Optimizing Heart Transplant: Vanderbilt’s Novel Storage Method
Avery Fortier | March 5th, 2024
Organ transplant is often the only option for patients in the end stages of heart disease. However, it remains an imperfect solution: Buchan et al. found that 5-10% of patients experience severe primary graft dysfunction, characterized by the organ failing within 24 hours of transplant without alternative cause [1]. Even if the transplant is successful, Grady et al. saw that many patients remain hospitalized for weeks, posing a burden for them and their families [2].
One route to improving transplant outcomes lies in optimizing organ storage methods. Transplant organs must be brought from donor to recipient, at times requiring transport across thousands of miles. These travel hours are harmful. Once an organ is recovered, it is no longer receiving circulating blood, and “ischemic time” begins – time without oxygen, and therefore, with continual injury on a cellular level [3]. This degradation decreases the organ’s functionality and can ultimately harm recipient outcomes [3]. Traditionally, transplant organs are stored on ice, which slows metabolism to decrease ischemic injury. However, hypothermic temperatures also slow cell repair mechanisms and increase subsequent injury when the organ is re-introduced to oxygen [4].
Considering the balance that must be struck, a recent study found that 10˚C storage of donor lungs was more effective in maintaining their viability [5]. Vanderbilt’s own Dr. Matthew Bacchetta saw an opportunity to expand this method to the heart and the liver, starting in his translational laboratory. Dr. Bacchetta has a unique ability to approach challenges from different angles. This insight visibly extends to his contributions as a scientist, solving difficult problems in organ failure that are firmly connected to urgent patient needs. Specifically, Dr. Bacchetta leads the development of bio-engineered platforms, including a method for organ repair outside of the body and a portable support device for pulmonary hypertension patients. Though he is a cardiothoracic surgeon by trade, his extensive research spans livers, hearts, lungs, and soon even kidneys. It is no surprise that new findings from his laboratory are shaping clinical advancement at Vanderbilt.
Dr. Timothy Harris, MD, the postdoctoral fellow coordinating their cardiac storage project, offered insight into their progress: “We’re noticing that we are able to re-animate hearts not only after storage at 10˚C, but after prolonged ischemic injury. Our aim is to provide a means to increase the permissible ischemic time, which is considered 4 hours, to increase the donor pool of available organs.” Dr. Kaitlyn Tracy, MD, pursuing a parallel project in the liver, similarly observed improved organ function after storage at 10°C compared to conventional storage on ice in the group’s large-animal model. She shared: “We have observed a difference between the quality of the bile duct at 10°C compared to ice, which may be particularly relevant to expanding use of organs traditionally limited by biliary complications.” Such compelling results from the laboratory inspired cardiac surgeons at Vanderbilt Medical Center to implement 10˚C storage clinically. Dr. John Trahanas, MD, cardiac surgeon facilitating the clinical analysis, credits this leap as the “brainchild” of Dr. Ashish Shah, MD, Vanderbilt’s Director of Heart Transplant Surgery.
Dr. Shah’s project took off running. Since July 2023, the majority of heart transplant patients at Vanderbilt have received a heart that was stored at 10˚C. Globally, this is the first clinical instance of static 10˚C donor heart storage, and to date, Vanderbilt is the only institution offering such a method. So far, patients appear to have benefitted. Dr. Trahanas has observed a qualitative difference, sharing that “anecdotally, 10˚C has worked beautifully… the hearts came back much more vigorously, and the data shows no harm.” In fact, his recently accepted abstract for the 2024 American Association for Thoracic Surgery showed that 10˚C patients had a significantly shorter length of hospital stay post-transplant as compared to previous 0˚C patients [6]. Though the team is still compiling data from a larger sample size, initial results are promising.
The new method has also enabled Vanderbilt’s surgeons to utilize hearts that may otherwise have been declined for transplant. Typically, hearts on ice are not to be stored for longer than 4 hours; otherwise, they incur too great an ischemic injury [7]. This limits acceptable transport distance and the number of organs deemed viable for transplant, which is particularly important given extensive waiting lists. With 10˚C storage, though, Dr. Trahanas says Vanderbilt’s team has seen “repeated success” after 6 hours. One heart was even transplanted after 9 hours of storage, though the surgeon notes that he “still wouldn’t say we’re comfortable going to 9 hours.”
