Hypoplastic Left Heart Syndrome

10 Interesting Facts of Hypoplastic Left Heart Syndrome 

  1. Hypoplastic left heart syndrome is a rare congenital heart condition in which left-sided heart structures are variably underdeveloped and unable to support the systemic circulation
  2. Prenatal diagnosis through routine ultrasonography screening is the most common presentation
  3. A minority of neonates without known prenatal diagnosis are discharged from newborn nursery in good condition and present around the time of ductus arteriosus closure with poor perfusion in cardiovascular shock with mild associated cyanosis
  4. Diagnosis is based on history and physical examination findings; confirm diagnosis with echocardiography
  5. Urgent prostaglandin treatment is essential to reestablish and maintain patency of ductus arteriosus pending surgical treatment
  6. 3 operations are required to establish a stable Fontan (single ventricle) circulation
    • First stage is Norwood procedure performed in the neonatal period 
      • Removal of atrial septum creates a common atrial chamber for both systemic and pulmonary venous return
      • Aortic arch reconstruction is performed to create a neoaorta
      • Pulmonary artery is connected to the neoaorta to create a single-outlet right-sided heart
      • Pulmonary circulation is supplied by a modified Blalock-Taussig shunt or right ventricular to pulmonary artery conduit
      • Postprocedural oxygen saturation is usually around 80% 
    • Second stage is bidirectional Glenn performed around age 3 to 6 months 
      • Pulmonary circulation is restored by a superior cavopulmonary anastomosis accomplished by connecting superior vena cava directly to pulmonary arteries
      • Systemic shunt (ie, modified Blalock-Taussig shunt or ventricular to pulmonary artery conduit) is removed
      • Postprocedural oxygen saturation is now usually maintained in the 80% to 85% range 
    • Third stage is Fontan performed around age 3 to 4 years
      • Systemic venous pathway to lungs is completed with connection of inferior vena cava to pulmonary circulation
      • Postprocedural oxygen saturation is now normal
      • Saturations may be lower if there is a fenestration allowing right-to-left shunting from the Fontan baffle to the atrium
  7. Risk of sudden cardiac deterioration and death is high during the interstage period between Norwood and Glenn operations
  8. Most patients with Fontan circulation are expected to reach adulthood 
  9. Long-term surveillance is paramount to identify complications and early signs of failing Fontan circulation 
  10. Common complications after Fontan procedure include atrial arrhythmias, right ventricular pump failure, and thromboembolic events

Pitfalls

  • Although approximately 75% of patients receive a prenatal diagnosis, normal results of prenatal ultrasonography does not exclude the diagnosis 
  • The absence of murmur or significant manifestation at birth does not exclude diagnosis
    • In some neonates, murmur is not detectable and symptoms do not develop until ductal closure and drop in pulmonary vascular resistance that occurs hours to days after birth
  • Negative result for critical congenital heart disease pulse oximetry screening in newborn period does not exclude presence of disease 
    • Overall sensitivity of positive screening results is about 77% for critical congenital heart disease 
  • Maintain care with administration of oxygen, which is a potent pulmonary vasodilator; excess administration has the potential to drop pulmonary vascular resistance and diminish cardiac output, worsening symptoms
    • Goal oxygen saturation for neonate without a diagnosis of suspected congenital cyanotic heart disease is 90% to 95% 
    • Target oxygen saturation for patients with known and partially repaired congenital cyanotic heart disease is around 75% to 85% 
  • Patients are particularly susceptible to circulatory instability in the setting of minor illness (eg, vomiting, diarrhea, poor oral intake) during the interstage period between Norwood and Glenn procedures
    • Maintain care in evaluating and treating these fragile patients, especially during this critical interstage period, when risk of sudden death is high
  • Hypoplastic left heart syndrome is a rare congenital heart condition in which left-sided heart structures are variably underdeveloped and unable to support systemic circulation 
    • Condition includes a morphologically heterogeneous spectrum of abnormalities involving left-sided heart components (ie, mitral valve, left ventricular cavity, left ventricular outflow tract, aortic valve, ascending aorta, and aortic arch) 
    • More than 1 (and often all) left-sided heart structures are underdeveloped to variable degrees; the left ventricle may be moderately hypoplastic, diminutive, and nonfunctional, or it may be severely hypoplastic or absent 
  • Circulation in the immediate neonatal period is dependent on patency of 2 shunts 
    • Lesion is ductal-dependent; systemic circulation depends on right-to-left flow through the ductus arteriosus 
    • Patent foramen ovale is required for pulmonary venous return to reach systemic circulation 
    • Mixing of systemic and pulmonary venous return results in cyanosis 

Clinical Presentation

History

  • Prenatal history
    • Diagnosis is evident on routine prenatal ultrasonography screening in most patients
    • Up to 75% of cases are diagnosed prenatally 
  • General presentation features
    • Most infants are born at term 
    • Majority of neonates are asymptomatic or minimally symptomatic at birth 
    • Some infants receive diagnosis based on abnormal oxygen saturation screening in the newborn nursery 
    • Diagnosis occurs at a few days to a few weeks of life when the ductus arteriosus begins to close 
      • Pulmonary vascular resistance drops during transition from fetal to postnatal physiology
      • Uncontrolled pulmonary blood flow and large circulatory volume eventually develop and manifest as congestive heart failure, variable cyanosis, and progression to respiratory distress with circulatory collapse 
    • After uneventful hospital course and discharge to home in good condition, some infants experience the following: 
      • Acute, critical illness following ductal closure
      • Neonatal death at home 
  • Symptoms in neonates depend on patency of ductus arteriosus and atrial communication
    • Restrictive foramen ovale or intact atrial septum
      • Newborns are symptomatic immediately at birth
        • Severe respiratory distress from significant pulmonary venous congestion
        • Cyanosis owing to lack of mixing of systemic and pulmonary venous return at the level of the atrium
    • Patent foramen ovale
      • Relatively asymptomatic at birth and immediately thereafter
      • Often becomes symptomatic a few days after birth with closure of the ductus arteriosus and physiologic drop in pulmonary vascular resistance
      • Symptoms of congestive heart failure develop (eg, difficulty breathing, tachypnea, poor feeding) from combined increase in pulmonary blood flow and systemic afterload

