A new wrinkle for hypoplastic left heart syndrome patients

Robert Jaquiss, MD, pediatric cardiothoracic surgeon, Children's Hospital of Wisconsin; assistant professor, Surgery (Cardiothoracic), Medical College of Wisconsin.

The history of the treatment of children born with hypoplastic left heart syndrome (HLHS) is a remarkable story of a series of bold innovations. Prior to these, this diagnosis was considered the most lethal and hopeless of congenital heart malformations. In 2004, because of sequential improvements in surgical treatment and perioperative care, infants with HLHS now have an excellent prognosis. The newest of these innovations involves the placement of a shunt between the right ventricle and the pulmonary artery, and has come to be known as the Sano procedure, reflecting the name of the Japanese surgeon who popularized its use. In order to understand the place of the Sano procedure in the care of children with HLHS, following is a review of the development of contemporary management of HLHS, as well as the features of the diagnosis.

The hallmarks of HLHS include:
A. Obstruction to systemic blood flow.
B. Excessive pulmonary blood flow.
C. Frequently a restricted pulmonary outflow (atrial septal defect).
D. A single ventricle to pump blood to both the body and the lungs.

Without surgery, survival only is possible because of the presence of a patent ductus arteriosus that allows blood, which would otherwise go to the lung, to instead pass through the ductus out to the body. A major advance in the care of infants with HLHS was the development of intravenous prostaglandin infusions, which preserve ductal patency. Unfortunately this situation is not stable over the long term because of the progressive drop in pulmonary vascular resistance, which leads to pulmonary overcirculation and systemic undercirculation.

Beginning in the late 1970s and early 1980s a series of inventive surgical approaches to HLHS were proposed and tested with very limited success and few survivors.  However the lessons learned from these efforts, including a very novel procedure reported by S. Bert Litwin, MD, pediatric cardiothoracic surgeon at Children's Hospital of Wisconsin, were crucial in providing the underpinning for the successful strategies that followed. The feasibility of successful initial surgical palliation for HLHS eventually was established by William Norwood, MD, in 1983. He outlined three physiologic objectives met by the operation that has come to bear his name: 

1. Establishment of an unobstructed communication between the right ventricle and the aorta.
2. Limitation of pulmonary blood flow and pressure to nearly normal levels.
3. Establishment of a large interatrial communication.

Norwood's operation consists of disconnecting the right ventricle from the pulmonary artery and reconnecting the ventricle to the reconstructed aortic arch, resecting the interatrial septum, and providing pulmonary blood flow by means of a prosthetic shunt connecting a systemic artery to the pulmonary artery.

By the mid-1990s the Norwood operation had been adopted by most pediatric cardiac surgical units around the world. However, although the procedure represented a considerable improvement, there continued to be significant early and intermediate-term mortality. Children who survived surgery were noted to be remarkably unstable initially, with a continuing vulnerability to sudden collapse and death even after discharge from the hospital.

Although the reasons for the initial instability were not completely clear, it was felt that an imbalance between systemic and pulmonary blood flow was at least in part responsible. In particular, it was widely held that pulmonary overcirculation was a frequent occurrence at the expense of systemic blood flow. This concept led to a variety of preventive strategies focusing on reducing pulmonary blood flow, including the use of smaller systemic to pulmonary shunts that, in turn, led to excessively low oxygen saturation and even shunt thrombosis. Other approaches included drastic ventilatory techniques with intentional hypoxia and hypercarbia to try to induce an increase in the pulmonary vascular resistance. Despite these approaches, early mortality rates in the range of 30 to 50 percent commonly were reported with post-discharge mortality rates as high as 10 to 15 percent.

Advancements at Children's Hospital
Led by George Hoffman, MD, medical director of Anesthesia, James Tweddell, MD, medical director of Cardiothoracic Surgery, and Nancy Ghanayem, MD, pediatric intensivist, an alternative approach was developed at Children's Hospital of Wisconsin with a focus not on increasing pulmonary vascular resistance, but on reducing systemic resistance to maximize systemic oxygen delivery. All physicians also are faculty at the Medical College. Along with improved techniques for reconstructing the aorta and preserving coronary blood flow, the maximum oxygen delivery approach resulted in a remarkable improvement in early survival of children with HLHS at Children's Hospital with early mortality rates of less than 5 percent after the Norwood procedure. However, the problem of post-discharge attrition continued.

