Transplants: How far have we come and how can pediatricians play a role?

Transplants: How far have we come and how can pediatricians play a role? | Image Credit: © Microgen - © Microgen - stock.adobe.com.

In the following Q+A interview with Contemporary Pediatrics, David Rosenthal, MD, and Nicholas Avdimiretz, MD, highlight key successes in the heart and lung transplant space in multiple ways, from how far the space has advanced, to the constantly changing landscape, to how general providers play a role.

Rosenthal is the medical director of Thoracic Organ Transplantation and the director of the Pediatric Advanced Cardiac Therapies program at Stanford Medicine Children’s Health. Avdimiretz is the medical director of the Pediatric Lung and Heart-Lung Transplant Program at Stanford Medicine Children’s Health.

Contemporary Pediatrics:

Just how far has the idea and concept of heart and lung transplants come as we discuss it in 2024?

David Rosenthal, MD:

In the early days of heart transplant, survival was measured in weeks. Within a couple of years, results improved, and patients were living for months to a year, or 2. Then came an explosion of interest in heart transplants. This started the journey to modern heart and lung transplantation. Today, more than 90 percent of our patients are expected to survive the first year of heart transplantation and an infant who receives a transplantation is likely to survive more than 2 decades.^1,2

While receiving a transplant does not result in a fully “normal life,” it provides a far better one for patients. The benefits of transplantation, which at first were only realized in very cut-and-dry, straight forward cases, are now accessible to patients with very complex heart disease. This is a tremendous evolution and advancement in our field. For example, transplants are now available to patients who have very rare heart disease or who may have had multiple prior surgeries that weren’t successful.

One of the most pressing issues on the pediatric heart transplant agenda is continued work to make transplants more accessible to children. This has been a big change over recent years, with continued research and innovation targeted at organ accessibility. The results are far superior than what they were in the early days of transplantation, but there is more to be done to broaden the donor pool and make transplants more accessible for children.

One of the advances to help find a match sooner was pioneered by one of Stanford Children’s cardiologists.³ It’s an innovative donor heart matching technique, which uses CT scans to measure the volume of the donor and recipient hearts to see if they are a similar size, rather than traditional and less-precise height and weight measurements.

We’re seeing a similar evolution in lung transplant. As with any practice, the field is looking for ways to improve the effectiveness of lung transplants. We’ve made steady strides and are hoping for a similar trajectory to the progress with heart transplants. One challenge is that there are complex problems with the immune system that lung transplant must solve for. We are on our way to overcoming these challenges through innovative transplant approaches.

Contemporary Pediatrics:

What should general providers know about the technology, occurrences of transplants, and what are the most common transplants we see in pediatrics?

Rosenthal:

The most important thing to know for a general pediatrician, and even for a cardiologist, is that the field is changing constantly. What was learned during training continues to evolve as we research further and gather data. The indications for a patient to be considered for a heart transplant are changing. The baseline assumption should be that a patient with heart disease and no conventional therapies should get a heart transplant, or may benefit from treatments that a heart transplant or advanced heart failure programs can offer.⁴ But ultimately, it is on the transplant center to make this determination, in coordination with the general provider.

It’s also worth noting the most common cases for transplant. The most common transplants are performed for cardiomyopathy, which is a broad phrase that includes lots of conditions where the heart is formed in a normal manner, but does not work normally.⁵ Sometimes patients with cardiomyopathy present at birth, and other times the condition develops later in life. We most commonly find transplants for cardiomyopathy to be necessary in the first 2-to-3 years of life, and again during a second spike in adolescence.⁶ For some reason, it is less commonly required between the years of 3 and 10. Still, cardiomyopathy remains the first and most common indication for transplant in children, whether from familial ties or sporadic cases.

Contemporary Pediatrics:

What new technologies have helped pave the way for pediatric transplants, and what is exciting about the future?

Rosenthal:

The most impactful new technologies are ventricular assist devices (VAD) that help a failing heart do its job. These are pumps that are typically implanted surgically, and generally used in patients that are already ill. They are critical tools in helping stabilize patients long enough for a transplant. With VADs, we’ve been able to dramatically improve the survival period when children are on the waitlist for a heart transplant. We’ve also been able to improve the condition of those patients so that the transplant itself goes more smoothly and the recovery process is faster. In some cases, we’ve been able to reverse cardiomyopathy or heart failure and avoid transplantation either for a period of time, or perhaps indefinitely.

Another technological advancement is in the ability to maintain heart function for a donor heart that’s being transported. This is mostly for adults, but we’re seeing increased use and application in children as the technology becomes more mature.

Right now, it is a system that helps maintain heart function for a heart donor that is being transported from one location to another. Historically, that has been a very vulnerable time for transplant, as the heart has been removed surgically from the donor and is being transported to the candidate. Traditionally, it was “kept on ice” to limit damage in transport. However, there have been recent technologies developed that mimic the environment of a beating heart, nourishing the organ with oxygen.