Physical examination

  • General
    • Birth weight is often normal 
    • Neonates are usually born in good condition, depending on specific morphology of cardiac lesions 
    • Degree of cyanosis is often subtle and occasionally not clinically obvious in the immediate newborn period
    • Cardiovascular collapse presents rapidly as postnatal ductus arteriosus closure occurs and pulmonary vascular resistance drops 
  • Single S2 may be appreciated owing to hypoplasia of aortic valve
  • Patent ductus arteriosus murmur may or may not be appreciated
  • Signs in affected neonates depend on patency of atrial communication and ductus arteriosus
    • Restrictive foramen ovale or intact atrial septum (about 10% of neonates) 
      • Signs are present immediately after birth
        • Cyanosis is profound
        • Tachypnea with severe respiratory distress
      • Rapid decompensation ensues without intervention (eg, balloon or blade atrial septostomy)
    • Patent foramen ovale (about 90% of neonates)
      • Birth and early neonatal period
        • Neonates often appear healthy at birth
        • Cyanosis may be clinically subtle
        • Signs of patent ductus arteriosus may or may not be appreciated
          • Continuous, harsh murmur and wide pulse pressure
      • Signs develop a few days after birth with closure of ductus arteriosus and increased pulmonary blood flow (secondary to drop in pulmonary vascular resistance)
        • Cyanosis is variable
          • Often saturation lingers around 90% owing to mixing of circulation offset by high pulmonary blood flow 
        • Signs of congestive heart failure develop
          • Tachypnea and pulmonary rales
          • Hepatomegaly
          • Right ventricular parasternal lift
        • Signs of cardiogenic shock develop
          • Weak or absent peripheral pulses 
          • Cool and delayed capillary refill in all extremities
          • Hypotension
        • Progressive respiratory distress occurs and circulatory collapse eventually develops
  • Cardiovascular examination caveats to note include:
    • Ductal murmur may not be evident; a pressure gradient between pulmonary and aortic side of circulation is required to appreciate murmur 
      • Occasionally, a nonspecific pulmonary flow or tricuspid regurgitation murmur may be appreciated
    • Differential cyanosis is lacking (pre- and postductal oxygen saturation are the same) because mixing occurs at the level of the atrium 
    • Cardiovascular shock presents without major difference between brachial and femoral pulses 
  • Dysmorphic features
    • Those involving the face, eye, ear, and musculoskeletal system suggest an associated congenital syndrome 
    • Nonspecific dysmorphic features are present in up to 40% of patients 

Causes

  • Disease is complex and multifactorial with poorly defined genetic component 
    • Nonsyndromic disease appears genetically heterogeneous; identified pathologic variants are often associated with variable expressivity and reduced penetrance 
    • Syndromic disease (hypoplastic left heart syndrome occurring as part of another defined syndrome) is present in 5% to 12% of cases
    • May develop progressively in some fetuses secondary to left-sided heart obstruction in utero 
    • May develop in some fetuses secondary to a primary defect in myocardial growth and abnormal cardiac partitioning during embryogenesis 
  • Observed overall recurrence risk for future pregnancies for all causes of hypoplastic left heart
    • Risk for hypoplastic left heart in a sibling of affected child is 2% to 8% 
    • Risk for hypoplastic left heart in a third affected sibling when 2 other children are affected is about 25% 
    • Risk for some form of congenital heart disease in siblings is up to 22% 

What increases the risk of Hypoplastic Left Heart Syndrome?

Age
  • Affects neonates
    • Occurrence is about 1 in 5000 live births 
    • Accounts for about 2% to 3% of children born with congenital heart defects 
Sex
  • Male to female ratio is about 2 to 1 
Genetics
  • Candidate gene associations include abnormalities in:
    • NOTCH1 (chromosome 9): gene product that provides instructions for making a receptor protein implicated in cardiac development 
      • Gene associations are present between occurrence of hypoplastic left heart and bicuspid aortic valve (OMIM #109730) 
        • Bicuspid aortic valve disease represents a spectrum of abnormalities from minor aortic valve disease to hypoplastic aortic arch, which may in turn result in abnormal fetal growth of left-sided heart structures
        • First-degree relatives of proband with hypoplastic left heart have an increased occurrence of bicuspid aortic valve 
        • Inheritance of NOTCH1-associated aortic valve disease is autosomal dominant 
    • HAND1 (chromosome 5): gene product is a transcription factor essential for cardiac development 
      • Abnormalities in this region responsible for hypoplastic left heart syndrome 1 (OMIM #241550) 
    • NKX2 (chromosome 5): gene product is a cardiac homeobox transcription factor 
      • Abnormalities in this region responsible for hypoplastic left heart syndrome 2 (OMIM #614435) 
      • Inheritance of hypoplastic left heart syndrome 2 is autosomal dominant 
    • Less well characterized gene associations include:
      • ETS1 (chromosome 11): gene product is a transcription factor implicated in cardiac development 
      • GJA1 (chromosome 6): gene product is connexin protein 43 
      • MYH6 (chromosome 14): gene product is α-myosin heavy chain 
      • ERBB4 (chromosome 2): gene product is a cell surface receptor 
Other risk factors/associations
  • Major or minor central nervous system abnormality is present in up to 30% of infants 
    • Agenesis of the corpus callosum is most common 
  • Associated congenital syndromes occur in 5% to 12% of patients with hypoplastic left heart syndrome
    • Jacobsen syndrome (11q deletion)
      • Syndrome with most consistent incidence of hypoplastic left heart syndrome 
      • Up to 10% of patients affected with hypoplastic left heart syndrome have Jacobsen syndrome 
    • Turner syndrome (monosomy X) 
    • Edwards syndrome (trisomy 18) 
    • Patau syndrome (trisomy 13) 
    • Down syndrome (trisomy 21) 
    • CHARGE syndrome and VACTERL association 
    • Holt-Oram syndrome 
    • Rubinstein-Taybi syndrome 
    • Smith-Lemli-Opitz syndrome 
    • Kabuki syndrome 
    • DiGeorge syndrome 
    • Noonan syndrome 
  • Associated additional cardiac abnormalities occur in up to 7.5% of patients and may include: 
    • Transposition of the great arteries
    • Atrial isomerism
    • Total anomalous pulmonary venous drainage
  • Significant other extracardiac anomalies occur in about 1% of patients
    • Most common include diaphragmatic hernia and omphalocele 

How is Hypoplastic Left Heart Syndrome diagnosed?

Diagnostic Procedures

Primary diagnostic tools

  • Most diagnoses occur in the prenatal period with routine prenatal ultrasonography screening 
    • Suspicion may arise based on first trimester ultrasonography and confirmation can be made during second trimester 
    • Secondary prenatal work-up includes:
      • Imaging
        • Detailed fetal ultrasonography to evaluate for extracardiac anomalies 
        • Focused fetal echocardiography to better delineate specific cardiac anomalies and function; repeat at 4 to 6 week intervals and at 36 weeks or beyond to evaluate for development of high-risk features that may affect delivery 
      • Standard fetal karyotyping to evaluate for genetic abnormalities 
        • Advanced genetic testing may be indicated in consultation with geneticist when suspicion for genetic abnormality is high despite normal standard karyotype 
        • Advanced testing may include high-resolution banding, fluorescence in situ hybridization for specific defects, and telomeric and subtelomeric probes 
  • Postnatal diagnosis is suspected based on physical examination findings in neonates without known prenatal diagnosis
    • Confirm diagnosis with echocardiography 
    • Other nondiagnostic cardiac tests obtained during initial diagnosis include chest radiograph and ECG 
    • Baseline assessment of end-organ function with attention to degree of acidosis and presence of hypoglycemia guides preoperative medical management 
    • Additional preoperative assessment
      • Genetic and neurologic evaluation is suggested for patients before surgical repair 
      • Transthoracic echocardiography is used for initial surgical planning in most cases 
      • Advanced cardiac imaging (eg, cardiac MRI, cardiac catheterization) has no role in initial diagnosis, but it may be used for planning before stage 2 and 3 surgical procedures 

