Tetralogy of Fallot (TOF)

most common congenital cyanotic heart disease.one of the conotruncal family of heart lesions.. It accounts for 7 to 10% of all congenital heart abnormalities.

1. Dr. Syed Kamrul Hasan Medical Officer, NICU Sylhet Women’s Medical College Hospital Tetralogy of Fallot

2. Introduction Tetralogy of Fallot is one of the conotruncal family of heart lesions in which the primary defect is an anterior deviation of the infundibular septum. The consequences of this deviation are the 4 components:

3. Epidemiology Tetralogy of Fallot occurs approximately 400 times per million live births. It accounts for 7 to 10% of all congenital heart abnormalities, making it the most common cyanotic heart defect. Males and females are affected equally. Genetically it is most commonly associated with Down's syndrome and DiGeorge syndrome.

4. History Tetralogy of Fallot was initially described in 1671 by  Niels Stensen .  A further description was published in 1888 by the French physician Louis Arthur Fallot , after whom it is named. In 1924, Maude Abbott coined the term " tetralogy of Fallot ".

5. French physician Étienne - Louis-Arthur Fallot , who first described TOF in the late 19th century.

6. The first surgical repair was carried out in 1944 at Johns Hopkins.The procedure was conducted by surgeon Alfred Blalock  and cardiologist Helen B. Taussig . 15-months old Eileen Saxon was the first person to receive a Blalock-Thomas- Taussig shunt. The first total repair of tetralogy of Fallot was done by a team led by C. Walton in 1954 on an 11 years old boy.

7. Risk Factors Poor maternal nutrition Viral illness during pregnancy Parent having tetralogy of fallot Children born to mother with Polyketonuria Presence of down syndrome

8. Cause It’s cause is thought to be due to environmental or genetic factors or a combination. It is associated with chromosome 22 deletions and  DiGeorge syndrome. Specific genetic associations include : JAG1,NKX25, ZFPM2,VEGF,NOTCH1, TBX1, and FLT4.

9. Development of TOF A. During the fifth week, pairs of opposing ridges appear in the truncus (right superior truncus swelling & left inferior truncus swelling). B. Hence, while growing toward the aortic sac, the swellings twist around each other, foreshadowing the spiral course of the future septum.

10. C. After complete fusion, the ridges form the aorticopulmonary septum, dividing the truncus into an aortic and a pulmonary channel.

11. TOF, is due to an unequal division of the conus resulting from anterior displacement of the conotruncal septum. Defect in bulbus cordis and truncus arteriosus .

12. Pathophysiology Physiologically the pulmonary stenosis causes concentric right ventricular hypertrophy without cardiac enlargement and an increase in right ventricular pressure. When the right ventricular pressure is as high as the left ventricular or the aortic pressure, a right to left shunt appears to decompress the right ventricle.

13. Once the right and left ventricular become identical, increasing severity of pulmonary stenosis reduces the flow of blood into the pulmonary artery and increases the right to left shunt. As the systolic pressures between two ventricle are identical there is little or no left to right shunt and the VSD is silent.

14. The flow from the right ventricle into the pulmonary artery occurs across the pulmonary stenosis producing an ejection systolic murmur More severe the pulmonary stenosis , the less the flow into the pulmonary artery and the bigger the right to left shunt, more the cyanosis

15. Thus the severity of cyanosis is directly proportional to the severity of pulmonary stenosis The VSD of TOF is always large enough to allow free exit to the right to left shunt Thus Congestive failure not occurs in TOF.

16. CLINICAL MANIFESTATIONS Clinical findings are variable & mainly depends on the degree of right ventricular outflow obstruction. Cyanosis : Patient with mild obstruction are minimally cyanotic or even acyanotic Those with maximal obstruction are deeply cyanosed since birth Most have progressive cyanosis by 4 months of age

17. Paroxysmal Hypercyanotic Attacks : This is the hallmark of sever TOF & usually occurs during first 2 years of life, most commonly by 4-6 months of age. Spells occur most frequently in the morning on awakening or after episodes of vigorous cry. The attacks are due to further reduction of an already compromized pulmonary blood flow & more severe systemic hypoxia.

