Tetralogy of Fallot (TOF) P.pptx one of the congenital anomalies of the heart

Tetralogy of Fallot,one of the congenital anomalies of the heart,very common

1. Tetralogy of Fallot (TOF) Adesanwo Sophie and Ajisafe Damilola Department of Medicine, University of Ilorin Most common cyanotic congenital heart disease

2. Outline Introduction Normal Embryological Development Genetic and Molecular Etiology Environmental and Maternal Risk Factors Epidemiology Anatomic Subtypes Pathophysiology Clinical Presentation Differential Diagnoses Investigations Management and Treatment Complications of Tetralogy of Fallot Prognosis Recent Advancements Conclusion

3. Introduction Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, accounting for 5–10% of all congenital cardiac defects. First described by Étienne-Louis Arthur Fallot in 1888, TOF is a conotruncal abnormality defined by four key anatomical features: Ventricular septal defect (VSD) Right ventricular outflow tract obstruction (RVOTO) Overriding aorta Right ventricular hypertrophy (RVH)

4. Ventricular septal defect (VSD): A large, anteriorly malaligned , usually subaortic defect leading to equalization of right and left ventricular pressures. Right ventricular outflow tract obstruction (RVOTO): May occur at the infundibular, valvular, or supravalvular level, or as a combination. Overriding aorta: The aortic root is displaced rightward, receiving blood from both ventricles. Right ventricular hypertrophy (RVH): Develops from chronic pressure overload due to RVOTO. TOF has major clinical importance as a cause of cyanosis in infancy and childhood. The degree of obstruction to right ventricular outflow largely determines symptom severity and timing of presentation.

5. Normal Embryological Development The heart develops between the third and eighth weeks of gestation, beginning as a linear tube that undergoes looping, septation, and conotruncal division. The conotruncal region—forming the right and left ventricular outflow tracts, pulmonary trunk, and ascending aorta—develops through fusion and spiraling of truncal and bulbar ridges derived from neural crest cells. Proper septation ensures that the aorta connects to the left ventricle and the pulmonary artery to the right ventricle. This process involves signaling pathways and transcription factors such as NOTCH, WNT, TBX1, NKX2.5, and GATA genes. Disruption of this process causes anterior and cephalad deviation of the infundibular septum, producing a malaligned VSD, RVOTO, and overriding aorta—the embryologic basis of TOF. Other conotruncal defects arising from similar disruptions include truncus arteriosus, transposition of the great arteries, interrupted aortic arch, and double outlet right ventricle.

6. Genetic and Molecular Etiology About 75–80% of TOF cases are nonsyndromic , occurring in isolation. Roughly 7% are linked to identifiable mutations in key cardiac developmental genes such as: NOTCH1 for neural crest differentiation and conotruncal septation., FLT4 for vascular endothelial growth and morphogenesis and TBX1 located within 22q11.2, crucial for outflow tract patterning. Other implicated genes include NKX2.5, GATA4/6, HAND1/2, ZFPM2, and NFATC. Familial clustering occurs in about 3% of cases, often associated with NKX2.5 mutations. The remaining 20–25% are syndromic , linked to chromosomal or single-gene defects, including: 22q11.2 deletion syndromes (DiGeorge, velocardiofacial ) – up to 40% of TOF with pulmonary atresia., Trisomy 21 (Down syndrome), Alagille syndrome (JAG1, NOTCH2), Kabuki syndrome (KMT2D, KDM6A), CHARGE (CHD7 ), Noonan (PTPN11, SOS1, RAF1) and other rare associations: VACTERL and Goldenhar syndromes . Therefore, genetic testing, especially for 22q11.2 deletion is recommended for all TOF cases to inform prognosis and counseling .

7. Environmental and Maternal Risk Factors The exact cause remains unclear in most cases, but several maternal and environmental factors increase risk: Maternal rubella infection in the first trimester. Alcohol use or teratogenic drugs (e.g., isotretinoin, valproate). Poor nutrition, especially folate deficiency. Advanced maternal age (>40 years). Maternal diabetes or poorly controlled metabolic disease. Family history of congenital heart disease. Fetal chromosomal abnormalities such as Down or DiGeorge syndromes. These factors likely disrupt neural crest migration or interfere with conotruncal septation signaling pathways.

