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    Tetralogy of Fallot

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    Mar.20.2025

    Tetralogy of Fallot

    Synopsis

    Key Points

    • Tetralogy of Fallot is a congenital heart condition with the following features: r1
      • Large ventricular septal defect
      • Right ventricular outflow tract obstruction secondary to infundibular and/or pulmonary valvular stenosis
      • Overriding aorta
      • Right ventricular hypertrophy
    • Exact cause is unknown; however, chromosomal band 22q11.2 deletion is occasionally associated r1r2
    • Primary diagnostic tools include history, physical examination, and echocardiography
    • Definitive treatment involves complete surgical repair
    • Patients have excellent survival rate if both the obstruction of the right ventricular outflow tract is corrected and the ventricular septal defect has been closed completely
    • Patients who have undergone repair are at long-term risk for development of arrhythmias and pulmonary regurgitation

    Urgent Action

    • Neonates with severe right ventricular outflow tract obstruction
      • Administer IV alprostadil to maintain ductal patency and pulmonary blood flow until the neonate can undergo surgical repair
    • Hypercyanotic spells in children r1r3r4
      • Place child in knee to chest position
      • Provide supplemental high-flow oxygen
      • If cyanosis persists, sequentially treat as needed with the following:
        • Fluid bolus
        • Morphine sulfate
        • Propranolol
        • Phenylephrine
        • Sedation with intubation and ventilation
      • Extracorporeal membrane oxygenation or urgent surgical intervention may be required if hypoxia is refractory to above measures

    Pitfalls

    • Patients with uncorrected tetralogy of Fallot, and some patients after repair, require prophylaxis for subacute bacterial endocarditis before certain dental procedures

    Terminology

    Clinical Clarification

    • Tetralogy of Fallot is a congenital heart condition with the following features: r1
      • Ventricular septal defect
      • Right ventricular outflow tract obstruction secondary to infundibular and/or pulmonary valvular stenosis
      • Overriding aorta
        • Aorta arises over the ventricular septal defect rather than the left ventricle, allowing blood flow from both ventricles into the aorta
      • Right ventricular hypertrophy

    Diagnosis

    Clinical Presentation

    History

    • Age at presentation varies by severity of right ventricular pulmonary outflow obstruction
      • Most commonly presents in infancy or neonatal period c1
      • Severe right ventricular outflow tract obstruction presents in neonates c2
      • Moderate obstruction
    • Prenatal detection
      • Possible; however, right ventricular outflow to lungs in fetus is limited in utero, limiting visualization of typical physiology
      • Usually occurs during evaluation for other congenital anomalies
    • Neonates
      • Severe pulmonary outflow obstruction
        • Presents with cyanosis around the time of ductus arteriosus closure (usually first few hours to days of life) r5c3
        • Progresses to circulatory collapse without urgent intervention r5c4
    • Infants and young children
      • Moderate right ventricular outflow tract obstruction
        • May present based on abnormal cardiac examination finding (eg, murmur) detected by primary care physician c5
        • May present with paroxysmal hypercyanotic attacks (ie, blue or tet spells) c6
          • Characterized by paroxysms of hyperpnea, irritability, and increased cyanosis; syncope may follow c7c8c9
          • Often triggered by agitation or occurs after first morning wakening r5c10
          • Problematic during the first 2 years of life r5
          • May last for a few minutes to hours r5
          • Episodes are often followed by a short period of generalized weakness and sleep c11c12
      • Mild right ventricular outflow tract obstruction
        • May present with subtle, progressive cyanosis c13
          • May present later in the first year of life as infundibular hypertrophy increases, resulting in subsequent decrease in pulmonary flow r5
        • May present with progressive heart failure
          • Children may play for a while and then stop to sit, squat, or lie down to relieve exertional dyspnea r5c14
    • Older children and adults
      • Uncorrected tetralogy of Fallot is associated with very mild degrees of right ventricular outflow tract obstruction
        • Rarely presents in older age groups with right-sided heart failure symptoms (eg, dyspnea, exertional syncope, lightheadedness) c15c16c17
        • Characteristically, patients assume squatting position to relieve dyspnea caused by physical effort r5
      • Chronic pulmonary regurgitation commonly develops in adults after successful repair in early childhood r6
        • May present with progressive exercise intolerance, right- or left-sided heart failure symptoms, or tachyarrhythmias

