ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Fixed, widely split S2, RV heave.
Grade I–III/VI systolic ejection murmur at the pulmonary area.
Large shunts cause a diastolic flow murmur at the lower left sternal border (increased flow across the tricuspid valve).
ECG shows rsR′ in lead V1.
Atrial septal defect (ASD) is an opening in the atrial septum permitting the shunting of blood between the atria. There are three major types: ostium secundum, ostium primum, and sinus venosus. Ostium secundum is the most common type and represents an embryologic deficiency in the septum secundum or too large of a central hole in the septum primum. Ostium primum defect is associated with atrioventricular septal defects. The sinus venosus defect is frequently associated with abnormal pulmonary venous return, as the location of the sinus venosus is intimately related to the right upper pulmonary vein.
Ostium secundum ASD occurs in 10% of patients with congenital heart disease and is two times more common in females than in males. The defect is most often sporadic but may be familial or have a genetic basis (Holt-Oram syndrome). After the third decade, atrial arrhythmias or pulmonary vascular disease may develop. Irreversible pulmonary hypertension resulting in cyanosis as atrial level shunting becomes right-to-left and ultimately right heart failure can occur and is a life-limiting process (Eisenmenger syndrome).
Most infants and children with an ASD have no cardiovascular symptoms. Older children and adults can present with exercise intolerance, easy fatigability, or, rarely, heart failure. The direction of flow across the ASD is determined by the compliance of the ventricles. Because the right ventricle is normally more compliant, shunting across the ASD is left-to-right as blood follows the path of least resistance. Therefore, cyanosis does not occur unless RV dysfunction occurs, usually as a result of pulmonary hypertension, leading to reversal of the shunt across the defect.
Peripheral pulses are normal and equal. The heart is usually hyperactive, with an RV heave felt best at the mid to lower left sternal border. S2 at the pulmonary area is widely split and often fixed. In the absence of associated pulmonary hypertension, the pulmonary component is normal in intensity. A grade I–III/VI ejection-type systolic murmur is heard best at the left sternal border in the second intercostal space. This murmur is caused by increased flow across the pulmonic valve, not flow across the ASD. A mid-diastolic murmur is often heard in the fourth intercostal space at the left sternal border. This murmur is caused by increased flow across the tricuspid valve during diastole. The presence of this murmur suggests high flow with a pulmonary-to-systemic blood flow ratio greater than 2:1.
Radiographs may show cardiac enlargement. The main pulmonary artery may be dilated and pulmonary vascular markings increased in large defects owing to the increased pulmonary blood flow.
The usual ECG shows right axis deviation. In the right precordial leads, an rsR′ pattern is usually present. A mutation in the cardiac homeobox gene (NKX2-5) is associated with an ASD, and AV block would be seen on the ECG.
Echocardiography shows a dilated right atrium and RV. Direct visualization of the exact anatomic location of the ASD by two-dimensional echocardiography, and demonstration of a left-to-right shunt through the defect by color-flow Doppler, confirms the diagnosis and has eliminated the need for cardiac catheterization prior to surgical or catheter closure of the defect. Assessment of all pulmonary veins should be made to rule out associated anomalous pulmonary venous return.
E. Cardiac Catheterization
Although cardiac catheterization is rarely needed for diagnostic purposes, transcatheter closure of an ostium secundum ASD is now the preferred method of treatment.
If a catheterization is performed, oximetry shows a significant step-up in oxygen saturation from the superior vena cava to the right atrium. The pulmonary artery pressure and pulmonary vascular resistance are usually normal. The Qp:Qs may vary from 1.5:1 to 4:1.
Surgical or catheterization closure is generally recommended for symptomatic children with a large atrial level defect and associated right heart dilation. In the asymptomatic child with a large hemodynamically significant defect, closure is performed electively at age 1–3 years. Most defects are amenable to nonoperative device closure during cardiac catheterization, but the defect must have adequate tissue rims on all sides on which to anchor the device. The mortality for surgical closure is less than 1%. When closure is performed by age 3 years, late complications of RV dysfunction and dysrhythmias are avoided.
Patients usually tolerate an ASD well in the first two decades of life, and the defect often goes unnoticed until middle or late adulthood. Pulmonary hypertension and reversal of the shunt are rare late complications. Infective endocarditis (IE) is uncommon. Spontaneous closure occurs, most frequently in children with a defect less than 4 mm in diameter, therefore outpatient follow-up is recommended. Exercise tolerance and oxygen consumption in surgically corrected children are generally normal, and restriction of physical activity is unnecessary.
et al: Transcatheter device closure of atrial septal defects: a safety review. JACC Cardiovasc Interv 2013 May;6(5):433–442
et al: Guidelines for the echocardiographic assessment of atrial septal defect and patent foramen ovale: from the American Society of Echocardiography and Society for Cardiac Angiography and Interventions. J Am Soc Echocardiogr Aug 2015;28(8):910–958. doi: 10.1016/j.echo.2015.05.015
2. Ventricular Septal Defect
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Holosystolic murmur at lower left sternal border with RV heave.
Presentation and course depend on size of defect and the pulmonary vascular resistance.
Clinical features are failure to thrive, tachypnea, and diaphoresis with feeds.
Left-to-right shunt with normal pulmonary vascular resistance.
Large defects may cause Eisenmenger syndrome if not repaired early.
Ventricular septal defect (VSD) is the most common congenital heart malformation, accounting for about 30% of all congenital heart disease. Defects in the ventricular septum occur both in the membranous portion of the septum (most common) and the muscular portion. VSDs follow one of four courses:
A. Small, Hemodynamically Insignificant Ventricular Septal Defects
Between 80% and 85% of VSDs are small (< 3 mm in diameter) at birth and will close spontaneously. In general, small defects in the muscular interventricular septum will close sooner than those in the membranous septum. In most cases, a small VSD never requires surgical closure. Fifty percent of small VSDs will close by age 2 years, and 90% by age 6 years, with most of the remaining closing during the school years.
B. Moderate-Sized Ventricular Septal Defects
Asymptomatic patients with moderate-sized VSDs (3–5 mm in diameter) account for 3%–5% of children with VSDs. In general, these children do not have clear indicators for surgical closure. Historically, in those who had cardiac catheterization, the ratio of pulmonary to systemic blood flow is usually less than 2:1, and serial cardiac catheterizations demonstrate that the shunts get progressively smaller. If the patient is asymptomatic and without evidence of pulmonary hypertension, these defects can be followed serially as some close spontaneously over time.
C. Large Ventricular Septal Defects with Normal Pulmonary Vascular Resistance
These defects are usually 6–10 mm in diameter. Unless they become markedly smaller within a few months after birth, they often require surgery. The timing of surgery depends on the clinical situation. Many infants with large VSDs and normal pulmonary vascular resistance develop symptoms of failure to thrive, tachypnea, diaphoresis with feeds by age 3–6 months, and require correction at that time. Surgery before age 2 years in patients with large VSDs essentially eliminates the risk of pulmonary vascular disease.
