• In longstanding unrepaired TOF, right ventricular hypertension induces fibrosis leading to RV systolic and diastolic dysfunctions and ventricular arrhythmias.
• Neonate with TOF should be carefully assessed by echo to see if the PS is so severe that ductal patency is needed. If this is the case, give PGE1 infusion and do early surgery.
• Cyanotic spells can occur in acyanotic TOF also.
• Treatment of cyanotic spells includes oxygen, volume expansion, sedation with morphine or ketamine and vasopressors like phenylephrine.
• Patients with relative anemia are at more risk of cerebrovascular accidents and hypercyanotic spells.

Interventional catheterization procedures

• Preoperative-

Palliation of cyanosis by RVOT stent placement or balloon valvuloplasty. This avoids need for BT shunt which may cause pulmonary artery distortion.
Coil embolization of aortopulmonary collaterals.

• Postoperative- For residual pulmonary artery obstruction- ballooning and stenting.

Primary repair

• This is done via median sternotomy.
• Approaches-
  • Atrial route- This is the preferred route. The VSD is closed by a Dacron patch. RVOT obstruction is resected. Atrial route was earlier done only for patients with coronaries crossing the RVOT. Now it is done for other patients also as it avoids the need for ventriculotomy.
  • Right ventriculotomy- A vertical incision is made over the infundibulum. RVOT obstruction is relieved. VSD is closed by a Dacron patch. RVOT is patched with pericardium. If the pulmonary annulus is hypoplastic (Z score preoperatively and visual impression of the surgeon intraoperatively), the initial incision is extended onto the pulmonary artery. A transannular patch is placed. A monocusp pericardial valve may be placed to avoid pulmonary regurgitation.
  • Combined atrial and transpulmonary approach- avoids need for ventriculotomy.
• AP collaterals- These are coiled prior to surgery to avoid steal phenomenon during cardiopulmonary bypass which causes neurologic sequelae. If it constitutes the sole blood supply to the lung, it should be incorporated into the final repair.

Palliative procedures

• Initial palliative BT shunt is not preferred due to PA distortion, ventricular volume loading and the surgical risks of an additional thoracotomy. Primary repair is directly done. But palliation may need to be done in severe PA hypoplasia and aberrant LAD form RCA.
• Blalock Thomas Taussig shunt and central shunt are used now. Waterston shunt and Potts shunt are not used now. Modified BTT shunt is the most commonly used one. It is done opposite to the side of the aortic arch. Shunt size in newborn is usually 3.5 to 4 mm.

Surgical results-

• Early primary repair is not associated with higher incidence of early complications or late reintervention compared to late repair. Also, primary repair is not associated with more reintervention for residual obstruction  compared to staged repair. Hence, early primary repair is preferred though repair in first 3 months of life increases intensive care morbidity.
• Hospital survival for repair is 100% even for early surgery. 20 year survival after primary repair is 98% for TOF with PS and slightly lower for TOF with primary atresia.
• In TOF with PS, after primary repair, at 2 years 25% needed reoperation usually for residual obstruction in RV or PA. The indication for reoperation in older patients is different and is residual VSD.

Long-term follow-up

• Early repair may be associated with less long term incidence of arrhythmias, ventricular dysfunction and cognitive dysfunction.

Sudden death and arrhythmias

• Incidence of sudden death is 1.2% at 10 years, 2.2% at 20 years, 4% at 25 years and 6% at 30 years.
• Sudden death is not more in patients who underwent surgery before 80s.
• Ventricular arrhythmias are more in patients who undergo surgery at older age. These patients are predisposed to ventricular arrhythmias before surgery itself due to their older age and surgery does not decrease the chance of ventricular arrhythmias.
• Ventricular arrhythmias are more in patients with PR and in those with RV dilation.
• EP studies are not clearly shown to predict sudden death in patients with ventricular arrhythmias.
• Other predictors of sudden death are significant PR, sustained ventricular arrhythmias, QRS duration more than 180 msec and LV dysfunction.
• Other arrhythmias noted in the long term are sinus dysfunction, atrial flutter , atrial fibrillation and supraventricular tachycardia. The incidence of supraventricular tachycardia is 10% at 12 years after repair.