    Physical examination

    • Cyanosis in the neonatal or infant period is the most common finding c18
    • Cardiac findings
      • Combination of a loud systolic murmur with a single second heart sound is highly characteristic c19c20
      • S₂ is single, or pulmonic component of S₂ is soft
      • Murmur is primarily caused by turbulence through right ventricular outflow tract r5
        • Usually, loud and harsh
          • Louder, longer, and harsher murmurs suggest increasing severity, from mild to moderate, of right ventricular outflow tract obstruction; however, severe obstruction often results in a less prominent murmur r5
        • Usually systolic ejection in quality at the upper sternal border; may sound more holosystolic at the lower sternal border
          • Presence of continuous murmur suggests presence of significant collaterals r5
        • May transmit widely, particularly to lung fields
        • Maximum intensity is usually at left upper sternal border
      • Early systolic ejection click may precede murmur
    • Signs of heart failure (eg, tachypnea, rales, hepatosplenomegaly) are less common in infants but may be present in patients presenting outside infancy c21c22c23c24c25c26
    • Findings associated with long-standing cyanosis (eg, digital clubbing, dusky blue skin, gray sclerae with engorged blood vessels) are uncommon unless diagnosis is delayed until late childhood or adulthood r5c27c28c29c30
    • Findings during paroxysmal hypercyanotic attacks may include:
      • Acute increase and progressive worsening of cyanosis c31
      • Murmur disappears or decreases in intensity as flow across right ventricular outflow tract diminishes r5
      • Severe spells may progress to convulsions or hemiparesis r5c32c33

    Associated congenital anomalies

    • Other associated cardiac defects are variable and may include: r5
      • Anomalies of the aortic arch
        • Right-sided aortic arch in about 20% of cases r5
      • Anomalies of the pulmonary arteries
        • Including absence of branch pulmonary artery, often on the left and associated with ipsilateral pulmonary hypoplasia
      • Coronary artery anomalies in 5% to 14% of patients r7
      • Patent ductus arteriosus and atrial septal defects
      • Multiple ventricular septal defects
      • Complete atrioventricular septal defect
        • Often in association with Down syndrome
      • Congenital absence of pulmonary valve
        • Often with a distinct presentation associated with upper airway obstruction secondary to aneurysmal dilation of pulmonary arteries, resulting in bronchial compression
      • Incidental persistence of left superior vena cava draining into coronary sinus is common but not clinically significant
      • Aorticopulmonary collaterals
    • Associated congenital syndromes, such as the following:
      • 22q11.2 deletion spectrum
        • DiGeorge syndrome
        • Shprintzen velocardiofacial syndrome (CATCH 22 syndrome [cardiac defects, abnormal facial features, thymic hypoplasia, cleft palate, and hypocalcemia])
      • Down syndrome (trisomy 21)
      • Trisomy 13 and trisomy 18
      • Alagille syndrome

    Causes and Risk Factors

    Causes

    • Exact mechanism is unknown,r8 but maldevelopment of the embryonic conotruncus is suspected, which is associated with genetic disorder c34c35

    Risk factors and/or associations

    Age
    • Typically detected in neonates or infants r9c36
    • Rarely, diagnosis may be delayed until adulthood if pulmonary obstruction is relatively mild and/or the patient has not received routine health care r10c37
    Genetics
    • Suspected genetic influence; in approximately 15% of cases, tetralogy of Fallot is associated with chromosomal band 22q11.2 deletion r2c38c39
    • Trisomy 13, trisomy 18, and trisomy 21 syndromes occasionally coexist with tetralogy of Fallot r1c40c41c42
    Other risk factors/associations
    • Maternal history of alcohol use disorder, uncontrolled diabetes, or phenylketonuria r1c43c44c45
    • Maternal exposure to hydantoin, trimethadione, retinoic acid, or carbamazepine r1c46c47c48c49c50c51c52c53
    • Maternal factors associated with increased risk of any congenital heart disease r11
      • Conotruncal cardiac abnormalities
      • Pregestational diabetes
      • Phenylketonuria
      • Autoimmune disease (anti–SS-A [anti-Sjögren syndrome–related antigen A] and anti–SS-B [anti-Sjögren syndrome–related antigen B] autoantibodies)
      • Rubella infection
      • Family history of congenital heart disease in first-degree relative
      • Use of retinoids
      • Use of ACE inhibitors or paroxetine
      • Conception via in vitro fertilization

    Diagnostic Procedures

    Primary diagnostic tools

    • Clinical history and physical examination, typically in a neonate, raise suspicion for the diagnosis c54
    • Chest radiography should follow as initial imaging in all suspected cases c55
    • ECG is done for patients with suspected congenital heart disease and also as part of the assessment after repairs to detect any potential dysrhythmias c56
    • Echocardiography confirms the diagnosis
    • In adults, cardiac MRI is the gold standard imaging modality for quantification of right ventricular size and function in patients with repair; useful to quantify ventricular size and function, pulmonary valve function, pulmonary artery anatomy, and left-sided heart abnormalities in patients with repair r12c57
    • Laboratory tests that assess oxygenation status, including arterial blood gas analysis and pulse oximetry, may be useful in the management of patients with moderate to severe cyanosis c58c59

    Laboratory

    • Pulse oximetry c60
    • Arterial blood gas measurement c61
      • Establishes oxygenation status and detects metabolic acidosis

