Aortic valvular atresia is a congenital condition in which the aortic valvular cusps are fused at birth. It frequently forms as a spectrum of malformations of the left ventricular outflow tract (LVOT). The atresia can be characterized as sub-valvular, valvular, or supra-valvular, depending on the site of the anomaly. Most commonly, the defect presents as aortic stenosis, though in rare cases, it can manifest as complete atresia. When atretic, the valve can be dome-shaped, monocuspid, bicuspid, or even quadricuspid, and the associated leaflets are dysplastic or fused, not permitting flow through the abnormal valve. It is sometimes but not always associated with congenital ventricular hypoplasia, which can be part of hypoplastic left heart syndrome (HLHS). In this condition, there is abnormal or under-development of the left heart as well as aortic structures. In HLHS, there is often underdevelopment of the mitral valve as well, though there is a universal association with aortic valve abnormalities. Isolated aortic valvular atresia is exceedingly rare, and in context, total aortic valvular atresia can be regarded as the most advanced manifestation of hypoplastic left heart syndrome.
In a classic case of aortic valve atresia, there is generally an anatomic connection between the right and left sides of the heart, usually in the form of either a patent foramen ovale, another form of atrial septal defect, or in cases with a functioning mitral valve: a ventricular septal defect. The right ventricle is generally dilated rather than thickened, and the left ventricle is hypoplastic and thick-walled, being much smaller than the right ventricle. The mitral valve has been noted to usually be small, and in some cases, there is associated mitral valve atresia as well.
No pathological case report in the literature has shown transposition of the great vessels, and the pulmonary trunk arises normally from the right ventricle with appropriate branching. Due to the lack of an aortic valve, the aortic root generally arises from the base of the heart. The coronary arteries arise normally from the aortic root, but the ascending aorta and arch of the aorta are generally hypoplastic. The branches of the aorta are normal in caliber, and all studied cases report a large ductus arteriosus that empties into the descending aorta, providing mixed-oxygenation blood for the fetus.
HLHS presents in a familial pattern and is frequently picked up during screening for congenital bicuspid aortic valve through the use of echocardiography. 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.
The extent of malformations do 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.
Aortic valvular atresia results in about 1% incidence in live births. 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. Isolated aortic valvular atresia had a 73% male predilection, with combined aortic and mitral stenosis, as well as HLHS, having over 70% male predominance. Unfortunately, reliable worldwide epidemiological data is not available.
In a classic case of aortic valvular atresia, blood from the pulmonary circulation returns to the left side of the heart and is able to cross over to the right side 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.
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 starts to become 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 with a modest drop in levels with crying. This can be moderately improved with oxygenation.
On physical examination, a precordial bulge can be present, though it is not a reliable indicator. Over 50% of patients, however, 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 3cm 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 as well can 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.
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 development of 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 a narrowing of the heart base along with 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.
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 Wolff-Parkinson-White pattern, as well as right bundle branch block, have been reported. There is a reported lack of a Q wave in lead V6, and this has been reported as a possible exclusion marker for aortic valvular atresia. It should be noted, though, that the lack of this finding is not specific for 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, as well as ST-segment depressions in the left precordial leads, have also frequently been reported.
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. If there is a hypoplastic left ventricle (LV), a univentricular repair can be attempted. This consists of a three-stage repair, involving a Norwood procedure initially, followed by a Bidirectional-Glenn procedure, and completed with the Fontan procedure.
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 a high risk, but it allows for biventricular physiology and complete correction initially.
Another two-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.
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. Conduit reintervention continues to be the main cause of post-procedure reintervention even though techniques in conduit placements and materials continue to advance.
The differential diagnosis for this condition should be considered in the context of the anatomy of the infant heart. When evaluated with 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.
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. If the diagnosis of aortic valvular atresia is suspected after birth, prostaglandin E1 should be started immediately prior to the patent ductus arteriosus closing. After the intervention, whether by single or staged operation, follow up studies show that mortality is significantly reduced. 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. In terms of freedom from reoperation, several follow up studies average between 14% to 29% 5-year average. The overall 10-year survival is almost 90%.
Complications can occur during surgery. Operational mortality is about 7%, in one study being due to failures of extracorporeal membrane oxygenation (ECMO). Reintervention after surgery is based on several factors. Conduit exchanges left ventricular outflow tract (LVOT) repairs, and aortic arch repairs may also need to be done. Residual VSD may also have to be repaired. 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.
There is no known prevention of this congenital anomaly. Pregnant women should be advised by their providers to follow all regular pregnancy followups and continue vitamin supplementation as needed. Further genetic linkages, including loss of function mutations in NOTCH1 genes, can be a slight predictor of the risk of LVOTO. This will have to be explored further for full understanding.
The management of aortic valvular atresia is complex and multidisciplinary. Advancements in genetic testing, prenatal echocardiography, and interventional cardiology have all made the treatment of aortic valvular atresia a highly team-based endeavor. To achieve good surgical outcomes, the need for operation, as well as the type of surgery, should be ascertained prior to or soon after birth. At Kitasato University in Japan, the decision to pursue biventricular repair or univentricular repair after initial Norwood palliation was made on the basis of having over 80% right ventricular end-diastolic volume index (RVEDVI). Decisions such as these require a team of medical professionals as well as close communication between surgeons and patient families. In addition, if a two-stage operation is attempted, a right heart catheterization is frequently done to assess pulmonary pressures prior to the second stage.
To improve outcomes, pediatric cardiac surgeons are tracking their hospital outcomes more and more. By utilizing large cohort studies, such as the Congenital Heart Surgeons Study, The U.S. Natural History Study of Congenital Heart Disease Nos. 1 and 2, and the New England Regional Infant Cardiac Program to name a few, a large amount of clinical data can be evaluated to improve surgical techniques and indications.
In the postoperative period, the role of support staff, including nurses, nursing assistants, and pharmacists, is vital. Nursing staff monitors patients for complications such as hypoxia, surgical site infections, as well as common postoperative complications such as atelectasis, pneumonia, and deep venous thrombosis. If complications result, prompt communication between medical teams is vital to improve outcomes and save patients. In the discharge period, close communication between surgeons and outpatient pediatricians is vital to monitor common post-surgical complications. [Level I]
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