Careful analysis of the course of those children who died in the intermediate term (as opposed to early after surgery) suggested they may have had a particularly vulnerable physiologic circumstance and that there may have been warning signs of impending potentially fatal hemodynamic crises. Furthermore, a fuller realization of the inherent vulnerability of the post-Norwood circulation led to the concept of reduced physiologic reserve and increased caloric requirement. The response to these concepts was an enhanced focus on nutritional support and physiologic surveillance, which has come to be termed home monitoring.  This program includes intense instruction of parents in nutritional support, including the liberal use of gastrostomy tubes as needed, as well as having parents record daily their child's weight and oxygen saturation. Parents are instructed to report any aberrations in oxygenation, food intake or weight gain as well as any other alarming symptom or sign. With the introduction of home monitoring, there has been a remarkable reduction in post-Norwood discharge mortality at Children's Hospital.

Unfortunately, the improved results at Children's Hospital have not been replicated at other units, and other centers have explored alternative ways to improve their results.  To this end, the details of the post-Norwood circulation have undergone increased scrutiny, beyond considerations of systemic and pulmonary flow. In particular, it has been pointed out that the systemic diastolic blood pressure is abnormally low after the Norwood procedure because of "run-off" of blood into the pulmonary circuit. This is crucial because the majority of coronary artery flow occurs during diastole. Several investigators have speculated that myocardial ischemia caused by low diastolic blood pressure may explain much of the excess mortality in HLHS patients. 

As a solution to systemic to pulmonary shunt-related myocardial ischemia, the relocation of the shunt inflow to the right ventricle was proposed. This shunt arrangement meets Norwood's second requirement, but importantly results in normal systemic diastolic blood pressure. This concept was advanced in the late 1990s by two Japanese groups and preliminary encouraging results were presented by Sano in 2000. Since then, numerous groups, including Norwood's own, have reported improving survival after initial surgery. Careful physiologic monitoring has demonstrated statistically significantly increased diastolic blood pressures in RV-shunted patients, as opposed to systemic-shunted patients operated on in the same institution.

Sano or RV shunt at Children's Hospital
So how does the Sano or RV shunt fit in at Children's Hospital? To answer this question it is important to point out that the results at Children's Hospital, both early and intermediate term, with conventional (systemic to pulmonary shunts) Norwood procedures are as good as, and in most cases better than, the best results reported to date with the Sano shunt from other institutions. Furthermore, several reported experiences with the Sano procedure have suggested that children with RV shunts may become more cyanotic early and have more pulmonary artery distortion related to the end of the shunts. Nonetheless, the theoretical rationale for the Sano approach appears to be sound and its use has resulted in improved results in most centers where it has been introduced. At present, we are engaged in a head-to-head prospective trial comparing the Sano to the conventional Norwood procedure, based on the lack of unequivocal data demonstrating the superiority of one approach over the other. The trial, led by Ghanayem in cooperation with colleagues at the University of Michigan, Children's Hospital of Philadelphia and Boston Children's Hospital offers the best, most logical way for us to continue to improve the care for our patients with HLHS.

Understanding arrhythmias at all ages

Janette Strasburger, MD, director of Cardiac Services, Children's Hospital of Wisconsin-Fox Valley (a member of Children's Hospital and Health System); professor, Pediatrics (Cardiology), Medical College of Wisconsin.

As part of the Herma Heart Center, working in the Fox Valley cardiology section of Children's Hospital of Wisconsin, I spend as much as 25 percent of my time performing National Institutes of Health (NIH) funded research. My particular interest is in the cardiac health of the fetal patient. This is an exciting new area of clinical medicine and investigation, which promises to expand dramatically in the next 10 years.