    Imaging

    • Plain chest radiography c62
      • Obtain for all patients with suspected congenital heart disease
      • Classic findings in anteroposterior view include:
        • Boot-shaped cardiac silhouette with prominent right ventricle r5
          • Upturned apex reflects right ventricular hypertrophy
          • Concavity at upper left heart border in area usually occupied by pulmonary arteries
          • Narrow base
          • Otherwise, normal heart size overall
        • Diminished overall pulmonary vascularity
        • Clearer than normal hilar areas secondary to diminished pulmonary blood flow and/or small pulmonary arteries
        • Aorta
          • Caliber is usually large
          • Aorta arches to the right in about 20% of patients, resulting in indentation of the leftward-positioned tracheobronchial shadow r5
    • Echocardiography c63
      • Obtain for all patients with suspected congenital heart disease to confirm diagnosis
      • Common findings include ventricular septal defect(s), obstruction of right ventricular outflow tract, and anomaly of right-sided aortic arch r10
      • Transthoracic 2-dimensional echocardiography with color flow Doppler imaging r9
        • Obtained for most patients to assess structural and physiologic information
      • Transesophageal echocardiography r9
        • May be used preoperatively or intraoperatively
    • Cardiac MRI r13r14c64
      • Provides information to decide if or when repair or reoperation is necessary
        • Localizes and quantifies pulmonary or systemic blood flow through a ventricular septal defect
        • Assesses right ventricular function and outflow tract obstruction
        • Measures pulmonary regurgitation or stenosis r13
        • Detects fibrosis of right ventricular muscle
        • Documents stenosis in distal pulmonary artery bed
      • For adults, useful to quantify ventricular size and function, pulmonary valve function, pulmonary artery anatomy, and left-sided heart abnormalities in patients with repair r12
    • CT r13c65
      • Provides anatomical information to decide if or when repair or reoperation is necessary
      • Mostly done when MRI is contraindicated (eg, for a patient who has metal implants)
      • Disadvantages include need for ionizing radiation and iodinated contrast material

    Functional testing

    • ECG c66
      • Obtained for patients with suspected congenital heart disease
      • Done as part of assessment after repairs to detect any potential dysrhythmias
      • Interpretation
        • Common findings include: r1
          • Right axis deviation
          • Evidence of right ventricular hypertrophy
            • Upright T wave in leads V₃R and V₁ r5
            • Dominant R waves in the anterior precordial leads (eg, Rs, R, qR, qRs) r5
            • Large S waves in the lateral precordial leads
          • Right atrial enlargement (eg, tall, peaked T waves in lead V₁) r5
        • QRS complex prolongation of more than 180 milliseconds shows propensity for sustained ventricular tachycardia and sudden cardiac death r15
      • Exercise testing r16c67
        • Used to detect exertional arrhythmias and assess functional work capacity
        • Typically performed in long-term evaluation of patients after surgical correction of tetralogy of Fallot

    Procedures

    Cardiac catheterization with angiography c68c69
    General explanation
    • Percutaneous catheters placed in peripheral blood vessels and advanced into central circulation
    • Angiography delineates anatomical structures
    • Measures pressure and oxygen saturation in the heart and great vessels and measures cardiac contractility and function
    • Usually performed with use of light sedation; may require general anesthesia when performed on neonates
    Indication
    • Diagnostic catheterization is typically unnecessary, but it may be performed before initial corrective surgery or reoperation in the following situations: r10
      • To define coronary artery vascular anatomy and determine branch pulmonary artery pressures
      • To assess right ventricular outflow pressure or extent of pulmonary artery obstruction
      • To assess ventricular function and presence of residual septal defects
      • To assess pulmonary regurgitation and right-sided heart failure
    • May be required in the following scenarios:
      • Stabilization after potentially lethal cardiac dysrhythmia
      • Abnormal cardiac stress test results during monitoring
      • New-onset unexplained heart failure
    Contraindications
    • No absolute contraindications
    • Relative contraindications
      • Contrast material allergy
      • Hemodynamic instability
      • Uncompensated congestive heart failure
      • Uncontrolled coagulopathy
    Complications
    • Death
    • Myocardial infarction or stroke
    • Arrhythmias
    • Perforation of heart or great vessels
    • Iodinated contrast medium reactions (eg, allergy, renal injury)
    • Local vascular complications (eg, thrombosis, bleeding, embolization, arteriovenous fistula formation)
    • Infection