D. Large Ventricular Septal Defects with Pulmonary Vascular Obstructive Disease
The direction of flow across a VSD is determined by the resistance in the systemic and pulmonary vasculature, explaining why flow is usually left-to-right. In large VSDs, ventricular pressures are equalized, resulting in increased pulmonary artery pressure. In addition, shear stress caused by increased volume in the pulmonary circuit causes increased resistance over time. The vast majority of patients with inoperable pulmonary hypertension develop the condition progressively. The combined data of the multicenter National History Study indicate that almost all cases of irreversible pulmonary hypertension can be prevented by surgical repair of a large VSD before age 2 years.
Patients with small or moderate left-to-right shunts usually have no cardiovascular symptoms. Patients with large left-to-right shunts are usually ill early in infancy. These infants have frequent respiratory infections and gain weight slowly. Dyspnea, diaphoresis, and fatigue are common. These symptoms can develop as early as 1–6 months of age. Older children may experience exercise intolerance. Over time, in children and adolescents with persistent large left-to-right shunt, the pulmonary vascular bed undergoes structural changes, leading to increased pulmonary vascular resistance and reversal of the shunt from left-to-right to right-to-left (Eisenmenger syndrome). Cyanosis will then be present.
1. Small left-to-right shunt
No lifts, heaves, or thrills are present. The first sound at the apex is normal, and the second sound at the pulmonary area is split physiologically. A grade II–IV/VI, medium- to high-pitched, harsh pansystolic murmur is heard best at the left sternal border in the third and fourth intercostal spaces. The murmur radiates over the entire precordium. No diastolic murmurs are heard.
2. Moderate left-to-right shunt
Slight prominence of the precordium with moderate LV heave is evident. A systolic thrill may be palpable at the lower left sternal border between the third and fourth intercostal spaces. The second sound at the pulmonary area is most often split but may be single. A grade III–IV/VI, harsh pansystolic murmur is heard best at the lower left sternal border in the fourth intercostal space. A mitral diastolic flow murmur indicates that pulmonary blood flow and subsequently the pulmonary venous return are significantly increased by the large shunt.
3. Large ventricular septal defects with pulmonary hypertension
The precordium is prominent, and the sternum bulges. Both LV and RV heaves are palpable. S2 is palpable in the pulmonary area. A thrill may be present at the lower left sternal border. S2 is usually single or narrowly split, with accentuation of the pulmonary component. The murmur ranges from grade I to IV/VI and is usually harsh and pansystolic. Occasionally, when the defect is large or ventricular pressures approach equivalency, a murmur is difficult to hear. A diastolic flow murmur may be heard, depending on the size of the shunt.
In patients with small shunts, the chest radiograph may be normal. Patients with large shunts have significant cardiac enlargement involving both the left and right ventricles and the left atrium. The main pulmonary artery segment may be dilated. The pulmonary vascular markings are increased.
The ECG is normal in small left-to-right shunts. Left ventricular hypertrophy (LVH) usually occurs in patients with large left-to-right shunts and normal pulmonary vascular resistance. Combined ventricular enlargement occurs in patients with pulmonary hypertension caused by increased flow, increased resistance, or both. Pure RV hypertrophy occurs in patients with pulmonary hypertension secondary to pulmonary vascular obstruction induced by long standing left to right shunt (Eisenmenger syndrome).
Two-dimensional echocardiography can reveal the size of a VSD and identify its anatomic location. Multiple defects can be detected by combining two-dimensional and color-flow imaging. Doppler can further evaluate the VSD by estimating the pressure difference between the left and right ventricles. A pressure difference greater than 50 mm Hg in the left ventricle compared to the right ventricle confirms the absence of severe pulmonary hypertension.
E. Cardiac Catheterization and Angiocardiography
The ability to describe the VSD anatomy and estimate the pulmonary artery pressures on the basis of the gradient across the VSD allows for the vast majority of isolated defects to be repaired without cardiac catheterization and angiocardiography. Catheterization is indicated in those patients with increased pulmonary vascular resistance. Angiocardiographic examination defines the number, size, and location of the defects.
Patients who develop symptoms can be managed with anticongestive treatment, particularly diuretics and systemic afterload reduction, prior to surgery or if it is expected that the defect will close over time.
Patients with cardiomegaly, poor growth, poor exercise tolerance, or other clinical abnormalities who have a significant shunt (> 2:1) typically undergo surgical repair at age 3–6 months. A synthetic or pericardial patch is used for primary closure. In most centers, these children have surgery before age 1 year. As a result, Eisenmenger syndrome has been virtually eliminated. The surgical mortality rate for VSD closure is below 2%.
Transcatheter closure of muscular VSDs is also a possibility. Perimembranous VSDs have also been closed in children during catheterization, but a high incidence of complete heart block after placement of the occluding device has slowed the acceptance of this approach.
Significant late dysrhythmias are uncommon. Functional exercise capacity and oxygen consumption are usually normal, and physical restrictions are unnecessary. Adults with corrected defects have normal quality of life.
et al: Mortality and complications in 3495 children with isolated ventricular septal defects. Arch Dis Child Sep 2016;101(9):808–813. doi: 10.1136/archdischild-2015-310154
K: Current management of ventricular septal defect. Cardiol Young 2006;16(Suppl 3):131–135
3. Atrioventricular Septal Defect
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Murmur often inaudible in neonates.
Loud pulmonary component of S2.
Common in infants with Down syndrome.
ECG with extreme left axis deviation.
Atrioventricular septal defect (AVSD) results from incomplete fusion of the embryonic endocardial cushions. The endocardial cushions help to form the “crux” of the heart, which includes the lower portion of the atrial septum, the membranous portion of the ventricular septum, and the septal leaflets of the tricuspid and mitral valves. AVSD accounts for about 4% of all congenital heart disease. Sixty percent of children with Down syndrome have congenital heart disease, and of these, 35%–40% have an AVSD.
AVSDs are defined as partial or complete. The physiology of the defect is determined by the location of the AV valves. If the valves are located in the midportion of the defect (complete AVSD), both atrial and ventricular components of the septal defect are present and the left- and right-sided AV valves share a common ring or orifice. In the partial form, there is a low insertion of the AV valves, resulting in a primum ASD without a ventricular defect component. In partial AVSD, there are two separate AV valve orifices and usually a cleft in the left-sided valve.
Partial AVSD behaves like an isolated ASD with variable amounts of regurgitation through the cleft in the left AV valve. The complete form causes large left-to-right shunts at both the ventricular and atrial levels with variable degrees of AV valve regurgitation. If there is increased pulmonary vascular resistance, the shunts may be bidirectional. Bidirectional shunting is more common in Down syndrome or in older children who have not undergone repair.
The partial form may produce symptoms similar to ostium secundum ASD. Patients with complete AVSD usually have symptoms such as failure to thrive, tachypnea, diaphoresis with feeding, or recurrent bouts of pneumonia.
In the neonate with the complete form, the murmur may be inaudible due to relatively equal systemic and pulmonary vascular resistance (PVR). After 4–6 weeks, as PVR drops, a nonspecific systolic murmur develops. The murmur is usually not as harsh as that of an isolated VSD. There is both right- and left-sided cardiac enlargement. S2 is loud, and a pronounced diastolic flow murmur may be heard at the apex and the lower left sternal border.