8. Epidemiology Accounts for 5–10% of all congenital heart diseases Occurs in ~1 in 3,000 live births (0.23–0.63 per 1,000) Affects both sexes , though some studies note a slight male predominance Represents one-third of cyanotic CHDs in children under 15 years Survival after repair: >90% at 16 years, ~75% at 30 years Unrepaired TOF: poor prognosis — 66% at 1 year, 40% at 3 years, 3% at 40 years Adults with TOF form one of the largest congenital heart disease survivor groups May coexist with extracardiac anomalies (cleft palate, hypospadias, skeletal defects) often linked to 22q11.2 deletion Illustrates how advances in surgery and genetics have greatly improved long-term survival and quality of life

9. Anatomic Subtypes Four main subgroups are recognized: 1. TOF with pulmonary stenosis – the most common form. 2. TOF with pulmonary atresia – complete atresia of the pulmonary valve; pulmonary flow depends on a patent ductus arteriosus or major aortopulmonary collateral arteries (MAPCAs). .

10. 3. TOF with absent pulmonary valve syndrome – seen in 3–6% of cases, featuring aneurysmal dilatation of the pulmonary arteries and often a right-sided aortic arch. 4. TOF with common atrioventricular canal (AVSD) – a rare variant usually associated with Down syndrome

11. About 40% of patients have associated anomalies such as atrial septal defect, patent ductus arteriosus, supravalvular pulmonary stenosis, branch pulmonary artery hypoplasia or discontinuity, anomalous coronary arteries, or aortic regurgitation. Recognizing these associations is essential for surgical planning and prognosis.

12. Pathophysiology of TOF

13. Pathophysiology of Tetralogy of Fallot (TOF) Embryologic & Genetic Basis Abnormal neural crest cell migration → misaligned infundibular septum Results in: Large, nonrestrictive VSD RV outflow tract obstruction (RVOTO) of varying severity Pulmonary valve often hypoplastic or stenotic Right aortic arch in ~25% of cases Key genetic disruptions: NOTCH, WNT, TBX1, VEGF, MTHFR Syndromic forms (20–25%) : 22q11.2 deletion, Alagille, Noonan Maternal risk factors: Rubella, diabetes, alcohol, poor folate, ↑age Hemodynamic Mechanisms VSD = equal pressures in both ventricles Shunt direction depends on resistance: Pulmonary > systemic → Right-to-left (cyanotic) Pulmonary < systemic → Left-to-right (pink Fallot) RVOTO caused by: Infundibular or valvular stenosis Annular hypoplasia RV outflow muscle hypertrophy Dynamic obstruction → Tet spells (triggered by exertion, crying, or stress)

14. Component Description Hemodynamic Effect Ventricular Septal Defect (VSD) Large, nonrestrictive defect in membranous septum Equalizes ventricular pressures; shunt direction depends on RVOTO severity RV Outflow Tract Obstruction (RVOTO) Subvalvular or valvular stenosis Increases RV pressure; determines degree of cyanosis Overriding Aorta Aorta positioned above both ventricles Receives mixed oxygenated and deoxygenated blood Right Ventricular Hypertrophy (RVH) Develops from chronic pressure overload Leads to stiffness, arrhythmias, and eventual RV failure The Four Classical Defects and Their Interactions As obstruction worsens, the right-to-left shunt increases, reducing pulmonary blood flow and systemic oxygenation. Chronic hypoxia causes polycythemia, hyperviscosity , and digital clubbing .

15. Electrical and Mechanical Sequelae Atrial arrhythmias (flutter or fibrillation) occur in 10–35% of repaired adults due to right atrial dilation and fibrosis. Ventricular arrhythmias result from surgical scarring and chronic RV dysfunction. Sudden cardiac death risk increases with prolonged QRS (>180 ms ), marked RV dilation, or biventricular failure. Long-term sequelae (post-repair): Pulmonary regurgitation → RV dilation/fibrosis → Arrhythmias → RV dysfunction → Potential sudden death