    Differential Diagnosis

    Most common

    • Isolated ventricular septal defect c70d1
      • Distinguishing features
        • Ventricular septal defect is the most common congenital cardiac defect; increased pulmonary pressures are noted
        • Characterized by a hole in the intraventricular septum, typically resulting in shunting of blood from left to right ventricle
      • Differentiating tests
        • Chest radiography does not show the classic boot-shaped heart visualized in tetralogy of Fallot
        • Echocardiography is the definitive study; it shows a septal defect but does not show other identifying characteristics of tetralogy of Fallot (eg, pulmonary stenosis, right ventricular hypertrophy, overriding aorta)
    • Pulmonary atresia with intact ventricular septum c71
      • Distinguishing features
        • Deficiency of development of pulmonary valve or infundibulum and atretic right ventricular outflow tract
        • Cardiac auscultation reveals a single loud second heart sound, which is similar to tetralogy of Fallot; unlike tetralogy of Fallot, however, there are no audible murmurs
      • Differentiating tests
        • Echocardiography is the definitive study and shows severe right ventricular hypertrophy; however, it does not show other identifying characteristics of tetralogy of Fallot (eg, pulmonary stenosis, overriding aorta)
    • Patent ductus arteriosus c72
      • Distinguishing features
        • Abnormal persistence of blood vessels between aorta and pulmonary artery after birth; left to right shunting of blood occurs when pulmonary vascular resistance has diminished
        • Commonly associated with hypoxia and prematurity
        • Tachycardia and exertional dyspnea may be present
      • Differentiating tests
        • Chest radiography shows prominent pulmonary vasculature but does not show classic boot-shaped heart visualized in tetralogy of Fallot
        • Echocardiography is the definitive study
    • Aortic stenosis c73d2
      • Distinguishing features
        • As degree of stenosis increases, symptoms (eg, angina, dyspnea, fatigue, syncope)—particularly on exertion—may develop
        • Rarely symptomatic in children younger than 5 years
        • Systolic heart thrills may be palpable at base of heart, in jugular notch, and along carotid arteries
      • Differentiating tests
        • Echocardiography is the definitive study; it shows stenotic aortic valve and possible left ventricular hypertrophy but shows no other identifying characteristics of tetralogy of Fallot (eg, pulmonary stenosis, right ventricular hypertrophy, overriding aorta)

    Treatment

    Goals

    • Optimize and preserve cardiopulmonary function
    • Prevent serious long-term effects of untreated tetralogy of Fallot

    Disposition

    Admission criteria

    Criteria for ICU admission
    • Respiratory distress and cyanosis
    • Severe metabolic acidosis (pH less than 7.2)

    Recommendations for specialist referral

    • Transport neonates and infants suspected of having or diagnosed with tetralogy of Fallot to a medical center equipped to evaluate and manage complex congenital heart disease
    • Refer children with cyanotic heart disease to a pediatric cardiologist for further evaluation
    • After tetralogy of Fallot is diagnosed, refer the patient to a cardiothoracic surgeon (who has expertise in congenital heart disease) for surgical repair
    • Adults who have undergone tetralogy of Fallot repair should have their cases managed in conjunction with a cardiologist (who has expertise in treating congenital heart disease) at least once per year

    Treatment Options

    Neonates with severe disease presenting with profound cyanosis require emergent treatment with alprostadil (prostaglandin E₁) to provide adequate pulmonary blood flow r5

    • Administer alprostadil at birth to maintain patent ductus. Continue infusion until the neonate is transferred to a specialized center for surgical repair
    • Anticipate apnea with administration r5r17

    Before surgery, hypoxic or hypercyanotic spells in neonates or infants are treated with comfort measures, oxygen, and medications

    • Hypercyanotic spells in children r1r3r4
      • Calm and hold infant r5
      • Place the patient in knee to chest position to increase systemic vascular resistance and promote systemic venous return to right side of heart r5c74
        • Ensure that the patient's clothing is not restrictive
      • Administer supplemental high-flow oxygen to reduce severity of hypoxia; goal is to increase oxygen saturation to more than 90% r4c75
        • Administration of oxygen does not reverse cyanosis caused by right to left intracardiac shunting
      • Avoid premature attempts to obtain blood samples; may result in further agitation and worsening of hypercyanotic spell r5
      • If cyanosis persists, sequentially treat as needed with the following stepwise protocol:
        • Fluid bolus to improve venous return
        • Morphine for analgesia and sedation as well as relaxing the outflow tract of the right ventricle and reducing ventilatory drive during hypercyanotic spells
        • Propranolol to reduce right ventricular outflow tract muscle bundle spasm and improve pulmonary blood flow during acute episodes
          • Prophylactic treatment may prevent occurrence of cyanotic spells in patients before surgery is performed r18
        • Phenylephrine bolus to increase systemic vascular resistance, improve right ventricular outflow, and decrease right to left shunting
        • Intubation and ventilation to sedate, reduce muscle spasms, and reduce oxygen consumption
      • In cases of refractory hypoxia despite the aforementioned management, extracorporeal life support or surgical intervention may be necessary

    Usually, medications are required only for urgent treatment of hypercyanotic spells in the setting of severe right ventricular outflow tract obstruction

    Full surgical repair within the first year of life, either as primary treatment or after a palliative procedure, is the mainstay of treatment r19