Residual defects and hemodynamic abnormalities

• Branch PA stenosis
  • After shunt procedures.
  • After RVOT patch, due to compression by the redundant patch.
  • Treated by ballooning or stenting- the complications include aneurysms, stent migration and stent thrombosis.
  • Redundant RVOT patch should be surgically revised.
• Membranous subaortic stenosis- uncommon late complication.
• Coronary to RV fistula
• Pulmonary regurgitation
  • All patients have PR by echo.
  • Some have audible PR.
  • Pan-diastolic PR with end-diastolic velocity of 1 m/s indicates mild PR and good pulmonary valve anatomy.
  • PR signal ending before the end of diastole indicates that pulmonary valve function is poor and that the RV is stiff. This occurs due to equalization of PA diastolic pressure and RV diastolic pressure in diastole itself.
  • PR may occur due to increased pulmonary arterial impedance which is due to either stenosis of main or branch pulmonary arteries or elevated LA pressure due to causes like LV dysfunction. If branch PA stenosis is the cause of PR, it may be treated by interventional catheterization. If LV dysfunction is the cause of PR, it may decrease with treatment of the LV dysfunction.
  • For significant PR, pulmonary valve replacement (homograft) will be needed.
• Tricuspid regurgitation
  • Present in many.
  • Not audible unless RV pressure is elevated.
  • May need repair.
• Aortic dilation
  • Aorta is dilated in TOF patients after repair. This dilation may progress.
  • Avoid isometric exercise and high blood pressure.
  • Serial monitoring for enlargement and development of AR is needed.

Exercise testing

• Reduced exercise capacity is present in patients with PA stenosis, PR or RV dysfunction.

Bacterial endocarditis

• Prophylaxis is needed in unoperated patients, palliated patients, in repaired patients for 6 months and in repaired patients with prosthetic valves.

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• Some patients may have left to right shunt will full arterial oxygen saturation.
• PA pressure is normal or low, never is it high.
• All patients have subpulmonic obstruction.
• VSD is non-restrictive usually. So, RVH is in proportion to the LV mass.
• Rarely, VSD is restrictive. Then RVH will be severe due to suprasystemic RV pressure.
• Exercise produces cyanosis due to decrease in systemic vascular resistance leading to increased right to left shunting.
• Hypercyanotic episode is due to acute increase in infundibular obstruction.

Clinical features

• Fetal diagnosis is possible by echo.
• Newborn with severe RVOT obstruction may have only mild cyanosis till ductus closes.
• Hypercyanotic spells or tetralogy spells-
  • More common in patients with iron deficiency anemia.
  • Mechanisms-
    • Acute increase in subpulmonic obstruction due to contraction due to catecholamines or due to hypovolemia.
    • Decreased systemic vascular resistance
• Severe cyanosis.
• Hyperpnea due to hypoxia and metabolic acidosis.
• Can be lethal.
• Murmur intensity is markedly decreased.
• Squatting-
  • Usually after exercise.
  • Instinctive- to increase arterial saturation.
  • Increased systemic vascular resistance decreases shunting.
• Left parasternal impulse is present.
• S2 is single in almost all patients.
• S2 is often loud due to anterior aorta.
• No S3 or S4.
• Wide pulse pressure if
  • PDA
  • AP collaterals or
  • Palliative shunt.
• Mid-systolic murmur
  • Site – inferior to the site of valvular PS murmur
  • Crescendo-decrescendo or plateau shaped
  • Harsh
  • Intensity is inversely proportional to RVOT obstruction
  • Decreases during hypercyanotic spell
  • Absent in TOF with PA
• EDM
  • AR
  • PR
    • In TOF with PA
    • Harsh sawing to and fro murmur
    • Pathognomonic
• AES (aortic ejection sound) – in older patients.
• Continuous murmur-
  • PDA
  • AP collaterals (murmur in back)
• Postoperative-
  • S2 is single (only A2).
  • MSM of PS is often heart due to some degree of residual PS.
  • Low frequency EDM of PR is heart in many.
  • PSM if residual VSD.