Fetal surgery is in the not-too-distant future. We already are providing effective drug therapy to babies with life threatening heart rhythm disorders before they are born by treating the mother with medication, or by giving medication directly into the fetal thigh or hip. I often provide advice for maternal-fetal medicine specialists around the country on medication dosing. We work as a consortium of researchers, including faculty at several large perinatal programs in the Chicago area, as well as Children's Hospital and Froedtert Hospital in Milwaukee and the University of Wisconsin Medical Physics Department in Madison. In addition, we are collaborating with senior cardiovascular research scientists at NASA's Johnson Space Center in Houston on a project on the effects of weightlessness on heart rhythm. We also are working with basic science researchers in Lausanne, Switzerland on new diagnostic techniques for fetal heart conditions. 

Why should we study the fetus?
Most of us think of an older male who dies suddenly, but sudden death in the life cycle of the human strikes at different rates at different ages. Sudden cardiac death is rare in children, but tragically occurs often when a child is playing sports. As a pediatric cardiac center, we have supported communities to resuscitate these children through Project ADAM, a program of Children's Hospital that helps schools develop and sustain automated external defibrillator programs.

During the latter months of pregnancy the risk of intrauterine death is 1 in 500. In the first year of life the risk of Sudden Infant Death Syndrome is about 1 in 2,000. Only recently have we recognized that some deaths before birth or in the first year of life may be caused by heart rhythm abnormalities and may be preventable. Women with high blood pressure during pregnancy, or with lupus run as much as a 1 in 30 to 1 in 50 chance of having a miscarriage after fifth month of pregnancy. 

Once a baby is born, many diagnostic modalities are available such as echocardiography (ECG) and MRI scanning.  In utero, ECG cannot be reliably recorded because the mother's skin and the substances surrounding the fetus act to insulate the fetal ECG signal. At the University of Wisconsin Medical Physics Department, Ron Wakai, PhD, professor of Medical Physics, uses a sophisticated Superconducting Quantum Interference Device (or SQUID magnetometer) to record fetal heart rhythms, allowing us to diagnose and treat these rhythm abnormalities. This technology is called magnetocardiography or MCG. It is completely safe for the mother and fetus, and records the weak magnetic signals accompanying the electrical conduction of the heart.
My role as an electrophysiologist is to interpret the signals that are processed and transmitted. In addition, my partner Michele Frommelt, MD, pediatric cardiologist in Milwaukee, uses new echocardiographic techniques to monitor fetuses with serious congenital heart disease. As a team, we are able to diagnose and monitor a fetus throughout the pregnancy, and plan the delivery and the baby's medical care to achieve the best possible outcome and future for the child.

Much more research is needed to understand the importance of the fetal environment in the development of acquired cardiovascular disease in the adult. Studies have linked intrauterine growth restriction to adult coronary artery disease, and birth weight recently has been found to be an important determinant of physical strength as an adult. Exposures to toxic agents may have life-long effects on the heart and brain. Through our work, we have found that thickening of the heart muscle, a process called remodeling, can begin in utero. This may be important in understanding why many adults suffer from atrial arrhythmias in their later years.

Herma Heart Center branches out to community locations

Pamela Sayger, DO, medical director, Pediatric Cardiology, Children's Hospital of Wisconsin Clinics-Gurnee (a member of Children's Hospital and Health System); assistant professor, Pediatrics (Cardiology), Medical College of Wisconsin.

With the ever-growing need for pediatric cardiology services and a desire to have a more full-time community presence, Children's Hospital has begun three outreach clinics, including Children's Hospital of Wisconsin Clinics-Fox Valley, Children's Hospital of Wisconsin Clinics-Kenosha and Children's Hospital of Wisconsin Clinics-Gurnee. As the medical director of Pediatric Cardiology for the clinic in Gurnee, Ill., I provide full-time care to children with congenital heart disease and other common cardiac problems such as heart murmurs, chest pain, hypertension and syncope. I also provide care in Kenosha, while my colleague, Janette Strasburger, MD, provides similar care to children in the Fox Valley of Wisconsin.

The regional clinics have full-service capabilities to perform pediatric and fetal echocardiograms, arrhythmia monitoring with event recorders and holter monitors, and electrocardiograms.

