The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Edgar C.K. Ho. This current second edition chapter is a revision and update of the original author’s work.

A 7-year old male presents in the office for a school physical examination. In the course of the interview, his mother mentions that he seems to get short of breath with exercise recently. It is especially noticeable during his swimming lessons when he tires before the other children do in his class. He has otherwise been in good health since his last physical exam one year ago. His records for the past year show 3 office visits for minor upper respiratory illnesses and no emergency room visits. He has never had wheezing during his colds.

Exam: T 37 degrees C, HR 92, RR 25, BP (right arm) 97/70, oxygen saturation 98% in room air. Height and weight are at the 25th percentile. He is cooperative, well nourished, and in no distress. HEENT and neck exams are normal. His chest is symmetrical. Heart exam reveals no palpable thrill, normal 1st and 2nd heart sounds, no clicks or rubs, grade 1/6 systolic ejection murmur heard along the left sternal border with radiation to the back between the scapulae, and no diastolic murmur. Lungs are clear to auscultation. Abdomen negative for organomegaly or palpable masses. Extremities noted to have slightly diminished femoral pulses, no peripheral edema, clubbing or cyanosis of the nail beds. His neurologic exam is normal.

He receives his immunizations, tuberculin skin test, and, because of the new onset heart murmur, a CXR and EKG are ordered. He returns in 3 days to have his skin test read and to review his cardiac tests. Before entering the exam room the nurse re-measures his vital signs and records in his chart: BP (left arm) 127/86, HR 88, RR 24. His CXR shows a cardiac/thoracic ratio of 0.55, normal cardiac configuration, and normal pulmonary vasculature. His EKG has tall R waves of 40mm in lead V5 and 35mm in lead V6. An echocardiogram is performed the following day and demonstrates a coarctation of the aorta and bicuspid aortic valve. A MRI shows a discrete narrowing of the distal aortic arch just beyond the origin of the left subclavian artery and also reveals an aberrant right subclavian artery originating from the proximal descending aorta below the coarctation.

Congenital heart disease (CHD) in a moderate or severe form has an incidence of 6 in every 1,000 live births. Acyanotic congenital heart disease accounts for 70% of all congenital heart disease. These defects include atrial septal defect (ASD), tricuspid stenosis and regurgitation (TS and TR), milder forms of Ebstein's anomaly of the tricuspid valve, pulmonic stenosis and regurgitation (PS and PR), partial anomalous pulmonary venous drainage to right side of heart, ventricular septal defect (VSD), mitral stenosis and regurgitation (MS and MR), aortic stenosis and regurgitation (AS and AR), atrioventricular (AV) canal defect, patent ductus arteriosus (PDA), and coarctation of the aorta. As opposed to cyanotic CHD in which hypoxia is the main concern, development of congestive heart failure (CHF) is the main concern in acyanotic CHD. CHF presents as sweating, feeding difficulties, poor growth or failure to thrive (FTT), S3 gallop, and if left-sided, also tachypnea, subcostal retractions, and/or pulmonary rales. Chest radiographs in CHF may demonstrate cardiomegaly and increased pulmonary vascular congestion and edema. Echocardiograms are the primary diagnostic modality, but magnetic resonance imaging provides excellent anatomic evaluation and often yields even more information than angiography.

VSD, ASD and PDAs account for a large percentage of all congenital heart defects. They share common physiologic hemodynamics and will be discussed together. These defects represent abnormal communication between the high-pressure left side of the heart and the low-pressure right side of the heart. The pressure differential results in left-to-right shunting of blood through the defect consequently leading to turbulence of abnormal blood flow producing a heart murmur in systole and sometimes in diastole, excessive blood flow into the lungs causing pulmonary vascular congestion leading to shortness of breath, increased volume overload of the myocardium resulting in hypertrophy and chamber dilation, and eventual CHF. Untreated defects with large shunts will eventually result in injury to the pulmonary arterioles, vascular obstruction, and pulmonary hypertension. The development of permanent injury to the pulmonary vessels is a function of the duration of exposure to this excessive blood flow, and occurs more rapidly in VSD and PDA than in ASD. If this process is not reversed, eventually the Eisenmenger's complex of right to left shunting may occur as the elevated right-sided pressures (pulmonary hypertension) exceed left-sided pressures.

Ventricular Septal Defect
VSD is the most common form of CHD at 15-20% of all cases of isolated CHD. It may occur in any of the following septal locations: 1) perimembranous; 2) infundibular; 3) muscular; 4) inlet. The VSD's hemodynamic impact is related to the size of the defect and can range from insignificant to severe. Cardiac auscultation findings may include a II-III/VI harsh holosystolic murmur along the lower left sternal border (harsher in small VSDs due to more turbulence) and a prominent P2 as the pulmonic valve closes later than the aortic valve. Frequently, a VSD murmur is not heard on the day of birth since pulmonary vascular resistance and pulmonary pressure may still be high. After birth, as the pulmonary vascular resistance decreases, the left-to-right shunt increases resulting in a new emergence or increased severity of murmur on day 2 or day 3 of life.