18. Cyanotic Spells are characterized by Sudden onset of dyspnoea . Sometimes gasping respiration & syncope Sudden deepening of cyanosis Alteration in consciousness, from irritability to syncope. Sometimes convulsion & hemiparesis Temporary disappearance or decrease in the intensity of the systolic murmur at pulmonary area Metabolic acidosis

19. Easy fatigability & dysponea on exertion Squatting is of diagnostic significance & is highly typical of infants with TOF Failure to thrive Squatting position

20. Physical Examination Varying degrees of cyanosis Conjunctiva are congested Clubbing of the fingers and toes occurs after 3 months of age and is proportional to the level of cyanosis. Stunted growth Precordium may be bulged due to right ventricular hypertrophy.

21. Clubbing of the fingers and toes

22. Apex beat is tapping in character, but not shifted A systolic thrill may be palpable at the left sternal border, with a harsh midsystolic murmur in that location. The shorter the murmur, the more severe the infundibular pulmonary stenosis . Left parasternal heave may be present The first heart sound (S1) is usually normal

23. Second heart sound is characteristically single & loud, because the pulmonary component is too soft to be heard. An ejection systolic murmur is heard at pulmonary area A continuous murmur is heard if a PDA or large collateral vessels are present.

24. Cardiac findings in cyanotic tetralogy of Fallot : A long ejection systolic murmur at the upper and mid left sternal border and a loud, single S2 are characteristic auscultatory findings of TOF.

25. Diagnosis Based on the clinical features and relevant investigation

26. Investigations Complete blood counts : Haemoglobin & haematocrit values are usually elevated which is proportional to the degree of cyanosis PBF shows microcytic hypochromic anaemia

27. Chest X-ray Boot shaped heart (due to ventricular hypertrophy). It means apex is lifted up. Concavity in the region of pulmonary artery Right sided aortic arch. Oligaemic lung fields. Hilar vessels are few, Lung vessels also few.

28. Chest X-ray of TOF Patient

29. Electrocardiogram Right axis deviation and evidence of right ventricular hypertrophy.

30. Echocardiography Confirms the diagnosis and provides information about the extent of aortic override of the septum, the location and degree of the right ventricular outflow tract obstruction, the size of the pulmonary valve annulus and main and proximal branch pulmonary arteries and the side of the aortic arch.

31. PLAX view showing the overriding aorta and a large subaortic VSD (star). RVH is also present

32. Color flow imaging showing VSD jet

33. Cardiac catheterization To assess the anatomy of RVOT and main PA branches, RV and LV function, site and size of VSD and competence of aortic valve. Identical systolic pressure in RV and LV and low systolic pressure in PA (diagnostic of TOF)

34. Aortography or coronary arteriography outlines the course of the coronary arteries. In 5-10% of patients with the tetralogy of Fallot , coronary artery abnormalities may be present

35. COMPLICATIONS Hypercyanotic Spells Sever polycythaemia Cerebral thrombo -embolism & stroke: usually occurring in the cerebral veins or dural sinuses and occasionally in the cerebral arteries. Thromboses occur most often in patients younger than 2 years.

36. Brain abscess : As deoxygenated blood enters the systemic circulation & brain , bypassing lungs without clearing the germs by pulmonary scavenger cells. Patients with a brain abscess are usually older than 2 years. The onset of the illness is often insidious and consists of low-grade fever or a gradual change in behavior, or both.

37. Some patients have an acute onset of symptoms that may develop after a recent history of headache, nausea, and vomiting. Seizures may occur; localized neurologic signs depend on the site and size of the abscess and the presence of increased intracranial pressure. CT or MRI confirms the diagnosis. Antibiotic therapy may help keep the infection localized, but surgical drainage of the abscess is usually necessary.

38. Bacterial endocarditis may occur in the right ventricular infundibulum or on the pulmonic , aortic, or, rarely, tricuspid valves. Endocarditis may complicate palliative shunts or, in patients with corrective surgery, any residual pulmonic stenosis or VSD. Delayed growth, development & puberty Others : Hyperuricemia & gout Relative IDA Bleeding disorders

39. ASSOCIATED ANOMALIES Tetralogy of Fallot may present with other anatomical anomalies, including: Stenosis of the left pulmonary artery, in 40% A bicuspid pulmonary valve, in 60% Right-sided aortic arch, in 25% Coronary artery anomalies, in 10% PDA may be present Congenital absence of the pulmonary valve

40. Absence of a branch pulmonary artery A patent foramen ovale  or  atrial septal defect, in which case the syndrome is sometimes called a pentalogy of Fallot An  atrioventricular septal defect partially or totally anomalous pulmonary venous return.