Imaging

  • Routine prenatal ultrasonography screening
    • First trimester ultrasonography
      • Finding of increased nuchal translucency may indicate aneuploidy or other anatomic abnormalities, such as heart defects 
    • Second trimester ultrasonography
      • Optimum period for imaging and detecting fetal cardiac abnormalities is between 18 and 22 weeks of gestation 
      • Of note, some variants of hypoplastic left heart are not easily recognizable until later in the third trimester 
      • Abnormal 4-chamber view or outflow tract is an indication for further investigation with focused fetal echocardiography 
  • Echocardiography
    • Assess for presence and size of atrial communication (ie, patent foramen ovale, atrial septal defect) 
    • Assess for patency and size of ductus arteriosus 
    • Defines morphology of underdeveloped left-sided heart structures and hypoplasia of ascending aorta
      • Typical findings include:
        • Absence or hypoplasia of the mitral valve and aortic root 
          • Doppler may show degree of stenosis of valves or atresia 
        • Hypoplastic ascending aorta and transverse aortic arch
          • Juxtaductal discrete coarctation is occasionally present 
        • Variable small left ventricle and left atrium 
          • Left ventricular endocardial fibroelastosis may be noted 
        • Large right atrium and right ventricle
    • Can identify presence of left ventricular coronary sinusoids, degree of tricuspid regurgitation, myocardial function, and any additional cardiac anomalies 
  • Chest radiograph
    • Findings are variable 
    • Nonspecific findings may develop rapidly in first 2 days to 2 weeks of life or later, depending on ductal closure 
      • Cardiomegaly
      • Increased pulmonary vascular markings (both arterial and venous)
      • Pulmonary edema

Functional testing

  • ECG
    • Initial findings may resemble a normal newborn ECG pattern with dominant pattern of right-sided heart 
    • Typically normal sinus rhythm 
    • Other common but nonspecific findings include:
      • Right axis deviation
      • Right ventricular hypertrophy (eg, tall R waves in right and anterior leads [V₁, V₃R]) 
      • Right atrial enlargement (eg, prominent P waves in right and anterior leads [V₁, V₃R]) 
      • Decreased or absent left ventricular forces in lateral precordial leads (V₅, V₆) 

Differential Diagnosis

Most common

  • Critical coarctation of the aorta
    • Other left-sided, obstructive congenital heart lesions may mimic hypoplastic left heart syndrome because systemic circulation depends on ductal flow 
    • Presents in the neonatal period with heart failure and cardiogenic shock with closure of the ductus arteriosus
    • Aortic coarctation is associated with an often loud, harsh murmur that radiates to the back, best heard at the left sternal border; thrill may be palpable in the suprasternal notch 
      • Note that murmur may be soft or absent when cardiac output is low
    • An additional clinical clue is 4-extremity blood pressure differential and difference in pulses between upper and lower extremities
      • Systolic blood pressure is often above 20 mm Hg or higher in upper extremities compared with lower extremities, and pulses are bounding or full in upper extremities and weak or absent in lower extremities 
    • Chest radiograph may be remarkable for the figure 3 sign formed by the aortic nob, the stenotic segment, and the dilated poststenotic segment of the aorta 
    • Differentiate by clinical presentation with chest radiograph findings, echocardiographic evidence of narrowing of the thoracic aorta just distal to the bifurcation of the left subclavian artery, and absence of echocardiographic evidence of hypoplastic left heart
  • Neonatal sepsis
    • May present similarly to hypoplastic left heart syndrome with a shocklike state and/or respiratory distress in the early neonatal period
    • Temperature instability may or may not be present; cyanosis can be a presenting sign of fulminant sepsis 
    • Risk factors for early onset sepsis may be identified in history (eg, preterm birth, maternal colonization with group B Streptococcus, prolonged rupture of membranes longer than 18 hours, maternal intra-amniotic infection) 
    • Other signs and symptoms are nonspecific; therefore, differentiating sepsis from cardiac disease can be challenging 
    • Differentiate by lack of significant response to prostaglandin E1 and echocardiography results inconsistent with hypoplastic left heart
    • Definitive diagnosis relies upon clinical course (eg, response to antibiotics) and positive results of culture tests (eg, blood culture, cerebrospinal fluid culture)
  • Pulmonary disease
    • May present similarly with difficulty breathing and hypoxia
    • Many pulmonary diseases in the newborn deserve consideration, including meconium aspiration syndrome, pneumonia, respiratory distress syndrome, and transient tachypnea of the newborn (Related: Meconium Aspiration Syndrome)
    • Most pulmonary diseases can be differentiated by history and physical examination findings
      • Severe hypoperfusion is not as characteristic for infants presenting with pulmonary disease in the neonatal period compared with hypoplastic left heart disease
    • Response to supplemental oxygen administration (hyperoxia test) is an important clinical tool to assist in separating pulmonary from cardiac causes of cyanosis
      • Administration of 100% oxygen for 10 to 20 minutes will increase PaO₂ in patients with pulmonary disease; little improvement in PaO₂ is noted in patients with intracardiac shunting secondary to cyanotic congenital heart disease 
    • Definitively diagnose by chest radiograph findings, response to oxygen administration, and absence of echocardiographic findings to support hypoplastic left heart disease
  • Neonatal myocarditis
    • May present similarly to hypoplastic left heart syndrome with a shocklike state with heart failure in the early neonatal period; arrhythmia may be a prominent manifestation
    • Common causes are viral infection and systemic autoimmune responses 
    • ECG may show nonspecific T-wave changes, ST-segment increase or decrease, pathologic Q waves, and nearly any kind of arrhythmia; laboratory results may show increased creatine kinase or troponin I 
    • Other signs and symptoms are nonspecific; therefore, differentiating myocarditis from congenital heart disease can be challenging
    • Differentiate by ECG findings and echocardiography results consistent with dilated cardiomyopathy and absence of findings to support hypoplastic left heart
    • Gold standard diagnostic testing involves histologic, immunohistologic, and polymerase chain reaction–based analysis of endomyocardial biopsies 

Treatment Goals

  • Provide advanced cardiovascular and respiratory support in the immediate newborn period or at time of diagnosis to stabilize neonate before first stage of surgery
    • Primary goal is to obtain or maintain patency of fetal ductus arteriosus and foramen ovale
  • Goal of stage 1 repair is to accomplish the following:
    • Construct a reliable source of unobstructed systemic flow from the right ventricle 
    • Provide unobstructed pulmonary venous flow while limiting pulmonary arterial flow to avoid heart failure and prevent pulmonary vascular disease 
    • Provide nonrestrictive coronary blood flow 
  • Goal of stages 2 and 3 is to gradually divert systemic venous return directly to the pulmonary system, thereby creating a system driven by a single ventricle with diminished volume load and eventual resolution of cyanosis after stage 3 
  • Monitor, treat, and prevent potential complications of disease

Admission criteria

Inpatient stay is required following transition from ICU after each surgical procedure

  • About 3 weeks of inpatient stay is usually required following stage 1 Norwood procedure 
  • About 10 days of inpatient stay is usually required following stage 2 procedure 
  • Inpatient stay following stage 3 procedure is variable and largely dependent on degree of persistent postoperative pleural drainage 
Criteria for ICU admission
  • All neonates require admission to neonatal ICU or cardiac care unit in the newborn period and for postoperative care following each stage of surgery
    • Length of stay in ICU following stage 1 of Norwood procedure is usually around 1 week and 1 to 2 days following both stage 2 and 3 procedures 

Recommendations for specialist referral

  • Management requires a multidisciplinary team of experts with experience managing complex congenital heart disease 
    • Prenatal period requires expertise in antenatal diagnosis and counseling and high-risk maternal-fetal management
    • Neonatal period requires management at specialized fetal medicine center with neonatal intensive care or cardiac intensive care services, pediatric cardiac surgical team, and cardiology team
    • Infants and children require management at a center with expertise handling complex congenital heart disease with intensive care or cardiac intensive care services, pediatric cardiac surgical team, and cardiology team
    • Adolescents and adults require adult congenital heart disease specialists and transplant teams for lifelong surveillance and management
    • Patients with single ventricle congenital heart defects must receive a pediatric palliative care consult 
  • Consult geneticist in the presence of multiple congenital anomalies, dysmorphic features, known chromosomal abnormality, or when clinical suspicion of genetic defect is high despite normal standard karyotype 

