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Nov.14.2022

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
    • 36-year survival rate after corrective surgical repair is 85% r3
  • 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 obstruction
    • Administer IV alprostadil to maintain ductal patency and pulmonary blood flow until the neonate can undergo surgical repair
  • Hypercyanotic spells in children r1r4
    • Place child in knee-to-chest position to increase systemic vascular resistance and promote systemic venous return to right side of heart
    • Provide supplemental oxygen to enable pulmonary vasodilation and systemic vasoconstriction
    • If cyanosis persists, sequentially treat as needed with the following:
      • Morphine sulfate
      • Propranolol
      • Phenylephrine

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 of presentation varies by severity of right ventricular pulmonary outflow obstruction
    • Most commonly presents in infancy or neonatal period c1
    • Severe right ventricular outflow 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 r5
  • Infants and young children
    • Moderate right ventricular outflow obstruction
      • May present based on abnormal cardiac examination finding (eg, murmur) detected by primary care physician
      • May present with paroxysmal hypercyanotic attacks (ie, blue or tet spells) c4c5
        • Characterized by paroxysms of hyperpnea, irritability, and increased cyanosis; syncope may follow
        • Often triggered by agitation or occurs after first morning wakening r5
        • 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
    • Mild right ventricular outflow obstruction
      • May present with subtle, progressive cyanosis
        • 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 period of time and then stop to sit, squat, or lie down to relieve exertional dyspnea r5c6
  • Older children and adults
    • Uncorrected tetralogy of Fallot is associated with very mild degrees of right ventricular outflow obstruction
      • Rarely presents in older age groups with right-sided heart failure symptoms (eg, dyspnea, exertional syncope, lightheadedness) c7c8c9
      • Characteristically, patients assume squatting position to relieve dyspnea caused by physical effort r5
    • Chronic pulmonary regurgitation commonly develops in adults following 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 c10c11
  • Cardiac findings
    • Combination of a loud systolic murmur with a single second heart sound is highly characteristic c12c13
    • 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 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 of infancy c14c15c16c17c18c19
  • Findings associated with long-standing cyanosis (eg, digital clubbing, dusky blue skin, grey sclerae with engorged blood vessels) are uncommon unless diagnosis is delayed until late childhood or adulthood r5c20c21c22c23
  • Findings during paroxysmal hypercyanotic attacks may include:
    • Acute increase and progressive worsening of cyanosis
    • Murmur disappears or decreases in intensity as flow across right ventricular outflow tract diminishes r5
    • Severe spells may progress to convulsions or hemiparesis r5

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:
    • 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 18
    • Alagille syndrome

Causes and Risk Factors

Causes

  • Exact mechanism is unknownr1, but maldevelopment of the embryonic conotruncus is suspected, which is associated with genetic disorder c24c25

Risk factors and/or associations

Age
  • Typically detected in neonates or infants r8c26
  • Rarely, diagnosis may be delayed until adulthood if pulmonary obstruction is relatively mild and/or the patient has not received routine health care r9c27
Genetics
  • Suspected genetic influence; in approximately 15% of cases, tetralogy of Fallot is associated with chromosomal band 22q11.2 deletion r2c28
  • Trisomy 13, trisomy 18, and trisomy 21 syndromes occasionally coexist with tetralogy of Fallot r1c29c30c31
Other risk factors/associations
  • Maternal history of alcohol abuse, uncontrolled diabetes, or phenylketonuria r1c32c33c34
  • Maternal exposure to hydantoin, trimethadione, retinoic acid, or carbamazepine r1c35c36c37c38c39c40c41c42

Diagnostic Procedures

Primary diagnostic tools

  • Clinical history and physical examination, typically in a neonate, raise suspicion for the diagnosis c43
  • Chest radiography should follow as initial imaging in all suspected cases
  • ECG is done in patients with suspected congenital heart disease as well as part of the assessment after repairs to detect any potential dysrhythmias
  • 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 r10
  • 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