Smaller defects (2-4 mm) are usually asymptomatic and more likely to spontaneously close (50% by 2 years). About 30-40% of small perimembranous and muscular defects spontaneously close within the first six months of life. Small defects usually do not require surgery or activity restrictions and patients are monitored with periodic follow-up. Larger defects are more likely to be symptomatic and less likely to spontaneously close. The defect may lead to CHF, which can manifest around six to eight weeks of age. Surgical repair may be indicated. Postoperative complications include conduction defects, such as AV conduction abnormalities and transient right bundle branch block.

Atrial Septal Defect
ASD is a defect in the septum dividing the right and left atria. These account for 10% of all CHD and are more common in females. There are three different types based on location: 1) sinus venosus; 2) secundum; 3) primum. Secundum defects are the most common and occur through the fossa ovalis. Sinus venosus defects are located near the opening of the SVC. Endocardial cushions separate the atrioventricular valves and form the lower portion of the atrial septum and the upper portion of the interventricular septum. Primum defects are a form of endocardial cushion defects involving the lowest part of the atrial septum between the atrioventricular valves. These are almost always associated with abnormal development of atrioventricular valves, most commonly a cleft mitral valve. Primum defects can be associated with Down syndrome, Ellis-Van Creveld syndrome, and Holt-Oram syndrome. Most patients remain asymptomatic, but some individuals can develop right atrial and ventricle dilation, leading to atrial arrhythmias and ventricular dysfunction. Patients may have a hyperactive precordium, right ventricular heave, fixed wide split S2, systolic ejection murmur at the second left intercostal space (increased flow across the pulmonic valve), or a mid-diastolic murmur at the lower right sternal border (increased flow across the tricuspid valve). Flow across the ASD is low velocity and not turbulent, so there is no audible murmur from the ASD itself.

Similar to VSDs, smaller defects are expected to spontaneously close while larger ones usually require surgical intervention with patch closure. Cardiac dysrythmias and mitral valve prolapse may be late sequelae of a treated or untreated ASD. Atrial flutter or fibrillation may also occur in adults with a history of atrial septal defect, regardless of the treatment.

Patent Ductus Arteriosus
PDA results from retention of the fetal ductus arteriosus, which normally closes at about one to two weeks of age. This defect accounts for 5-10% of CHD and is more common in females. PDA is associated with coarctation of the aorta, VSD, prematurity, prenatal indomethacin exposure, and rubella exposure during the first trimester. As pulmonary vascular resistance decreases, blood shunts from the aorta into the pulmonary artery, resulting in increased pulmonary artery blood flow and left atrial and ventricular overload. There is minimal blood flow across small lesions and pressures in the right atrium and ventricle are usually normal. A large PDA results in pulmonary overcirculation and low aortic diastolic pressure, leading to extensive aortic runoff and systemic end-organ hypoperfusion. Pulmonary vascular obstructive disease may occur as early as one year of age. Clinical presentation includes bounding arterial pulses, a widened pulse pressure, an enlarged heart, a prominent apical impulse, a classic continuous machine-like murmur at the base, and a mid-diastolic murmur at the apex. Small defects are usually asymptomatic, while large PDAs present with recurrent pulmonary infections, CHF, and failure to thrive. Closure may occur spontaneously. Indomethacin can be used for medical closure. Some require surgical closure with placement of an embolic device, such as an intravascular coil or PDA occluder, ligation, or division. PDA is the only CHD that is considered surgically "cured" without long-term sequelae.

Pulmonic Stenosis
PS is a right ventricular outflow tract obstruction presenting as 1) valvular; 2) subvalvular; or 3) supravalvular. This defect accounts for 7-10% of all CHD. These usually are isolated lesions, but may have bicuspid or fusion of two or more leaflets of the pulmonic valve. Obstruction leads to right ventricular hypertrophy and eventual right ventricular dysfunction. Symptoms depend on the pressure gradient and range from asymptomatic to right-sided congestive heart failure. Patients with mild PS are usually asymptomatic. Patients with moderate to severe PS may present with right ventricular lift, split S2 with delay, ejection click followed by systolic murmur, heart failure, and even cyanosis in critical PS due to right-to-left shunt through a patent foramen ovale.

Mild PS may be monitored while moderate to severe PS requires intervention. Newborns with severe PS may require prostaglandin E1 infusion to keep the ductus arteriosus patent for adequate pulmonary blood flow. Percutaneous balloon valvuloplasty to dilate the stenosis, surgical resection of the obstructive tissue, or addition of a patch may be used. Post-operative pleural effusion can occur after alleviating right ventricle outflow obstruction.