    • Most pediatric cardiothoracic centers prefer to perform complete repair when infants are aged 3 to 9 months owing to most of cases being physiologically balanced and thriving in the neonatal period but not requiring immediate intervention r20r21
    • Neonatal intervention is indicated for symptomatic neonates presenting with severe cyanosis or hypercyanotic spells
    • Primary neonatal repair is recommended if the patient weighs more than 3 kg and has well-developed pulmonary arteries r22
    • Early palliative interventions may be offered for selected patients to allow deferral of a full intracardiac repair until later in infancy when surgical mortality is lower
      • Neonates with low birth weight or prematurity, small or discontinuous pulmonary arteries, chromosomal anomalies, other congenital anomalies, or other comorbidities have better outcomes with a staged approach r22r23
      • Traditionally involved surgical placement of a systemic to pulmonary artery shunt r24
      • Transcatheter stenting of the ductus arteriosus or right ventricular outflow tract is increasingly used as alternative method to provide a source of pulmonary blood flow with a lower risk of complications than a surgical shunt r19r24r25

    Drug therapy

    • Prostaglandin
      • Alprostadil (prostaglandin E₁) c76
        • Continuous IV or intra-arterial infusion
          • Alprostadil Solution for injection [Ductus Arteriosus Patency]; Neonates: 0.05 to 0.1 mcg/kg/minute continuous IV or intra-arterial (umbilical) infusion, initially. Titrate dose to target clinical response, then reduce the dose to the lowest possible dose that maintains the response. Usual dose: 0.01 to 0.1 mcg/kg/minute. Max: 0.4 mcg/kg/minute.
          • Alprostadil Solution for injection [Ductus Arteriosus Patency]; Infants: 0.05 to 0.1 mcg/kg/minute continuous IV or intra-arterial (umbilical) infusion, initially. Titrate dose to target clinical response, then reduce the dose to the lowest possible dose that maintains the response. Usual dose: 0.01 to 0.1 mcg/kg/minute. Max: 0.4 mcg/kg/minute.
    • Opioid
      • Morphine c77
        • Morphine Sulfate Solution for injection; Infants and Children: 0.05 to 0.1 mg/kg/dose IV/IM; may repeat dose as needed until desired response is achieved.
      • β-Blocker c78
        • Propranolol c79
          • Oral
            • Propranolol Hydrochloride Oral solution [Cardiovascular Disease]; Infants and Children: 1 mg/kg/day PO divided every 6 hours, initially. After 1 week, may titrate dose by 1 mg/kg/day every 24 hours as necessary. Average dose: 2.3 mg/kg/day (range: 0.8 to 5 mg/kg/day). Usual Max: 5 mg/kg/day. May further increase dose gradually if the patient becomes refractory after initial control. Max: 10 to 15 mg/kg/day. Alternatively, 4 mg/kg/day PO divided every 6 hours has been used as an initial dose.
          • IV
            • Propranolol Hydrochloride Solution for injection; Infants and Children: 0.15 to 0.25 mg/kg/dose (Max: 1 mg/dose) IV; may repeat once. Alternatively, 0.01 to 0.02 mg/kg/dose IV has been used, reserving higher doses for refractory spells.
      • Phenylephrine c80
        • Phenylephrine Hydrochloride Solution for injection; Neonates: 5 to 20 mcg/kg/dose IV once, followed by 0.1 to 5 mcg/kg/minute continuous IV infusion.
        • Phenylephrine Hydrochloride Solution for injection; Infants and Children: 5 to 20 mcg/kg/dose IV once, followed by 0.1 to 5 mcg/kg/minute continuous IV infusion.

    Nondrug and supportive care

    Endocarditis prophylaxis r26r27r28

    • Consider for dental procedures involving manipulation of gingival or periapical region of teeth or manipulation of oral mucosa r29
    • Indicated for patients with the following: r30
      • Unrepaired cyanotic congenital heart disease
      • Repairs using prosthetic material during the first 6 months after corrective surgery
      • Prosthetic valves (including transcatheter valve) or prosthetic material used for valve repair
      • Residual defects at the site or adjacent to the site of prosthetic patch after corrective repair
      • Previous episodes of infective endocarditis