Laboratory

  • Pulse oximetry c44
  • Arterial blood gas measurement c45
    • Establishes oxygenation status and detects metabolic acidosis

Imaging

  • Plain chest radiography c46
    • Obtain in 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 c47
    • Obtain in 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 r9
    • Transthoracic 2-dimensional echocardiography with color flow Doppler imaging r8
      • Used in most patients to assess structural and physiologic information
    • Transesophageal echocardiography r8
      • May be used preoperatively or intraoperatively
  • Cardiac MRI r11r12c48
    • Provides information to decide if/when repair or reoperation is necessary
      • Localizes and quantifies pulmonary/systemic blood flow through a ventricular septal defect
      • Assesses right ventricular function and outflow tract obstruction
      • Measures pulmonary regurgitation or stenosis r11
      • Detects fibrosis of right ventricular muscle
      • Documents stenosis in distal pulmonary artery bed
    • In adults, useful to quantify ventricular size and function, pulmonary valve function, pulmonary artery anatomy, and left-sided heart abnormalities in patients with repair r10
  • CT r11c49
    • Provides anatomic information to decide if/when repair or reoperation is necessary
    • Mostly used in patients for whom MRI is contraindicated (eg, patient has metal implants)
    • Disadvantages include need for ionizing radiation and iodinated contrast material

Functional testing

  • ECG c50
    • Obtained in 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 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 V₁) r5
      • QRS complex prolongation greater than 180 milliseconds shows propensity for sustained ventricular tachycardia and sudden cardiac death r13
    • Exercise testing r14c51
      • Used to detect exertional arrhythmias and assess functional work capacity
      • Typically performed in long-term evaluation of patients after corrective surgery of tetralogy of Fallot

Procedures

Cardiac catheterization with angiography c52c53
General explanation
  • Percutaneous catheters placed in peripheral blood vessels and advanced into central circulation
  • Angiography delineates anatomic structures
  • Measures pressure and oxygen saturation in the heart and great vessels and measures cardiac contractility and function
  • Usually performed under 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: r9
    • To define coronary artery vascular anatomy and to 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 c54d1
    • 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 c55
    • 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 c56
    • Distinguishing features
      • Abnormal persistence of blood vessel 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 c57d2
    • 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 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

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

  • Hypercyanotic spells in children r1r4
    • Place child in knee-to-chest position to increase systemic vascular resistance and promote systemic venous return to right side of heart
    • Provide supplemental oxygen to enable pulmonary vasodilation and systemic vasoconstriction
    • If cyanosis persists, sequentially treat as needed with the following:
      • Morphine sulfate
      • Propranolol
      • Phenylephrine

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 r15

  • Most pediatric cardiothoracic centers prefer to perform complete repair when infants are aged 3 to 9 months owing to the majority of cases being physiologically balanced and thriving in the neonatal period but not requiring immediate intervention r16r17
  • Neonatal intervention is indicated in symptomatic neonates presenting with severe cyanosis or hypercyanotic spells
  • Primary neonatal repair is recommended if patient weighs >3 kg and has well developed pulmonary arteries r18
  • Early palliative interventions may be offered to selected patients to allow deferral of a full intracardiac repair until later in infancy when surgical mortality is lower
    • Neonates with low weight, small pulmonary arteries, or multiple comorbidities have better outcomes with a staged approach r18
    • Traditionally involved surgical placement of a systemic-to-pulmonary artery shunt r19
    • 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 r15r19

Drug therapy

  • For neonates with severe right ventricular outflow obstruction
    • Alprostadil (prostaglandin E₁) c58
      • Administer at birth to maintain patent ductus in newborns and increase pulmonary blood flow. Continue infusion until neonate is transferred to a specialized center for surgical repair
      • 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. After a therapeutic response is achieved, 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. After a therapeutic response is achieved, 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.
      • Anticipate apnea with administration r5r20
  • Stepwise protocol for treatment of hypercyanotic spells in infants or children r1r4
    • Morphine sulfate c59
      • Sedates the patient, relaxes the outflow tract of the right ventricle, and reduces ventilatory drive during hypercyanotic spells r1r4
      • 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-blockers c60
      • Relaxes the right ventricular outflow tract and improves pulmonary blood flow during acute episodes r4r21
      • Prophylactic treatment may prevent occurrence of cyanotic spells in preoperative patients (optimum dose unavailable) r21
      • Propranolol c61
        • 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.
        • Intravenous
          • 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 c62
      • Increases systemic vascular resistance, improves right ventricular outflow, and decreases right to left shunting r5
      • 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