If severe pulmonary vascular obstructive disease is present, there is usually dominant RV enlargement. S2 is palpable at the pulmonary area and no thrill is felt. A nonspecific short systolic murmur is heard at the lower left sternal border. No diastolic flow murmurs are heard. If a right-to-left shunt is present, cyanosis will be evident.
Cardiac enlargement is always present in the complete form and pulmonary vascular markings are increased. Often, only the right heart size may be increased in the partial form, although a severe mitral valve cleft can rarely lead to left heart enlargement as well.
In all forms of AVSD, there is extreme left axis deviation with a counterclockwise loop in the frontal plane. The ECG is an important diagnostic tool. Only 5% of isolated VSDs have this ECG abnormality. First-degree heart block occurs in over 50% of patients. Right, left, or combined ventricular hypertrophy is present depending on the particular defect and the presence or absence of pulmonary hypertension.
Echocardiography is the diagnostic test of choice. The anatomy can be well visualized by two-dimensional echocardiography. Both AV valves are at the same level, compared with the normal heart in which the tricuspid valve is more apically positioned. The size of the atrial and ventricular components of the defect can be measured. AV valve regurgitation can be detected. The LV outflow tract is elongated (gooseneck appearance), which produces systemic outflow obstruction in some patients.
E. Cardiac Catheterization and Angiocardiography
Cardiac catheterization is not routinely used to evaluate AVSD but may be used to assess pulmonary artery pressures and resistance in the older infant with Down syndrome, as this patient group is predisposed to early-onset pulmonary hypertension. Increased oxygen saturation in the RV or the right atrium identifies the level of the shunt. Angiocardiography reveals the characteristic gooseneck deformity of the LV outflow tract in the complete form.
Spontaneous closure of this type of defect does not occur and therefore surgery is required. In the partial form, surgery carries a low mortality rate (1%–2%), but patients require follow-up because of late-occurring LV outflow tract obstruction and mitral valve dysfunction. The complete form carries a higher mortality rate. Complete correction in the first year of life, prior to the onset of irreversible pulmonary hypertension, is obligatory.
B: Atrioventricular septal defect: from fetus to adult. Heart 2006;92:1879–1885
JF: Three-dimensional echocardiography for the assessment of atrioventricular valves in congenital heart disease: past, present and future. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2015;18(1):62–71. doi: 10.1053/j.pcsu.2015.01.003
PATENT (PERSISTENT) DUCTUS ARTERIOSUS
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Continuous machinery type murmur.
Bounding peripheral pulses if large ductus present.
Presentation and course depends on size of the ductus and the pulmonary vascular resistance.
Clinical features of a large ductus are failure to thrive, tachypnea, and diaphoresis with feeds.
Left-to-right shunt with normal pulmonary vascular resistance.
PDA is the persistence of the normal fetal vessel joining the pulmonary artery to the aorta. It closes spontaneously in normal-term infants at 1–5 days of age. PDA accounts for 10% of all congenital heart disease. The incidence of PDA is higher in infants born at altitudes over 10,000 ft. It is twice as common in females as in males. The frequency of PDA in preterm infants weighing less than 1500 g ranges from 20% to 60%. The defect may occur as an isolated abnormality or with associated lesions, commonly coarctation of the aorta and VSD. Patency of the ductus arteriosus may be necessary in some patients with complex forms of congenital heart disease (eg, hypoplastic left heart syndrome [HLHS], pulmonary atresia). Prostaglandin E2 (PGE2) is a product of arachidonic acid metabolism and continuous intravenous infusion maintains ductal patency.
The clinical findings and course depend on the size of the shunt and the degree of pulmonary hypertension.
1. Moderate to large patent ductus arteriosus
Pulses are bounding, and pulse pressure is widened due to diastolic runoff through the ductus. S1 is normal and S2 is usually narrowly split. In large shunts, S2 may have a paradoxical split (eg, S2 narrows on inspiration and widens on expiration). Paradoxical splitting is caused by volume overload of the LV and prolonged ejection of blood from this chamber.
The murmur is characteristic. It is a rough machinery murmur maximal at the second left intercostal space. It begins shortly after S1, rises to a peak at S2, and passes through the S2 into diastole, where it becomes a decrescendo murmur and fades before the S1. The murmur tends to radiate well to the anterior lung fields but relatively poorly to the posterior lung fields. A diastolic flow murmur is often heard at the apex.
2. Patent ductus arteriosus with increased pulmonary vascular resistance
Flow across the ductus is diminished. S2 is single and accentuated, and no significant heart murmur is present. The pulses are normal rather than bounding.
In an isolated PDA, the appearance of the chest radiograph depends on the size of the shunt. If the shunt is small, the heart is not enlarged. If the shunt is large, both left atrial and LV enlargement may be seen. The aorta and the main pulmonary artery segment may also be prominent.
The ECG may be normal or may show LVH, depending on the size of the shunt. In patients with pulmonary hypertension caused by increased blood flow, biventricular hypertrophy usually occurs. In pulmonary vascular obstructive disease, pure right ventricular hypertrophy (RVH) occurs.
Echocardiography provides direct visualization of the ductus and confirms the direction and degree of shunting. High-velocity left-to-right flow argues against abnormally elevated pulmonary vascular resistance, and as pulmonary vascular resistance drops during the neonatal period, higher velocity left-to-right shunting is usually seen. If suprasystemic pulmonary vascular resistance is present, flow across the ductus will be seen from right to left. Associated cardiac lesions and ductal-dependent pulmonary or systemic blood flow must be recognized by echocardiography, as closure of a PDA in this setting would be contraindicated.
E. Cardiac Catheterization and Angiocardiography
PDA closure in the catheterization laboratory with a vascular plug or coils is now routine in all but the smallest of neonates and infants.
Surgical closure is indicated when the PDA is large and the patient is small. Caution must be given to closing a PDA in patients with pulmonary vascular obstructive disease and right-to-left shunting across the ductus as this could result in RV failure. Patients with large left-to-right shunts require repair by age 1 year to prevent the development of progressive pulmonary vascular obstructive disease. Symptomatic PDA with normal pulmonary artery pressure can be safely coil or device-occluded in the catheterization laboratory, ideally after the child has reached 5 kg.
Patients with nonreactive pulmonary vascular obstruction, pulmonary vascular resistance greater than 10 Wood units (normal, < 3), and a ratio of pulmonary to systemic resistance greater than 0.7 (normal, < 0.3) despite vasodilator therapy (eg, nitric oxide) should not undergo PDA closure. These patients are made worse by PDA closure because the flow through the ductus allows preserved RV function and maintains cardiac output to the systemic circulation. These patients can be managed with pulmonary vasodilator therapy, but eventually may require heart-lung transplant in severe cases.