16. Pathophysiology in Children vs. Adults Feature Children Adults Dominant Presentation Cyanosis due to severe RVOTO Post-repair sequelae (chronic pulmonary regurgitation) Pulmonary Blood Flow Initially aided by ductus arteriosus; closure worsens cyanosis Not applicable; pulmonary regurgitation develops over time Complications / Consequences Severe cyanosis; survival may depend on aortopulmonary collaterals (in pulmonary atresia) RV dilation, fibrosis, dysfunction → arrhythmias, exercise intolerance, sudden cardiac death Hemodynamics Right-to-left shunt predominates Chronic volume overload of RV due to regurgitation

17. Clinical Presentation The manifestations of TOF depend on RVOTO severity, patient age, and repair status. Infants and Children Cyanosis: May be present at birth or develop later (“pink Tets ”). Tet spells: Sudden episodes of tachypnea, agitation, pallor, or cyanosis triggered by crying, feeding, or fever; may cause syncope or seizures. Feeding difficulty and failure to thrive: Due to hypoxemia and increased energy expenditure. Dyspnea and fatigue: Worsen with age or exertion. Squatting: Increases systemic vascular resistance and improves oxygenation. Occasional hemoptysis: From ruptured bronchial collaterals.

18. Clinical Presentation Adults Exercise intolerance: From RV dysfunction or pulmonary insufficiency post-repair. Palpitations: Due to atrial or ventricular arrhythmias. Fatigue and reduced exercise capacity: Common in long-term survivors. Chronic hypoxemia in unrepaired cases: May lead to secondary erythrocytosis, stroke, or cerebral abscess. Special Variants Absent pulmonary valve: Causes airway compression from dilated pulmonary arteries; may present with respiratory distress rather than cyanosis. Pulmonary atresia: Severe cyanosis develops as the ductus arteriosus closes unless collateral circulation is adequate.

19. Physical Examination Infants and Children Cyanosis: Develops within first six months in most cases. Clubbing: Appears with chronic hypoxia. Growth delay: Common in long-standing cyanosis. Heart sounds: Normal S₁, single S₂ (soft or absent pulmonary component). Murmurs: Harsh systolic ejection murmur at left upper/mid-sternal border. Intensity correlates with RVOTO severity. Continuous murmur over back/axilla in pulmonary atresia with collateral flow. Thrills/heaves: Midsternal systolic thrill and prominent RV impulse may be palpable. Vitals: Low-volume pulse, normal or low BP; polycythemia uncommon in neonates.

20. Physical Examination Adults (Post-Repair or Unrepaired) Pulmonary regurgitation: Causes RV dilation, tricuspid regurgitation, and RV dyssynchrony (often with right bundle branch block). Arrhythmias: Both atrial and ventricular types contribute to late morbidity and mortality. Chronic hypoxemia complications: Hyperviscosity , stroke, endocarditis, and cerebral abscess in unrepaired cases. Murmur changes: May diminish post-repair; residual murmurs indicate valvular or outflow abnormalities.

21. Differential Diagnoses Typical TOF Presentation: Cyanosis, hypercyanotic (“Tet”) spells, dyspnea, failure to thrive Other Cyanotic CHDs (R→L shunt): d-TGA with Pulmonary Stenosis: Severe cyanosis, early onset; echo shows abnormal great arteries + VSD DORV with Severe Pulmonary Stenosis: Cyanosis & “Tet spells”; echo shows both arteries from RV + VSD position Tricuspid Atresia: Hypoplastic RV, cyanosis via ASD/VSD; no pulmonary ejection murmur Ebstein Anomaly: Apical tricuspid valve displacement, right-to-left atrial shunt; murmur + echo differentiation Isolated Severe Valvular Stenosis: Pulmonary or aortic stenosis; cyanosis & hypertrophy without overriding aorta or VSD; confirmed by echo Respiratory Causes: Bronchiolitis / Pneumonia: Tachypnea, hypoxemia, fever; CXR shows infiltrates/hyperinflation Pneumothorax: Sudden cyanosis; asymmetric breath sounds, hyperresonance, CXR confirmation

22. Investigations Investigations aim to: Confirm the diagnosis, Define the anatomical and physiological severity of right ventricular outflow tract obstruction (RVOTO), Identify associated cardiac anomalies, and Guide surgical planning and follow-up. They include bedside tests, laboratory studies, ECG, chest radiography, echocardiography, advanced imaging (CT/MRI), and invasive catheterization.

