Transcatheter Closure of ASD's - The Amplatzer Device

• Andrew Pelech, MD, pediatric cardiologist

Increasingly, the cardiac cath lab is used to treat, not just diagnose children with heart disease. In addition to providing key hemodynamic information prior to surgery, about 40 percent of all cath cases involve some form of dilatation, occlusion or stenting.

We are involved in a Phase 2 study of transcatheter closure of some ASDs. The initial part of the study includes prospective collection of baseline data on children undergoing operative repair of secundum ASDs, to be followed with closure of selected atrial defects in the cath lab.

The most common form of atrial septal defect is the ostium secundum ASD. It is located in the floor of the fossae ovalis and represents a deficiency in the embryonic septum primum. Atrial defects account for 10 percent of all significant structural heart disease. We close about 40 a year at Children's Hospital.

The hemodynamics of an atrial septal defect depend essentially on the magnitude and duration of the shunt flow across the defect and the reactivity of the pulmonary vascular bed. In large defects, significant left to right shunt volume causes right ventricular volume overload and right heart dilatation. Pulmonary vascular occlusive disease and pulmonary artery hypertension may develop in adulthood, as well as the potential for atrial arrhythmias, paradoxical emboli and stroke. It is recommended patients with significant shunts (pulmonary to systemic flow ratios exceeding 1.5 to 1) be considered for closure, either surgically or by the occlusion device. Primum ASD and sinus venous ASDs generally are not amenable to transcatheter device closure. Children need to be heavier than 8 kg to be included in the study.

Because transesophageal echocardiographic imaging is required in addition to cardiac catheterization techniques, the procedure is done under general anesthesia in the cath lab. The size of the defect is determined both by echo and with a special balloon sizing catheter.

Employing a long plastic sheath placed across the defect, a device, called an Amplatzer, is put into position. The Amplatzer device is an ingenious pre-formed "basket" of wire which resumes its pre-formed mushroom-like shape when extruded from the catheter sheath. The wire is made of a special alloy-nitinol which does not break, accepts growth of cardiac endothelial tissue lining and is absorbed into the heart septal wall. Specialized dacron fibers are contained within the basket component of the device and immediately stop shunt flow. The position of the device is checked by echo and fluoroscopy prior to release.

Currently, patients are required to stay in the hospital overnight. However, soon they will go home as other outpatients and be followed up periodically for one year.

When "Half-Hearted" Is a Huge Gift

• Maryanne Kessel, RN, heart transplant coordinator

Since 1985, our congenital heart surgery program has used more than 500 human heart valves (homografts) and tissue specimens to repair children's congenital heart defects.

To date, there are no synthetic choices that have come close to matching the quality of real tissue. Manufactured grafts require ongoing anticoagulation and calcify more quickly. Valve or tissue-only donations that can be used as grafts include pulmonary valve and pulmonary arteries, aortic valve and aorta and, more recently, mitral valves. (Only a few centers in the United States have performed mitral valve homograft surgery. We have done one). The congenital heart lesions which benefit from these grafts include TOF, pulmonary atresia with VSD, TGA, HLHS and truncus arteriosus. These grafts allow the donation of one child's heart to help two or three children with congenital heart disease move toward a healthier life. Several children with homografts from 10 years ago are going strong.

Once donated, these grafts are preserved by an outside lab, then shipped back to us where they are stored in a cryo-freezer. They can be stored for more than 10 years.

Surgery for a child cannot be scheduled if the appropriate-sized graft is not available. Therefore, it is imperative for us to store a range of valve sizes.

Retrieval of a heart for the purpose of grafting can occur up to 24 hours after death. Staff at the Wisconsin Donor Network are available to answer questions about donor suitability. They also are very skilled in discussing these tough subjects with families.

Pulmonary Atresia with VSD

Elliot May, CVPA

Pulmonary atresia with ventricular septal defect is characterized by underdevelopment of the right ventricular outflow tract with atresia of the pulmonary valve, a large VSD and overriding of the aorta. Severity depends on the development of the pulmonary arteries. When a large patent ductus arteriosus is associated, pulmonary atresia with VSD is managed as a severe form of Tetralogy of Fallot. In this subtype, the pulmonary arteries usually are normal in size and distribute blood to all segments of the lungs. When a small patent ductus arteriosus is present, or when there is no patent ductus arteriosus, pulmonary artery blood supply is provided partially or entirely by major aorticopulmonary collateral arteries (MAPCAs). This form of pulmonary atresia with VSD is discussed here. Intermediate forms of this cardiac anomaly exist and are approached individually depending upon the specific anatomy.

Surgical technique
Surgical techniques to repair pulmonary atresia with ventricular septal defect with MAPCA dependent pulmonary blood supply vary and depend on individual anatomy and surgeon preference.