Presence of a symptomatic PDA is common in preterm infants. Indomethacin, a prostaglandin synthesis inhibitor, is often used to close the PDA in premature infants. Indomethacin does not close the PDA of full-term infants or children. The success of indomethacin therapy is as high as 80%–90% in premature infants with a birth weight greater than 1200 g, but it is less successful in smaller infants. Indomethacin (0.1–0.3 mg/kg orally every 8–24 hours or 0.1–0.3 mg/kg parenterally every 12 hours) can be used if there is adequate renal, hematologic, and hepatic function. Because indomethacin may impair renal function, urine output, BUN, and creatinine should be monitored during therapy. If indomethacin is not effective and the ductus remains hemodynamically significant, surgical ligation should be performed. If the ductus partially closes so that the shunt is no longer hemodynamically significant, a second course of indomethacin may be tried.
Patients with an isolated PDA and small-to-moderate shunts usually do well without surgery. However, in the third or fourth decade of life, symptoms of easy fatigability, dyspnea on exertion, and exercise intolerance appear in those patients who develop pulmonary hypertension and/or HF. Percutaneous closure can be done later in life if there has not been development of severe pulmonary vascular disease. For those with severe and irreversible pulmonary hypertension prognosis is not good and heart-lung transplant may be needed.
Spontaneous closure of a PDA may occur up to age 1 year, especially in preterm infants. After age 1 year, spontaneous closure is rare. Because endocarditis is a potential complication, some cardiologists recommend closure if the defect persists beyond age 1 year, even if it is small. Most of these patients undergo percutaneous occlusion as opposed to surgical ligation.
ME: Treatment options for pediatric patent ductus arteriosus: systematic review and meta-analysis. Chest Sep 2015;148(3):784–793. doi: 10.1378/chest.14-2997
et al: Long-term outcome of coil occlusion in patients with patent ductus arteriosus. Circ J 2011 Feb;75(2):407–412
RIGHT-SIDED OBSTRUCTIVE LESIONS
1. Pulmonary Valve Stenosis
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
No symptoms in mild or moderate stenosis.
Cyanosis and a high incidence of right-sided HF in ductal-dependent lesions.
RV lift with systolic ejection click heard at the third left intercostal space.
S2 widely split with soft to inaudible P2; grade I–VI/VI systolic ejection murmur, maximal at the pulmonary area.
Dilated pulmonary artery on chest radiograph.
Pulmonic valve stenosis accounts for 10% of all congenital heart disease. The pulmonary valve annulus is usually small with moderate to marked poststenotic dilation of the main pulmonary artery. Obstruction to blood flow across the pulmonary valve causes an increase in RV pressure. Pressures greater than systemic are potentially life-threatening and are associated with critical obstruction. Because of the increased RV strain, severe right ventricular hypertrophy (RVH) and eventual RV failure can occur.
When obstruction is severe and the ventricular septum is intact, a right-to-left shunt will often occur at the atrial level through a patent foramen ovale (PFO). In neonates with severe obstruction and minimal antegrade pulmonary blood flow (critical PS), left-to-right flow through the ductus is essential, making prostaglandin a necessary intervention at the time of birth. These infants are cyanotic at presentation.
Patients with mild or even moderate valvular pulmonary stenosis are acyanotic and asymptomatic. Patients with severe valvular obstruction may develop cyanosis early. Patients with mild to moderate obstruction are usually well developed and well nourished. They are not prone to pulmonary infections. The pulses are normal. The precordium may be prominent, often with palpable RV heave. A systolic thrill is often present in the pulmonary area. In patients with mild to moderate stenosis, a prominent ejection click of pulmonary origin is heard at the third left intercostal space. The click varies with respiration, being more prominent during expiration than inspiration. In severe stenosis, the click tends to merge with S1. S2 varies with the degree of stenosis. In mild pulmonic stenosis, S2 is normal. In moderate pulmonic stenosis, S2 is more widely split and the pulmonary component is softer. In severe pulmonary stenosis, S2 is single because the pulmonary component cannot be heard. A rough systolic ejection murmur is best heard at the second left interspace. It radiates well to the back. With severe pulmonary valve obstruction, the murmur is usually short. No diastolic murmurs are audible.
The heart size is normal. Poststenotic dilation of the main pulmonary artery and the left pulmonary artery often occurs.
The ECG is usually normal with mild obstruction. In severe obstruction, RV hypertrophy with an RV strain pattern (deep inversion of the T wave) occurs in the right precordial leads (V3R, V1, V2). Right atrial enlargement may be present. Right axis deviation occurs in moderate to severe stenosis.
The diagnosis often is made by physical examination, but the echocardiogram confirms the diagnosis, defines the anatomy, and can identify any associated lesions. The pulmonary valve has thickened leaflets with reduced valve leaflet excursion. The transvalvular pressure gradient can be estimated accurately by Doppler, which provides an estimate of RV pressure and can assist in determining the appropriate time to intervene.
E. Cardiac Catheterization and Angiocardiography
Catheterization is reserved for therapeutic balloon valvuloplasty. In severe cases with associated RV dysfunction, a right-to-left shunt at the atrial level is indicated by a lower left atrial saturation than pulmonary vein saturation. Pulmonary artery pressure is normal. The gradient across the pulmonary valve varies from 10 to 200 mm Hg. In severe cases, the right atrial pressure is elevated, with a predominant “a” wave. Angiocardiography in the RV shows a thick pulmonary valve with a narrow opening producing a jet of contrast into the pulmonary artery. Infundibular (RV outflow tract) hypertrophy may be present and may contribute to obstruction to pulmonary blood flow.
Treatment of pulmonic stenosis is recommended for children with RV systolic pressure greater than two-thirds of systemic pressure. Immediate correction is indicated for patients with systemic or suprasystemic RV pressure. Percutaneous balloon valvuloplasty is the procedure of choice. It is as effective as surgery in relieving obstruction and causes less valve insufficiency. Surgery is needed to treat pulmonic valve stenosis when balloon pulmonic valvuloplasty is unsuccessful.
Patients with mild pulmonary stenosis live normal lives. Even those with moderate stenosis are rarely symptomatic. Those with severe valvular obstruction may develop cyanosis in infancy as described earlier.
After balloon pulmonary valvuloplasty or surgery, most patients have good maximum exercise capacity unless they have significant PI. Limitation of physical activity is unwarranted. The quality of life of adults with successfully treated pulmonary stenosis and minimal PI is normal. Patients with PI, a frequent side effect of intervention, may be significantly limited in exercise performance. Severe PI leads to progressive RV dilation and dysfunction, which may precipitate ventricular arrhythmias or right heart failure in adulthood. Patients with severe PI may benefit from replacement of the pulmonic valve.
et al: Long-term pulmonary regurgitation following balloon valvuloplasty for pulmonary stenosis risk factors and relationship to exercise capacity and ventricular volume and function. J Am Coll Cardiol Mar 9, 2010;55(10):1041–1047
GF: Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 4: Congenital Heart Disease: a scientific statement from the American Heart Association and American College of Cardiology. Circulation Dec 1, 2015;132(22):e281–e291. doi: 10.1161/CIR.0000000000000240
2. Subvalvular Pulmonary Stenosis
Isolated infundibular (subvalvular) pulmonary stenosis is rare. More commonly it is found in combination with other lesions, such as in ToF. Infundibular hypertrophy that is associated with a small perimembranous VSD may lead to a “double-chambered RV” characterized by obstruction between the inflow and outflow portion of the RV. One should suspect such an abnormality if there is a prominent precordial thrill, no audible pulmonary ejection click, and a murmur maximal in the third and fourth inter-costal spaces rather than in the second intercostal space. The clinical picture is otherwise identical to that of pulmonic valve stenosis. Intervention, if indicated, is always surgical because this condition does not improve with balloon catheter dilation.
