If continuity is present, DORV is excluded.
- Parasternal short axis (SAX) view is then examined;
- RV outflow tract (RVOFT) present infront of AO with a pulmonary valve recorded: TOF.
- RVOFT infront of AO and ends blindly with no pulmonary valve recorded: pulmonary atresia with VSD.
- Otherwise, features of PTA are searched for.
Parasternal short axis view of the echocardiogram of a patient with tetralogy of Fallot demonstrates the anterocephalad deviation of the outlet septum into the right ventricular outflow tract.
- RV = LV = AO.
- RA: Normal.
- PA: Low pressure, but may be difficult to enter by the catheter due to severe PS.
- RV angiography:
- To demonstrate flow from RV into both AO & PA.
- To assess PS.
Tetralogy of Fallot with pulmonary atresia. The right ventriculogram opacifies the aorta through the ventricular septal defect. Aortic collaterals (arrow) and possibly a patent ductus supply the tiny pulmonary arteries.
Pigtail catheter was passed via inferior vena cava to right atrium to right ventricle to main pulmonary artery. Injection was taken. This shows adequately sized main, right and left pulmonary arteries. In levophase, left sided chambers can be seen filling.
Pigtail catheter was passed through femoral artery to aortic root to left ventricle and injection was made. This left ventriculogram in LAO view shows aortic override and a large subaortic VSD. Dye can be seen entering the right ventricle.The override is about 50%.
PS tends to progress even to pulmonary atresia.
Prognosis is poorer in patients with more severe cyanosis and in the presence of hypoxic spills.
Complications of polycythemia & endocarditis are common.
- At 1 year: 30 %
- At 3 years: 50 %
- At 5 years: 75 %
Depending on facilities, experience, and anatomy of pulmonary & coronary arteries, therapeutic options include:
- Palliation with Propranolol.
- Palliative surgery as abridge to total correction or in patients non-amenable for total correction:
- Systemic-to-pulmonary shunt: to optimize pulmonary blood flow.
- Other palliative procedures.
- Early total correction is done in most patients at the time of diagnosis, with > 90% survival for 10 years post-operatively. Best surgical results are achieved when repair is done before the age of 5 years.
- Blalock-Taussig (BT) shunt : anastomosis of the end of subclavian artery (SCA) to the side of pulmonary artery (PA), on the side opposite to the aortic (AO) arch.
- Modified BT shunt: graft between SCA & PA.
- Waterston (WS) shunt : anastomosis of the back of ascending AO to Right PA.
- Potts shunt: descending AO-to-Left PA.
- Central shunt: ascending AO-to-pulmonary trunk.
- Bidirectional Glenn (BDG) shunt: Superior vena cava to right pulmonary artery.
- Other procedures:
- RV infundibulectomy, to relieve PS.
- Surgical Pulmonary valvulotomy to relieve PS.
- Balloon Pulmonary valvuloplasty to relieve PS.
- Annular patch to enlarge the pulmonary trunk.
- PS is relieved accordingly, e.g. Excision of subvalvular obstruction, valvotomy …etc.
- Infundibulum may need enlargement.
- VSD is closed.
- Patent foramen ovale (PFO) should always be sought & closed.
- Valved conduit from RV to pulmonary trunk in presence of:
- Pulmonary atresia,
- or a coronary artery crossing the right ventricular outflow tract (RVOFT).
- LV dysfunction due to increase of pulmonary venous return.
- RV dysfunction due to development of pulmonary regurgitation (PR).
- Complete heart block (CHB), or bundle branch block ( BBB).
- Bleeding, especially with marked Polycythemia & clotting defects.