Paroxysmal hypercyanotic spell

  • Calm and hold infant r5
  • Place patient in knee-to-chest position r5
    • Ensure that patient’s clothing is not restrictive
  • Administer oxygen with goal to increase oxygen saturation to more than 90% r4c63
    • 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
  • Administer medications in stepwise fashion, starting with morphine, if hypercyanotic spell does not appear to be reversing r5
  • Unusually severe spells recalcitrant to stepwise medical therapy may require the following: r5
    • Sodium bicarbonate administration to treat resultant metabolic acidosis r4
      • Expect rapid recovery from spell once pH returns to reference range r5
    • Sedation and paralysis followed by intubation and mechanical ventilation
    • Emergent palliative systemic to pulmonary shunt or complete corrective surgery
  • Definitive surgical treatment is indicated once paroxysmal hypercyanotic spells begin r5

Endocarditis prophylaxis r22r23r24

  • Consider for dental procedures involving manipulation of gingival or periapical region of teeth or manipulation of oral mucosa r25
  • Indicated for patients with: r26
    • 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 r27

  • 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/class IA sports (eg, bowling, cricket, golf, yoga) r28
  • After corrective surgery, patients without significant valvular dysfunction, outflow tract obstruction, and evidence of arrhythmia
    • May consider moderate/class II to high-intensity/class III sports r28
  • 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 r16c64
General explanation
  • Complete surgical repair includes:
    • Separation of pulmonary and systemic circulation
      • Accomplished by closure of ventricular septal defect with a polyethylene terephthalate patch c65
    • Enlargement of right ventricular outflow tract to relieve right ventricle outflow obstruction; accomplished by:
      • Resection of infundibular stenosis c66
      • Relieving of pulmonary stenosis
        • Valve-sparing approach is preferred when feasible to minimize occurrence of postoperative pulmonary valve incompetence r29r30
        • 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 r10c67
  • Transatrial approach is used when feasible to avoid risk of late-onset arrhythmia associated with ventriculotomy r31
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 r32r33
  • 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, 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 obstruction
    • Pulmonary valvular insufficiency; marked regurgitation may lead to right ventricular enlargement
      • Increased risk in 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 dilatation
      • 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 dilatation and aortic valve insufficiency
    • Sudden cardiac death
Interpretation of results
  • Findings after repair r34
    • Complete right bundle branch block is common (80%-90%) r34
    • 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 r34
Palliative systemic to pulmonary shunt placement c68
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 r18c69
      • Shunt is made between subclavian artery and pulmonary artery
    • Waterston shunt c70
      • Shunt attaches ascending aorta to right pulmonary artery
    • Potts shunt c71
      • 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 obstruction
  • Emergent treatment of refractory paroxysmal hypercyanotic spell
Contraindications
  • Atrial septal defect
Complications
  • Postoperative pulmonary overcirculation leading to heart failure
  • Chylothorax, diaphragmatic paralysis, Horner syndrome r5
  • Shunt thrombosis
  • Other: intracerebral bleeding, acute necrotizing enterocolitis
  • Child will eventually outgrow shunt as 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 in patients with uncorrected tetralogy of Fallot
  • Other coexisting cardiac abnormalities that may require a modified surgical approach
    • Persistent foramen ovale/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 in patients with uncorrected tetralogy of Fallot without evaluation and risk assessment by a cardiologist
    • Pregnancy is generally well tolerated in women with repaired tetralogy of Fallot if significant hemodynamic abnormalities are not present before pregnancy r35
    • Offer fetal echocardiography given higher risk of congenital heart disease r9
    • Consider testing for 22q11.2 microdeletion, given higher risk in offspring born to mothers with conotruncal defects, when maternal status is unknown r36