3. Supravalvular Pulmonary Stenosis
Supravalvular pulmonary stenosis is a relatively rare condition defined by narrowing of the main pulmonary artery. The clinical picture may be identical to valvular pulmonary stenosis, although the murmur is maximal in the first inter-costal space at the left sternal border and in the suprasternal notch. No ejection click is audible, as the valve itself is not involved. The murmur radiates toward the neck and over the lung fields. Children with William syndrome can have supravalvular and peripheral pulmonary stenosis as well as supravalvular aortic stenosis.
4. Peripheral (Branch) Pulmonary Artery Stenosis
In peripheral pulmonary stenosis, there are multiple narrowings of the branches of the pulmonary arteries, sometimes extending into the vessels in the periphery of the lungs. Systolic murmurs may be heard over both lung fields, anteriorly and posteriorly, radiating to the axilla. Mild, nonpathologic pulmonary branch stenosis produces a murmur in infancy that resolves by 6 months of age. William syndrome, Alagille syndrome, and congenital rubella are commonly associated with severe forms of peripheral pulmonary artery stenosis. Surgery is often unsuccessful, as areas of stenoses near and beyond the hilum of the lungs are not accessible to the surgeons. Transcatheter balloon angioplasty and even stent placement are used to treat this condition, with moderate success. In some instances, the stenoses improve spontaneously with age.
5. Ebstein Malformation of the Tricuspid Valve
In Ebstein malformation of the tricuspid valve, the septal leaflet of the tricuspid valve is displaced toward the apex of the heart and is attached to the endocardium of the RV rather than at the tricuspid annulus. As a result, a large portion of the RV functions physiologically as part of the right atrium. This “atrialized” portion of the RV is thin-walled and does not contribute to RV output. The portion of the ventricle below the displaced tricuspid valve is diminished in volume and represents the functioning RV.
The clinical picture of Ebstein malformation varies with the degree of displacement of the tricuspid valve. In the most extreme form, the septal leaflet is markedly displaced into the RV outflow tract, causing obstruction of antegrade flow into the pulmonary artery and there is very little functioning RV as the majority of the ventricle is “atrialized.” The degree of tricuspid insufficiency may be so severe that forward (antegrade) flow out the RV outflow tract is further diminished leading to a right-to-left atrial level shunt and cyanosis. At the opposite extreme when antegrade pulmonary blood flow is adequate, symptoms may not develop until adulthood when tachyarrhythmias associated with right atrial dilation or reentrant electrical pathways occur. These older patients typically have less displacement of the septal leaflet of the tricuspid valve and therefore more functional RV tissue.
The chest radiograph shows cardiomegaly with prominence of the right heart border. The extent of cardiomegaly depends on the degree of tricuspid valve insufficiency and the presence and size of the atrial level shunt. Massive cardiomegaly with a “wall-to-wall heart” (the heart shadow extends across the entire chest cavity from right-to-left) occurs with severe tricuspid valve displacement and/or a restrictive atrial level defect.
ECG may be normal but usually shows right atrial enlargement and right bundle-branch block (RBBB). There is an association between Ebstein anomaly and Wolff-Parkinson-White (WPW) syndrome, in which case a delta wave is present (short PR with a slurred upstroke of the QRS).
Echocardiography is necessary to confirm the diagnosis and may aid in predicting outcome. Degree of tricuspid valve displacement, size of the right atrium, and presence of associated atrial level shunt all affect outcome.
In cyanotic neonates, PGE2 is used to maintain pulmonary blood flow via the ductus arteriosus until pulmonary vascular resistance decreases, facilitating antegrade pulmonary artery flow. If the neonate remains significantly cyanotic, surgical intervention is required.
The type of surgical repair varies and depends on the severity of the disease. For example, in order to decrease the amount of tricuspid regurgitation surgery may involve atrial plication and tricuspid valve repair. The success of the procedure is highly variable. Late arrhythmias are common due to the preexisting atrial dilation. If a significant Ebstein malformation is not treated, atrial tachyarrhythmias frequently begin during adolescence and the enlarged atrialized RV could impede LV function. Postoperative exercise tolerance improves but remains lower than age-related norms.
PW: Ebstein anomaly review: what’s now, what’s next? Expert Rev Cardiovasc Ther Oct 2015;13(10):1101–1109. doi: 10.1586/14779072.2015.1087849
1. Coarctation of the Aorta
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Absent or diminished femoral pulses.
Upper to lower extremity systolic blood pressure gradient of > 20 mm Hg.
Blowing systolic murmur in the back or left axilla.
Coarctation of the aorta is a narrowing in the aortic arch that usually occurs in the proximal descending aorta near the takeoff of the left subclavian artery near the ductus arteriosus. The abdominal aorta is rarely involved. Coarctation accounts for about 6% of all congenital heart disease. Three times as many males as females are affected. Many affected females have Turner syndrome (45, XO). The incidence of associated bicuspid aortic valve with coarctation is 80%–85%.
The cardinal physical finding is decreased or absent femoral pulses. Infants with severe coarctation have equal upper and lower extremity pulses from birth until the ductus arteriosus closes (ductal patency ensures flow to the descending aorta distal to the level of obstruction). Approximately 40% of children with coarctation will present as young infants. Coarctation alone, or in combination with VSD, ASD, or other congenital cardiac anomalies, is the leading cause of HF in the first month of life.
Coarctation presents insidiously in the 60% of children with no symptoms in infancy. Coarctation is usually diagnosed by a pulse and blood pressure (> 15 mm Hg) discrepancy between the arms and legs on physical examination. The pulses in the legs are diminished or absent. The left subclavian artery is occasionally involved in the coarctation, in which case the left brachial pulse is also weak. The pathognomonic murmur of coarctation is heard in the left axilla and the left back. The murmur is usually systolic but may spill into diastole, as forward flow continues across the narrow coarctation site throughout the cardiac cycle. A systolic ejection murmur is often heard at the aortic area and the lower left sternal border along with an apical ejection click if there is an associated bicuspid aortic valve.
In the older child, radiographs may show a normal-sized heart, or more often some degree of LV enlargement. The aorta proximal to the coarctation is prominent. The aortic outline may indent at the level of the coarctation. The poststenotic segment is often dilated. This combination of abnormalities results in the “figure 3” sign on chest radiograph. Notching of the ribs caused by marked enlargement of the intercostal collaterals can be seen. In patients with severe coarctation and associated HF, marked cardiac enlargement and pulmonary venous congestion occur.
ECGs in older children may be normal or may show LVH. ECG usually shows RVH in infants with severe coarctation because the RV serves as the systemic ventricle during fetal life.
