Fetal echocardiography and fetal intervention

Michele Frommelt, MD, pediatric cardiologist, Herma Heart Center, Children's Hospital of Wisconsin; associate professor, Pediatrics (Cardiology), Medical College of Wisconsin.

Fetal echocardiography has made substantial differences in the world of pediatric cardiology. It has taught us much about the natural history of congenital heart disease in utero; in particular, that certain lesions are progressive and undergo significant change throughout gestation. Fetal echocardiography has guided us in identifying candidates for prenatal cardiac intervention and has aided us to technically perform these procedures with recent success. It has enabled us to diagnose, monitor and treat arrhythmias, and allows us to rapidly observe conversion to a normal sinus rhythm with prompt resolution of ventricular dysfunction and fetal hydrops. With prenatal identification, we are able to counsel families about their child's cardiac disease and the anticipated course after birth. Recognition of congenital heart disease in utero often affects the location and timing of delivery, and allows avoidance of hemodynamic compromise, especially with ductal-dependent lesions.

Natural history of congenital heart disease

The development and utilization of fetal echocardiography has given pediatric cardiologists a unique opportunity to observe and follow the natural history of congenital heart disease in utero. Our understanding of many aspects of cardiac development and cardiovascular physiology has been significantly enhanced by these antenatal observations and has led to the development of fetal cardiac intervention as a new and innovative field within pediatric cardiology. It has become clear that congenital heart disease is a dynamic process that evolves over the course of gestation.

One of the most important hypotheses that has been substantiated from observations in fetal echocardiography is the altered flow theory. Diminished forward flow into a chamber or great vessel resulting in abnormal growth of fetal cardiac structures has been observed by fetal echocardiography, especially in fetuses with early obstructive or regurgitant lesions. Many examples exist to validate this theory, but perhaps the best studied is the fetus with critical valvar aortic stenosis.
In 1989, the in utero evolution of hypoplastic left heart syndrome was observed in a fetus initially diagnosed with critical aortic stenosis. Since that time, several fetal cardiac centers have reported retrospective collaborative data, which suggests that serial measurements of left heart growth and assessment of flow direction across the foramen ovale and distal aortic arch may identify fetuses at risk for severe left heart hypoplasia at term. It now is postulated that many cases of hypoplastic left heart syndrome are dynamic and progressive throughout gestation, resulting from altered left ventricular outflow or altered left ventricular inflow. The new and innovative field of prenatal cardiac intervention is just in its infancy, but recent successes with balloon dilatation of the aortic valve suggest that we may be able to alter the development and incidence of hypoplastic left heart syndrome
at term.

Fetal intervention

Fetal echocardiography plays a major role in fetal cardiac intervention. As mentioned previously, retrospective studies suggest that serial measurements of left heart growth and assessment of fetal blood flow patterns may predict the severity of post-natal left ventricular hypoplasia. Also, Doppler assessment of pulmonary venous flow patterns in the fetus with hypoplastic left heart syndrome can predict the severity of atrial septal restriction. It appears that candidates for fetal aortic valvuloplasty or fetal atrial septoplasty can be selected using criteria obtained from serial fetal echocardiograms.

In 2000, the world experience of fetal aortic balloon valvuloplasty was reported. The early clinical experience, albeit small (n=12), was quite poor, with only one "long-term" survivor. However, more encouraging data recently was reported at the 2005 World Congress of Cardiology meetings. Under an innovative therapy protocol at the Children's Hospital of Boston and the Brigham and Women's Hospital, fetal aortic valvuloplasty was offered to 40 mothers whose fetuses had aortic stenosis and were judged to be at risk for the development of hypoplastic left heart syndrome. Six families declined to participate, while 34 fetuses underwent aortic valvuloplasty, with technical success in 27. Fetal complications included in utero demise in four, death related to prematurity in one, bradycardia in 15, and a pericardial effusion in two. Maternal complications were rare, although the procedure itself required laparatomy in 50 percent of mothers. Of the 22 liveborn infants s/p valvuloplasty, six had a biventricular circulation and 16 had hypoplastic left heart syndrome. This preliminary data supports the hypothesis that some forms of hypoplastic left heart syndrome may be "preventable" with in utero intervention. 

