Pediatric Heart Transplants: rethinking the waitlist, by Power, Sweat...Almond et al.

 Here's a paper on the design of the waitlist for pediatric heart transplants.  It's accompanied by an editorial in the journal, and a discussion at Stanford Medical School.

Here's the article

Alyssa Power, MD,a,* Kurt R. Sweat, PHD,b,* Alvin Roth, PHD,b John C. Dykes, MD,a Beth Kaufman, MD,a Michael Ma, MD,c Sharon Chen, MD, MPH,a Seth A. Hollander, MD,a Elizabeth Profita, MD,a David N. Rosenthal, MD,aLynsey Barkoff, NP,a Chiu-Yu Chen, MD, PHD,a Ryan R. Davies, MD,d Christopher S. Almond, MD, MPH, Contemporary Pediatric Heart Transplant Waitlist Mortality  Journal of the American College of Cardiology, Volume 84, Issue 7, 13 August 2024, Pages 620-632

ABSTRACT

BACKGROUND In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy.

OBJECTIVES This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks.

METHODS Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality.

RESULTS Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order.

CONCLUSIONS The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed. 

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Here's the accompanying editorial in JACC

Getting to Transplant Should Not Be the Goal, by David L.S. Morales MD and Benjamin S. Mantell MD, PhD

And here's the Stanford article:

Heart transplant list doesn’t rank kids by medical need, Stanford Medicine-led study finds. More babies and children survive the wait for a heart transplant than in the past, but improvements are due to better medical care, not changes to wait-list rules, a new study finds. August 5, 2024 - By Erin Digitale

“The current system is not doing a good job of capturing medical urgency, which is one of its explicit goals,” said the study’s co-lead author, economist Kurt Sweat, PhD, who conducted the research as a graduate student in economics at Stanford University. "

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Kurt's job market paper was on heart transplants for adult patients.

Friday, April 26, 2024

Kurt Sweat defends his dissertation

Update: here's another commentary on the article:

Fewer Kids Now Die While Awaiting Heart Transplant, but There’s Room for Improvement Twenty years of data show mortality has dropped. Still, with one in eight children dying on the wait list, more needs to be done.  By Yael L. Maxwell

Kurt Sweat defends his dissertation

Kurt Sweat defended his dissertation this week. As you can see in the picture below, we celebrated with the traditional toast, but instead of champagne we're drinking  In-N-Out milk shakes.

 

He and I are flanked by the other members of his committee: Itai Ashlagi, Paolo Somaini, Frank Wolak and Han Hong.  He was also advised by Dr. Chris Almond.

  His job market paper, and the other papers in his dissertation, all concern heart transplants.

Endogenous Priority in Centralized Matching Markets: The Design of the Heart Transplant Waitlist (Job Market Paper) 

[Link to current draft]

"Centralized matching markets that prioritize specific participants to achieve certain policy goals are common in practice, but priority is often assigned using endogenous characteristics of participants. In the heart transplant waitlist in the United States, the treatment that a patient receives is used to assign waitlist priority. Policymakers recently changed the prioritization in an attempt to reduce waitlist mortality by assigning higher priority to patients receiving specific treatments previously associated with high waitlist mortality. First, I document a significant response to waitlist incentives in treatments given and transplants that take place. Then, I develop and estimate a structural model of treatment and transplant choices to evaluate the effect of the policy change on patients' outcomes and doctors' decisions. I find three main results from my model. First, there is little change in aggregate survival, and the effect of the change has been mainly redistributive. Second, the change has effectively targeted patients with lower untransplanted survival, with these patients receiving higher expected survival under the current design. Third, the effect on survival is largely driven by changes in the decision to accept/decline offers for transplants rather than directly due to a change in treatment decisions. The policy implications suggest that future designs of the waitlist should disincentivize declining offers for transplants."

Welcome to the club, Kurt.

Global pacemaker retransplantation

 There are innovative approaches to global health care.  Here is one, that involves reusing pacemakers recovered from deceased donors and refurbished for use in countries where pacemakers are too expensive for wide use.  Unlike some of what we encounter in kidney transplants across borders, the legal bans that have to be overcome may not come from the war against the poor.  A careful clinical trial is underway. There is also an unregulated black market...