23. A. Bedside Test 1. Pulse Oximetry To estimate hypoxemia and cyanosis. Findings: Resting oxygen saturation usually 75–85%. Saturation <80% indicates significant right-to-left shunting and need for surgical evaluation. During “Tet spells,” saturation drops sharply due to dynamic infundibular spasm. Postoperative saturation decline may indicate residual RVOTO or shunt dysfunction. B. Laboratory Studies 1. Complete Blood Count (CBC) Findings: Polycythemia (elevated hematocrit and hemoglobin) as compensation for chronic hypoxemia. Anemia may result from malnutrition or infection. Thrombocytopenia or abnormal platelet function may accompany long-standing cyanosis, increasing bleeding risk. Hematocrit >65% predisposes to hyperviscosity and stroke; guides phlebotomy decisions in symptomatic cases.

24. 2. Coagulation Profile Chronic hypoxia alters platelet function and clotting factors, leading to prolonged bleeding/clotting times—important before surgery or dental procedures. 3. Arterial Blood Gas (ABG) and Serum Lactate To assess oxygenation, ventilation, and perfusion. Findings: Low PaO ₂ confirms hypoxemia. Elevated lactate or base deficit indicates poor tissue oxygenation and correlates with higher perioperative risk. Serial ABG monitoring is crucial during surgery to assess perfusion adequacy. 4. Blood Cultures Indicated in febrile patients to rule out bacterial endocarditis, a known complication of cyanotic congenital heart disease.

25. C. Electrocardiography (ECG) Findings: Right axis deviation and right ventricular hypertrophy (tall R in V1–V3, deep S in V5–V6). Right bundle branch block (RBBB) is common post-repair. QRS >180 ms strongly predicts ventricular arrhythmias and sudden cardiac death. QRS prolongation (>3.5 ms /year) suggests progressive RV dilation and dysfunction. Atrial arrhythmias (flutter/fibrillation) in older or repaired patients indicate atrial dilation or fibrosis. ECG findings are both diagnostic and prognostic, particularly for arrhythmia surveillance.

26. . D. Chest Radiography (CXR) Classic feature: “Boot-shaped heart” ( coeur en sabot) from RVH and pulmonary artery concavity. Other findings : Oligemic lung fields (decreased vascular markings). Cardiomegaly in repaired cases with RV failure. Prominent RV contour in older children/adults. Unilateral plethora indicates anomalous pulmonary artery origin. CXR provides a quick, noninvasive diagnostic clue, particularly valuable in low-resource settings

27. E. Echocardiography (2D and Doppler) Gold standard for TOF diagnosis. Findings: Large, nonrestrictive VSD with overriding aorta. Characterization of RVOTO ( subvalvar , valvar, or supravalvar ). RV hypertrophy, pulmonary annular hypoplasia, and valve morphology. Associated lesions (ASD, PDA, coronary anomalies). Doppler studies assess flow direction, turbulence, and pressure gradients. Echocardiography defines the anatomy preoperatively, evaluates residual defects postoperatively, and guides reoperation timing for pulmonary regurgitation.

28. F. Cardiac Catheterization Indications: When echocardiography is inconclusive or anatomy is complex. To measure RV and pulmonary pressures, assess VSD, and map pulmonary arteries or collaterals. To delineate coronary anatomy (vital for surgical planning). Risks: Procedure can precipitate a “Tet spell,” so reserved for essential cases. Cardiac catheterization remains valuable for both diagnostic clarification and interventional procedures (e.g., ductal or RVOT stenting ).

29. G. Cardiac MRI MRI is the gold standard for assessing RV size, function, and pulmonary regurgitation post-repair. Quantifies RV volume and ejection fraction. Measures regurgitant fraction to determine timing of valve replacement. Visualizes branch pulmonary arteries and aortic root dilation. Detects myocardial fibrosis (late gadolinium enhancement) with prognostic relevance. H. CT Angiography Offers higher spatial resolution for coronary and collateral mapping, useful when MRI is contraindicated. MRI and CT have largely replaced diagnostic catheterization in stable adults for noninvasive, high-resolution evaluation.