Aortic Stenosis
AS is the obstruction of the left ventricle outflow tract. AS accounts for 7% of CHD and is described by location: 1) valvular (most common); 2) subvalvular or subaortic; or 3) supravalvular (least common, associated with Williams Syndrome). As the child grows, the cardiac output increases resulting in an increased pressure gradient across the stenosis. Obstructed flow from the left ventricle results in increased pressure and hypertrophy. Mild AS is usually asymptomatic with some exercise intolerance and easy fatigability. Moderate AS may present with chest pain, dyspnea on exertion, dizziness, and syncope. Severe AS presents with weak pulses, left-sided heart failure, and chest pain and could lead to sudden death. Clinical exam may reveal a left ventricular thrust at the apex, systolic thrill at the right base or suprasternal notch, ejection click, or III-IV/VI systolic murmur at sternal border with radiation to carotids.

AS can be alleviated or even appropriately treated by percutaneous balloon valvuloplasty similar to that in PS. Surgical intervention with valvulotomy or valve replacement is indicated for symptomatic patients with high pressure gradients across the narrowed valve. There is no activity restriction in mild AS, but no competitive sports are allowed for moderate to severe AS. Lifelong anticoagulation therapy is required if a prosthetic valve replacement is performed.

Coarctation of the Aorta
Coarctation of the aorta accounts for 6-8% of CHD. It is a narrowing of the aorta that may occur anywhere along its length, but 98% of cases occur distal to the left subclavian artery, where the PDA inserts into the descending aorta. Various theories have been proposed to explain this abnormal development. One theory associates the presence of ductal tissue encircling the aorta at the site of the coarctation suggesting a constrictive effect of the ductal tissue. Varying degrees of aortic arch hypoplasia may coexist. In contrast to the previous lesions discussed, males are more commonly affected than females. Children with Turner syndrome are at increased risk compared to the general population. Other associated anomalies include a bicuspid aortic valve (85%) that may obstruct left ventricular outflow, or an aberrant origin of the right subclavian artery distal to the coarctation (1%).

Although present at birth, patients may be asymptomatic until childhood depending on the severity of constriction and associated cardiac lesions. Symptoms may include shortness of breath with exertion, leg pain with exercise, and chest pain with exercise. The classic clinical sign is a higher blood pressure and bounding pulses in the arms, especially the right as most defects are distal to the right subclavian artery, compared to decreased blood pressure and diminished pulses in the legs. In the few defects occurring proximal to the right subclavian artery, the BP and pulses of the right arm may be equal to the legs. It is useful to measure blood pressure in both arms and at least one leg to detect blood pressure differential. Obstruction of outflow from the left ventricle leads to left ventricular hypertrophy. In newborns, the ductus arteriosus usually allows for adequate lower body perfusion until it closes at its normal time. Severe obstruction leads to hypoperfusion, acidosis, heart failure, and shock. In severe cases, a ductus arteriosus patency should be maintained with a prostaglandin E1 infusion. A severe coarctation in association with a VSD causes increased left-to-right shunting across the VSD, leading to CHF within the first few months of life. Cardiac auscultation reveals a systolic murmur at the left sternal border, and especially on the back between the scapulae. Chest radiography may demonstrate cardiomegaly due to left ventricular hypertrophy, inferior rib notching due to erosion by collateral arterial circulation to bypass the obstruction, and a "reverse 3 sign" indicating the indentation of the aorta. The echocardiogram demonstrates narrowing of the distal aortic arch. The MRI produces a clearer picture than the echocardiogram of the anatomy of the coarctation. An angiogram is sometimes necessary to clarify the presence of associated cardiac lesions. Surgical repair is usually performed between the ages of one to two years. Urgent surgical repair is performed in infants with circulatory shock, cardiomegaly, blood pressure extremes or severe CHF. Rebound systemic hypertension may occur post-operatively and should be adequately managed. One postoperative complication is the syndrome of mesenteric arteritis, caused by reflex spasm of mesenteric arteries that are suddenly exposed to higher pressures after the coarctation is removed. The spasm can be severe enough to result in bowel ischemia. This complication is less common now as patients are being operated on at a younger age preventing the mesenteric arteries from prolonged exposure to low pressures.