Family planning

Perhaps the most important but somewhat immeasurable impacts of fetal echocardiography and prenatal diagnosis are those that affect the family. Since complex heart disease is overrepresented prior to birth, and heart disease may be associated with extracardiac abnormalities, a multidisciplinary approach is needed to best evaluate and support the mother, fetus and family. No one specialist has sufficient knowledge or training to work alone in this setting. Many centers, including Children's Hospital of Wisconsin, have developed specialized fetal cardiology programs where pediatric cardiologists, perinatologists, neonatologists, cardiac surgeons, geneticists, social workers and even psychologists work together to provide complete care for the fetus and family.  

Once the diagnosis of congenital heart disease is confirmed, a complete anatomic survey of the fetus is performed. Genetic counseling is offered if a chromosomal abnormality is suspected and other subspecialties may need to be involved in the setting of extracardiac disease.  Arrangements for delivery should be discussed, as many of the lesions diagnosed prenatally require prompt resuscitation and/or intervention. Delivery at a tertiary care facility avoids transport-related morbidity and is likely to improve overall mortality. Also, delivery at a tertiary care facility allows the parents to be close to their infant as the mother recovers from the birth and allows the family to have access to the medical and surgical team caring for their child. These factors certainly improve the already stressful experience parents face when delivering a newborn with critical congenital heart disease.       

Future

During the next 20 years, it is likely there will be continued improvements in screening for congenital heart disease, with improved diagnostic accuracy, even in the low-risk population. Advances in ultrasound technology and image resolution may lead to earlier diagnosis and possibly earlier intervention. Collaborative studies will add to our present knowledge of fetal cardiac development and physiology, and will guide therapies. Fetal cardiac intervention already has had some success in the setting of critical aortic stenosis and likely will continue to expand and improve. We hope the recognition of critical congenital heart disease in utero will improve the long-term outcome of our patients, including neurodevelopmental outcomes and quality of life.

Surgical techniques in orthotopic cardiac transplantation

Michael Madrzak, PA-C, chief physician assistant, Cardiothoracic Surgery, Herma Heart Center, Children's Hospital of Wisconsin.

The first human-to-human heart transplantation was performed by Christian Barnard, MD, at the Groote Schuur Hospital in Capetown, South Africa on Dec. 3, 1967.  This monumental task was made possible through the development of cardiopulmonary bypass, intraoperative hypothermia and the surgical techniques perfected in canine models by Norman Shumway, MD, and Richard Lower, MD, at Stanford University. With the development and introduction of transvenous endomyocardial biopsy and the use of effective multidrug immunosuppressive regimens, cardiac transplantation has become an accepted therapeutic option for end-stage cardiac failure.

Heart procurement

Following a median sternotomy and pericardial incision, the donor heart is exposed and inspected for gross abnormalities. It is prepared for explantation by mobilization and separation of the great vessels, inferior and superior vena cavae. Heparin is administered, the aorta is cross-clamped and cold preservation solution is infused into the aortic root. Division of the inferior vena cava and left inferior pulmonary vein allow for venting of the blood and  preservation solution. Crucial at this stage is the cold saline slush poured in the chest to achieve rapid surface cooling of the heart. Removal of the heart by division of the remaining great vessels follows completion of the preservation solution infusion (Figure 1). 

Careful planning and coor-dination with the recipient team especially is important in transplantation for patients with congenital heart disease. If the transplant recipient has a complex congenital heart malformation, such as hypoplastic left heart syndrome or heterotaxy syndrome, extra length of donor superior vena cava or pulmonary artery tissue may be required.

The most important factor in organ preservation is hypothermia, allowing for safe ischemic times between four and six hours. Immediately after its removal, the heart is placed in a cold saline bath within a sterile sealed container, triple bagged with layers of cold saline and finally placed within the ice filled transplant cooler.

Surgical placement techniques

The standard by which all other techniques are compared dates back to 1960, with the pioneering work of Shumway and Lower. In their paper presented at the annual meeting of the American College of Surgeons, they first described their technique, as used in canine models. Referred to as the Lower-Shumway (biatrial) technique, it involves creating and connecting donor and recipient atrial cuffs. Pulmonary artery and aortic anastomoses are performed with standard vascular surgical technique (Figure 2). Although long the gold standard, this technique has been modified over the last decade due to several known potential complications including tricuspid valve insufficiency, sinus node dysfunction and thrombus formation. These complications are directly related to the resulting enlarged and potentially distorted atria and proximity of the atrial suture line to the sinus node.

