Aortic Valvular Atresia

Etiology

HLHS presents in a familial pattern and is frequently picked up during screening for congenital bicuspid aortic valve through the use of echocardiography.[2] A literature review shows that HLHS has shown to be present in up to 8% of siblings of patients with already diagnosed HLHS. In addition, it is present in 3.5% of first-degree relatives of these index patients, along with over a 20% incidence of other cardiovascular congenital malformations.[3]

The extent of malformations does not stay in the left heart; there are reports of associated conotruncal abnormalities as well as thoracic aortic aneurysms in probands with congenital left heart disease. A screening study in 2015 found an over 20% incidence of other congenital malformations, such as bicuspid aortic valve and coarctation of the aorta in relatives of patients with HLHS. Occasionally the condition does occur with Turner syndrome, which is itself associated with bicuspid aortic valve and coarctation of the aorta. Additionally, it can be associated with dextrocardia, mesocardia, and there have also been reports of association with DiGeorge syndrome and chromosome 22-q11 deletion.[4]

Epidemiology

Aortic valvular atresia results in about 1% incidence in live births.[5] HLHS has about a 0.163 discovery rate per 1000 live births, as first seen in the Report of the New England Regional Infant Cardiac Program.[6] Isolated aortic valvular atresia had a 73% male predilection, combined aortic and mitral stenosis, and HLHS had over 70% male predominance.[7] Unfortunately, reliable worldwide epidemiological data are not available.

Pathophysiology

In a classic case of aortic valvular atresia, blood from the pulmonary circulation returns to the left side of the heart and can cross over to the right via either an atrial or ventricular septal defect. The right ventricle pumps this mixed-oxygenated blood through the pulmonary trunk and the patent ductus arteriosus, which supplies the descending aorta and coronary arteries in a retrograde manner, and as a side effect, results in high pressures within the right side of the heart. Cyanosis results from this mixed venous blood in the systemic circulation, and pulmonary edema frequently develops due to increased pressures in the pulmonary arteries. Heart failure is thought to develop due to poor circulation in the coronary arteries, which are supplied in a retrograde fashion through the hypoplastic ascending aorta.[5]

History and Physical

The presentation of aortic valvular atresia can be rapidly seen in the post-natal period. The chief initial findings of the condition are dyspnea, cyanosis, and rapidly progressive heart failure. Dyspnea and/or tachypnea is thought to be the most sensitive sign for aortic valvular atresia, as it develops in about 60% of live births. While the disease may not initially present with cyanosis, as the ductus arteriosus remains open shortly after birth, cyanosis becomes apparent as the ductus closes. The average age of development of cyanosis is 2 days. Measured oxygen (O₂) saturation can be variable. A small number of patients (16%) can show low O₂ saturation at rest and a modest drop in levels with crying. This can be moderately improved with oxygenation.

A precordial bulge can be present on physical examination, though it is not a reliable indicator. However, over 50% of patients have a pulmonary systolic ejection murmur, the intensity of which can vary from grade 1 to grade 3. The murmurs can be heard clearest along the left sternal border. The second heart sound at the cardiac base is mostly single, though sometimes can have a very close split and rarely have an ejection click. Heart failure is quick to develop in about 60% of these patients, with the average age of development being 2.5 days. It is almost always associated with hepatomegaly, with about 3 cm of protrusion beyond the right costal margin. An S3 heart sound can sometimes be heard, along with chest rales, edema, and palpable spleen. Blood pressure can also be lower than average, hovering around 65/45 mmHg, and pulse pressure is generally narrow. No clinically significant pressure difference is noted between upper and lower extremity measurements.[5]

Evaluation

Evaluation begins in the prenatal period. Frequently, color Doppler is used during the echocardiographic examination of the heart. Infants with a lack of Doppler flow through the aortic valve should be immediately considered to be at high risk of aortic valvular atresia. A key point when assessing these patients is the risk of developing HLHS, as patients with even a normal-sized or slightly dilated left ventricle can develop HLHS at birth.