I collaborate with many professionals and organizations, including the full-time Children's Hospital fetal concerns nurse, to serve southeastern Wisconsin and northern Illinois. I also work with fetal-maternal medicine specialists from Evanston, Ill., who see high-risk obstetrics patients at our Gurnee clinic twice a week. I perform fetal echocardiograms on expectant mothers who are at risk for or who have a suspicion of congenital heart disease, and consult with these families regarding the management and prognosis of their defect.
In the past year and a half, two in utero diagnosis of hypoplastic left heart syndrome have been made at the Gurnee clinic. These babies both have had stage I Norwood and stage II Glenn operations in Milwaukee and continue to be followed by me in Gurnee. This allows families to remain close to home for all but the most technical cardiac care.

In addition, I am a consulting pediatric cardiologist at 10 hospitals in the surrounding area and work closely with Children's Hospital of Wisconsin neonatologists who staff the nursery at Victory Hospital in Waukegan, Ill. I also work closely with four new pediatric hospitalists who provide pediatric care 24 hours a day, seven days a week at Condell Medical Center in Libertyville, Ill.

Future direction and goals for the Gurnee clinic include development of an obesity, hypertension and dyslipidemia program, which will coincide with a preventive cardiology program at the main Children's Hospital clinic in Milwaukee. These all are opportunities to provide seamless care for our patients who may require some of their medical care in Milwaukee, while keeping them closer to home whenever possible.

Annual Gallen lectureship held

Maryanne Kessel, RN, MS, director, Herma Heart Center, Children's Hospital of Wisconsin.

The annual William J. Gallen lectureship was held Thursday, June 10, and Friday, June 11, with a focus on adults with congenital heart disease. This was a timely topic as we begin planning for our Adult Congenital Heart Disease Program with Froedtert Hospital, and fitting since many of the patients who qualify for this program are former patients of Gallen.

Gary Webb, MD, director of the 8,000-patient Toronto Congenital Cardiac Center for Adults, was the guest speaker.
The current incidence of congenital heart disease is 0.5 to 0.8 percent nationwide with 85 percent surviving into adulthood. We estimate there are 800,000 adults in the United States living with congenital heart disease, more than 9,000 of them in the state of Wisconsin.

Half of these adults are considered medium to high maintenance and soon the number of adult patients will equal the number of pediatric patients.

William Joseph Gallen, MD, was appointed to the Medical/Dental Staff at Children's Hospital of Wisconsin in 1957. He currently is an honorary staff member. Gallen has contributed greatly to the field of pediatric cardiology and has earned several awards.

Medical management of neonates prior to heart surgery

Beth Ann Johnson, MD, MA, pediatric cardiac fellow, Herma Heart Center, Children's Hospital of Wisconsin; instructor, Pediatrics (Neonatology), Medical College of Wisconsin.

Infants with critical congenital heart disease present in several different ways. Some infants are diagnosed in-utero and are delivered in tertiary care hospitals prepared to manage neonatal cardiac lesions. Some infants are diagnosed after brief periods of cyanosis non-responsive to oxygen in the newborn nursery prior to discharge. Still others are diagnosed after becoming acutely and critically ill at home. No matter the presentation, infants with congenital heart disease require careful management during the interim between diagnosis and surgery. The focus of care during this period is optimizing the infant's clinical condition for the critical hours in the operating room and the critical days thereafter.

The immediate priority following diagnosis is the clinical stabilization of the infant.  Infants who present in cardiac shock require immediate, effective resuscitation. These infants frequently need crucial interventions such as intubation, volume expanders and occasionally pressor support. Another important part of stabilization is acquiring reliable vascular access. Cardiac lesions requiring surgical intervention in the neonatal period usually require intravenous infusion of prostaglandin E to maintain ductal patency providing an alternative source of pulmonary or systemic blood flow. Prostaglandin therapy, while necessary, frequently causes side effects of its own that require close observation and anticipation by the medical team.  Apnea requiring intubation, and capillary leak requiring volume therapy, are common side effects of prostaglandin therapy. Other possible consequences of IV prostaglandin therapy include fever, rash and thickened bronchial secretions. The approach to medical management before surgery does vary tremendously between institutions and providers.

