Evolving strategies and technologies in pediatric heart failure and pediatric heart transplantation

Remarkable progress has been made in the surgical and medical treatment of pediatric heart failure over the past 35 years. The first human heart transplant was performed in South Africa in December 1967. The first pediatric heart transplant was performed three days later in Brooklyn, New York, on a 2 1/2-week-old infant with Ebstein anomaly. This patient died six hours later due to persistent severe acidosis.

Dismal outcomes were common, and after 1967, pediatric heart transplants were placed on hold until outcomes could be improved. Finally, in 1984, the first successful pediatric heart transplants were performed at several centers around the United States. These successes were driven by the discovery of cyclosporine, an immunosuppressive medication that revolutionized the care of patients after transplant.

Before the 1980s, many diagnoses in pediatric cardiology carried a fatal prognosis, including:

  • Severe dilated cardiomyopathy
  • Severe myocarditis
  • Restrictive cardiomyopathy
  • Severe neonatal Ebstein anomaly
  • Many forms of complex congenital heart disease

"The increased availability of pediatric heart transplantation and advances in reparative and palliative surgery for neonates with complex congenital heart disease provided new options for these patients and their families," says Jonathan N. Johnson, M.D., pediatric transplant cardiologist at Mayo Clinic in Rochester, Minn.

While the care for and management of pediatric heart transplant patients has improved markedly, there remains one large limiting factor that impacts transplantation in pediatric cardiology: donor availability. Despite the availability of more than 50 pediatric transplant centers in the United States, the number of donor hearts has plateaued in the past few years, effectively limiting the number of transplants that can be performed.

In 2010, according to the Organ Procurement and Transplantation Network of the Department of Health and Human Services, 359 heart transplants were performed in patients younger than 18 years. Meanwhile, it's estimated that at least 40 infants and young children die every year in the U.S. while awaiting a heart for transplantation. "Clearly, with this limited donor supply, it is critical that new strategies are developed to improve the length and quality of life in transplant recipients," says Dr. Johnson.

New strategies in pediatric heart transplantation

Pediatric patients who have undergone or are awaiting heart transplantation can have complex medical issues, and a true multidisciplinary approach is required before, during and after the transplant. At Mayo Clinic in Minnesota, pediatric transplant patients are evaluated concurrently by cardiac surgery, pediatric cardiology, intensive care, infectious diseases, pulmonology, pharmacy, social services and child life teams. The input of experts across the varied fields allows for optimal care for these patients.

While the initial pediatric heart transplants were often performed on patients with normal anatomy but abnormal function, such as dilated cardiomyopathy, advances in congenital heart surgery permit transplantation in patients with extracardiac concerns, including coarctation of the aorta, pulmonary artery or vein stenosis, and abnormal systemic venous return to the heart (such as interrupted inferior vena cava and left or bilateral superior vena cava). It is now rare that a patient cannot receive a transplant simply because of abnormal arterial or venous connections.

Once a heart has been transplanted, extreme care goes into ensuring that the allograft is not rejected by the recipient's immune system. The Mayo Clinic team has developed a grading system for determining a patient's likelihood of experiencing rejection; the immunosuppressive regimen is modified depending on patient risk factors such as:

  • Blood type
  • Age
  • History of rejection
  • Presence of antibodies specific to donor antigens

Newer immunosuppressive agents, including tacrolimus, mycophenolate and sirolimus, are regularly used and appear to have improved adverse effect profiles compared with older immunosuppressive medications.

One of the greatest long-term risks to the pediatric heart transplant patient is the development of coronary vasculopathy. This potential risk factor requires regular screening using both coronary angiography and intravascular ultrasound (IVUS). The use of sirolimus in particular is thought to reduce the appearance and progression of coronary vasculopathy.

New strategies in pediatric heart failure

With the limited availability of donor hearts, the need has arisen for therapies with which to bridge the patient to transplantation, allowing longer wait times.

Arguably one of the greatest advancements in adult cardiology in the past 30 years has been use of ventricular assist devices (VADs) in the treatment of severe heart failure. While the use of VADs in adult patients is now routine, the lack of appropriately sized pediatric VADs has been problematic. The paucity of devices is at least partially attributable to the need for critical design features in VADs to handle smaller outputs; simple miniaturization of effective adult VADs has been unsuccessful.

Currently, several companies are producing pediatric VADs. Two types have been used in pediatric patients younger than 5 years at Mayo Clinic in Rochester, Minn. VADs designed for adults can be used in teenagers who are close to adult size. While these pediatric VADs have shown promise and have been very effective, the known risk of neurologic embolic events, particularly in infants, has prompted investigation of new devices.

In February 2010, the National Heart, Lung, and Blood Institute recognized the need for more effective pediatric-sized VADs and awarded contracts worth almost $24 million to four institutions for preclinical testing of different versions of pediatric VADs. It is hoped that this four-year program, titled Pumps for Kids, Infants, and Neonates (PumpKIN), will provide cardiologists with more tools in the care of critically ill children with heart failure.

Pediatric heart transplantation at Mayo Clinic

The first pediatric heart transplant at Mayo was performed in 1991. Since then, of the 400-plus total heart transplants performed at Mayo Clinic in Rochester, Minn., 40 have been in pediatric patients (less than 18 years old) and 25 more have been in adult patients with congenital heart disease. Multiorgan transplants in patients with congenital heart disease, including heart-kidney and heart-liver combined transplants, have also been performed.

Pediatric patient survival at one month and one year after transplant has been excellent. Pediatric transplant cardiologists work closely with their surgical and adult transplant colleagues to ensure optimal care is delivered to all heart transplant patients.

Failing Fontans

The Mayo Clinic Center for Congenital Heart Disease has established a transplant, heart failure and VAD program specifically directed at pediatric and adult patients who have had a Fontan procedure. The team includes pediatric cardiology, adult congenital disease, cardiovascular surgery, gastroenterology, radiology and infectious disease experts.

"This is a population of patients in dire need of options when their surgically created circulation fails, and collaboration among the various specialists is critical to their management," says Dr. Johnson.