Treatment Options

Prenatal diagnosis allows for counseling of parents, postnatal management planning, and potential fetal intervention 

  • Counseling involves review of potential prognosis, outcome, and treatment strategies
    • Some may elect for termination of pregnancy 
  • Care plans include early involvement with multidisciplinary team and delivery at specialized pediatric cardiac surgical center with expertise managing hypoplastic left heart syndrome 
    • Allows for early initiation of prostaglandin treatment and immediate transcatheter intervention (eg, balloon atrial septostomy) when needed
  • Preferred mode of delivery is largely based on general obstetric indications 
    • Specialized delivery room care planning is reasonable for patients with severely restrictive or intact atrial septum 
  • Fetal catheter intervention is limited and considered experimental
    • Atrial septoplasty may be attempted to alleviate restrictive or intact atrial septum 
    • Critical aortic stenosis may be addressed with balloon dilation of valve 
  • Maternal hyperoxygenation is another experimental approach
    • Supplemental oxygen provided to mother improves fetal cardiovascular hemodynamics
    • Has potential to promote growth of hypoplastic fetal left heart structures

Stabilization and management in the immediate postnatal period

  • Begin prostaglandin infusion to ensure patency or reestablish patency of ductus arteriosus to support systemic blood flow 
  • Intubation and mechanical ventilation allow for controlled hemodynamic stabilization and eliminate work of breathing 
    • Positive-pressure ventilation may reduce pulmonary edema 
    • Other maneuvers to increase pulmonary vascular resistance and reduce pulmonary overcirculation may include:
      • Allowing mild permissive hypercapnia or adding inhaled CO₂ 
      • Decreasing the concentration of inspired O₂ 
      • Inhaled nitrogen is rarely considered 
  • Treat shock related to heart failure
    • Isotonic volume resuscitation may be initially required 
    • Initiate ionotropic support (eg, dobutamine) 
    • Careful afterload reduction with diuretics may be required in consultation with pediatric cardiologist once ductal patency is established 
    • Extracorporeal membrane oxygenation may be indicated as rescue therapy for unresponsive cardiogenic shock 
  • Urgent balloon atrial septostomy or early stage 1 surgery may be necessary for infants with restrictive or intact atrial septum 
    • Preoperative medical stabilization involves correction of acidosis and hypoglycemia, and prevention of hypothermia 
    • Minimize excess oxygen administration as this may result in worsening of symptoms from pulmonary vasodilatation 
      • Target goal baseline oxygen saturation is around 75% to 85% in patients with known mixing lesions and 90% to 95% in patients without a clear diagnosis 

Long-term treatment options are surgical; comfort care without intervention is an alternative in some circumstances

  • Best outcomes are achieved at centers equipped with a multidisciplinary team with expertise managing patients with complex congenital heart lesions 
  • Surgical treatment strategy usually involves 3-staged palliative procedures
    • Aim is to use the single right ventricle to support the entire systemic circulation in series rather than in the normal parallel configuration driven by dual ventricular system 
    • Staged procedures gradually redirect systemic venous drainage directly into lungs 
      • Stage 1 (Norwood procedure): modification of circulation to provide unobstructed systemic outflow from the right ventricle with adequate pulmonary blood flow. Performed in neonatal period 
        • Optimally performed at 2 to 7 days postdelivery; significantly increased mortality and morbidity risk when undertaken beyond 14 days 
        • A hydrid procedure (combination of surgery and cardiac catheterization) is an alternate stage 1 procedure that avoids use of cardiac bypass in high-risk patients 
      • Stage 2 (bidirectional Glenn shunt anastomosis): superior cavopulmonary anastomosis is performed in infancy 
        • Optimal timing is between ages 3 and 6 months 
      • Stage 3 (Fontan operation): total cavopulmonary connection performed between ages 18 months and 5 years 
        • May be performed early (18 months to 3 years) or delayed until clinical deterioration is evident (usually around age 3-5 years)
    • Emergent management for shunt thrombosis after stage I palliation (Norwood operation) includes:
      • Shunt thrombosis is a relatively common complication that can present with clinical decompensation
      • Systemic anticoagulation with heparin bolus IV and consideration of ongoing infusion
      • IV phenylephrine or epinephrine to increase systemic blood pressure in effort to improve flow through shunt
      • Intubation, mechanical ventilation, and neuromuscular blockade to maximize oxygen delivery and minimize oxygen consumption
      • Anticipate interventional catheterization, manual shunt manipulation, surgical shunt revision, or extracorporeal membrane oxygenation
  • Primary cardiac transplantation
    • Neonatal transplants are rare owing to absence of neonatal donor availability 
    • Consider for neonates with severe right ventricular dysfunction and/or moderate to severe tricuspid regurgitation 
  • Comfort care without intervention
    • Controversial; not frequently done given success of surgical procedures
    • May be offered to patients with severe cases and a low likelihood of survival with interventions 

Interstage management is complex and individualized in consultation with pediatric cardiologist and interdisciplinary team

  • Interventional procedures to alleviate complications (eg, shunt obstruction, stenosis) are not uncommon 
  • Medical strategy for maximizing cardiac output is individualized
  • Long-term medications commonly include:
    • Anticoagulation
      • Long-term anticoagulation is required for most patients after surgical procedures 
        • Low-dose heparin
          • Use in the immediate postoperative period to bridge transition to maintenance regimen 
        • Low-dose aspirin is preferred for most patients
          • Transition from heparin to aspirin is indicated once oral feeding is established 
        • Clopidogrel
          • May be added to aspirin regimen in some patients
        • Warfarin or low-molecular-weight heparin
          • May be recommended for patients with Fontan circulation who have a history of thrombosis, poor hemodynamics, and atrial tachyarrhythmias, and for those undergoing Fontan revision 
    • Endocarditis
      • Select patients will require prophylaxis for:
        • Invasive dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa 
        • Invasive procedures performed in the context of treating established infection involving respiratory, gastrointestinal, or genitourinary tract or skin 
      • Specific indications may include:
        • Prosthetic valve or with prosthetic material used for cardiac valve repair
        • Unrepaired cyanotic congenital heart disease
        • Previous infective endocarditis
        • Repaired congenital heart disease with palliative shunts, conduits, or other prostheses
        • Completely repaired congenital heart disease with synthetic material for the first 6 months following repair
        • Cardiac transplant with valvulopathy
      • Oral antibiotic options include amoxicillin, cephalexin, clindamycin, and azithromycin 
      • Parenteral options include ampicillin, cefazolin, and clindamycin 
    • ACE inhibitors
      • May be required for select patients with impaired ventricular function 
    • Pulmonary vasodilators
      • May be required for select patients with exercise intolerance related to pulmonary hypertension 
    • Diuretics, digoxin, and bisoprolol may be used in some cases 

Drug therapy

  • Prostaglandin E1
    • Alprostadil (Prostaglandin E1)
      • Alprostadil Solution for injection [Ductus Arteriosus Patency]; Neonates: 0.05—0.1 mcg/kg/minute IV infusion initially; usual maintenance dosage range is 0.01—0.1 mcg/kg/minute IV. May increase to max of 0.4 mcg/kg/minute if response is not adequate; however, higher infusion rates do not usually produce greater effects.
        • Titrate infusion up until perfusion, oxygenation, and acidosis improves. 
        • Primary adverse effect is apnea; higher dose poses increased risk for apnea. 
        • Be prepared to establish a stable airway during initiation of therapy; however, intubation solely for transport of an infant with an otherwise patent and maintainable airway (without apnea) on stable dose of prostaglandin is not necessary. 
  • Dobutamine
    • Dobutamine Hydrochloride Solution for injection; Neonates: 0.5 to 1 mcg/kg/minute continuous IV/IO infusion; titrate to clinical response. Usual dosage range: 2 to 20 mcg/kg/minute.