A complete anatomic diagnosis usually is established once the infant is stable, or occasionally during active resuscitation if the infant is not responding as expected to therapeutic interventions. The cardiac anatomy usually is described via transthoracic echocardiography, a "minimally-invasive" diagnostic tool that has revolutionized cardiac imaging. Via echocardiography, important anatomic variations affecting medical management and surgical procedure are identified. In rare cases, further studies, such at cardiac catheterization, may be required to clarify coronary artery anatomy or the presence of collateral blood vessels. Recently, the diagnostic tool of magnetic resonance imaging (MRI) is being applied to cardiac anatomy and may be used to provide additional anatomic information.

Another important goal of care prior to surgery is evaluating the patient for secondary organ effects. Especially if the patient presents in cardiac shock, secondary organs, such as the kidney, gut and brain may have suffered from inadequate oxygen delivery. Careful pre-operative evaluation investigates for the presence of such effects. Renal function tests are measured initially and followed daily. If elevated, suggesting tissue perfusion injury, surgery may be delayed to allow for improvement in renal function. If hypoperfused, the gut can receive similar injury. At the extreme, hypoperfusion can lead to necrotizing enterocolitis (NEC). This concern of NEC causes many providers to refrain from preoperative enteral feedings, especially in the face of left-sided obstructive lesions.  Preoperative evaluation also includes a head ultrasound, assessing for intra-ventricular hemorrhages and occasionally defining abnormal anatomy. The presence of intracranial bleeding also may affect the timing of surgery and cardiopulmonary bypass. Preoperative management also involves special attention to the possibility of infection.  Blood cultures routinely are ordered at presentation and depending on prenatal and postnatal risk factors, prophylactic antibiotics may be started.

As cardiac anomalies are a component of numerous syndromes and chromosomal anomalies, preoperative care of the neonate with congenital heart disease includes careful examination for other associated anomalies. Such determinations significantly can alter the infant's morbidity and mortality risk. Evaluations frequently include chromosome studies such as a karyotype or fluorescent in-situ hybridization (FISH) techniques to specifically evaluate for a deletion at 22q11. Occasionally the consultation of a geneticist is requested.

At Children's Hospital, neonates usually have surgery between 3 and 7 days old. These important preoperative days allow providers time to optimize the infant's clinical condition for surgery and educate the parents regarding in the infant's medical condition. If the infant's cardiac lesion was not diagnosed prenatally, parents suddenly are overwhelmed by their infant's critical illness as well as large amounts of complicated information regarding cardiac anatomy and neonatal surgery. The days between  diagnosis and cardiac surgery allow complex information to be presented several times and parent's questions to be answered. The interim between diagnosis and surgery also allows parents to travel to the tertiary hospital (the mother frequently is inpatient at a different hospital following delivery) and become familiar with both the intensive care environment and support services available at Children's Hospital.

For infants with congenital heart disease requiring surgery in the neonatal period, the goals of preoperative management include clinical stabilization, medical optimization for the physiologic stress of cardiac surgery and family education. Achieving these goals requires teamwork and communication between a large number of providers, including (but not limited to) perinatologists, neonatologists, cardiologists, cardiovascular surgeons, cardiac intensivists and nursing teams. This dedicated team, working together with the family, allows for the best possible outcome.

Director of Herma Heart Center appointed

Maryanne Kessel, RN, MS, recently was promoted to director of Herma Heart Center. In 2003, Kessel was named program administrator of Herma Heart Center and has done much to build the program including formally moving cardiology and cardiothoracic surgery into a "center" system to provide seamless care to patients with congenital heart disease, and developing regional programs and partnerships to serve children closer to their homes throughout the region.

Kessel has established a formal Herma Heart Center research component to allow coordinated physician and nursing research to advance patient care. She also has worked with medical leadership to begin developing a comprehensive Adults with Congenital Heart Disease Program and to further organize care provided through the cardiac Fetal Concerns Program.

Kessel started at Children's Hospital in 1987 and recently received her master's degree in health care from Concordia University.