Cyanotic Heart Disease

Etiology

The etiology of CHD is still largely unknown. Many cases of CHD are multifactorial and result from a combination of genetic predisposition and environmental risk factors. CCHD is usually isolated and sporadic, but it can also be associated with genetic syndromes. Approximately 15% to 20% of infants with CCHD are related to known chromosomal abnormalities, most of these are aneuploidies (trisomy 21, 13, and 18 and Turner syndrome). Potential environmental risk factors include maternal illnesses, including diabetes and phenylketonuria, maternal exposure to toxins or drugs and viral infections during pregnancy.

Epidemiology

Congenital heart disease (CHD) affects 8 to 9 per 1000 live births, and approximately 25% are considered CCHD. The incidence of CHD increase to 2% to 6% for a second pregnancy after the birth of a child with CHD or if a parent is affected. Tetralogy of Fallot (TOF) is the most common CCHD (5% of all CCHD). Transposition of the great arteries (TGA) is the second most common CCHD (approximately 2% of all CCHD), and it is the most common CCHD manifesting in the first week after birth. It is estimated that 35% of infant deaths due to congenital malformations are related to cardiovascular anomalies.

Pathophysiology

In fetal circulation, gas exchange occurs in the placenta. From the placenta, oxygenated blood travels through the umbilical vein into the Inferior vena cava (IVC) through the ductus venosus (DV), bypassing the liver circulation. In the heart, most of the oxygenated blood is shunted from the right atrium to the left atrium through the foramen ovale (FO). From the left atrium, blood is pumped to the left ventricle and into the aorta to reach systemic circulation. A small portion of blood is pumped from the right atrium to right ventricle and the pulmonary artery. From the pulmonary artery, blood is shunted to the aorta through the ductus arteriosus (DA), bypassing the lungs. Deoxygenated blood return to the placenta by the umbilical arteries.[5][6][7]

CCHD is silent in fetal life because fetus receives oxygenated blood from the placenta and either the FO or DA can increase systemic blood flow. After DA and FO closure soon after birth, most CCHD become symptomatic. Cyanosis may be caused by persistence of fetal circulation, right-to-left shunting across the FO and ductus DA in the presence of pulmonary outflow tract obstruction or persistent pulmonary hypertension of the newborn.

History and Physical

The diagnosis of CCHD might be missed prenatally, or during birth hospitalization; therefore, clinicians should be aware of its clinical manifestation during the first weeks of life. History alone may be not sufficient to differentiate between congenital heart disease, pulmonary disease, an inborn error of metabolism and sepsis. Additional physical exam findings and diagnostic evaluations would be necessary to identify CCHD. Thorough family history must also be obtained giving the genetic component of CCHD.

The history associated with CCHD include:

• Irritability or decreased level of activity
• Diaphoresis and crying with feedings
• Decrease amount of formula per feed
• History of longer time per breastfeed
• Poor weight gain
• Fast and/or irregular breathing
• Bluish or purple discoloration of the skin or mucous membranes
• Older children may present with exercise intolerance, including dyspnea, diaphoresis cyanosis or palpitations during exercise

Physical findings associated with CCHD include: 

• Cyanosis
• Tachypnea
• Increased work of breathing
• Pulmonary edema
• Tachycardia
• Heart murmur
• Hepatomegaly (Liver edge located more than 2.5 cm below the right costal margin)
• Weak femoral pulses
• Signs of poor perfusion or shock
• Lethargy

Evaluation

Fetal Echocardiogram

A fetal echocardiogram should be performed in all fetuses with a suspected cardiac abnormality noted on obstetric ultrasound. Prenatal ultrasound can identify structural heart disease. However, the sensitivity of congestive heart disease detection is highly variable, depends on the operator expertise, gestational age fetal position, and type of cardiac defect.[8][9][10]

Pulse Oximetry Screening

The pulse oximetry screening for CCHD in newborns was added to the Recommended Uniform Screening Panel in the United States in 2011, and it was endorsed by the American Academy of Pediatrics in 2012. Screening is performed in the well-infant nursery when the baby is at least 24 hours of age, or as late as possible if the baby is to be discharged from the hospital before 24 hours of life. Earlier screening can lead to false-positive results.