The vast anatomic variability seen in pulmonary atresia with VSD makes the surgical approach patient specific. The ultimate goal is complete repair, achieved by constructing central pulmonary arteries from the MAPCAs, closing the VSD and establishing continuity between the right ventricle and reconstructed pulmonary arteries. Staged approach to repair, by performing sequential aorticopulmonary collateral artery unifocalization, or recruitment procedures is preferred by some surgeons. Alternatively, early single stage total repair sometimes is performed. Regardless of the approach chosen, total repair with VSD closure should proceed as early as the patient's pulmonary anatomy will allow.

Postoperative considerations
The postoperative course varies and depends on anatomy and surgical course. Invasive monitors utilized postoperatively include arterial, central venous and left atrial catheters. An oximetric catheter is utilized to monitor cardiac output. Vasoactive infusions required for hemodynamic management might include dopamine or dobutamine, epinephrine, nitroprusside and milrinone.

Excessive postoperative bleeding can occur when extensive pulmonary artery angioplasty is required for repair. Atrioventricular conduction abnormalities are occasionally encountered since ventricular septal defect closure requires manipulation near atrioventricular conduction tissue. Atrioventricular pacing capability should be readily available. Arterial oxygen saturation and intracardiac pressures should be normal following surgery. Length of hospital stay required following repair is variable, but one to two weeks is average.

Fetal Echocardiography

Michele Frommelt, MD, pediatric cardiologist

Who should be screened?
Indications for a detailed fetal echocardiogram, using multiple anatomic views and Doppler analysis, include fetal arrhythmias, fetal extracardiac anomalies, fetal chromosomal anomalies, an abnormal four-chamber view on a routine screening obstetrical ultrasound, a family history of congenital heart disease, specific maternal diseases (such as diabetes mellitus) and evidence of fetal distress. The likelihood of a positive yield depends highly on the indication.

The most important indication for a detailed fetal echo is the suspicion of an abnormal heart on a screening obstetric ultrasound. In this setting, the incidence of structural heart disease is greater than 50 percent. Because these patients primarily are referred based on an abnormal four-chamber view, the heart disease identified often is quite severe and commonly includes forms of right or left heart hypoplasia.

Another common indication for a fetal echo is a family history of congenital heart disease, especially in siblings. If the father has a history of congenital heart disease, the risk in the fetus increases 3 percent. If the mother has a positive history, the risk to the fetus is as high as 15 to 20 percent. Also, certain forms of congenital heart disease tend to recur more frequently, especially left-sided obstruction lesions such as aortic valve atresia and coarctation.

The role of echocardiography in detecting and treating fetal arrhythmias has been well established. In patients who present with a sustained tachyarrhythmia, structural heart disease is not uncommon, especially in those with atrial fibrillation/flutter. Fetal hydrops often occurs, leading to maternal drug therapy. Sustained bradyarrhythmias, such as complete heart block, are often quite problematic and frequently associated with either structural heart disease or maternal autoimmune disease. Prognosis is extremely poor in those patients with heart block and complex congenital heart disease, with an in utero mortality greater than 90 percent.

The association of extracardiac congenital malformations with congenital heart disease has been well established. However, the frequency of congenital heart disease is variable and dependent on the organ system involved. Chromosomal abnormalities are commonly associated with congenital heart disease, demanding a detailed view of the fetal heart in all cases. We are well aware of the high incidence of atrioventricular septal defects in patients with Trisomy 21.

Maternal diseases such as insulin-dependent diabetes mellitus increase the risk of congenital heart disease in the fetus three- to four-fold. Structural anomalies are more common, but also hypertrophic cardiomyopathy can occur in the setting of chronic hyperinsulinemia, which can improve with better diabetic control.

Non-immune fetal hydrops is reported to be associated with heart disease in at least 50 percent of cases and likely represents the end-stages of congestive heart failure in the fetus. This is commonly seen with sustained arrhythmias, such as chronic supraventricular tachycardia or complete heart block, or severe structural heart disease such as Ebstein's anomaly of the tricuspid valve with severe valve insufficiency.

What are the benefits?
At present, the major benefit of the fetal echocardiogram is to be able to provide the family with valuable information regarding the prognosis of the specific defect, so further management can be planned and coordinated with the multidisciplinary team. Medical therapy may be indicated in the treatment of sustained tachycardias and can influence long-term outcome. If the structural defect is severe with the likelihood of fetal death, termination of pregnancy may be considered. If the defect is found to be a ductal-dependent lesion, such as hypoplastic left heart, arrangement for delivery at a tertiary care facility is critical, so the infant can be stabilized and prostaglandin therapy initiated. A positive family history for congenital heart disease yielded few cases of detectable congenital heart disease. One may argue this is not a cost-effective indication, however the peace of mind a normal fetal study can give parents who have another child with severe congenital heart disease cannot be understated.