Health Maintenance
Special health maintenance is indicated in patients with acyanotic CHD. Growth impairment is directly proportional to the severity of hemodynamic disturbance. Patient with acyanotic CHD tend have more weight than height growth delay (versus both weight and height in cyanotic CHD). Contributing factors are caloric deprivation and reduced adipose stores, lower birth weight, increased caloric requirements, coexisting musculoskeletal, neurologic, renal, or gastrointestinal malformations, mild steatorrhea, and excess protein loss. Up 10% of individuals may have genetic syndromes. Poor nutrition results from anorexia, fatigability, vomiting, fluid restriction, and frequent respiratory infections. Cardiac drugs (i.e., diuretics) may exacerbate anorexia and cause early satiety. Systemic and respiratory illnesses can increase the body temperature and raise the metabolic rate by up to 13% for each degree centigrade above normal. Hypertrophic cardiac muscle can account for up to 30% of total oxygen consumption compared to the usual 10%. The caloric intake for catch-up growth is estimated at 140 to 200 calories per kg per day. In infants unable to gain sufficient weight with breastfeeding, supplementation can be achieved with a higher caloric density formula or tube feedings. In most patients, catch-up growth is largely complete within six to 12 months of surgery. The CDC (Centers for Disease Control) recommends that the routine immunization schedule should be followed with some exceptions: 1) Varicella and MMR (measles, mumps, and rubella) vaccines are indicated at 12 months of age rather than at 15 months; 2) Polyvalent pneumococcal vaccine (the pneumococcal vaccine usually used in adults) is recommended at two years of age (this is in addition to pneumococcal conjugate vaccine give at 2, 4, 6, and 12 to 15 months); and 3) Influenza vaccine should be given yearly beginning at age six months in this higher-risk population. Prophylaxis against bacterial endocarditis should be instituted in patients undergoing certain procedures. In 2007, the American Heart Association (AHA) released the most recent revision of the 1997 guideline on infective endocarditis prophylaxis. The new guidelines advise prophylaxis for conditions that are associated with the highest risk for adverse outcomes secondary to infective endocarditis. These conditions include: 1) prosthetic cardiac valve or prosthetic material used for valve repair, 2) previous infective endocarditis, 3) unrepaired cyanotic CHD (including palliative shunts and conduits), 4) completely repaired CHD with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first six months after the procedure as endothelization of prosthetic material usually occurs during that time period, 5) repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endotheliazation) and 6) cardiac transplant recipients who develop cardiac valvulopathy. Antibiotic prophylaxis is no longer recommended for any other form of CHD other than those listed above.

Questions

1. True/False: Congenital heart disease is always detectable at birth.

2. True/False: Equal blood pressures in the right arm and left leg rule out the diagnosis of coarctation of the aorta.

3. Name the three most common acyanotic congenital heart lesions?

4. True/False: The presence of palpable femoral pulses rules out the diagnosis of aortic coarctation.

5. Explain how a child with an isolated VSD (classified as an acyanotic lesion) could become cyanotic?

6. True/False: Medical students and residents will typically not hear the murmur of a VSD during the initial newborn assessment in the nursery because the murmur of a VSD is subtle and low pitched.

References

1. Hoffmann JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002;39:1890-1900.

2. Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson Textbook of Pediatrics, 18th ed. 2007, Saunders.

3. Miyague NI, Cardoso SM, Meyer F, et al. Epidemiological study of congenital heart defects in children and adolescents. Analysis of 4,538 cases. Arq Bras Cardiol 2003;80:274-278.

4. Norton ME. Teratogen Update: Fetal Effects of Indomethacin Administration During Pregnancy. Teratology 1997;56:282-292.

5. Silberbach M, Hannon D. Presentation of Congenital Heart Disease in the Neonate and Young Infant. Pediatr Rev 2007;28:123-131.

6. Suarez VR, Thompson LL, Jain V, et al. The effect of in utero exposure to Indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate. Am J Obstet Gynecol 2002;187:886-888.

7. Wilson W, Taubert KA, Gewitz M, et al. Prevention of Infective Endocarditis: Guidelines From the American Heart Association: A Guideline From the AHA Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee. Circulation 2007;116:1736-1754.

8. Centers for Disease Control and Prevention. Birth-18 Years and Catch-up Immunization Schedules. http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html. US 2013.

Answers to questions

1. False. The physiologic pulmonary hypertension present in a newborn can prevent blood flow across a septal defect or PDA. These can be detected several hours after birth or several days after birth. Other congenital heart disease lesions may remain occult for a longer period of time.

2. False. An aberrant right subclavian artery originating below a coarctation will produce equal pressures in the right arm and leg.

3. VSD, ASD, PDA. Of these, VSD is the most common.

4. False. Development of collateral vessels to the lower body can produce palpable femoral pulses.

5. Congestive heart failure and pulmonary edema may cause hypoxia. If the hypoxia is severe enough, visible cyanosis will result, although this can be overcome with oxygen and other treatments for pulmonary edema and congestive heart failure. A second mechanism is that long standing excessive pulmonary blood flow leads to pulmonary hypertension and Eisenmenger's complex, right to left shunting and cyanosis.

6. False. They cannot hear the murmur of a VSD on day 1 because on day 1, pulmonary vascular resistance is still high, which restricts left to right flow through the VSD. On day 2, pulmonary vascular resistance is lower, so left to right shunting through the VSD increases making the murmur louder.