30. Management and Treatment Acute Medical Management Surgical Management Long-Term and Adult Considerations Medical Therapy in Chronic or Symptomatic Patients

31. A. Acute Medical Management Tetralogy of Fallot, particularly in neonates and infants, can present with hypercyanotic or “Tet” spells — life-threatening episodes resulting from sudden worsening of right ventricular outflow tract (RVOT) obstruction and right-to-left shunting. The goals of acute management are to increase pulmonary blood flow, reduce infundibular spasm, and improve systemic oxygenation. Key interventions include: 1. Knee-Chest Positioning: Increases systemic vascular resistance, reducing right-to-left shunting across the ventricular septal defect (VSD). This simple maneuver is often lifesaving. 2. Oxygen Therapy: Reduces pulmonary vascular resistance and relieves hypoxemia. Though it doesn’t correct the shunt, it supports oxygenation during spells.

32. 3. Beta-Blockers (e.g., Propranolol 2–6 mg/kg/day): Relieve dynamic RVOT obstruction by relaxing infundibular spasm and slowing heart rate to improve filling. 4. Intravenous Fluids: Increase right ventricular preload and promote pulmonary blood flow. 5. Morphine (0.1–0.2 mg/kg IM/SC or IV): Sedates, decreases respiratory drive, and reduces agitation that can worsen spells. 6. Phenylephrine (0.02 mg/kg IV) or Sodium Bicarbonate: Phenylephrine raises systemic vascular resistance; bicarbonate corrects acidosis and reduces hyperpnea that worsens cyanosis. Rationale: Prompt recognition and intervention are essential, as untreated Tet spells may cause syncope, seizures, or death. These measures stabilize the patient pending surgical correction.

33. B. Surgical Management Surgery is the definitive treatment for TOF, aiming to relieve RVOT obstruction, close the VSD, and normalize circulation. Surgical timing depends on cyanosis severity, pulmonary artery anatomy, and comorbidities Palliative procedures Definitive Intracardiac Repair

34. Palliative Procedures 1. Modified Blalock–Taussig Shunt (MBTS): Connects the subclavian artery to the pulmonary artery to increase pulmonary blood flow. Indications: Neonates with severe cyanosis, small pulmonary arteries, or anatomy unsuitable for immediate repair. Advantage: Allows pulmonary artery growth before definitive repair. Other shunts: Classic Blalock-Taussig shunt, Waterston-Cooley shunt, Pott’s anastomosis, Central shunt 

35. 2. Ductus Arteriosus or RVOT Stenting: Maintains pulmonary blood flow without cardiopulmonary bypass in select neonates. Rationale: Palliative procedures improve oxygenation and survival in high-risk neonates but are not curative

36. Procedure: VSD closure with a patch. Relief of RVOT obstruction by infundibular resection or pulmonary valvotomy. Transannular patch or valve-sparing repair based on pulmonary valve anatomy. Preservation of the His bundle to prevent atrioventricular block. In select cases, a small atrial septal defect is left to decompress the right atrium. Definitive Intracardiac Repair Usually within the first year of life; neonatal repair is increasingly common in specialized centers .

37. Definitive Treatment in Special Scenarios: RV-to-PA Conduits: Used in pulmonary atresia, hypoplastic RVOT, or reoperations for severe regurgitation/stenosis. Reintervention may be required as conduits have limited lifespan. TOF with Absent Pulmonary Valve: May require pulmonary artery plication, airway relief procedures, and valved conduits. Outcomes: Mortality for primary repair is <3% in experienced centers. Long-term risks include conduction abnormalities, residual RVOT obstruction, and pulmonary regurgitation.

38. C. Long-Term and Adult Considerations Even after repair, patients remain at risk for complications. Pulmonary Regurgitation (PR) and RV Dysfunction: Common after transannular patching, leading to RV dilation and possible valve replacement. MRI is the gold standard for RV assessment. Arrhythmias: Ventricular tachyarrhythmias and sudden cardiac death remain key risks. ICD implantation or radiofrequency ablation may be indicated. Exercise Tolerance: Regular follow-up with ECG, echocardiography, and exercise testing helps monitor declining function. Special Guidelines: Adults with repaired or unrepaired TOF should be followed by congenital heart disease (CHD) specialists. Imaging (Echo, MRI, CT, cardiac cath ) is used for assessing residual lesions and RV function. Risk stratification and interventions follow AHA/ACC 2018 guidelines.