A modification to the standard biatrial approach was developed in 1991. Termed the Bicaval technique, it avoids right atrial suture lines by connecting the donor and recipient superior and inferior vena cavae.  Pulmonary venous anastomosis is completed by the standard left atrial cuff technique (Figure 3). Studies comparing the bicaval and biatrial techniques demonstrate improved post-transplant survival, atrial geometry, hemodynamics, decreased tricuspid insufficiency, fewer arrhythmias, less pacing requirement, reduced vasopressor requirements and shorter hospital stay. This technique does not, however, address the problems of left atrial thrombus development. Other considerations include the longer ischemic times necessary to complete the additional anatomosis and the risk of superior or inferior vena caval anastomotic stenosis.  

This approach has been utilized at Children's Hospital of Wisconsin since 2000.
A third, less commonly used approach (8 percent of heart transplants) is total heart transplantation. In this approach, the left atrial anastomosis is replaced with separate anastomoses of the left and right sided pulmonary vein cuffs. This technique does avoid the potential post-operative difficulties associated with a biatrial connection. The price paid is in longer ischemic times and potential issues with vena caval or pulmonary vein stenosis. Additionally, unreachable anastomotic bleeding sites can be problematic.

Berlin Pediatric Heart ventricular assist device

Christopher Brabant, perfusionist, Cardiothoracic Surgery, Herma Heart Center,
Children's Hospital of Wisconsin.

Editor's note: Children's Hospital of Wisconsin was the first in the upper Midwest to implant the Berlin Pediatric Heart in a pediatric patient Feb. 19, 2006. While similar technology has been used at Children's Hospital to bridge patients to transplant, the Berlin Heart has been found to have advantages in pediatric patients.

The function of a ventricular assist device (VAD) is to unload the heart and provide adequate peripheral circulation with acceptable organ perfusion. Ventricular assist devices of various design and function principles have been used for temporary support of failing hearts for the purpose of facilitating myocardial recovery or keeping the patient alive until transplantation. 

Until fairly recently, scientific and engineering efforts have preferentially focused on circulatory support systems for adults. As a result, there has been limited experience using assist devices in pediatric patients. The adult ventricular assist devices cannot be used for children because of the physical size of the VAD compared to the limited size of the pericardial space in pediatric patients. 

There are formidable technical challenges in the development of a pediatric VAD. Resistance to blood flow is much greater in the smaller cannulae required for infant and pediatric ventricular assistance. Thrombus formation also may be greater in pediatric ventricular assist devices due to the relative immaturity of the younger patient's coagulation system. Finally, it is important to remember the development of ventricular assist devices is based on a four chambered heart model. Many pediatric patients who require devices have univentricular hearts with concomitant anatomic anomalies that make cannulation and blood flow to and from the VAD insufficient for the maintenance of adequate end organ perfusion. 

In 1992, the Berlin Heart VAD (Berlin Heart Mediprodukt GmbH, Berlin, Germany) was introduced into clinical practice. It offered the first commercially available system with miniaturized blood pumps and cannulae. The Berlin Heart VAD consists of a paracorporeal air-driven blood pump constructed of a poly-urethane housing with an integrated diaphragm that forms a continuous interior blood contact. The Berlin Heart system also consists of cannulae for connection of the blood pumps to the heart chambers and great vessels, as well as electro-pneumatic driving systems capable of coping with the high resistance of small-bore cannulae for pediatric patients. The Berlin Heart VAD is appropriate for all age ranges because the blood pumps and cannulae are available in different sizes. 

The decision for implantation of a ventricular assist device largely depends on institutional experience and is made by assessing the individual clinical situation of each patient with the help of a careful diagnostic approach. Surveillance before implantation is directed at measuring indices of cardiac output. Evidence of worsening systemic perfusion with early signs of organ dysfunction despite maximal medical management is criteria for a ventricular assist device. 

Severe multisystem organ failure is a clear contraindication for the implantation of a ventricular assist system.  However, early stages of end organ failure can be reversed by circulatory mechanical assistance. Other contraindications include irreversible septic shock, severe neurologic injury, uncontrolled hemorrhage and parent or guardian denial of treatment.  

In February 2006, a 6-year-old boy with a history of a ventricular septal defect repaired during infancy was admitted to Children's Hospital of Wisconsin with a three-week history of decreased exercise tolerance, fatigue, dyspnea, diarrhea and vomiting. Prior to admission, the patient had an active lifestyle with a history of mild left ventricular dysfunction following his initial surgical repair. Echocardiogram at admission revealed severe biventricular dysfunction. His non-invasive tissue saturations as well as his mixed venous oxygen saturation were low, consistent with diminished cardiac output. He also had mild renal and hepatic dysfunction and modest respiratory insufficiency at rest. Within 24 hours of admission, the patient's clinical condition deteriorated, he was intubated and required escalating medical and pharmacological support. It was determined that criteria for mechanical circulatory support were met and the Berlin Heart was selected for circulatory assistance given the small size of the patient (BSA<1m2). 