Nondrug and supportive care

Developmental intervention

  • Refer all patients for formal developmental evaluation and early intervention services owing to risk for neurodevelopmental delay

Respiratory syncytial virus prophylaxis

  • Palivuzumab is recommended for prophylaxis of bronchiolitis in infants aged 1 year and under who have hemodynamically significant congenital heart disease

Anticipatory guidance following complete repair (post-Fontan)

  • Exercise
    • Encourage active lifestyle with routine self-limited aerobic exercise
    • Low-intensity competitive sports may be an option for some patients
      • Obtain cardiac assessment before clearance for any competitive sports (eg, chest radiograph, ECG, echocardiography, exercise testing with oxygen saturations)
      • Safe participation in low-intensity competitive sports depends on underlying ventricular function, oxygen saturation with exercise, and risk for arrhythmia
        • Consider class 1A sports safe for most patients
          • Examples include billiards, bowling, cricket, curling, golf, and riflery
        • Consider class 1B sports safe for patients with normal ventricular function and oxygen saturation
          • Examples include baseball, softball, table tennis, volleyball, and fencing
  • Reproduction
    • Encourage preconception assessment and counseling by high-risk obstetrician and adult congenital heart disease specialist
    • Certain medications are contraindicated during pregnancy (eg, warfarin, ACE inhibitors)
Procedures
Norwood (stage 1) procedure

General explanation

  • Surgical goal is to modify the circulation with aim to provide unobstructed systemic outflow from the right ventricle and secure adequate pulmonary blood flow 
    • Atrial septum is removed to create a common atrial chamber that receives both the systemic and pulmonary venous return 
    • Aortic arch reconstruction (neoaortic arch) is performed to repair any narrowing in the aortic arch; homograft material is usually required 
    • Main pulmonary artery is disconnected at its bifurcation and attached to a reconstructed aortic arch so that the right ventricle ejects directly into the systemic circulation 
  • Alternate source of pulmonary blood flow is established via a connection between the systemic and pulmonary circulation; options include either: 
    • Classic procedure: modified Blalock-Taussig shunt (ie, small synthetic tube, usually polytetrafluoroethylene, is placed off a main branch from aortic arch, usually innominate or subclavian artery, to right pulmonary artery) 
      • Potential downfall of this type of shunt is that continuous flow through shunt occurs in forward direction throughout the cardiac cycle and may result in coronary steal from lower systemic diastolic pressure 
    • Modified procedure (Sano modification): right ventricle to pulmonary artery conduit (ie, polytetrafluoroethylene tube is connected between right ventricle and pulmonary arteries) 
      • Advantages of procedure compared with Blalock-Taussig shunt are: 
        • Pulsatile flow through this type of shunt occurs during systole, avoiding drop in diastolic pressure and potential risk for coronary steal
        • Slight survival advantage may exist at 12 months with use of right ventricle to pulmonary artery conduit compared with use of Blalock-Taussig shunt; however, there is no significant difference in risk of death or heart transplant at 6 years postintervention 
      • Primary concerns with procedure compared with Blalock-Taussig shunt are:
        • The requirement for small ventriculotomy, risking potential for impaired ventricular function and arrhythmia 
        • Risk for unplanned catheter-based reintervention for conduit stenosis is higher in right ventricle to pulmonary artery conduit than Blalock-Taussig shunt 
  • Procedure requires cardiopulmonary bypass

Indication

  • Decision on specific procedure is individualized and largely surgeon- and institution-dependent
  • Some morphologically distinct subgroups may have improved outcomes with specific procedure used to establish pulmonary blood flow
    • Term infants with aortic atresia experience lower mortality with right ventricle to pulmonary artery conduit compared with Blalock-Taussig shunting procedure 
    • Preterm infants with a patent aortic valve experience lower mortality with Blalock-Taussig shunting procedure compared with right ventricle to pulmonary artery conduit 

Complications

  • Intraoperative risk of coronary torsion and insufficiency is high 
  • Early mortality (within 30 days) is around 2% to 15% 
  • Risk factors for poor outcome and mortality following Norwood procedure include:
    • Coexisting genetic syndrome or other significant cardiac abnormalities 
    • Smaller diameter of the ascending aorta 
    • Obstruction to pulmonary venous return (ie, restrictive or intact atrial septum) 
    • Lower gestational age (younger than 37 weeks) and low birth weight (less than 2500 g) 
    • Lower socioeconomic score 
    • Higher degree of pre-Norwood tricuspid regurgitation (more than 2.5-mm jet width) 
  • Common early postoperative complications include:
    • Bleeding with coagulopathy requiring replacement products is common 
    • Prolonged mechanical ventilation is common
      • Usually 3 to 7 days, though sometimes longer with prolonged chylothorax 
    • Necrotizing enterocolitis in up to 18% of patients
      • Enteral nutrition is often held or slowly advanced given high risk of intestinal malperfusion 
    • Clinical seizures in up to 17% of patients 
    • Arrhythmias occur in up to 15% of patients
      • Most common is supraventricular tachycardia; junctional ectopic tachycardia, ventricular tachycardia, and complete heart block are less common 
    • Infection occurs in up to 10% of patients 
    • Stroke and intracranial hemorrhage in up to 5% of patients 
    • Phrenic and recurrent laryngeal nerve injury
    • Renal and hepatic dysfunction
    • Feeding difficulties upon initiation of feeds are common
      • Up to 25% require nasogastric or gastrostomy tube feedings
  • Late postoperative complications (following discharge)
    • Interstage mortality (period between stage 1 and stage 2 procedure) can reach 20% 

Interpretation of results

  • Result of surgery is provision of a univentricular circulation driven solely by the right ventricle
  • A balanced circulation is the aim with equal volume of blood flow to both the systemic and pulmonary circuits with each cardiac cycle to achieve adequate oxygenation while avoiding excess volume load 
    • Goal systemic oxygen saturation is around 80% 
  • Success of procedure is improved at centers with multispecialty teams with experience managing patients
    • Early 30-day survival is around 85% to 90% at large centers 

Postoperative management

  • Challenging in neonates following Norwood procedure
    • Balancing flow to systemic and pulmonary circulation is often tenuous
      • Avoid high inspired oxygen and hypocarbia; either may lower pulmonary vascular resistance and result in volume loading of the pulmonary circulation with resultant cardiac failure 
      • Vasodilators (eg, milrinone) and α-blockers (eg, phenoxybenzamine, phentolamine) may be needed to lower systemic vascular resistance to reduce afterload and encourage systemic perfusion
    • Maintain oxygen saturation near goal of 80% and monitor mixed venous saturation to help optimize oxygen delivery 
  • Chest wall is sometimes left open for 24 to 48 hours following procedure before closure in ICU 
  • Use of low-dose heparin infusion reduces the risk of shunt thrombosis in immediate postoperative period 
Hybrid (alternate stage 1) procedure