Diagnostic studies

• ECG-
  • RVH is evident beyond 3 months when neonatal RVH should have resolved.
  • Right axis deviation is present.
  • In older untreated patients, RV fibrosis may cause ventricular ectopy or arrhythmias.
• Chest X-ray-
  • No cardiomegaly.
  • Upturned apex- boot-shaped heart or coeur en sabot.
  • Concavity of left heart border due to RV infundibular hypoplasia and MPA hypoplasia.
  • Decreased pulmonary vascularity.
  • Right aortic arch in 25%.
• Blood investigations-
  • Hematocrit more than 65% will cause hyperviscosity syndrome.
  • Microcytosis due to iron deficiency can cause cerebrovascular events and should be avoided.
• Echocardiography-
  • With more than 50% override, look for bilateral conus to rule out DORV.
  • TR will not occur despite RV hypertension.
  • In the first few days of life, PS severity is underestimated due to elevated PVR and due to PDA.
  • The VSD is just below the RCC, at 10’O clock position.
• Cardiac catheterization-
  • Stenting for PS has been done along with surgery.
  • AP collaterals can be closed with coils.
  • RV hypertension is equal to LV hypertension.
  • PA anatomy and coronary anatomy clarifications are the usual indications for cath study.
  • PA pressure is normal or low. Elevation suggests diffuse distal pulmonary arterial stenosis.
  • With AP collaterals, calculation of right to left ventricular shunt gives a falsely low value.
  • Pulmonary artery anatomy delineation is especially important in patients who have undergone palliative aortopulmonary shunts.
  • AP collaterals usually originate from the descending aorta. Occasionally they originate from the brachicephalic vessels as in pulmonary atresia.

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In ASD, it may be due to a prominent sinus venosus valve, thebesian valve or eustachian valve diverting inferior vena caval blood to the left atrium through the ASD.

In VSD, it may be due to the development of right ventricular outflow tract obstruction.

Cyanosis is bluish discoloration of skin and mucosa due to reduced Hb of 5gm/dl. This may be central when arterial saturation is low or peripheral when arterial saturation is normal and cyanosis is due to increased oxygen extraction from blood due to decreased blood flow as in shock and vasoconstriction.

The best place to look for central cyanosis is the tip of the tongue as this place is never pigmented and always has a good blood flow.

When in doubt, determine arterial oxygen. Note that due to left shift of Hb dissociation curve in a newborn, 90 % SaO2 correlates with only 45 mm Hg PO2 while in an older person it correlates with 65 mm Hg PO2.

 Normally, venules contain 2 gm/dl of reduced Hb, so an additional 3 gm/dl is needed to cause cyanosis. This is accomplished by a reduction of SaO2 to 80% in a person with Hb level of 15 gm/dl ( 15 x 20%= 3).

Causes of central cyanosis are cardiac, respiratory and nervous. Cardiac cause is right to left shunt. Pulmonary causes include lung diseases and pulmonary AV fistula. Nervous system causes are those which affect ventilation like CNS depression, Pickwickian syndrome and respiratory muscle paralysis.

Causes of peripheral cyanosis are heart failure, shock, acrocyanosis of newborn, and methemoglobinemia.

The hyperoxitest helps to differentiate cardiac from pulmonary disease as the cause of cyanosis in newborn. With inhalation of 100% oxygen, in right to left shunt the PO2 does not rise to more than 100 mm Hg while with pulmonary disease it does. In right to left shunt the PO2 does not increase because even though the PO2 of the blood passing through the lung increases to 600 mm Hg, this gets mixed with the low PO2 blood passing to the left side through the right to left shunt and the resulting mixture has still a low PO2 because of the sigmoid shape of the Hb dissociation curve. (SaO2 of 50% is achieved at a PO2 of 27 mm Hg. This occurs in the sharp rising part. The plateau starts at an SaO2 of around 90%.)

Polycythemia occurs in cyanotic children and is beneficial as long as hematocrit is below 65%. Higher values cause hyperviscosity syndromes. 

Clubbing occurs due to megakaryocytes bypassing the pulmonary circulation and getting trapped in the nailbed where they deliver growth factors. It occurs at 6 months of age and occurs first in the thumb.

Paradoxical embolism can occur.

Cortical venous thrombosis can occur, especially in age less than 2 yrs, due to hyperviscosity.

Brain abscess can occur due to bypassing of phagocytic filtering in the lungs.

Platelets are decreased in number and function. PT and APTT are prolonged.

IQ is lower than expected.

Scoliosis is often present.

Hyperuricemia occurs in adults.