CCHD screening will only identify cardiac lesions with the right to left shunt and cyanosis. Screening is recommended in the right hand and either foot. Positive screen result includes one of the following:

• Any Oxygen Saturation less than 90%
• Oxygen Saturation less than 95% in both extremities, on 3 measures, each separated by 1 hour
• More than 3% absolute difference in oxygen saturation between the right hand and foot on 3 measures, each separated by 1 hour

Differential cyanosis, lower oxygen saturation in the lower extremities, can be seen in PPHN with interrupted aortic arch, and coarctation of the aorta. Reverse cyanosis, lower oxygen saturation in the right hand, is a manifestation of TGA with concurrent CoA or IAA. Positive pulse oximetry screen will require prompt evaluation, including 4-limb blood pressure measurement, chest radiography, ECG, and echocardiography.

The seven primary CCHD screening targets are hypoplastic left heart syndrome (HLHS), pulmonary atresia (PA), Tetralogy of Fallot (TOF), total anomalous pulmonary venous return (TAPVR), transposition of great arteries (TGA), tricuspid atresia, and truncus arteriosus. Secondary screening targets are coarctation of the aorta (CoA), interrupted aortic arch (IAA), critical aortic stenosis, DORV, Ebstein anomaly and single ventricle complex. CCHD screening would miss about 15% of all CCHD cases; COA/IAA, TAPVR and TOF cases are the most common conditions missed. A failed newborn screen may also indicate other disease processes, such as pulmonary hypertension, primary pulmonary parenchymal disease, or hemoglobinopathies.

Hyperoxia Test

Hyperoxia test is the initial method to distinguish CCHD from pulmonary disease. The test consists in measuring an arterial blood gas at room air and 100% inspired oxygen after 10 minutes. Neonates with congenital heart disease are usually not able to increase PaO2 above 100 mm Hg during 100% oxygen administration. In patients with pulmonary disease, PaO2 generally increased greater than or equal to 100 mm Hg with 100% oxygen as ventilation-perfusion discrepancies are overcome. A positive result indicates the cardiac origin and further cardiac workup is indicated to rule out CCHD.

Electrocardiogram (ECG)

ECG identifies rhythm abnormalities, auricular or ventricular hypertrophy, dextrocardias, or abnormal axis deviation.

Chest X-Ray

Chest x-ray indicates whether pulmonary blood flow is increased, normal, or decreased. Can identify specific unique findings of CCHD - “egg-shaped” heart seen in TGA, “snowman” in TAPVR, “boot-shaped” heart in TOF, extreme cardiomegaly in Ebstein’s anomaly.  May also be helpful in the differentiation of pulmonary and cardiac disease.

Two-Dimensional Echocardiography

The definitive noninvasive test to determine the presence of CHD. Echocardiography with Doppler can determine the degree and direction of the shunt and the gradient of outflow tract obstruction.

Additional Imaging Modalities 

These include cardiac catheterization and angiography, magnetic resonance imaging (MRI) and CT scanning, to further visualize cardiac anatomy in preparation for cardiac surgery.

Summary of CCHD Evaluation Findings

Right Heart Obstructive Lesions

• Pulmonary atresia (PA)
• Tricuspid atresia
• Tetralogy of Fallot (TOF)
• Critical pulmonary stenosis

Right heart obstructive lesions lead to decrease pulmonary flow. PDA supplies pulmonary blood flow by shunting blood from the aorta to the pulmonary artery. There is a right-to-left intracardiac shunt. PFO shunts deoxygenated blood from the right atrium to the left atrium, and when  VSD is present, blood is shunted from the right ventricle to the left ventricle.

Screening Findings

Positive CCHD screening with oxygen saturation less than 90% without a difference in oxygenation between upper and lower extremities. Hyperoxia test is positive in these conditions. Chest x-ray shows decreased or normal pulmonary blood flow. ECG is an important tool to differentiate among these lesions. Left axis (0 to 90 degrees) is characteristic of pulmonary atresia; left superior axis (0 to -90 degrees) for tricuspid atresia, and right axis (90 to 180 degrees) for critical pulmonary stenosis and TOF.