This improves the distance a donor heart can travel, which is important for children because there aren’t many donors. Plus, it improves performance of the heart after transplant in ways that will ultimately shorten stays and perhaps even reduce mortality from surgery.

In the long term, we must look at expanding our donor pool. It’s why the field of xenotransplantation is moving so fast. But we also must continue to make better use of the donors we have. The field has traditionally avoided donors who aren’t adequate for transplant. Now, we’re figuring out how to make better use of them, saving organs that once couldn’t be used. Anything we can do to overcome the shortage of donors is a huge win for transplant worldwide.

Contemporary Pediatrics:

What messages do you have for general providers, whether that is practical knowledge of transplants or more specified clinical pearls?

Rosenthal:

It is critical to understand the intersection of the general provider and transplant worlds. Understanding who to refer to a transplant center and when to refer them is an important undertaking and a goal post that continues to move as research improves. Transplant is specialized care in partnership with the general provider. General providers need to be thinking about which patients could benefit from advances in heart failure therapies and when they should be connected with a specialist. This is the most important consideration.

The other important note is that general providers are responsible for interpreting the kind of care their patient needs. Understanding the outcomes from heart transplant is a very important piece of knowledge for general providers. It allows them to be able to work closely with patients and help explain the benefits of a particular treatment.

Contemporary Pediatrics:

For those awaiting lung transplants, are there new treatment options while in a waiting period? What does this landscape look like for so many waiting for a transplant and how do providers navigate this difficult process?

Nicholas Avdimiretz, MD:

There has been a changing landscape in the types of patients that we see for lung transplantation in childhood. Due to significant advances in cystic fibrosis (CF) care, particularly due to effective CF transmembrane conductance regulator (CFTR) modulator therapies, we no longer see as much end-stage lung disease from CF at early ages. Children we see for potential lung transplant are now more complex, with diagnoses like severe pulmonary hypertension, advanced lung diseases associated with heart conditions, and interstitial lung diseases of childhood.

These are patients who can decompensate very quickly. When they meet criteria for advanced lung disease, they require careful consideration around advanced lung disease therapies and possible transplantation as early as possible. This is because, in some instances, wait times can be long, especially for small lungs.

Because of this changing landscape, getting more complex patients to transplant once they are listed is crucial. For our sickest patients such as those in the intensive care unit, there are new technologies that allow for bridging to transplant in candidates who meet certain criteria. Newer methods include safer extracorporeal membrane oxygenation (ECMO) systems, some of which can keep the patient ambulatory during the wait list period. One of these includes a lung assist device, which uses a membrane oxygenator, while the candidate's own heart provides all the circulation.

This is revolutionary because of its portability, allowing patients to continue to rehabilitate up to lung transplant. We work closely with Stanford’s Center for Advanced Lung Therapies team to ensure each patient's bridging approach is optimized and individualized.⁷

Physiotherapy and rehab are of the utmost importance during this time, since stronger candidates tend to have better outcomes after lung transplant. We support our patients awaiting lung transplant by having them engage in a physiotherapy program, which they seem to look forward to. Waiting for an offer is the hardest part for many of our families, many of whom have to relocate due to distance.

Our multidisciplinary team does an excellent job at supporting this relocation. We meet with our listed patients and families regularly, and offer education for the entire family during this time to learn about the "ins" and "outs" of lung transplantation.

References:

1. Frequently asked questions. Stanford Medicine Children’s Health. Accessed August 5, 2024. https://www.stanfordchildrens.org/en/services/heart-transplant/faq.html

2. Dipchand AI, Laks JA. Pediatric heart transplantation: long-term outcomes. Indian J Thorac Cardiovasc Surg. 2020 Aug;36(Suppl 2):175-189. doi: 10.1007/s12055-019-00820-3. Epub 2019 May 29. PMID: 33061202; PMCID: PMC7538525.

3. Digitale, E. Matching kids to right-sized hearts: New method shortens transplant waits. SCOPE Beyond the Headlines. Stanford Medicine. Accessed August 5, 2024. https://scopeblog.stanford.edu/2018/11/05/matching-kids-to-right-sized-hearts-new-method-shortens-transplant-waits/

4. Heart transplant. Stanford Medicine Children’s Health. Accessed August 5, 2024. https://www.stanfordchildrens.org/en/services/heart-transplant/heart-transplant.html

5. Pediatric heart transplantation: practice essentials, background, indications. Published online June 30, 2022. Accessed August 5, 2024. https://emedicine.medscape.com/article/1011927-overview?form=fpf

6. Transplant outcomes report 2021-2022. Stanford Medicine Children’s Health. issuu. May 3, 2022. Accessed August 5, 2024. https://issuu.com/stanfordchildrens/docs/transplant-outcomes-report-2021-2022

7. Conditions and treatments. Stanford Medicine Children’s Health. Accessed August 5, 2024. https://www.stanfordchildrens.org/en/services/ceal/conditions.html