Because it is not approved for use by the United States Food and Drug Administration (FDA), the Berlin Heart VAD only can be implemented in the U.S. following an appeal for "compassionate use." Within 48 hours, hospital staff obtained approval from the FDA, contacted Berlin Heart Mediprodukt GmbH and obtained the required berlin heart system supplies from Germany. A physician and technical representative from the berlin heart company were present for the implantation and subsequent postoperative medical management. 

Five days after he was admitted to Children's Hospital, the patient received a Berlin Heart left ventricular assist device (LVAD) and was placed on the status 1-A list for a cardiac transplant. His immediate post LVAD recovery was unremarkable. After 25 days of LVAD support, he underwent heart transplantation. His recovery following transplantation went well and he was discharged approximately three weeks later and continues to do well now four months post transplantation.     

As the number of corrective and palliative procedures for previously inoperable forms of complex congenital heart disease increases, there is a concomitant growth in the need for pediatric ventricular assist devices. As of this writing, there have been more than 60 Berlin Heart Ventricular Assist devices implanted in pediatric patients at 14 institutions in North America. Although there has been only one recipient of the Berlin Heart ventricular assist device at Children's Hospital of Wisconsin, further utilization at this facility is likely.

Herma Heart Center Marfan Syndrome and Related Connective Tissue Disorder Clinic

Michael Earing, MD, cardiologist, Herma Heart Center, Children's Hospital of Wisconsin; assistant professor, Cardiology, Medical College of Wisconsin

Marfan syndrome is a disorder of the connective tissue characterized by a genetic mutation in the gene coding for the protein fibrillin on chromosome 15. The incidence is estimated to be about two to three per 10,000. Marfan syndrome is a pleiotropic disorder characterized by seemingly unrelated manifestations in different organs rising from a single mutation. The diagnosis is based on diagnostic criteria first presented in 1986 by a committee of international consultants. The criteria were revised and published in 1996.

The diagnostic criteria focus on three main organ systems: the skeleton, the eye, and the heart and aorta. However, the mutation results in abnormalities also in the skin, fascia, lung, skeletal muscle, and adipose tissue and likely the central nervous system. To establish a diagnosis of Marfan syndrome based on the Ghent criteria (an index case that refers to a patient with no family history), a patient needs to have a major criterion in two different organ systems and involvement of the third. If there is a family history, a patient needs one major criterion in an organ system and involvement of a second organ system. When the patient exemplifies the standard medical-textbook description of Marfan syndrome, the diagnosis is made easily. However, in many cases, the diagnosis is less obvious and a full range of objective findings needs to be gathered by physicians from multiple disciplines such as cardiology, genetics, ophthalmology and orthopedic surgery in order to establish or rule out the diagnosis. Further complicating the evaluation of these patients is that there is great variability in the phenotypic expression present even in family members with the same genetic mutations; many of the manifestations of Marfan syndrome can occur in the normal population; and finally, numerous other connective tissue disorders present with similar manifestations such as Ehlers-Danlos Syndrome, familial ectopic lentis syndrome, the MASS phenotype, and Stickler Syndrome.
While often difficult to establish a diagnosis, the management of these patients often can be even more challenging. Due to the abnormalities in multiple different organ systems, care of patients with Marfan syndrome requires a multidisciplinary team consisting of cardiology, genetics, ophthalmology, orthopedic surgery and cardiovascular surgery. With better understanding of this complex disorder and through the use of a multidisciplinary approach, the life expectancy for this patient population has increased from a mean age of death of 32 years in 1972 to more than 61 years in 1998.  

To diagnose and care for this complex patient group, Children's Hospital of Wisconsin has established the Marfan Syndrome and Related Connective Tissue Disorder Clinic as part of the Herma Heart Center. The goal of this program is to provide state-of-the-art comprehensive diagnostic and interventional care.

The clinic offers:

• Diagnosis and follow-up including X-rays, echocardiography, cardiac MRI.
• Medical management.
• Genetic counseling and testing.
• Orthopedic surgical care.
• Ophthalmology care.

Appointments are scheduled through Central Scheduling at (414) 607-5280 or toll-free at (877) 607-5280. For more information, I can be contacted at mearing@chw.org or (414) 266-2068.