Monitoring

  • Lifelong cardiovascular follow-up is required by an age-appropriate congenital heart disease specialist c72
    • 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 dilatation, aortic valve dysfunction, heart failure, and arrhythmias r35
    • All patients require yearly routine clinical monitoring with ECG r34
    • 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 r37
      • Patients aged 10 years or older: echocardiogram every 2 years and cardiac MRI at a minimum of every 36 months in stable patients r37
        • Obtain cardiac MRI every 12 months if there is evidence of moderate right ventricular dilation or dysfunction r37
    • 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 in 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 r37
  • Developmental monitoring for children r38c73
    • 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 r10c74

Complications and Prognosis

Complications

  • Risk of ventricular arrhythmias and sudden death after definitive repair r39c75
    • Implantable cardioverter-defibrillators are indicated for patients with repaired tetralogy of Fallot after spontaneous sustained ventricular tachycardia or cardiac arrest r40
    • Patients at high risk for arrhythmia or with severe residual hemodynamic abnormality may require prophylactic antiarrhythmic therapy, catheter ablation, or implantable defibrillator r5
    • Arrhythmias associated with significant right ventricular outflow obstruction, right ventricular enlargement, and/or severe pulmonary insufficiency may require revision of repair; arrhythmias may improve after restoration of improved hemodynamics r5
      • Pulmonary artery valve replacement reduces occurrence of ventricular arrhythmias
    • 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
    • Overall risk for sudden cardiac death after repair may be approximately 2% within about 20 years after repair r13
    • 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 r41r42
  • Thrombotic events c76
    • May be prevented with prompt treatment of dehydration to avoid worsening of hemoconcentration placing patient at increased risk r5
  • Palliative shunt thrombosis c77
    • Suspect with rapid onset of increasing cyanosis in patient with palliative shunt r5
  • Endocarditis with thromboembolic complications (eg, cerebral emboli, cerebral abscess) c78c79c80d3
    • 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 c81
    • Lower than normal exercise capacity, maximal heart rate, and cardiac output is 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 dilatation experience more severe limitations
  • Risk of neurodevelopmental and growth delay in children c82
  • Increased risk of congenital anomalies in offspring
  • Pulmonary insufficiency
    • Most adults eventually require pulmonary valve replacement r43
    • Indications for pulmonary valve replacement are controversial
    • Transcatheter pulmonary valves and valve stents are recent therapeutic advancements; they may serve as an alternative procedure for some patients in lieu of traditional valve replacement 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 of 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% r44
    • 25-year survival rate after corrective surgical repair is about 93% r45
    • Requirement for reoperation or reintervention approaches 32% by 25 years after corrective surgery r45
      • 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 r46
  • If condition goes untreated, mortality rates are high
    • 3% of patients with tetralogy of Fallot without surgical repair survive to age 40 years r11
  • Patients with repaired tetralogy of Fallot have increased risk for mortality, sudden cardiac death, ventricular tachycardia, pulmonary regurgitation, and heart failure r5r42r47
    • 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 r41r42
    • 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

  • Children with (1 or both) parents who have tetralogy of Fallot r9

Screening tests

  • Universal newborn pulse oximetry at time of nursery discharge, to screen for occult hypoxia that may be associated with congenital heart disease, is recommended r48r49c83
    • Screening protocol algorithms are available r49
  • Screen for chromosomal band 22q11.2 microdeletion before pregnancy in patients who have conotruncal cardiac abnormalities; provide appropriate genetic counseling r9c84
  • Offer fetal echocardiography in the second trimester to pregnant patients with conotruncal abnormalities to screen for fetal abnormalities, such as ventricular septal defect and aortic septal override r9c85

Prevention

  • Pregnant patients should avoid hydantoin, trimethadione, retinoic acid, and alcohol c86c87c88c89
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