39. Automatic Implantable Cardioverter Defibrillator Despite the surgical correction, some individuals continue to experience ventricular arrhythmias, putting them at a higher risk of sudden death. An automated implantable cardioverter-defibrillator may be beneficial for these patients. The technique is relatively safe and can be done under local anesthetic Radiofrequency Ablation Radiofrequency ablation (RFA) has only recently become a viable alternative for treating arrhythmias in adult patients with tetralogy of Fallot. This procedure may aid in the treatment of atrial or ventricular arrhythmias .

40. D. Medical Therapy in Chronic or Symptomatic Patients Pulmonary Vasodilators (e.g., Sildenafil): May reduce pulmonary pressure but do not halt progression. Afterload Reducers & Diuretics: Provide symptomatic relief but don’t reverse structural disease. Supportive Care: Includes oxygen therapy, heart failure management, and endocarditis prophylaxis.

41. Note Hypercyanotic spells are emergencies and each intervention has a physiological basis (e.g., knee-chest increases systemic resistance). Surgery corrects anatomy, not lifelong risk therefore continuous follow-up is mandatory. Pulmonary regurgitation and arrhythmias are the most common late issues. Anatomical variations (e.g., coronary anomalies, MAPCAs) influence repair strategy. Adult patients require lifelong specialized care.

42. Complications of Tetralogy of Fallot 1. Short-Term Complications Postoperative: Shunt-related: May cause recurrent laryngeal/phrenic nerve injury, shunt thrombosis (life-threatening), or improper shunt size leading to cyanosis or heart failure. Post-repair complications: Pericardial/pleural effusion, chylothorax, bleeding, wound infection, residual VSD, and RVOT obstruction. Arrhythmias: Junctional ectopic tachycardia (JET) in 15–20% of patients; managed with electrolytes, pacing, antiarrhythmics (amiodarone, esmolol), and sedation. Conduction injuries may lead to RBBB, bifascicular block, or complete heart block. RV Dysfunction: Due to hypertrophy, diastolic dysfunction, or transannular patch placement. Managed by careful fluid balance and beta-blockers.

43. 2. Long-Term Complications Common issues in adults with repaired TOF: Pulmonary Regurgitation: Occurs in ~40% by 35 years post-repair; may lead to RV/LV dysfunction and require valve replacement. Arrhythmias & Sudden Death: Atrial flutter/fibrillation and ventricular tachycardia are common. Risk factors include late repair, male sex, prolonged QRS (>180 ms ), and syncope. Sudden death risk is 6–9% at 30 years. Structural Issues: RV aneurysm, pulmonary artery stenosis, aortic root dilation (>55 mm needs surgery), tricuspid regurgitation, and ventricular hypertrophy. Neurodevelopmental & Psychosocial Problems: Mild cognitive impairment and learning difficulties are common; therapy and academic support may help. Infective Endocarditis: Ongoing risk, particularly during dental or surgical procedures—prophylactic antibiotics are required.

44. 4. Mortality in Unrepaired TOF High early mortality due to hypoxic spells (68%), cerebrovascular events (17%), and brain abscesses (13%). Survival declines sharply: ~66% at 1 year, 40% at 3 years, 11% at 20 years, 6% at 30 years, and 3% at 40 years. 3. Pregnancy Complications Repaired TOF: Usually well tolerated but risk increases with RV dysfunction or pulmonary hypertension. Maternal risks: Arrhythmias, heart failure, thromboembolism. Fetal risks: Prematurity, growth restriction, intrauterine demise, congenital defects. Unrepaired TOF: Carries high maternal-fetal mortality with risks of RV dilation, CHF, hemorrhage, thromboembolism, and brain abscess.

45. Prognosis Dramatic improvement due to surgical advances. Early complete repair (<1 year) → excellent survival & quality of life. Lifelong follow-up needed for residual hemodynamic & electrophysiologic issues. Without Surgery: ~50% die by age 6; only 3% survive >40 years. Surgical Survival & Early Outcomes: Modern surgical mortality: ~2%; >90% survive 20 years. Most children are NYHA Class I; normal growth & minimal functional limitation. Reoperations may be needed for pulmonary regurgitation or RVOTO.