    Sports participation r31

    • All patients (repaired or unrepaired) require comprehensive assessment with clinical assessment, ECG, imaging (eg, echocardiography) to assess ventricular function, and exercise testing before participation in competitive sports
    • Stable patients without corrective surgery and without clinical manifestations of heart failure
      • May consider low-intensity or class IA sports (eg, bowling, cricket, golf, yoga) r32
    • After corrective surgery, patients without significant valvular dysfunction, outflow tract obstruction, and evidence of arrhythmia
      • May consider moderate/class II to high-intensity or class III sports r32
    • After corrective surgery, patients with significant ventricular dysfunction, outflow tract obstruction, or recurrent or uncontrolled arrhythmia may not participate in any competitive sports
    Procedures
    Complete corrective surgery r21c81
    General explanation
    • Complete surgical repair includes:
      • Separation of pulmonary and systemic circulation
        • Accomplished by closure of ventricular septal defect with a polyethylene terephthalate patch c82
      • Enlargement of right ventricular outflow tract to relieve right ventricle outflow obstruction; accomplished by the following:
        • Resection of infundibular stenosis c83
        • Relieving of pulmonary stenosis
          • Valve-sparing approach is preferred when feasible to minimize occurrence of postoperative pulmonary valve incompetence; surgical strategies include intraoperative balloon pulmonary valvuloplasty, pulmonary valve reconstruction, and commissurotomy plus pulmonary cusp augmentation r23r33r34r35
          • Transannular patch or patch augmentation, when needed, to provide unobstructed flow from right ventricle to pulmonary arteries
          • Often includes pulmonary valve replacement, if surgery is performed in an adult r12c84
    • Transatrial or transventricular approaches may be used r23
      • Transatrial approach may be preferred when feasible to avoid risk of late-onset arrhythmia associated with ventriculotomy r36
    Indication
    • Polycythemia, pulmonary hypertension, cyanosis, and clubbing
    • Tricuspid, aortic, or pulmonary regurgitation
    • Cardiomegaly or conduction disturbances
    • Frequent paroxysmal hypercyanotic spells
    Contraindications
    • Very low birth weight
    • Small pulmonary arteries
    • Multiple ventricular septal defects
    • Presence of an anomalous coronary artery
    Complications
    • Perioperative mortality for elective procedures is close to zero in experienced centers r37r38
    • Immediate postoperative complications are uncommon and may include: r5
      • Residual ventricular septal defect with left to right shunting
      • Residual right ventricular outflow tract obstruction
      • Conduction abnormalities
        • Right bundle branch block is common
        • Transient heart block is rare
        • Premature ventricular contractions
      • Right ventricular failure
      • Myocardial infarction from interruption of aberrant coronary artery
      • Cardiopulmonary arrest
      • Postoperative bleeding
      • Other: intracerebral bleeding and acute necrotizing enterocolitis
    • Late postoperative complications may include:
      • Right ventricular heart failure, particularly in patients requiring large transannular outflow patch repair
      • Residual right ventricular outflow tract obstruction
      • Pulmonary valvular insufficiency; marked regurgitation may lead to right ventricular enlargement
        • Increased risk for patients requiring transannular patch repair r5
      • Tricuspid regurgitation if right ventricular enlargement develops
      • Conduction disturbances may develop owing to atrial and/or ventricular incisions and right-sided chamber dilation
        • Persistent right bundle branch block is common
        • Ventricular arrhythmia and sudden cardiac death
        • Permanent heart block is rare; requires permanently implanted pacemaker
        • Premature ventricular contractions; mainly a concern when associated with residual hemodynamic abnormalities
        • Atrial tachycardia
      • Aortic root dilation and aortic valve insufficiency
      • Sudden cardiac death
    Interpretation of results
    • Findings after repair r39
      • Complete right bundle branch block is common (80%-90%) r39
      • Residual pulmonary stenosis with elevated right ventricular pressure is not uncommon
      • Some degree of pulmonary insufficiency is common
      • Residual ventricular septal defect is not uncommon
    • Patient may be asymptomatic or develop symptoms related to residual right ventricular pressure overload, volume overload, or arrhythmia r39
    Palliative systemic to pulmonary shunt placement c85
    General explanation
    • Procedure is performed before complete repair to provide stable pulmonary blood flow, reduce intracardiac shunting, and facilitate pulmonary development
    • Procedures involve placement of temporary systemic to pulmonary shunt
      • Blalock-Taussig shunt r22c86
        • Shunt is made between subclavian artery and pulmonary artery
      • Waterston shunt c87
        • Shunt attaches ascending aorta to right pulmonary artery
      • Potts shunt c88
        • Shunt attaches descending aorta to left pulmonary artery
    Indication
    • Patients with comorbidities for whom complete surgical repair is not immediately feasible (eg, patients with concomitant hypoplastic pulmonary arteries, coronary artery anomaly, or other major congenital anomalies)
    • Patients with low birth weight or prematurity with severe right ventricular outflow tract obstruction
    • Emergent treatment of refractory paroxysmal hypercyanotic spell
    Contraindications
    • Atrial septal defect
    Complications
    • Postoperative pulmonary overcirculation leading to heart failure
    • Chylothorax, diaphragmatic paralysis, and Horner syndrome r5
    • Shunt thrombosis
    • Other: intracerebral bleeding and acute necrotizing enterocolitis
    • Child will eventually outgrow shunt, because more pulmonary blood flow is required to maintain adequate arterial oxygen saturation
    Interpretation of results
    • Results in improved pulmonary blood flow and decreased hypoxia