Here's the encouraging story from Helio.com:

After death, a new life for refurbished pacemakers in low-, middle-income countries, February 23, 2024

"Lack of access to pacemakers is a major challenge to the provision of CV health care in low- and middle-income countries; however, postmortem pacemaker utilization could offer an opportunity to deliver this needed care, according to Thomas Crawford, MD, an electrophysiologist and associate professor of internal medicine at University of Michigan Health and the medical director of My Heart Your Heart, a cardiac pacemaker reuse initiative at the University of Michigan Cardiovascular Center

...

"Crawford: The need is great. Each year, somewhere between 1 million and 2 million people worldwide die due to a lack of access to pacemakers and defibrillators. There is literature reflecting this. When you query pacemaker implantation data for the United States, it is roughly 800 pacemakers per 1 million population. When you query countries like, for example, Nigeria, it says four pacemakers per million. Quite a difference.

"Per capita gross domestic product is such that, in many countries, a pacemaker costs more than a person’s annual income.

...

"Healio: What are the regulations around using a refurbished pacemaker?

"Crawford: Pacemaker reuse is illegal in all jurisdictions. The FDA states that pacemaker reuse is an “objectionable practice.” We know we can do it, but we need to develop partnerships with other entities to give us credibility. One of those methods to do this is by engaging the government. FDA issues export permits for this type of activity. We created a protocol where we reprocess the device, working with Northeast Scientific, which provides the pacemaker cleaning and sterilization. We have received permission from the FDA to export them. We have to put a sticker on them saying “not for use in the United States.” We are doing this in countries in which governments will allow it. One of the limitations is needing a government letter from each of the recipient countries. We have about 12 countries now, and the collection of countries we are working with is purely accidental. It is not a normal methodological process. A lot of it is through contact with individuals and opportunities that arise.

...

"Healio: You are leading a randomized controlled trial called Project My Heart Your Heart: Pacemaker Reuse. What is the study design, and what do you and your colleagues hope to learn?

"Crawford: The objective of the clinical trial is to determine if pacemaker reutilization can be shown to be a safe means of delivering pacemakers to patients in low- and middle-income countries without resources. The target enrollment is 270 patients, all from outside the United States, who each have a class I indication for pacing and who attest that they do not have the ability to purchase a device on their own. They must consent to be randomly assigned to receive either a brand-new pacemaker, which we purchase, or a reprocessed pacemaker, for which we provide the leads and accessories. Donated devices are inspected according to specific protocols that evaluate physical and electrical suitability, including battery longevity, for future use. Devices deemed to be acceptable are shipped to a third-party vendor, Northeast Scientific, for disassembly, cleaning and re-sterilization. There will be about 130 participants in each arm. We will follow those patients and report any adverse events. The countries that have contributed patients include Kenya, Nigeria, Paraguay, Sierra Leone and Venezuela. We hope to soon begin enrolling patients in Mexico and Mozambique.

"I have had clinicians outside the U.S. who tell me they removed a pacemaker device, cleaned it, reprocessed it and then implanted it in someone else — but the government does not know about it. This practice does happen and it is not regulated in any way; patients and physicians know about it and keep it quiet. The difference with what we are doing and these other efforts is we bring it to a much higher level, because that is what the FDA requires. "

Cross-border transplantation between China and Hong Kong

 Here are two recent reports of the first cross-border transplant between China proper and Hong Kong.

From the Global Times:

First organ donation between mainland and HK saves 4-month old baby By Wan Hengyi

"A medical team of the Hong Kong Children's Hospital successfully transplanted a heart donated from the mainland to a 4-month-old baby in Hong Kong Special Administrative Region on Saturday, achieving a historic breakthrough in the sharing of human organs for emergency medical assistance between the two places for the first time.

"The donated heart, which had been matched by China's Organ Transplant Response System (COTRS) through several rounds and had no suitable recipient, was successfully matched in Hong Kong through the joint efforts between 24 departments and 65 medical experts in the mainland and Hong Kong.

"Cleo Lai Tsz-hei, the recipient of the transplant from Hong Kong, was diagnosed with heart failure 41 days after birth and was in critical condition. Receiving a heart transplant was the only way to keep her alive, according to media reports.

"Moreover, the acceptable heart donation for Cleo requires a donor weighing between 4.5 kilograms and 13 kilograms, and the chances of a suitable donor appearing in Hong Kong are slim to none.

...