General explanation

  • Involves a combination of interventional and surgical techniques to replicate the physiologic state of Norwood procedure 
  • Procedure requires standard sternotomy but does not require cardiopulmonary bypass 
  • Procedure involves:
    • Placement of a stent in ductus arteriosus to ensure patency and secure systemic blood flow 
      • Alternately, long-term prostaglandin infusion may be used 
    • Bilateral branch pulmonary artery banding to limit pulmonary flow 
    • Balloon septostomy to ensure atrial mixing with or without stent in atrial septum 
  • Downside to hybrid procedure compared with conventional stage 1 Norwood is the necessity for a more comprehensive and complex second-stage procedure
    • Stage 2 procedure following hybrid stage 1 approach is associated with higher operative mortality (up to 15%) compared with stage 2 procedure following Norwood approach 
  • Potential advantage over standard stage 1 is avoidance of cardiopulmonary bypass in fragile neonatal period 

Indication

  • Preferred by some for neonates at high risk for bypass (eg, low birth weight, unstable hemodynamics, poor ventricular function) in lieu of conventional Norwood 
  • May be preferred for neonates with borderline left-sided hypoplasia to allow for left ventricular growth and possibly approach biventricular repair as opposed to univentricular strategy 
  • May be considered as bridging therapy to heart transplant 

Complications

  • Interstage stent migration requiring reintervention

Interpretation of results

  • Outcomes after procedure are comparable with standard stage 1 procedure 
Superior cavopulmonary anastomosis (stage 2) procedure (also known as bidirectional Glenn shunt)

General explanation

  • Original shunt is removed (ie, Blalock-Taussig shunt or right ventricle to pulmonary artery conduit) 
  • The superior vena cava is disconnected from the heart and joined directly to the pulmonary arteries to allow passive flow of blood to the lungs
  • Azygos vein is ligated to prevent venous runoff to the lower body, ensuring that all superior vena cava flow is directed into the pulmonary circulation 
  • Procedure requires use of cardiopulmonary bypass 
  • Stage 2 is frequently combined with additional procedures to address arch obstruction, a restrictive atrial septal defect, or tricuspid valve insufficiency

Indication

  • Second stage is performed when pulmonary vascular resistance has fallen (usually between ages 4 and 6 months) and infant outgrows initial shunt 
  • At this point, a high-pressure system driving blood to the lungs is no longer necessary, and instead, passive pulmonary flow is established 
  • Exact timing of procedure may vary between institutions and depends on individual patient physiology and clinical parameters 
    • Oxygen saturation levels help to guide timing of operation
      • Falling oxygen saturation levels occur as child outgrows initial shunt 
    • Other clinical parameters, such as worsening congestive heart failure, decreased heart function, and/or poor weight gain may help to guide timing of operation 
    • Preprocedural cardiac catheterization or MRI at age 3 to 4 months helps define precise anatomy, physiology with hemodynamic measurements, and guide planning of operation 
      • Attention is given to assess the not uncommon occurrence of variable aortic arch obstruction amenable to preoperative balloon angioplasty 

Complications

  • Mortality
    • In-hospital mortality is close to 0 
    • 1-year survival is more than 95% 
  • Central venous pressure elevation
    • Often manifests as superior vena cava syndrome with cyanosis
      • Causes may include anatomic obstruction (eg, superior vena cava anastomotic narrowing, restrictive atrial septal defect), pulmonary artery hypoplasia, parenchymal pulmonary disease, and tricuspid valve insufficiency 
  • Arrhythmia
    • Most common is sinus node dysfunction 
  • Persistent effusions
    • May be pleural, pericardial, and/or peritoneal 
  • Phrenic nerve injury 
  • Embolic complications 

Interpretation of results

  • Improved mechanical efficiency of the right ventricle is expected with venous return from superior vena cava directed to the lungs and diminished volume load on the single functional ventricle 
  • Postprocedural oxygen saturations are expected in the 80% to 85% range
  • Anastomosis grows with child; children often remain stable for years until desaturations eventually become increasingly severe with activity, necessitating the third-stage operation 
Superior cavopulmonary anastomosis(stage 3) or establishment of Fontan circulation

General explanation

  • Remaining venous return from inferior vena cava is directed to the pulmonary vasculature to allow for all systemic venous blood to be passively directed to the lungs, effectively bypassing the right ventricle 
  • Final goal is to separate systemic and pulmonary circulations to allow function in series configuration (rather than normal configuration with parallel separation of circulation by 2 separate pumping chambers) 
  • The single ventricle circulates blood through both pulmonary and systemic vascular beds 
  • Fontan circulation is a common end point for patients with several cardiac lesions that lend to a functionally univentricular system (eg, tricuspid atresia, unbalanced atrioventricular canal defects, pulmonary atresia with intact ventricular septum) 
  • Procedure involves attaching inferior vena cava to the underside of the right pulmonary artery 
    • This can be accomplished by either of 2 means:
      • Extracardiac total cavopulmonary connection
        • Inferior vena cava is disconnected from the right atrium and a large-bore polytetrafluoroethylene tube is placed between inferior vena cava and pulmonary arteries 
      • Lateral tunnel procedure
        • Baffle is sewn within the right atrium to direct inferior vena cava flow along a lateral tunnel within the atrium 
  • Fenestration between Fontan circulation and common atrium to allow small amount of blood to bypass the lungs may be performed 
    • Fenestration acts as a pop-off valve (physiologically similar to a small atrial septal defect) 
      • May be advantageous in patients with temporarily increased pulmonary vascular resistance 
      • May be closed later through interventional procedure 
    • May improve systemic blood flow at the expense of a small degree of desaturation from right-to-left shunting and risk for future systemic embolization 
  • Procedure usually requires use of cardiopulmonary bypass
  • Stage 3 is frequently combined with additional procedures to address arch obstruction, tricuspid valve insufficiency, fistulas, and collaterals 

Indication

  • Exact timing of procedure may vary between institutions and depends on individual patient physiology and clinical parameters
    • Some centers perform final stage at a fixed age, usually around 4 years 
    • Many centers determine timing based on deteriorating symptoms and degree of desaturation 
      • Degree of desaturation often increases with increasing activity as child ages (crawling to walking to running)
    • Preprocedural cardiac catheterization or MRI in the interstage period assists to define precise anatomy, physiology with hemodynamic measurements, and to guide planning of operation
      • Attention is given to all of the following:
        • Assess pulmonary artery size, distribution, and pressures 
        • Exclude recurrent aortic arch obstruction, systemic venous fistula, and systemic arterial to pulmonary collaterals amenable to correction by preoperative interventional techniques 
        • Assess for decreased right ventricular function with associated tricuspid regurgitation; address moderate to severe tricuspid regurgitation with valve repair before Fontan procedure 

Complications

  • In-hospital mortality is usually between 3% and 4% 
  • Acutely increased central venous pressure may result in:
    • Pleural effusion
      • Persistent postoperative drainage requiring prolonged chest tube management is not uncommon 
    • Hepatic congestion 
    • Ascites 