Two-dimensional echocardiography and color-flow Doppler are used to visualize the coarctation directly, and continuous-wave Doppler estimates the degree of obstruction. Diastolic runoff flow is detected by continuous-wave Doppler if the obstruction is significant. In neonates with a PDA, a coarctation cannot be ruled out, as stenosis of the arch may evolve as the PDA closes. Identification of lesions such as a bicuspid aortic valve or mitral abnormalities may suggest the presence of a coarctation. In the face of poor LV systolic function, the gradient across the coarctation will be low, as the failing LV is unable to generate very much pressure proximal to the narrowing.
E. Cardiac Catheterization and Angiocardiography
Cardiac catheterization and angiocardiography are rarely performed for diagnosis in infants or children with coarctation, but are used if transcatheter intervention is planned.
Infants with coarctation of the aorta and HF may present in extremis secondary to LV dysfunction and low cardiac output. Resuscitative measures include PGE2 infusion (0.05–0.1 mcg/kg/min) to reopen the ductus arteriosus. End-organ damage distal to the coarctation is not uncommon, and inotropic support is frequently needed. Once stabilized, the infant should undergo corrective repair. In patients with poor LV function, balloon angioplasty of the coarctation is sometimes performed as a palliative measure. Recent data suggest that balloon angioplasty of the aorta can be the definitive procedure in many patients with good LV function. Surgery also has a high success rate. The main complication of both surgery and balloon angioplasty is recurrent coarctation. Fortunately, this complication is treatable in the catheterization laboratory. In older patients, particularly those of adult size, transcatheter stent placement is effective for recurrent coarctation.
Children who survive the neonatal period without developing HF do well through childhood and adolescence. Fatal complications (eg, hypertensive encephalopathy or intracranial bleeding) are uncommon in childhood. Infective endarteritis is rare before adolescence, but can occur in both repaired and unrepaired coarctation. Children with coarctation corrected after age 5 years are at increased risk for systemic hypertension and myocardial dysfunction even with successful surgery. Exercise testing is mandatory for these children prior to their participation in athletic activities.
et al: Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association. Circulation Jun 7, 2011;123(22):2607–2652. doi: 10.1161/CIR.0b013e31821b1f10
R: intermediate outcomes in the prospective, multicenter coarctation of the Aorta Stent Trial (COAST). Circulation May 12, 2015;131(19):1656–1664. doi: 10.1161/CIRCULATIONAHA.114.013937
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Harsh systolic ejection murmur at the upper right sternal border with radiation to the neck.
Thrill in the carotid arteries.
Systolic click at the apex.
Dilation of the ascending aorta on chest radiograph.
Aortic stenosis is defined as obstruction to outflow from the LV at or near the aortic valve producing a systolic pressure gradient of more than 10 mm Hg between the LV and the aorta. Aortic stenosis accounts for approximately 7% of congenital heart disease. There are three anatomic types of congenital aortic stenosis.
A. Valvular Aortic Stenosis (75%)
In critical aortic stenosis presenting in infancy, the aortic valve is usually a unicuspid diaphragm-like structure without well-defined commissures. A bicuspid aortic valve or a trileaflet valve with partially fused leaflets is another anatomic possibility that can be associated with aortic stenosis. Aortic stenosis is more common in males than in females.
B. Subvalvular Aortic Stenosis (23%)
In this type, a membranous or fibrous ring occurs just below the aortic valve that causes obstruction to LV outflow. The aortic valve itself and the anterior leaflet of the mitral valve are often malformed.
C. Supravalvular Aortic Stenosis (2%)
In this type, constriction of the ascending aorta occurs just above the coronary arteries. The condition is often familial, and two different genetic patterns are found, one with abnormal facies and mental retardation (William syndrome) and other with normal facies and no developmental delay.
Although isolated valvular aortic stenosis seldom causes symptoms in infancy, severe HF occasionally occurs when critical obstruction is present at birth. Response to medical therapy is poor; therefore, an aggressive approach using interventional catheterization or surgery is required. The physical findings vary depending on the anatomic type of lesion:
1. Valvular aortic stenosis
If the stenosis is severe with a gradient greater than 80 mm Hg, pulses are diminished with a slow upstroke; otherwise, pulses are usually normal. Cardiac examination reveals an LV thrust at the apex. A systolic thrill at the right base, the suprasternal notch, and over both carotid arteries may accompany moderate disease.
A prominent aortic ejection click is best heard at the apex. The click corresponds to the opening of the aortic valve. It is separated from S1 by a short but appreciable interval. It does not vary with respiration. S2 at the pulmonary area is normal. A loud, rough, medium- to high-pitched ejection-type systolic murmur is evident. It is loudest at the first and second intercostal spaces, radiating well into the suprasternal notch and along the carotids. The grade of the murmur correlates well with the severity of the stenosis.
2. Discrete membranous subvalvular aortic stenosis
The findings are the same as those of valvular aortic stenosis except for the absence of a click. The murmur and thrill are usually somewhat more intense at the left sternal border in the third and fourth intercostal spaces. In the setting of aortic insufficiency, a diastolic murmur is commonly heard.
3. Supravalvular aortic stenosis
The thrill and murmur are best heard in the suprasternal notch and along the carotids but are well transmitted over the aortic area and near the mid left sternal border. There may be a difference in pulses and blood pressure between the right and left arms if the narrowing is just distal to the takeoff of the innominate artery, with more prominent pulse and pressure in the right arm (the Coanda effect).
Of those not presenting in infancy, most patients with aortic stenosis have no cardiovascular symptoms. Except in the most severe cases, patients do well until the third to fifth decades of life. Some patients have mild exercise intolerance and fatigability. In a small percentage of patients, significant symptoms (eg, chest pain with exercise, dizziness, and syncope) manifest in the first decade. Sudden death is uncommon but may occur in all forms of aortic stenosis with the greatest risk in patients with subvalvular obstruction.
In most cases the heart is not enlarged. The LV, however, may be slightly prominent. In valvular aortic stenosis, dilation of the ascending aorta is frequently seen.
Patients with mild aortic stenosis have normal ECGs. Some patients with severe obstruction have LVH and LV strain but even in severe cases, 25% of ECGs are normal. Progressive LVH on serial ECGs indicates a significant obstruction. LV strain is one indication for surgery.
This is a reliable noninvasive technique for the evaluation of all forms of aortic stenosis. Doppler accurately estimates the transvalvular gradient, and the level of obstruction can be confirmed by both two-dimensional echocardiographic images and by the level of flow disturbance revealed by color Doppler.
E. Cardiac Catheterization and Angiocardiography
Left heart catheterization demonstrates the pressure differential between the LV and the aorta and the anatomic level at which the gradient exists. Catheterization is reserved for patients whose resting gradient has reached 60–80 mm Hg and in whom intervention is planned. For those with valvular aortic stenosis, balloon valvuloplasty is usually the first option. In subvalvular or supravalvular aortic stenosis, interventional catheterization is not effective and surgery is required.