"COTRS initiated the allocation of a donated heart of a child with brain death due to brain trauma in the mainland on December 15. As a very low-weight donor, no suitable recipients were found after multiple rounds of automatic matching with 1,153 patients on a national waiting list for heart transplants in the COTRS system. In the end, the medical assistance human organ-sharing plan between the Chinese mainland and Hong Kong was launched.

"Some netizens from the Chinese mainland asked why a baby from Hong Kong who has not lined up in the COTRS system can get a donated heart when there is a huge shortage of donated organs in the mainland.

"In response, the organ coordinator told the Global Times that the requirements for organ donation are extremely high, noting that all the prerequisites including the conditions of the donor and recipient, the time for the organ to be transported on the road and the preparation for surgery must reach the standards before the donation can be completed.

"The COTRS system has already gone through several rounds of matching, which is done automatically by computer without human intervention, said the organ coordinator. 

"Medical teams from both jurisdictions, as well as customs officers in Shenzhen and Hong Kong, carried out emergency drills to reduce the customs clearance time to eight minutes, racing against the four-hour limit for preserving donated hearts, said Wang Haibo, head of the COTRS for medical assistance contact between the mainland and Hong Kong.

"The collection of donated hearts began at 17:00 pm on Friday, and the hearts were delivered to the Hong Kong Children's Hospital at 20:00 pm under the escort of Hong Kong police on the same day. At 1:00 am on Saturday, Cleo's heart transplant operation in Hong Kong was successfully completed, and she has not required extracorporeal circulation support at present."

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And from the South China Morning Post:

Hong Kong could greatly benefit from cross-border organ imports mechanism, doctors say after local baby receives heart from mainland China  by Jess Ma

"Hong Kong could greatly benefit from cross-border organ donations given the city’s persistently low rate of residents willing to sign up to become donors, doctors have said after a local baby girl received a heart from mainland China in the first arrangement of its kind.

...

"Hong Kong’s organ donation rate is currently among the lowest in the world, at 3.9 donors per a million people in 2019, down from 5.8 in 2015, according to research conducted by the Legislative Council.

...

"Medical lawmaker David Lam Tzit-yuen and election committee legislators Elizabeth Quat Pei-fan and Rebecca Chan Hoi-yan urged the government to begin discussions on legal frameworks and procedures for cross-border transplants, saying that the mainland had a robust donation system and that organ sharing between the city and the mainland was not unusual.

"Human rights groups and lawyers have accused the mainland of forcibly harvesting organs from executed prisoners, a practice that then health minister Huang Jiefu publicly acknowledged in 2005. The government announced in 2015 that organ donations would only come from “voluntary civilian organ donors,” but critics argued prisoners were not excluded under the system.

But Chan argued that the mainland’s efforts to improve the transparency and ethics of its organ donation system over the past decade should be acknowledged.

“I disagree that this would be the beginning of a slippery slope. The transparency of the mainland’s organ donation system has been a lot clearer and stricter,” Chan said, adding that a lot of work had been done across the border to prohibit organ harvesting and trading."

First pig-to-human heart transplant (and some background on the trials with non human primates)

 Xenotransplants, of pig organs into humans, may be closer than I thought. A dramatic step was taken last Friday when a pig heart was successfully transplanted into a man who was still being kept alive by the heart yesterday when the NY Times reported it.  Following the news story, I'll link to a recent summary of the increasing success of transplanting pig hearts into non-human primates.  In the near term, the idea is that a pig heart might keep a patient alive until a human organ becomes available.

Here's the NY Times story:

In a First, Man Receives a Heart From a Genetically Altered Pig. The breakthrough may lead one day to new supplies of animal organs for transplant into human patients.  By Roni Caryn Rabin

"A 57-year-old man with life-threatening heart disease has received a heart from a genetically modified pig, a groundbreaking procedure that offers hope to hundreds of thousands of patients with failing organs.

"It is the first successful transplant of a pig’s heart into a human being. The eight-hour operation took place in Baltimore on Friday, and the patient, David Bennett Sr. of Maryland, was doing well on Monday, according to surgeons at the University of Maryland Medical Center.

“It creates the pulse, it creates the pressure, it is his heart,” said Dr. Bartley Griffith, the director of the cardiac transplant program at the medical center, who performed the operation.

“It’s working and it looks normal. We are thrilled, but we don’t know what tomorrow will bring us. This has never been done before.”

