Consensus statement on heart xenotransplantation in children: Toward clinical translation

Konstantinov, Igor E.; Cooper, David K. C.; Adachi, Iki; Bacha, Emile A.; Bleiweis, Mark S.; Chinnock, Richard; Cleveland, David C.; Cowan, Peter J.; Fynn-Thompson, F.; Morales, David; Mohiuddin, Muhammad M.; Reichart, B.; Rothblatt, Martine; Roy, Nathalie; Turek, Joseph W.; Urschel, Simon; West, Lori J.; Wolf, Eckhard

doi:10.1016/j.jtcvs.2022.09.001

Cited by 9 publications

(4 citation statements)

References 87 publications

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“…However, these children are often referred for paediatric heart transplantation after multiple prior operations. 36 The reality of multiple blood transfusions and incorporation of antigenic reconstructive materials can frequently lead to sensitisation. While extensive studies have examined desensitisation in adult patients, the challenges of small numbers and inter-patient variability require costly multi-centre studies to make meaningful progress in minimising sensitisation and its sequelae.…”

Section: Section 3 the Challenge For Paediatric Heart Transplantation...mentioning

confidence: 99%

Paediatric heart transplantation: life-saving but not yet a cure

Boucek,

Chinnock,

Scheel

et al. 2024

Cardiol Young

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In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic “advantages,” including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients’ post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding “incentives” such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.

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Section: Section 3 the Challenge For Paediatric Heart Transplantation...mentioning

confidence: 99%

Paediatric heart transplantation: life-saving but not yet a cure

Boucek,

Chinnock,

Scheel

et al. 2024

Cardiol Young

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“…Much remains to be discussed including ethical and regulatory issues. 101 The evolution of pediatric heart transplantation over the last five decades has allowed us to take better care of this very diverse group of patients that reach end-stage heart failure during childhood.…”

Section: Xenotransplantationmentioning

confidence: 99%

“…The potential use as a bridging strategy, especially given the lack of mechanical support options for this population is an intriguing concept. Much remains to be discussed including ethical and regulatory issues 101 …”

Section: Unmet Challenges and Future Directionsmentioning

confidence: 99%

Pediatric heart transplantation: Looking forward after five decades of learning

Dipchand,

Webber

2023

Pediatric Transplantation

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Heart transplantation has become the standard of care for pediatric patients with end‐stage heart disease throughout the world. Since the first transplant was performed in 1967, the number of transplants has grown dramatically with 13 449 pediatric heart transplants being reported to The International Society of Heart and Lung Transplant (ISHLT) between January 1992 and June 30, 2018. Outcomes have consistently improved over the last few decades, specifically short‐term outcomes. Most recent survival data demonstrate that recipients who survive to 1‐year post‐transplant have excellent long‐term survival with more than 60% of those who were transplanted as infants being alive 25 years later. Nonetheless, the rates of graft loss beyond the first year have remained relatively constant over time; driven primarily by our poor understanding and lack of treatments for chronic allograft vasculopathy (CAV). Acute rejection, CAV, graft failure, and infection continue to be the major causes of death within the first 5 years post‐transplant. In addition, renal dysfunction, malignancy, and the need for re‐transplantation remain as significant issues that require close follow‐up. Looking forward, key challenges include improving donor utilization rates (including donation after cardiac death (DCD) and the use of ex vivo perfusion devices), the development of non‐invasive biomarkers for rejection, efforts to mitigate the long‐term effects of immunosuppression, and prevention of CAV. It is not possible to cover the entire evolution of pediatric heart transplantation over the last five decades, but in this review, we hope to touch on key observations, lessons learned, and practice changes that have advanced the field, as well as glance ahead to the next decade.

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“…Many of these issues are addressed in adult xenotransplant. Yet, the pediatric transplant community has only just begun these discussions …”

mentioning

confidence: 99%