41. Treatment Counsel the parents about disease, treatment option & prognosis Treatment options : Medical Surgical

42. Medical Neonate with severe cyanosis is treated with IV infusion of prostaglandin E1(0.05 - .1 mcgm /kg/min) to keep the ductus arteriosus patent & thereby to improve pulmonary circulation and is life saving.

43. Treatment of cyanotic spells ( in hospital) Place the infant in a knee chest position Give O2 3-5 L/min Establish a calm environment by isolating the patient

44. If the spell persists , give the following : Intravenous fluids : 10ml/kg bolus normal saline followed by maintenance fluids Morphine : 0.1 -0.2 mg/kg SC for keeping the child calm and for muscle relaxation NaHCO3 : 1 mEq /kg IV to correct acidosis Propranolol : 0.1 mg/kg IV which relaxes the infundibular muscle and thereby reduce spasm

45. If these measures do not control the spell, then arrange to transfer the child to ICU Phenylephrine :10-20mcgm/kg bolus IM or SC followed by 0.1-0.5mcgm/kg/min IV infusion titrated according to heart rate and blood pressure. Phenylephrine raise systemic BP as well as systemic vascular resistance. This will reduce right to left shunt and ultimately promote pulmonary blood flow.

46. If the preceding steps do not relieve the spell or if the infant is rapidly deteriorating , intubation and ventilatory support should be given.

47. Treatment at home Educate parents to recognize the spells and know what to do. Propranolol : 0.25-1mg/kg/day orally to be continued to prevent cyanotic spell Fluid & Nutrition Provide high calorie diets to ensure growth Supplement Iron 3-6 mg/kg/day elemental iron orally to promote maturation of RBC Supplement vitamins & minerals

48. Counsel parents to pay special attention to fluid intake so as to prevent dehydration. Dehydration of any child with TOF should be referred immediately for prompt rehydration.

49. Surgical Total surgical repair Total surgical repair of TOF is a curative surgery. Different techniques can be used in performing TOF repair. However, a transatrial , transpulmonary artery approach is used for most cases. The repair consists of two main steps: closure of the VSD with a patch and reconstruction of the right ventricular outflow tract.

50. Diagrammatic representation of surgical repair of tetralogy of Fallot . 1. Patch closure of a VSD 2. Right ventricular outflow/main pulmonary artery outflow patch ( transannular patch)

51. This open-heart surgery is designed to relieve the right ventricular outflow tract stenosis by careful resection of muscle and to repair the VSD. Additional reconstructive surgery may be done on patients as required by their particular cardiac anatomy.

52. Timing of surgery in asymptomatic patients is usually between the ages of 2 months to one year. However, in symptomatic patients showing worsening blood oxygen levels, severe tet -spells (cyanotic spells), or dependence on prostaglandins from early neonatal period (to keep the ductus arteriosus open) need to be planned fairly urgently.

53. Surgery is now often carried out in infants one year of age or younger with less than 5% perioperative mortality. Post surgery, most patients enjoy an active life free of symptoms. Currently, long term survival is close to 90%.

54. Palliative surgery Classic Blalock- Taussing shunt: anastomosed between the subclavian artery and the ipsilateral PA, is usually performed for infants older than 3 months because the shunt is often thrombosed in young infants. Classic Blalock- Taussing shunt

55. Modified Blalock- Taussing shunt : a Gore-Tex interposition shunt is placed between the subclavian artery and the ipsilateral PA. This is the most popular procedure for any age, especially for infants younger than 3 months of age. Modified Blalock- Taussing shunt

56. The Waterston shunt : anastomosis between the ascending aorta and the right PA, is no longer performed because of a high incidence of surgical complications. The Potts operation : anastomosed between the descending aorta and the left PA, is no longer performed either. It may result in heart failure or pulmonary hypertension, as in the Waterston operation.

57. PROGNOSIS After successful total correction, patients are generally asymptomatic and are able to lead unrestricted lives.  If left untreated, TOF carries a 35% mortality rate in the first year of life, and a 50% mortality rate in the first three years of life. Patients with untreated TOF rarely progress to adulthood.

58. Notable cases Shaun White, American professional snowboarder and musician. Beau Casson , Australian cricketer Dennis McEldowney , New Zealand author and publisher

59. Take home message Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the first to be successfully repaired by congenital heart surgeons. The care of children with tetralogy of Fallot and their transition to adult life has been a success of modern medicine. Most of them now survive early repair and have an essentially normal childhood.

60. Thank you