What have we learned?
Since the initial experience with the detection of the fetal heart by M-mode echocardiography in 1972, nearly all forms of congenital heart disease have been detected prenatally. Serial observation of the fetal heart has taught us that although most cardiac defects develop within the first eight weeks of gestation, or during the period of embryogenesis, some cardiac lesions may be acquired or progress in utero. This has led to the theory that some cardiac lesions may actually develop during the period of morphogenesis, related to a lack of forward flow. For example, patients with left heart obstructive lesions such as aortic stenosis or coarctation may, at the initial prenatal exam, have normal or only mildly reduced LV dimensions. However, over time, significant left heart hypoplasia can develop, leading to the recommendation for Norwood palliation at the time of birth. Similarly, patients with Tetralogy of Fallot and mild right ventricular outflow tract obstruction in early gestation may go on to develop pulmonary atresia with significant hypoplasia of the branch pulmonary arteries. Based on these observations, serial echocardiography may be indicated in any fetus diagnosed with congenital heart disease, as it appears that fetal heart disease can change and progress, leading to altered long-term management.

What lies ahead?
In the future, fetal cardiac surgery will undoubtedly play an important role in the treatment of congenital heart disease. In the United Kingdom, balloon dilatation of the aortic valve in two fetuses with critical aortic stenosis has been reported. Implantation of fetal pacemakers also has been attempted, for treatment of complete heart block with hydrops fetalis. Soon, the pediatric cardiologist with an expertise in fetal echocardiography will be asked to select those fetuses who potentially would benefit from intrauterine repair or palliation. Accurate diagnosis will be very critical and more longitudinal collaborative studies will be needed to know the best time to intervene. Certainly, patients with lesions such as critical aortic stenosis with reduced left ventricular growth over time appear to be the most likely initial candidates.

Pharmacy Update on Phenoxybenzamine

Tom Nelson, Rph, pediatric pharmacist

The benefits of phenoxybenzamine in infants and children with congenital heart disease who are undergoing open cardiac repair are to provide "uniform and smooth reduction in systemic vascular resistance" and to "improve end-organ function." In the patients with hypoplastic left heart syndrome, the use of phenoxybenzamine results in a "more balanced pulmonary to systemic blood flow ration by lowering the systemic vascular resistance."

Phenoxybenzamine, unlike any other medication, is an irreversible antagonist to alpha-adrenergic receptors. Alpha-1 receptor blockade results in dilation of arterial and venous smooth muscle. Alpha-2 receptor blockade results in some dilation of arteries and veins, stimulating sympathetic output, decreasing vagal tone, decreasing platelet aggregation and stimulating the release of norepinephrine and acetylcholine from nerve endings. The predominate effect of phenoxybenzamine is dilation of arteries and veins from direct action, as well as from inhibition of vasoconstriction caused by endogenous catecholamines. This results in decreased peripheral resistance and a decreased blood pressure. Phenoxybenzamine, in theory, can cause tachycardia due to decreased peripheral resistance, increased cardiac output and enhanced norepinephrine release. Since phenoxybenzamine is an irreversible blocker of alpha receptors, the duration of action is determined by the synthesis of new alpha-receptors. Complete regeneration of receptors may take days to reach a functional level, however, some receptors are continuously being generated.

Epinephrine versus norepinephrine for pressor support when phenoxybenzamine is being used.

• Epinephrine's mechanism of action includes stimulation of alpha receptors, beta-1 receptors and beta-2 receptors.
• Norepinephrine's mechanism of action includes stimulation of alpha receptors and beta-1 receptors but not beta-2 receptors.
• Thus, when alpha receptors are blocked and beta-1 and -2 receptors are stimulated, additional dilation of arteries and veins can result.

The oral maintenance dose of phenoxy is 0.4 to 1.2 mg/kg/day divided every 8 hours with a maximum daily dose of 2 mg to 4 mg/kg/day. The current study at Children's Hospital comparing phenoxy and captopril in the HLHS population uses an oral maintenance dose of phenoxy of 0.5 to 1.5 mg/kg/day divided into three equal doses. Phenoxy differs from captopril in that it is an irreversible alpha blocker and works primarily by decreasing SVR. Captopril works on reninangiotensin as a preload and afterload reducer. Phenoxy may also have some antiarrhythmic benefits.

Side effects of phenoxybenzamine

• Incidence > 10 percent - postural hypotension with tachycardia and dizziness, nasal congestion and miosis.
• Incidence 1 to 10 percent - lethargy, weakness, headache, confusion, drowsiness, nausea, vomiting, diarrhea and dry mouth.