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And here's a just-published paper that gives some background:

Shu, S., Ren, J. & Song, J. Cardiac xenotransplantation: a promising way to treat advanced heart failure. Heart Fail Rev 27, 71–91 (2022). https://doi.org/10.1007/s10741-020-09989-x

Abstract: Cardiac xenotransplantation (CXTx) might be a promising approach to bridge the gap between the supply and demand of a donor heart. The survival of cardiac xenograft has been significantly extended in pig-to-nonhuman primate (NHP) CXTx, with records of 195 days and 945 days for orthotropic and heterotopic CXTx, respectively. ...

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Earlier:

Sunday, December 5, 2021

Organ shortages for transplantation: Pig kidneys won't be transplanted into people soon

Gaming organ allocation: Heart failure treatment responds to changes in the priority rules for heart transplants

Recent changes in the allocation of deceased donor hearts for transplantation have focused on what kinds of mechanical interventions a patient has.  And as choice of alternative interventions has changed priorities for donation, cardiologists have responded by changing the interventions they choose.

Several articles in JAMA Cardiology speak to this and related matters, and here's an editorial describing the issue:

Anticipating a New Era in Heart Transplantation
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
JAMA Cardiol. Published online April 15, 2020. doi:10.1001/jamacardio.2020.0611

The first paragraph gives this capsule history:

"The 50th anniversary of heart transplantation was celebrated in 2018. During those 50 years, heart transplantation as treatment of advanced heart failure evolved from a heroic intervention with uncertain outcomes to a guideline-directed treatment appropriate for selected patients to restore quality of life and to improve survival. Today, 1-year survival after heart transplant is nearly 90%, and the conditional half-life after heart transplant is now 13 years.1 Those robust outcomes reflect myriad breakthrough initiatives, including the definition of brain death; introduction of routine endomyocardial biopsy for rejection surveillance, development of potent immunosuppressive therapies, particularly those inhibiting calcineurin and in turn interleukin 2 production, and advances in therapies to support the failing ventricle, especially mechanical circulatory support devices. For more than 2 decades, the number of heart transplants performed in the United States has been approximately 2000 per year and, having recently increased, was 3551 in 2019.2 Taken together, the observed early and late benefits of heart transplant punctuate an incredible journey from heretical concept to clinical standard of care. The courageous pioneer physicians and especially the early patients who faced overwhelming risks are revered for establishing a foundational pillar in the care of patients with advanced heart failure. It is reasonable to assert that after 50 years, heart transplantation is a well-established success poised for the next era."

They then turn their attention to ways in which cardiologists have responded to changes in the deceased donor allocation system:

"Three articles in this issue of JAMA Cardiology further address new challenges in the process of care improvement for heart transplantation, some of which we think may require urgent attention.

"The first of these articles, by Hanff and colleagues,7 evaluated changes in the use of mechanical circulatory support under the auspices of new organ allocation rules introduced in October 2018 by the Organ Procurement and Transplantation Network. The new system was intended to redirect available donors to those patients of greatest need. The original status IA category was partitioned into 3 categories, and the original status IB category became category 4. A patient with advanced heart failure supported with a left ventricular assist device (LVAD) without LVAD-associated complications became a status 4 candidate. A similar patient with advanced heart failure experiencing manageable LVAD-associated complications became a status 3. Status 2 now captures those patients with LVAD device malfunction who may be facing eminent demise or need for LVAD replacement, whereas status 1 captures patients with life-threatening arrhythmias or patients being supported with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Evaluating data through June 2019, Hanff and colleagues7 noted an abrupt increase in the use of VA-ECMO support that was temporally associated with implementation of the new system. Concomitantly, LVAD support for advanced heart failure in patients awaiting heart transplant abruptly decreased from 35.1% before implementation of the new rules to 24.5% after their implementation."

Finally, they also consider center variability to understand what happens to patients when a proffered heart transplant is declined:

"In another article in this issue of JAMA Cardiology, Choi et al10 evaluated data in the US National Transplant Registry between 2007 and 2017 with the intention to assess transplant center variability in donor organ acceptance. The evaluable data emanated from 93 transplant centers and encompassed 19 703 donors and 9628 candidates, with 32% of the donors accepted as first-ranked candidates. After adjustment for pertinent donor, candidate, and geographic covariates, the center variability in acceptance rates was quite remarkable at 12% to 62%. For every 10% increase in center acceptance rate, waiting-list mortality decreased by 27%. Those centers with lower acceptance rates experienced higher waiting-list mortality among candidates listed for a heart transplant..."