Percutaneous balloon valvuloplasty is now standard initial treatment for patients with valvular aortic stenosis. Surgery should be considered in symptomatic patients with a high resting gradient (60–80 mm Hg) despite balloon angioplasty, or coexisting aortic insufficiency. In many cases, the gradient cannot be significantly diminished by valvuloplasty without producing aortic insufficiency. Patients who develop significant aortic insufficiency require surgical intervention to repair or replace the valve. The Ross procedure is an alternative to mechanical valve placement in infants and children. In this procedure, the patient’s own pulmonic valve is moved to the aortic position, and an RV-to-pulmonary artery conduit is used to replace the pulmonic valve. Fetal balloon valvuloplasty for critical aortic stenosis is currently being studied to prevent progression of hypoplastic left heart syndrome. Discrete subvalvular aortic stenosis is usually surgically repaired at a lesser gradient because continued trauma to the aortic valve by the subvalvular jet may damage the valve and produce aortic insufficiency. Unfortunately, simple resection is followed by recurrence in more than 25% of patients with subvalvular aortic stenosis. Supravalvar aortic stenosis may also require surgical repair and is commonly associated with William syndrome.
All forms of LV outflow tract obstruction tend to be progressive. Pediatric patients with LV outflow tract obstruction—with the exception of those with critical aortic stenosis of infancy—are usually asymptomatic. Symptoms accompanying severe unoperated obstruction (angina, syncope, or HF) are rare but imply serious disease. Children whose obstruction is mild to moderate have normal oxygen consumption and maximum voluntary working capacity. Children in this category with normal resting and exercising (stress) ECGs may safely participate in vigorous physical activity, including nonisometric competitive sports. Children with severe aortic stenosis are predisposed to ventricular dysrhythmias and should refrain from vigorous activity and avoid all isometric exercise.
S: Fetal intervention for critical aortic stenosis: advances, research and postnatal follow-up. Curr Opin Cardiol 2015 Jan;30(1):89–94
et al: 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol Jun 10, 2014;63(22):e57–185. doi: 10.1016/j.jacc.2014.02.536
et al: Long-term results of balloon valvuloplasty as primary treatment for congenital aortic valve stenosis: a 20-year review. Pediatr Cardiol Aug 2015;36(6):1145–1152. doi: 10.1007/s00246-015-1134-4
ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES
Late systolic “whooping” or “honking” murmur.
Typical symptoms include chest pain, palpitations, and dizziness.
Often overdiagnosed on routine cardiac ultrasound.
In this condition as the mitral valve closes during systole, it moves posteriorly or superiorly (prolapses) into the left atrium. Mitral valve prolapse (MVP) occurs in about 2% of thin female adolescents, a minority of whom have concomitant mitral insufficiency. Although MVP is usually an isolated lesion, it can occur in association with connective tissue disorders such as Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes.
Most patients with MVP are asymptomatic. Chest pain, palpitations, and dizziness may be reported, but it is unclear whether these symptoms are more common in affected patients than in the normal population. Chest pain on exertion is rare and should be assessed with cardiopulmonary stress testing. Significant dysrhythmias have been reported, including increased ventricular ectopy and nonsustained ventricular tachycardia. If significant mitral regurgitation is present, atrial arrhythmias may also occur. Standard auscultation technique must be modified to diagnose MVP. A midsystolic click (with or without a systolic murmur) is elicited best in the standing position and is the hallmark of this entity. Conversely, maneuvers that increase LV volume, such as squatting or handgrip exercise, will cause delay or obliteration of the click-murmur complex. The systolic click usually is heard at the apex but may be audible at the left sternal border. A late, short systolic murmur after the click implies mitral insufficiency and is much less common than isolated prolapse. The murmur is not holosystolic, in contrast to rheumatic mitral insufficiency.
Most chest radiographs are normal and are not usually indicated in this condition. In the rare case of significant mitral valve insufficiency, the left atrium may be enlarged.
The ECG is usually normal. Diffuse flattening or inversion of T waves may occur in the precordial leads. U waves are sometimes prominent.
Echocardiography assesses the degree of myxomatous change of the mitral valve, and the degree of mitral insufficiency. Significant posterior systolic movement of the mitral valve leaflets to the atrial side of the mitral annulus is diagnostic.
Invasive procedures are rarely indicated. Holter monitoring or event recorders may be useful in establishing the presence of ventricular dysrhythmias in patients with palpitations.
Propranolol may be effective in treatment of coexisting arrhythmias. Prophylaxis for infectious endocarditis is no longer indicated, based on 2007 AHA guidelines. The natural course of this condition is not well defined. Twenty years of observation indicate that isolated MVP in childhood is usually a benign entity. Surgery for mitral insufficiency is rarely needed.
RS: Epidemiology and pathophysiology of mitral valve prolapse: new insights into disease progression, genetics, and molecular basis. Circulation May 27, 2014;129(21):2158–2170
4. Other Congenital Left Heart Valvular Lesions
A. Congenital Mitral Stenosis
Congenital mitral stenosis is a rare disorder in which the valve leaflets are thickened and/or fused, producing a diaphragm- or funnel-like structure with a central opening. In many cases, the subvalve apparatus (papillary muscles and chordae) is also abnormal. When mitral stenosis occurs with other left-sided obstructive lesions, such as subaortic stenosis and coarctation of the aorta, the complex is called Shone syndrome. Most patients develop symptoms early in life with tachypnea, dyspnea, and failure to thrive. Physical examination reveals an accentuated S1 and a loud pulmonary closure sound. No opening snap is heard. In most cases, a presystolic crescendo murmur is heard at the apex. Occasionally, only a mid-diastolic murmur can be heard. ECG shows right axis deviation, biatrial enlargement, and RVH. Chest radiograph reveals left atrial enlargement and frequent pulmonary venous congestion. Echocardiography shows abnormal mitral valve structures with reduced leaflet excursion and left atrial enlargement. Cardiac catheterization reveals an elevated pulmonary capillary wedge pressure and pulmonary hypertension, owing to the elevated left atrial pressure.
Mitral valve repair or mitral valve replacement with a prosthetic mitral valve may be performed, even in young infants, but it is a technically difficult procedure. Mitral valve repair is the preferred surgical option, as valve replacement can have a poor outcome in infants.
Cor triatriatum is a rare abnormality in which the pulmonary veins join in a confluence that is not completely incorporated into the left atrium. The pulmonary vein confluence communicates with the left atrium through an opening of variable size, and may be obstructed. Patients may present in a similar way as those with mitral stenosis. Clinical findings depend on the degree of obstruction of pulmonary venous flow into the left atrium. If the communication between the confluence and the left atrium is small and restrictive to flow, symptoms develop early in life. Echocardiography reveals a linear density in the left atrium with a pressure gradient present between the pulmonary venous chamber and the true left atrium. Cardiac catheterization may be needed if the diagnosis is in doubt. High pulmonary wedge pressure and low left atrial pressure (with the catheter passed through the foramen ovale into the true left atrium) support the diagnosis. Angiocardiography identifies the pulmonary vein confluence and the anatomic left atria. Surgical repair is always required in the presence of an obstructive membrane, and long-term results are good. Coexisting mitral valve abnormalities may be noted, including a supravalvular mitral ring or a dysplastic mitral valve.
