Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle : Transplantation

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Prioritizing the Sickest Among the Sickest: A Matter of Tact and Moderation, but the Game Is Worth the Candle

Lescroart, Mickaël MD1; Coutance, Guillaume MD, PhD1,2

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Transplantation ():10.1097/TP.0000000000004519, January 19, 2023. | DOI: 10.1097/TP.0000000000004519
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In the context of donor organ shortage, national allocation agencies must undertake the difficult task of optimizing the allocation of this scarce resource. In most countries, the allocation of cardiac allografts is based on a clinical stratification of the risk of poor pretransplant outcomes, as assessed by the clinical condition and treatments received by the patient or by an individual score reflecting their intrinsic severity.1 Although the answers to this important clinical issue vary across the world, the idea remains the same: prioritizing the sickest patients to improve waitlist outcomes. Although 1-y posttransplant mortality has always been considered the gold-standard metric to evaluate the success of a heart transplant (HTx) program, a real move toward integrating the risk of death on the waitlist into the equation is ongoing.2 In this context, the transplant benefit, an alternative metric considering the risk of death both while on the waitlist and after HTx, has emerged. Importantly, several reports suggest that the higher the severity of transplant candidates, the higher the transplant benefit, thus supporting the concept of prioritizing the sickest patients.3

In the current issue of the journal, Agdamag et al4 analyzed in depth the impact of the implementation of the US 2018 allocation scheme in the high-risk subgroup of simultaneous heart-kidney (SHK) recipients who were on temporary mechanical circulatory support (tMCS) at transplant. In their article, the authors demonstrated a dramatic increase in the number of SHKs over the years, particularly for candidates on tMCS. Because of the high-priority status given to tMCS, the new scheme was associated with reduced waiting time and waitlist mortality for SHK candidates on tMCS. Posttransplant survival was comparable before and after the allocation change and did not significantly differ from that of SHK recipients without tMCS. These results support the concept of prioritizing high-risk HTx candidates to reduce waitlist mortality. Nevertheless, they should be interpreted in the context of profound changes in medical practice induced by the allocation scheme update that may have decreased, at the population level, the intrinsic severity of SHK candidates on tMCS.

First, the dramatic increase in the number of SHKs in the United States reflects a progressive move toward broader indications of SHK.5 The consequence is the transplantation of less severe patients with better kidney function. In the current study, the median estimated glomerular filtration rate (eGFR) at transplant was as high as 41.6 mL/min in the postallocation group transplanted on tMCS compared with 30.1 mL/min in the preallocation group at the population level. Although the indication of SHK relies on a multiparametric assessment,5 this level of eGFR raises questions about the indication of SHK. The improvement in eGFR on tMCS likely reflects the reversibility of the cardiorenal syndrome in a more favorable pressure/output environment, and the decision to indicate SHK may have been different in other medical settings. The absence of clear guidelines induces a large variability of practice across centers. However, although SHK was associated with increased survival in dialysis-dependent patients, that was not the case for nondialysis-dependent patients.6 In the context of the increasing number of SHKs, the safety net policy is urgently needed to avoid unnecessary kidney transplantation.

Second, whereas its hemodynamic impact is minimal and it has not been shown to provide any survival benefit in cardiogenic shock, the intra-aortic balloon pump (IABP) has been given a high-priority status in the new scheme. On reflection, the proportion of patients transplanted with IABP dramatically increased from 9% to 33%. IABP may represent a prototypal candidate for gaming the waitlist because the benefits of prioritization clearly outweigh the risks.7 The allocation-induced changes in medical practice may have disconnected the IABP indications from the intrinsic severity of transplant candidates. Importantly, the favorable posttransplant outcomes reported here were driven by the subgroup of patients on IABP, who experienced the same posttransplant survival as non-tMCS SHK recipients. On the contrary, recipients on extracorporeal membrane oxygenators (ECMOs) or Impella had a risk of death at 1 y, approximately twice as high as that of the IABP group (≃10% versus 20%). Although not statistically significant because of a lack of power, this difference is clinically relevant and should be considered when exporting these results to other countries where only invasive tMCS (ECMO, Impella) is considered in the allocation scheme.1

The prioritization of the most severe HTx candidates following the US scheme update has been shown to be efficient, not only by decreasing waitlist mortality but also by contributing to improving posttransplant outcomes in high-risk subgroups.8 However, this prioritization may require to be counterbalanced by considering the risk of death after HTx to avoid futile transplantations. In the United States, the high scrutiny of national agencies has always contributed to maintaining excellent posttransplant results, but the recent scheme changes have increased the number of high-risk HTx’s. The introduction of a “high emergency” status to patients on ECMO in France in 2004 was associated with an unacceptable increase in posttransplant mortality, leading to the limitation of emergency HTx indications. The current French allocation scheme includes an individual risk stratification of the risk of early death to avoid futile transplantations.1 Although the initial concerns of increased posttransplant mortality following the US scheme update have been removed at the population level,9 subgroups of high-risk patients have not yet been studied in depth. The reassuring outcomes presented by the authors should not overshadow the fact that all types of tMCS were not equivalent in terms of posttransplant outcomes.4 That being said, assuming higher posttransplant mortality in high-risk candidates with an expected very-high transplant benefit should no longer be considered taboo. We strongly believe that the game is worth the candle, particularly for candidates on ECMO support.10

Prioritizing the most severe HTx candidates is a clinically relevant evolution of allocation schemes supported by the consideration of the complete picture of transplantation, including not only posttransplant but also pretransplant outcomes, as assessed by the transplant benefit.

REFERENCES

1. Dorent R, Jasseron C, Audry B, et al. New French heart allocation system: comparison with Eurotransplant and US allocation systems. Am J Transplant. 2020;20:1236–1243.
2. Bakhtiyar SS, Godfrey EL, Ahmed S, et al. Survival on the heart transplant waiting list. JAMA Cardio. 2020;5:1227–1235.
3. Parker WF, Anderson AS, Gibbons RD, et al. Association of transplant center with survival benefit among adults undergoing heart transplant in the United States. JAMA. 2019;322:1789–1798.
4. Agdamag AC, Riad S, Maharaj V, et al. Temporary mechanical circulatory support use and clinical outcomes of simultaneous heart/kidney transplant recipients in the pre- and post-heart allocation policy change eras. Transplantation. doi: 10.1097/TP.0000000000004518.
5. Kobashigawa J, Dadhania DM, Farr M, et al. Consensus conference on heart-kidney transplantation. Am J Transplant. 2021;21:2459–2467.
6. Shaw BI, Samoylova ML, Sanoff S, et al. Need for improvements in simultaneous heart kidney allocation: the limitation of pretransplant glomerular filtration rate. Am J Transplant. 2021;21:2468–2478.
7. Lebreton G, Coutance G, Bouglé A, et al. Changes in heart transplant allocation policy: “unintended” consequences but maybe not so “unexpected….”. ASAIO J. 2021;67:e69–e70.
8. Gonzalez MH, Acharya D, Lee S, et al. Improved survival after heart transplantation in patients bridged with extracorporeal membrane oxygenation in the new allocation system. J Heart Lung Tranplant. 2021;40:149–157.
9. Parker WF, Churpek MM, Anderson AS. Is it too early to investigate survival outcomes of the new US heart allocation system? J Heart Lung Transplant. 2020;39:726.
10. Coutance G, Jacob N, Demondion P, et al. Favorable outcomes of a direct heart transplantation strategy in selected patients on extracorporeal membrane oxygenation support. Crit Care Med. 2020;48:498–506.
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