Left Heart Obstructive Lesions

• Hypoplastic left heart syndrome (HLHS)
• Interrupted aortic arch (IAA)/coarctation of the aorta (CoA)
• Critical aortic stenosis.

Left heart obstructive lesions lead to decreased systemic flow. PDA supplies systemic blood flow by shunting blood from the pulmonary artery to the aorta. There is a Left-to-right intracardiac shunt with secondary pulmonary over-circulation. PFO shunts oxygenated blood from the left atrium to the right atrium, and when VSD is present, blood is shunted from the left ventricle to the right ventricle.

Screening Findings

Positive CCHD screening with oxygen saturation less than 95%; there is a greater than 3% difference between upper and lower oxygen saturation. Negative hyperoxia test. Positive BP gradient between upper and lower extremities is seen in this lesions, except for HLHS. Chest x-ray shows increase pulmonary blood flow. ECG shows normal axis for a newborn (90 to 180 degrees), except for critical aortic stenosis which has left axis for a newborn (0 to 90 degrees).

Mixing Lesions

• Transposition of the great arteries (TGA)
• Total anomalous pulmonary venous return (TAPVR)
• Truncus arteriosus

Cyanosis presents from mixing pulmonary and systemic blood flow. These conditions are considered Ductal-independent lesions. PDA is not required, but they can present with or without PFO. 

Screening Findings

Positive CCHD screening with oxygen saturation less than 95%. There is no difference between upper and lower oxygen saturation, except for d-TGA with pulmonary hypertension or coarctation of the aorta, where O2 saturation is higher in the foot than in the right arm. Negative Hyperoxia Test. Chest x-ray shows normal to increased pulmonary blood flow. ECG shows normal axis for a newborn (90 to 180 degrees).

Treatment / Management

After fetal echocardiogram makes a diagnosis of CCHD, specialized delivery room planning in a tertiary care center is required for prompt evaluation and management.[11][12][13]

At birth, if a CCHD is suspected and cardiac investigation or pediatric cardiologist is not easily available, appropriate stabilization, oxygen therapy, infusion of prostaglandin E1, and prompt transportation to a tertiary care center is necessary. Prostaglandin E1 is useful for ductal-dependent lesions as bridging therapy for further interventions or cardiac surgery. Approximately 25% of children born with a CHD will need heart surgery or other interventions to survive. Balloon atrial septostomy is performed acutely in cases of TGA, allowing adequate blood mixing, and in cases of pulmonary hypertension, relieving right-sided pressures. The patient can undergo early corrective surgery or, in some cases, undergo palliation with a shunt prior to their corrective surgery. After the cardiac surgery is performed, it is essential that the primary source of each postoperative problem be identified and treated, for example, respiratory failure, cardiac rhythm disorders, heart failure, renal failure, seizures, thromboembolism and stroke, hemolysis, infections, postpericardiotomy syndrome, among others.

Routine immunizations should be given. Careful consideration for the timing of administration of live-virus vaccination is required in patients who are potential candidates for cardiopulmonary bypass, heart or heart-lung transplantation. Prophylaxis against the respiratory syncytial virus is recommended during respiratory syncytial virus season in infants with unrepaired congenital heart disease and significant hemodynamic abnormalities. Subacute bacterial endocarditis (SAB) prophylaxis is recommended for patients undergoing dental procedures for patients with high risk of adverse outcomes according to 2007 Statement of the American Heart Association (AHA). Other management considerations include treatment of iron-deficiency anemia, close observation for excessive polycythemia, avoidance of dehydration to prevent the risk of stroke. Parents who have a child with congenital heart disease require counseling regarding the probability of a cardiac malformation occurring in subsequent children.

Differential Diagnosis

• Pulmonary parenchymal disease
• Pulmonary hypertension
• Sepsis
• Inborn error of metabolism
• Hemoglobinopathy (methemoglobinemia)

Prognosis

One-year survival for infants with CCHDs has improved over time; however, mortality remains high. About 75% of babies born with a CCHD are expected to survive to 1 year of age. About 69% of babies born with critical CHDs are expected to survive to 18 years of age. Children with CCHD are at an increased risk for developmental delay and disability, heart rhythm disorders, heart failure, sudden cardiac arrest or stroke.