If the 10˚C method improves storage time but does not perfect it, then what could be the next step? The 10˚C strategy involves maintaining the isolated heart in a cooler, known as “static” storage, while other strategies actively provide the organ with support during storage. For example, the Organ Care System developed by the company TransMedics circulates blood through an organ while maintaining it at normal physiologic temperatures [8]. Though potentially effective, this method costs hundreds of thousands of dollars and is out of reach for many [9]. The 10˚C cooler utilized at Vanderbilt is reusable and does not require separately hiring storage personnel, creating an opportunity for widespread implementation and improved patient outcomes.
Mitigating organ injury is only the beginning. Dr. Trahanas imagines further progress along another plane: “We are discovering better ways to transport organs so that less damage is done. But where we really want to get is: how can we not only prevent damage, but promote repair? I envision 10, 20 years in the future, we may have a system that not only preserves organs but also allows for more intervention.” Certainly, researchers in the field will continue working towards such aspirations. In the meantime, Vanderbilt’s cardiac transplant team continues to lead innovation globally, thanks to the ambitious physician-scientists at its helm.
Disclosure: Author AKF is involved with the research laboratory described in this article.
References
[1] Buchan TA, Moayedi Y, Truby LK, Guyatt G, Posada JD, Ross HJ, Khush KK, Alba AC, Foroutan F. (2021). Incidence and impact of primary graft dysfunction in adult heart transplant recipients: A systematic review and meta-analysis. The Journal of Heart and Lung Transplantation, 40(7), 642–651. https://doi.org/10.1016/j.healun.2021.03.015
[2] Grady KL, Haller KB, Grusk BB, Corliss JW. Predictors of hospital length of stay after heart transplantation. J Heart Transplant. 1990 Mar-Apr;9(2):92-6. PMID: 2181091.
[3] Hess NR, Ziegler LA, Kaczorowski DJ. Heart Donation and Preservation: Historical Perspectives, Current Technologies, and Future Directions. J Clin Med. 2022 Sep 28;11(19):5762. doi: 10.3390/jcm11195762. PMID: 36233630; PMCID: PMC9571059.
[4] Minor T, von Horn C. Rewarming Injury after Cold Preservation. Int J Mol Sci. 2019 Apr 26;20(9):2059. doi: 10.3390/ijms20092059. PMID: 31027332; PMCID: PMC6539208.
[5] Ali A, Wang A, Ribeiro RVP, Beroncal EL, Baciu C, Galasso M, Gomes B, Mariscal A, Hough O, Brambate E, Abdelnour-Berchtold E, Michaelsen V, Zhang Y, Gazzalle A, Fan E, Brochard L, Yeung J, Waddell T, Liu M, Andreazza AC, Keshavjee S, Cypel M. (2021). Static lung storage at 10°C maintains mitochondrial health and preserves donor organ function. Science Translational Medicine, 13(611). https://doi.org/10.1126/scitranslmed.abf7601
[6] Trahanas J, Pasrija C, DeVries S, Bommareddi S, Harris TR, Dreher A, Petrovic M, Debose- Scarlett A, Siddiqi H, Fortier AK, Tracy KM, Keck C, Cortelli M, Scholl S, Bacchetta M, Shah A. Out of the Ice Age: Preservation of Cardiac Allografts with a Reusable 10°C Cooler. Accepted abstract at the 2024 American Association for Thoracic Surgery Annual Meeting.
[7] Al-Adhami A, Singh SSA, Sudeep DD, Singh R, Panjrath G, Shah A, Dalzell JR, Schroder J, Al-Attar N. Primary Graft Dysfunction after Heart Transplantation – Unravelling the Enigma. Current Problems in Cardiology. Volume 47, Issue 8, 2022, 100941, ISSN 0146-2806. https://doi.org/10.1016/j.cpcardiol.2021.100941.
[8] Stamp NL, Shah A, Vincent V, Wright B, Wood C, Pavey W, Cokis C, Chih S, Dembo L, Larbalestier R. Successful Heart Transplant after Ten Hours Out-of-body Time using the TransMedics Organ Care System. Heart, Lung and Circulation. Volume 24, Issue 6, 2015, Pages 611-613, ISSN 1443-9506, https://doi.org/10.1016/j.hlc.2015.01.005.
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