46. Long-Term Cardiac Outcomes: Pulmonary regurgitation: RV dilation, dysfunction, fibrosis. Arrhythmias: VT, atrial flutter; risk ↑ with older age at repair, QRS >180 ms. Exercise intolerance & heart failure: Secondary to RV dysfunction. Pulmonary valve replacement: Reduces RV overload & arrhythmia risk. Long-Term Survival: Repaired TOF → most survive into adulthood. Sudden cardiac death: 1–5% in adults. Early repair + maintained RV function → potential longevity into 70s–80s. Risk Stratification: RV/LV EF ≤35%, extensive fibrosis, peak VO₂ ≤17 mL/kg/min, BNP ≥127 ng/L, sustained atrial arrhythmias. Special Considerations: Reinterventions common for valve dysfunction or arrhythmias. Ongoing surveillance: ventricular function, arrhythmia, aortic root, endocarditis prophylaxis. Most patients achieve meaningful longevity & quality of life

47. Recent Advancements Mortality reduced from ~50% (pre-surgical era) to <3% in specialized centers. Management evolved from palliation → early complete repair → lifelong surveillance. Advances in Imaging & Diagnostics: Echocardiography (2D/3D): First-line; assess RVOT & coronary anatomy. Cardiac MRI: Gold standard for RV volume & pulmonary regurgitation. CT Angiography: Visualizes pulmonary arteries & MAPCAs when MRI contraindicated. Fetal Echocardiography (18–24 wks ): Early diagnosis, syndromic counseling. Genetic & Molecular Insights: Syndromic TOF: 22q11.2 deletion (~15%), JAG1, NKX2-5, NOTCH1 mutations. Future: Gene-targeted therapy & modulation of cardiac morphogenesis (experimental). Surgical Timing & Techniques: Early Complete Repair (3–6 months): Reduces hypoxia, RV hypertrophy, neurodevelopmental delay; mortality <2%. Valve-Sparing Techniques: Preserve pulmonary valve; reduce PR, arrhythmias, RV dilation. Hybrid & Minimally Invasive: RVOT/ductal stenting for high-risk neonates.

48. Interventional & Postoperative Management: Transcatheter Pulmonary Valve Replacement (TPVR): Melody™ & Sapien XT™; >85% 5-year freedom from reintervention. Arrhythmia Management: ICD for QRS ≥180 ms or prior VT; ablation/CRT as needed. Neurodevelopmental Care: Early evaluation; cognitive & executive function monitoring. Lifelong Surveillance & Adult TOF Care: Monitor RV function, pulmonary valve, residual VSD/RVOT obstruction, arrhythmia, aortic root. QRS >180 ms → higher risk of RV dilation & sudden cardiac death. Future Frontiers: Tissue-engineered & growth-adaptive valves. AI-assisted imaging & predictive modeling for RV function & intervention timing. 3D printing & virtual surgical planning for precision surgery.

49. Conclusion Tetralogy of Fallot is one of the most well-understood and successfully treated congenital heart diseases. Once a fatal condition, it is now largely correctable, thanks to advances in surgery, imaging, and long-term cardiac care. Early diagnosis through echocardiography, timely repair, and good perioperative management have allowed most children with TOF to live into adulthood with excellent quality of life. However, TOF is not “cured” by surgery. It is a lifelong condition. Patients still need ongoing follow-up for complications such as pulmonary regurgitation, right ventricular dysfunction, and arrhythmias. Today, the focus has shifted beyond survival. The goal is now to ensure long-term health, prevent late complications, and support overall well-being. With continuous monitoring, modern imaging, and multidisciplinary care, patients with TOF can lead full, active lives.

50. References Elsaka , O., et al. (2023). Tetralogy of Fallot: Diagnosis and Management. ResearchGate. https://www.researchgate.net/publication/368470046_Tetralogy_of_Fallot_Diagnosis_and_Management Horenstein, M. S., et al. (2024). Tetralogy of Fallot. In StatPearls [Internet]. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK513288/ Archampong , E. Q., et al. (2017). Bajan’s Principles and Practice of Surgery (5th ed.). Adeoye, & Akanbi. (2025). Congenital Heart Disease Lecture for 500-Level Medical Students, University of Ilorin.