Interpretation of results

  • Cyanosis is no longer present and volume load on the systemic ventricle is acutely diminished 
  • Functional end point is a single ventricle circulation; systemic flow is delivered by right ventricle and pulmonary flow is delivered passively 
    • Secondary effect is chronic elevation of systemic venous pressure, which is responsible for many of the potential complications encountered following Fontan procedure
  • Overall outcome depends mostly on factors unrelated to underlying cardiac lesion itself (eg, preoperative pulmonary artery pressures, preoperative ventricular function) 
  • With improved surgical technique and recent procedural modifications, firm long-term outcome figures are yet to be determined
    • Data among patients with Fontan physiology (of which only a minority is hypoplastic left heart syndrome patients) show 13-year survival rate of about 97% for extracardiac total cavopulmonary connection 
    • However, among patients with Fontan circulation, hypoplastic left heart syndrome patients experience a 4-fold increased likelihood of developing heart failure than patients with more favorable morphology 

Monitoring

  • Prenatal monitoring of known fetal cardiac defect
    • Appropriate fetal surveillance is indicated and may include:
      • Regular fetal cardiotocography and nonstress testing in the third trimester 
      • Biophysical profile in the third trimester determined by ultrasonography 
      • Serial fetal echocardiography in second and third trimester
    • Not rigorously standardized and often individualized based on severity of defects
  • Postoperative monitoring
    • Intensive postoperative monitoring is required and managed by expert multidisciplinary team in the neonatal ICU or cardiac care unit
    • Often involves invasive and continuous monitoring of hemodynamics, mixed venous saturations, frequent echocardiography, and biochemical assessments of perfusion 
  • Interstage monitoring
    • Between stage 1 (Norwood) and stage 2 (bidirectional Glenn)
      • In the few months following hospital discharge after stage 1 Norwood procedure up to stage 2 procedure, risk for mortality is high (2%-20%) 
      • Minor illness associated with fluid loss (eg, vomiting, diarrhea) or poor feeding (eg, upper respiratory infection) are poorly tolerated and can lead to sudden unexpected cardiac instability (eg, hypoxemia, hypovolemia, increased systemic vascular resistance) 
      • Risk may be diminished with an intensive home monitoring program that often includes:
        • Daily oxygen saturation, body weight measurements, and strict enteral intake volumes 
        • Review and reiteration of caregiver education, including basic life-support training 
        • Strict criteria for notification to health care professionals including
          • Oxygen saturation less than 75% or more than 90%, acute weight loss of 30 g or more, inability to gain 20 g over 2 to 3 days, or enteral intake less than 100 mL/kg/day 
      • Clinical follow-up is usually weekly or every 2 weeks with multidisciplinary care team
      • Echocardiography is usually performed with clinical follow-up
      • Advanced cardiac imaging (eg, MRI, catheterization) is obtained once oxygen saturations begin to deteriorate in anticipation of second-stage repair
    • Between stage 2 (bidirectional Glenn) and stage 3 (Fontan)
      • Risk for mortality is much less than risk between first and second stage 
      • Clinical follow-up is usually about every 3 to 6 months 
      • Echocardiography is performed with clinical follow-up to assess Glenn flow, right ventricular function, valvular competence, and adequacy of arch reconstruction 
      • Advanced cardiac imaging (eg, MRI, catheterization) is obtained once oxygen saturations begin to deteriorate in anticipation of final stage repair 
      • Periodic developmental surveillance and reevaluation is recommended 
    • Post–stage 3 repair (Fontan) monitoring
      • Clinical follow-up is usually about every 6 to 12 months 
      • Transthoracic echocardiography is performed with clinical follow-up to assess fenestration, right ventricular function, valvar pathology, reconstructed aortic arch, and potential signs of Fontan pathway obstruction 
        • Transesophageal echocardiography is indicated if right atrial thrombus is suspected and for delineation of fenestrations
      • ECG, Holter monitoring, exercise stress testing, and, based on individual factors, cardiac MRI and cardiac catheterization 
      • Monitor for liver disease
        • Annual laboratory assessment
          • Standard hepatic laboratory tests, including AST, ALT, γ-glutamyltransferase, albumin, total protein, and total bilirubin 
          • CBC, with attention to declining platelet counts, which may indicate portal hypertension 
          • Prothrombin time 
        • Hepatic imaging (either CT scans or MRI) every 3 to 4 years 
        • Additional testing, such as liver biopsy, may be indicated in consultation with a hepatologist, based on abnormal screening results or physical findings suggestive of advanced liver disease (eg, hepatomegaly, splenomegaly, gynecomastia, vascular ectasias, jaundice) 
      • Formal cardiopulmonary exercise testing, 24-hour ECG recording, and cardiac MRI is considered at the time of transition from pediatric to specialized adult congenital heart disease services 
      • General guidelines for outpatient management of complex congenital heart disease are available 
      • Periodic developmental surveillance and reevaluation are recommended throughout childhood 