    Comorbidities

    • For conditions requiring dental procedure, bowel surgery, or bladder surgery, administer subacute bacterial endocarditis prophylaxis to patients with uncorrected tetralogy of Fallot
    • Other coexisting cardiac abnormalities that may require a modified surgical approach
      • Persistent foramen ovale or atrial septal defect
      • Pulmonary artery anomalies
      • Persistent left-sided superior vena cava to coronary sinus anomaly
      • Additional ventricular septal defects
      • Coronary artery anomalies

    Special populations

    • Pregnant patients
      • Pregnancy is not advisable for patients with uncorrected tetralogy of Fallot without evaluation and risk assessment by a cardiologist
      • Pregnancy is generally well tolerated in females with repaired tetralogy of Fallot if significant hemodynamic abnormalities are not present before pregnancy r40
      • Offer fetal echocardiography, given higher risk of congenital heart disease r10
      • Consider testing for 22q11.2 microdeletion, given higher risk for offspring born to mothers with conotruncal defects, when maternal status is unknown r41

    Monitoring

    • Lifelong cardiovascular follow-up is required by an age-appropriate congenital heart disease specialist c89
      • Key issues for follow-up and surveillance include assessment for residual right ventricular outflow tract disease, chronic pulmonary regurgitation, right ventricular dilation or dysfunction, aortic root dilation, aortic valve dysfunction, heart failure, and arrhythmias r40
      • All patients require yearly routine clinical monitoring with ECG r39
      • Routine imaging is indicated to assess degree of right ventricular dilation, presence of right ventricular dysfunction, and quantifying regurgitant fraction r5
        • Children younger than 10 years: yearly echocardiogram r42
        • Patients aged 10 years or older: echocardiogram every 2 years and cardiac MRI at a minimum of every 36 months for stable patients r42
          • Obtain cardiac MRI every 12 months if there is evidence of moderate right ventricular dilation or dysfunction r42
      • Frequency of imaging and other testing is individualized based on type of repair, age, preexisting cardiac dysfunction, symptoms, and clinical findings. Monitoring may include the following:
        • Holter monitoring and exercise studies may be indicated for symptomatic patients (eg, those with syncope) and patients at high risk for arrhythmia (eg, those with frequent premature ventricular contractions associated with significant hemodynamic abnormality, those with wide QRS complex) r5
        • Electrophysiology may be indicated for select patients at risk for ventricular tachycardias
        • Lung perfusion scan if there is evidence of significant increase in right ventricular pressure or pulmonary artery narrowing r42
    • Developmental monitoring for children r43c90
      • Key issues include surveillance for developmental delay, developmental disorders, and motor and neurocognitive disabilities
      • Periodic individualized developmental surveillance, screening, evaluation, and reevaluation are recommended throughout childhood
      • Identification of specific deficits allows appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning
    • In adults, serial cardiac MRI examinations allow for longitudinal follow-up of patients with repair and provides useful information that aids in timing of pulmonary valve replacement r12c91

    Complications and Prognosis

    Complications

    • Arrhythmias
      • Atrial tachyarrhythmias and sinus node dysfunction r44
        • Prevalence increases with advancing age in patients with tetralogy of Fallot
        • Adults with tetralogy of Fallot have increased risk for developing reentrant atrial arrhythmias, atrial flutter, and atrial fibrillation
        • Catheter ablation is generally most effective method of treatment
        • Pacemaker implantation is indicated for sinus node dysfunction or tachycardia-bradycardia syndrome
      • Bradyarrhythmia r44
        • Less common but can occur in adults with repaired tetralogy of Fallot owing to atrial scarring or surgical injury to the atrioventricular conduction
      • Ventricular arrhythmias
        • Adults have increased risk of ventricular arrhythmias and sudden death after definitive repair of tetralogy of Fallot r45c92
        • Most commonly, monomorphic ventricular tachycardia, which is often fast and poorly tolerated r44
        • Overall risk for sudden cardiac death after repair may be approximately 2% within about 20 years after repair sudden cardiac death r15
        • Arrhythmia suppression may be achieved via catheter ablation, antiarrhythmic drugs, and implantable devices r44
        • Invasive risk stratification, implantable cardioverter-defibrillator placement, or both are indicated only for patients determined to be at increased risk for sudden cardiac death r44
          • Implantable cardioverter-defibrillators are indicated for patients with repaired tetralogy of Fallot after spontaneous sustained ventricular tachycardia or cardiac arrest r46
          • Patients at high risk for arrhythmia or with severe residual hemodynamic abnormality may require prophylactic antiarrhythmic therapy, catheter ablation, or an implantable defibrillator r5
          • Right ventricular dysfunction, lower left ventricular ejection fraction, older age at repair, and repair preceded by palliative shunt are factors associated with a higher risk of malignant arrhythmia r47r48
          • Right bundle branch block pattern is common after repair; increased duration of postoperative QRS interval may predict risk of future arrhythmia and sudden death r5
          • Arrhythmias associated with significant right ventricular outflow tract obstruction, right ventricular enlargement, and/or severe pulmonary insufficiency may require revision of repair; arrhythmias may improve after restoration of improved hemodynamics r5
            • Pulmonary valve replacement reduces occurrence of ventricular arrhythmias
    • Thrombotic events c93
      • May be prevented with prompt treatment of dehydration to avoid worsening of hemoconcentration placing the patient at increased risk r5
    • Palliative shunt thrombosis c94
      • Suspect with rapid onset of increasing cyanosis in a patient with palliative shunt r5
    • Endocarditis with thromboembolic complications (eg, cerebral emboli, cerebral abscess) c95c96c97d3
      • Patients with uncorrected tetralogy of Fallot, and some patients after repair, require prophylaxis for subacute bacterial endocarditis before certain dental procedures
    • Reduced exercise capacity after definitive repair c98
      • Lower than normal exercise capacity, maximal heart rate, and cardiac output are common r5
        • May be more common in patients requiring placement of transannular outflow tract patch
      • Patients with increasingly severe chronic pulmonary regurgitation resulting in right ventricular dilation experience more severe limitations
    • Risk of neurodevelopmental and growth delay in children c99c100
    • Increased risk of congenital anomalies in offspring c101
    • Pulmonary insufficiency c102
      • Most adults eventually require pulmonary valve replacement r49r50
      • Indications for pulmonary valve replacement are controversial
      • Transcatheter pulmonary valves and valve stents are recent therapeutic advancements; they may serve as alternatives to traditional valve replacement for some patients r5