Initial chest radiography after birth can show a "globular" heart pattern or the heart shape associated with truncus arteriosus. This includes narrowing the heart base, a rounded apex, and a “shoulder” on the left heart border. Though a "bulge" for the pulmonary artery might be expected, it is only present in a small minority of cases. Chest radiography also reveals pulmonary edema in many cases, and sometimes, patients can have upper or middle-lobe lung collapse.[5]

The initial electrocardiogram classically shows right axis deviation, right ventricular hypertrophy, and right atrial enlargement, though it can also show a pattern considered normal for patient age. This is generally attributed to the hypoplastic left side of the heart, but there are a few reported cases of left axis deviation and, rarely, left ventricular hypertrophy. There are occasionally problems with bundle branch conduction, and the Wolff-Parkinson-White pattern and the right bundle branch block have been reported. There is a reported lack of a Q wave in lead V6, which has been reported as a possible exclusion marker for aortic valvular atresia. It should be noted that the lack of this finding is not specific to aortic valvular atresia, as other congenital heart conditions or even normal infants may lack the Q-wave in this lead. T-wave depressions in leads I and II and ST-segment depressions in the left precordial leads have also frequently been reported.[5][8]

Treatment / Management

Several surgical approaches can be attempted depending on the underlying physiology. Since aortic valvular atresia exists as part of a spectrum, including HLHS and ventricular septal defect (VSD), the surgical approach should be contingent upon the underlying structure of the infant's heart. A univentricular repair can be attempted if there is a hypoplastic left ventricle (LV). This consists of a 3-stage repair, involving a Norwood procedure initially, followed by a Bidirectional-Glenn procedure, and completed with the Fontan procedure.[9](B3)

An initial procedure called the Yasui procedure can be undertaken soon after birth if there is an option for biventricular repair with an existing VSD. In patients with a left ventricle that is not hypoplastic due to an existing VSD, a conduit is created from the left ventricle into the pulmonary artery through the VSD. The pulmonary artery is transected, and the proximal portion is anastomosed to the aorta. The distal portion of the pulmonary artery is attached via a valved conduit to the right ventricle. This procedure is high-risk, but it initially allows for biventricular physiology and complete correction.[10][11](B2)

Another 2-pronged approach can be attempted, as well. This involves the Norwood procedure initially, allowing for some time with univentricular physiology, and then a staged Rastelli operation at an average of 9 months from the first procedure. This was first done in 1981 by Norwood et al, and the approach consists of reconstructing the ascending aorta using the Damus-Kaye-Stansel method and then subsequently repairing the VSD and right ventricular conduit to the pulmonary artery.[12][13][14]

The methodology for choosing one surgical approach versus another is complex and continues to be debated. Biventricular repair, either in single versus staged operations, continues to have improving outcomes and compares favorably to univentricular palliation.[12][14] Conduit reintervention continues to be the main cause of postprocedure intervention, even though techniques in conduit placements and materials continue to advance.[11](B2)

Differential Diagnosis

The differential diagnosis for this condition should be considered in the context of the anatomy of the infant's heart. When evaluated with a 2-D echo during pregnancy, the diagnosis may not always be apparent initially. Though not always cyanotic at birth, dyspnea and cyanosis can present in many of the other cardiac congenital heart diseases, including the following:

• Coarctation of the aorta
• Tetralogy of Fallot
• Truncus arteriosus
• Ebstein anomaly
• Tricuspid valve atresia
• Pulmonic valve atresia
• Transposition of the great arteries
• HLHS
• Anomalous pulmonary venous return

Prognosis

The prognosis for aortic valvular atresia without intervention is uniformly fatal after physiologic closure of the patent ductus arteriosus (PDA), and it accounts for 25% of cardiac-related deaths in neonates.[5][15] If the diagnosis of aortic valvular atresia is suspected after birth, prostaglandin E1 should be started immediately prior to the patent ductus arteriosus closing.[16] Follow-up studies show that mortality is significantly reduced after the intervention, whether by single or staged operation. A study of 27 patients with 23 years of follow-up from 1990 to 2013 showed an average reintervention rate of about 50%. In addition, the Norwood procedure in this cohort had no deaths in between stages.[10] In terms of freedom from reoperation, several follow-up studies average between 14% and 29% 5-year average.[11][17] The overall 10-year survival is almost 90%.[11]

Complications

Complications can occur during surgery. Operational mortality is about 7%, in one study being due to failures of extracorporeal membrane oxygenation (ECMO).[10] Reintervention after surgery is based on several factors. Conduit exchanges, LVOT repairs, and aortic arch repairs may also need to be done.[11] Residual VSD may also have to be repaired.[17] As with all pediatric cardiac surgeries, patients can be at risk for plastic/mucinous bronchitis, protein-losing enteropathy, and pulmonary arteriovenous malformations, the latter of which has no defined etiology.[18]