Complications

  • Death
    • Condition is fatal without intervention; most infants die without treatment in the first week of life
    • Surgical mortality risk
      • Norwood procedure is one of the highest-risk heart operations performed for congenital heart disease
        • However, hospital survival among infants treated at most experienced centers is now more than 90% 
      • Stage 2 and 3 procedures do not pose as high a risk as first-stage Norwood procedure
    • Interstage periods
      • Highest risk of mortality occurs in the out-of-hospital interstage period between stage 1 and 2 
        • Between 2% and 20% of infants die in this critical interim period 
        • Intensive interstage monitoring and timely interventional procedures to address complications have diminished risk of sudden death closer to the 2% mark 
        • Potential causes of death may include:
          • Residual aortic arch obstruction
          • Shunt stenosis or thrombosis
            • Patients are extremely vulnerable to shunt thrombosis with dehydration 
            • Even a minor viral illness that results in poor feeding or diarrhea can lead to dehydration-related shunt thrombosis 
          • Restrictive atrial septal defects
          • Imbalance of pulmonary and systemic blood flow
          • Coronary ischemia
          • Chronic volume overload of the single ventricle
      • Out-of-hospital period between stage 2 and completion of stage 3 surgical procedures has much lower mortality risk 
    • Post-Fontan
      • Midterm survival following Fontan is approximately 55% to 80% 
      • Sudden death is responsible for up to 30% of mortality among adults post-Fontan 
  • Complications in patients with Fontan circulation and hypoplastic left heart
    • Congestive heart failure
      • May develop from worsening right ventricular dysfunction and/or tricuspid or neoaortic valve incompetence 
      • Functional severity of heart failure typically worsens with age 
      • A minority of patients undergo transplant for failing Fontan circulation later in life 
      • Many patients who develop heart failure after staged procedures are not transplantation candidates owing to development of associated multiorgan failure and/or high antigen load precluding donor matching 
    • Fontan circulation obstruction
      • May occur in residual total cavopulmonary connection pathway or aortic arch
    • Arrhythmia
      • Atrial dysrhythmias are particularly common, especially in patients following intra-atrial tunnel technique 
        • Common types include atrial tachycardia, atrial fibrillation, sinus node dysfunction, and supraventricular tachycardia 
      • Reported incidence varies between 13% and 54% at age 20 years 
      • Pacemaker requirement is approximately 23% by age 20 years 
    • Thromboembolic events
      • Fontan circulation is associated with a hypercoagulable state and endothelial dysfunction 
      • In addition, exposure of synthetic material to venous flow (ie, extracardiac conduit and lateral tunnel techniques) predisposes to clot formation 
      • Bimodal incidence occurs; first peak is during the first postoperative year and again 10 years later 
      • Reported incidence is 18% to 21% at 10 years 
      • Wide regional variability exists regarding preference of chronic anticoagulation medication 
      • Risk factors are many and may include:
        • Dehydration
        • Low-flow state or stasis in the Fontan or pulmonary circuit
        • Right-to-left shunting
        • Increased venous pressure, hepatic dysfunction, protein-losing enteropathy
        • Prolonged postoperative immobilization
        • Ventricular dysfunction and atrial arrhythmias
      • Of note, transthoracic echocardiography may detect thrombus; however, transesophageal echocardiography may be required to exclude thrombus 
      • Associated with a high mortality rate; up to 25% mortality is reported after development of thromboembolic event 
    • Chronic hepatic congestion
      • Development of impaired liver function and hepatic fibrosis is common 
      • Often asymptomatic and discovered on results of screening laboratory tests
      • May evolve to cirrhosis 
      • Development of hepatocarcinoma is rare, and profound hepatic impairment is not described 
    • Protein-losing enteropathy
      • Often a result of failing Fontan circulation reflecting chronic venous congestion of the gastrointestinal tract 
      • Cumulative 10-year risk is about 13% 
      • Presents with peripheral edema, ascites, and pleural and pericardial effusions 
      • Hypoalbuminemia and increased stool alpha-1 antitrypsin concentrations are presenting abnormalities in laboratory test results 
      • Associated with a high mortality rate; 5-year survival is about 46% after development 
    • Protein-losing enteropathy
      • Rare presenting complication of failing Fontan circulation with resultant loss of proteins in bronchial lumens 
      • May present with expectoration of long, branching bronchial casts; may manifest as airway obstruction 
      • Pulmonary decompensation is usually evident on presentation 
    • Chronic cyanosis
      • May develop secondary to complications after Fontan procedure
      • Often owing to worsening residual or developing right-to-left shunts 
    • Exercise intolerance
      • Most patients experience decreased exercise capacity that worsens with age 
      • Ability to participate in individual and group sporting events is variable 
      • Resistance training is counterintuitively beneficial for most patients; regular exercise is encouraged 
      • Restrictive lung disease and impaired diffusion capacity is common 
    • Chronic venous stasis disease
      • Presents with lower-extremity edema, varicosities, stasis dermatitis, and venous ulcers
    • Renal dysfunction
      • Decreased GFR is not uncommon 
    • Anesthesia risk
      • Increased risk for perioperative complications and death, particularly with poor ejection fraction 
    • Impaired pulmonary venous return with positive-pressure ventilation 
      • Especially positive end-expiratory pressure
    • Endocarditis
      • Patients may be at risk for endocarditis and require prophylaxis 
    • Pregnancy risk
      • Most experts recommend avoidance of pregnancy owing to risk to mother (arrhythmia, heart failure, hypertension) and fetus (prematurity, small for gestational age, fetal death) 
      • Infertility and frequent miscarriages are not uncommon 
    • Growth delay
      • Children are usually small and underweight for age 
    • Neurodevelopmental issues
      • Higher risk of unfavorable neurodevelopmental outcome may exist for patients compared with patients with other forms of complex congenital heart disease 
        • Mild cognitive impairment, impaired social interaction, and deficits in core communications skills may be present 
        • Delayed motor development may be present 
      • Patients who undergo 3‐stage single-ventricle palliation are at risk for significant neurocognitive deficits, and contributing factors include older age at Fontan, sepsis, and hypoxemia 
        • Completion of Fontan operation at an older age may provide hemodynamic benefits but may be associated with poorer neurocognitive outcomes
      • Data are limited and somewhat conflicting overall
        • Most suggest that the majority function within normal limits without serious restrictions 
    • Psychiatric disorders
      • High risk of psychiatric morbidity may exist among adolescents with single-ventricle congenital heart disease pathology, particularly anxiety disorders and attention-deficit/hyperactivity disorder 
  • Heart transplantation
    • About 4% to 7% of patients undergo transplantation within 20 years of Fontan completion 
    • Survival after transplantation is less favorable than survival following transplantation for other reasons (eg, idiopathic cardiomyopathy, biventricular congenital heart disease) 

Prognosis

  • Mortality
    • Natural course of untreated disease is death in the first few days to weeks of life
    • Prenatal diagnosis (as compared with postnatal) appears to have no significant impact on overall pre- or postoperative mortality, although it results in better hemodynamic stability in postnatal period 
    • Most mortality occurs before stage 1 procedure and during interstage between stage 1 and stage 2 procedures 
      • Most neonates survive initial surgery, and two-thirds will be alive after the third-stage Fontan operation 
    • Overall survival into adulthood among patients currently treated is estimated at about 70% to 85% 
  • Morbidity
    • All patients require lifelong medical care, with regular surveillance for and management of heart failure or other complications 
    • Anticoagulation is required for most 
    • Psychological demands are significant 
  • Overall less favorable outcomes are associated with:
    • Presence of additional anomalies and/or chromosomal syndrome 
    • Certain morphologic subtypes of disease
      • Lesions involving aortic atresia and/or mitral stenosis are associated with poor outcomes, likely owing to associated concomitant coronary artery anomalies 
      • Lesions involving highly restrictive or intact atrial septum, even with prompt resuscitation and adequate decompression of atrial septum 
    • Prematurity 
    • Smaller center and surgeon volumes 
    • Low socioeconomic group 

Screening

At-risk populations

  • Any infant may be affected; however, sibling with disease or known congenital syndrome associated with disease places patient at increased risk

Screening tests

  • Routine prenatal ultrasonography screening
    • Up to 75% of diagnosis occur in the prenatal period through use of routine ultrasonography 
  • Universal oxygen saturation screening in newborn period
    • Technique for critical congenital heart disease screening
      • Protocol is intended to assess asymptomatic neonates after 24 hours of life before discharge from the healthy-newborn nursery 
      • Obtain preductal and postductal oxygen saturation (2 separate sites) with pulse oximetry 
        • Preductal site is right hand
        • Postductal site is either foot
    • Abnormal results (positive screen) include:
      • Any oxygen saturation less than 90% 
      • Oxygen saturation less than 95% in the right hand and either foot on 3 measurements separated by 1 hour each 
      • Greater than 3% absolute difference in pre- and postductal oxygen saturation on 3 measurements separated by 1 hour each 
    • Screening test characteristics:
      • Overall sensitivity of positive screening test is about 77% and specificity is about 99% for critical congenital heart disease
      • False-positive rate is high when screening occurs before 24 hours of life and in high-altitude elevation 
    • Actions following positive screen results include:
      • Exclude alternate causes of hypoxemia (eg, sepsis, pulmonary disease, persistent pulmonary hypertension) 
      • Obtain echocardiography to evaluate for congenital heart lesion before discharge home 
      • Consult pediatric cardiologist for further diagnostic and management recommendations 

Prevention

  • Fetal intervention to prevent/minimize impact of hypoplastic left heart syndrome is considered experimental
    • Fetal aortic valvuloplasty may be attempted to facilitate flow through the left heart and improve growth of left-heart structures 
      • Adequate ventricular growth may occur in up to 30% of patients with successful opening of the aortic valve
    • Atrial septostomy may be attempted to alleviate restrictive or intact atrial septum 

References

Brawn WJ: Hypoplastic left heart. Paediatr Child Health. 21(1):19-24, 2011

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