MW: Evolution of mitral valve replacement in children: a 40-year experience. Ann Thorac Surg 2012 Feb;93(2):626–633
Patients at risk for progressive aortic dilation and dissection include those with isolated bicuspid aortic valve, Marfan syndrome, Loeys-Dietz syndrome, Turner syndrome, and type IV Ehlers-Danlos syndrome.
Patients with bicuspid aortic valves have an increased incidence of aortic dilation and dissection, regardless of the presence of aortic stenosis. Histologic examination demonstrates cystic medial degeneration of the aortic wall, similar to that seen in patients with Marfan syndrome. Patients with an isolated bicuspid aortic valve require regular follow-up even in the absence of aortic insufficiency or aortic stenosis. Significant aortic root dilation requiring surgical intervention typically does not occur until adulthood.
2. Marfan and Loeys-Dietz Syndromes
Marfan syndrome is an autosomal dominant disorder of connective tissue caused by a mutation in the fibrillin-1 gene. Spontaneous mutations account for 25%–30% of cases, and thus family history is not always helpful. Patients are diagnosed by the Ghent criteria and must have at a minimum, major involvement of two body systems plus involvement of a third body system or a positive family history. Body systems involved include cardiovascular, ocular, musculoskeletal, pulmonary, and integumentary. Cardiac manifestations include aortic root dilation and MVP, which may be present at birth. Patients are at risk for aortic dilation and dissection and are restricted from competitive athletics, contact sports, and isometric activities. β-Blockers (eg, atenolol), ACE inhibitors, or angiotensin receptor blockers (eg, losartan) are used to lower blood pressure and slow the rate of aortic dilation. A recent study of atenolol versus losartan in children and young adults with Marfan syndrome showed no difference in the rate of aortic dilation between the two medications. Elective surgical intervention is performed in patients of adult size when the aortic root dimension reaches 50 mm or if there is an increase of greater than 1 cm in root dimension in 1 year. The ratio of actual to expected aortic root dimension is used to determine the need for surgery in the young child. Surgical options include replacement of the dilated aortic root with a composite valve graft (Bentall technique) or a David procedure in which the patient’s own aortic valve is spared and a Dacron tube graft is used to replace the dilated ascending aorta. Young age at diagnosis was previously thought to confer a poor prognosis; however, early diagnosis with close follow-up and early medical therapy has more recently been associated with more favorable outcome. Ventricular dysrhythmias may contribute to the mortality in Marfan syndrome.
Loeys-Dietz syndrome is a connective tissue disorder first described in 2005. Many patients with Loeys-Dietz were thought to have Marfan syndrome in the past. Loeys-Dietz is a result of a mutation in the transforming growth factor β (TGFβ) receptor and is associated with musculoskeletal, skin, and cardiovascular abnormalities. Cardiovascular involvement includes mitral and tricuspid valve prolapse, aneurysms of the PDA, and aortic and pulmonary artery dilation. Dissection and aneurysm formation of arteries throughout the body can occur including in the head and neck vessels.
Cardiovascular abnormalities are common in Turner syndrome. Patients are at risk for aortic dissection, typically during adulthood. Risk factors include hypertension regardless of cause, aortic dilation, bicuspid aortic valve, and coarctation of the aorta. There are rare reports of aortic dissection in adult Turner syndrome patients in the absence of any risk factors suggesting that there is a vasculopathic component to this syndrome. Patients with Turner syndrome require routine follow-up from adolescence onward to monitor for this potentially lethal complication.
et al: 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol Jun 10, 2014;63(22):2438–2488
CORONARY ARTERY ABNORMALITIES
Several anomalies involve the origin, course, and distribution of the coronary arteries. Abnormal origin or course of the coronary arteries are often asymptomatic and can go undetected. However, in some instances these children are at risk for sudden death. The most common congenital coronary artery abnormality in infants is anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and is discussed in more detail here.
Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery
In this condition, the left coronary artery arises from the pulmonary artery rather than the aorta. In neonates, whose pulmonary artery pressure is high, perfusion of the left coronary artery may be adequate and the infant may be asymptomatic. By age 2 months the pulmonary arterial pressure falls, causing a progressive decrease in myocardial perfusion provided by the anomalous left coronary artery. Ischemia and infarction of the LV is the result. Immediate surgery is indicated to reimplant the left coronary artery and restore myocardial perfusion.
Neonates appear healthy and growth and development are relatively normal until pulmonary artery pressure decreases. Detailed questioning may disclose a history of intermittent abdominal pain (fussiness or irritability), pallor, wheezing, and sweating, especially during or after feeding. Presentation may be subtle, with nonspecific complaints of “fussiness” or intermittent “colic.” The colic and fussiness are probably attacks of true angina. Presentation may be fulminant at age 2–4 months with sudden, severe HF due to LV dysfunction and mitral insufficiency. On physical examination, the infants are usually well developed and well nourished. The pulses are typically weak but equal. A prominent left precordial bulge is present. A gallop and/or holosystolic murmur of mitral regurgitation is sometimes present, though frequently auscultation alone reveals no obvious abnormalities.
Chest radiographs show cardiac enlargement, left atrial enlargement, and may show pulmonary venous congestion if left ventricular function has been compromised.
On the ECG, there is T-wave inversion in leads I and aVL. The precordial leads also show T-wave inversion from V4–V7. Deep and wide Q waves are present in leads I, aVL, and sometimes in V4–V6. These findings of myocardial infarction are similar to those in adults.
The diagnosis can be made with two-dimensional echo techniques by visualizing a single large right coronary artery arising from the aorta and visualization of the anomalous left coronary artery arising from the main pulmonary artery. Flow reversal in the left coronary (heading toward the pulmonary artery, rather than away from the aorta) confirms the diagnosis. LV dysfunction, echo-bright (ischemic) papillary muscles, and mitral regurgitation are commonly seen.
E. Cardiac Catheterization and Angiocardiography
Angiogram of the aorta fails to show the origin of the left coronary artery. A large right coronary artery fills directly from the aorta, and contrast flows from the right coronary system via collaterals into the left coronary artery and finally into the pulmonary artery. Angiogram of the RV or main pulmonary artery may show the origin of the anomalous vessel. Rarely, a left-to-right shunt may be detected as oxygenated blood passes through the collateral system without delivering oxygen to the myocardium, and passes into the pulmonary artery.
The prognosis of ALCAPA depends in part on the clinical appearance of the patient at presentation. Medical management with diuretics and afterload reduction can help stabilize a critically ill patient, but surgical intervention should not be delayed. Surgery involves reimplantation of the anomalous coronary button onto the aorta. The mitral valve may have to be replaced, depending on the degree of injury to the papillary muscles and associated mitral insufficiency. Although a life-threatening problem, cardiac function nearly always recovers if the infant survives the surgery and postoperative period.
et al: Reoperation and mechanical circulatory support after repair of anomalous origin of the left coronary artery from the pulmonary artery: a twenty-year experience. Ann Thorac Surg 2011;92(1):167–172; discussion 172–173
et al: Long-term results after repair of anomalous origin of left coronary artery from the pulmonary artery: Takeuchi repair versus coronary transfer. Eur J Cardiothorac Surg Feb 1, 2017;51(2):308–315. doi: 10.1093/ejcts/ezw268