    Prognosis

    • Patients who undergo complete surgical repair as neonates or infants have an excellent survival rate and improvement in clinical manifestations if both the obstruction of the right ventricular outflow tract is corrected and the ventricular septal defect has been closed completely
      • Marked improvement in symptoms is usually maintained for at least 20 years after definitive surgical repair r5
      • A 2019 systematic review reported that long-term survival exceeds 90% r8
      • 25-Year survival rate after corrective surgical repair is about 93% r51
      • 36-Year survival rate after corrective surgical repair is 85% r52
      • Requirement for reoperation or reintervention approaches 32% by 25 years after corrective surgery r51
        • Pulmonary regurgitation and branch pulmonary artery stenosis are the most common causes for reoperation or reintervention requirement
        • Pulmonary valve replacement (either surgical or catheter deployed) is commonly required in adolescence or adulthood r6r7
      • Overall, patients requiring complete repair during the neonatal period experience higher mortality rates, longer ICU stays, and longer total hospital stays r53
    • If the condition goes untreated, mortality rates are high
      • 3% of patients with tetralogy of Fallot without surgical repair survive to age 40 years r13
    • Patients with repaired tetralogy of Fallot have increased risk for mortality, sudden cardiac death, ventricular tachycardia, pulmonary regurgitation, and heart failure r5r48r54
      • Right ventricular dysfunction, lower left ventricular ejection fraction, older age at repair, and repair preceded by palliative shunt are factors associated with a higher risk of malignant arrhythmia r47r48
      • Mild to moderate pulmonary outflow tract obstruction is usually well tolerated
      • Severe residual gradients across right ventricular outflow tract may require reoperation

    Screening and Prevention

    Screening

    At-risk populations

    • Tetralogy of Fallot in 1 or both parents increases risk for tetralogy of Fallot in offspring r10
    • Certain maternal medical conditions and medication use can increase risk for congenital heart disease, including tetralogy of Fallot, in offspring

    Screening tests

    • Screen for chromosomal band 22q11.2 microdeletion before pregnancy in patients who have conotruncal cardiac abnormalities; provide appropriate genetic counseling r10c103
    • Screening for congenital heart disease via fetal echocardiography in the second trimester is recommended in the presence of the following, which increase the likelihood of fetal congenital heart disease to more than 1% (or greater than about 3 times the background population risk): r11
      • Maternal factors
        • Conotruncal cardiac abnormalities r10c104
        • Pregestational diabetes
        • Phenylketonuria
        • Autoimmune disease (SS-A and/or SS-B antibody positive)
        • Rubella infection
        • Family history of congenital heart disease in first-degree relative
        • Use of retinoids
      • Fetal factors identified on routine antenatal screening ultrasonography
        • Abnormalities of the heart
        • Extracardiac anomalies
        • Fetal hydrops
        • Chromosomal abnormalities
        • Monochorionic twins
        • Nuchal translucency 3.5 mm or greater
    • Fetal echocardiography may also be considered in the following scenarios:
      • Maternal use of ACE inhibitors or paroxetine
      • Nuchal translucency of 3.0 to 3.4 mm
      • Conception via in vitro fertilization
    • Universal newborn pulse oximetry at the time of nursery discharge, to screen for occult hypoxia that may be associated with congenital heart disease, is recommended r55r56c105
      • Screening protocol algorithms are available r56

    Prevention

    • Pregnant patients should avoid hydantoin, trimethadione, retinoic acid, and alcohol c106c107c108c109
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