CS; Cold storage; DBD; DCD; Donation after brain death; Donation after circulatory determination of death; Donation after neurological death; ESMP; Ex-situ machine perfusion; Heart beating donation; In-situ perfusion; Non heart beating donation; Thoraco-abdominal nromothermic regional perfusion; taNRP; Medicine (all); General Medicine
Abstract :
[en] [en] BACKGROUND: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP.
METHOD: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival.
FINDINGS: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13).
INTERPRETATION: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use.
FUNDING: None of the authors have a financial relationship with a commercial entity that has an interest in the subject.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Louca, John; University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 0SP, UK
Öchsner, Marco; University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Rd, Cambridge CB2 0SP, UK
Shah, Ashish; Vanderbilt Heart Transplant Unit 1215, 21st Ave, Nashville, Tennessee 37232, USA
Hoffman, Jordan; Vanderbilt Heart Transplant Unit 1215, 21st Ave, Nashville, Tennessee 37232, USA
Vilchez, Francisco González; Spanish Registry on Heart Transplantation, Madrid, Spain
Garrido, Iris; Hospital Universitario Virgen de La Arrixaca, Ctra. Madrid-Cartagena, s/n, El Palmar, Murcia 30120, Spain
Royo-Villanova, Mario; Hospital Universitario Virgen de La Arrixaca, Ctra. Madrid-Cartagena, s/n, El Palmar, Murcia 30120, Spain
Domínguez-Gil, Beatriz; Organización Nacional de Trasplantes, Madrid, Spain
Smith, Deane; Department of Cardiothoracic Surgery, Langone, 1300 Franklin Avenue, Suite ML-2, Garden City, NY, USA
James, Leslie; Department of Cardiothoracic Surgery, Langone, 1300 Franklin Avenue, Suite ML-2, Garden City, NY, USA
Moazami, Nader; Department of Cardiothoracic Surgery, Langone, 1300 Franklin Avenue, Suite ML-2, Garden City, NY, USA
Rega, Filip; Departments of Cardiac Surgery and Cardiology, The University Hospital Leuven, Leuven, Belgium
Brouckaert, Janne; Departments of Cardiac Surgery and Cardiology, The University Hospital Leuven, Leuven, Belgium
Van Cleemput, Johan; Departments of Cardiac Surgery and Cardiology, The University Hospital Leuven, Leuven, Belgium
Vandendriessche, Katrien; Departments of Cardiac Surgery and Cardiology, The University Hospital Leuven, Leuven, Belgium
Tchana-Sato, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie cardio-vasculaire et thoracique
Bandiougou, Diawara; Department of Cardiovascular Surgery, CHU Liege, Liege, Belgium
Urban, Marian; Department of Cardiothoracic Surgery, University of Nebraska Medical Centre, 2410 Atherholt Road, Omaha, NE, USA
Manara, Alex; The Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, Bristol BS 10 5NB, UK
Berman, Marius; Royal Papworth Hospital Biomedical Campus, Cambridge, CB2 0AY, UK
Messer, Simon; Golden Jubilee Hospital, Agamermnon Street, Glasgow G81 4DY, UK
Large, Stephen; Royal Papworth Hospital Biomedical Campus, Cambridge, CB2 0AY, UK
Dhital, K.K., Iyer, A., Connellan, M., et al. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series. Lancet 385:9987 (2015), 2585–2591.
Kilic, A., Hickey, G., Mathier, M., et al. Outcomes of adult heart transplantation using hepatitis C–positive donors. J Am Heart Assoc, 9(2), 2020, e014495.
Messer, S.J., Axell, R.G., Colah, S., et al. Functional assessment and transplantation of the donor heart after circulatory death. J Heart Lung Transplant 35:12 (2016), 1443–1452.
Smith, F., Hogg, R., Rushton, S., Cardiothoracic Advisory Group (CTAG) Clinical Audit Group. Annual report on cardiothoracic organ transplantation for 2018/2019 (1 April 2019 – 31 March 2019). [Internet] Bristol (UK): NHSBT. August 2019 Available from: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/16795/nhsbt-annual-report-on-cardiothoracic-organ-transplantation-201819.pdf. (Accessed 10 December 2021)
UNOS. Heart transplant sets all-time record in 2021. [Internet]. USA: UNOS. 2022 Available from: https://unos.org/news/in-focus/heart-transplant-all-time-record-2021/. (Accessed 7 March 2022)
Jawitz, O.K., Raman, V., DeVore, A.D., et al. Increasing the US heart transplant donor pool with donation after circulatory death. J Thorac Cardiovasc Surg 159:5 (2020), e307–e309.
Domínguez-Gil, B., Ascher, N., Capron, A.M., et al. Expanding controlled donation after the circulatory determination of death: statement from an international collaborative. Intensive Care Med 47:3 (2021), 265–281.
Dhanani, S., Hornby, L., van Beinum, A., et al. Resumption of cardiac activity after withdrawal of life-sustaining measures. N Engl J Med 384:4 (2021), 345–352.
Ali, A.A., White, P., Xiang, B., et al. Hearts from DCD donors display acceptable biventricular function after heart transplantation in pigs. Am J Transplant 11:8 (2011), 1621–1632.
Hessheimer, A.J., Coll, E., Torres, F., et al. Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation. J Hepatol 70:4 (2019), 658–665.
Hessheimer, A.J., de la Rosa, G., Gastaca, M., et al. Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: outcomes and risk factors for graft loss. Am J Transplant 22:4 (2022), 1169–1181.
Padilla, M., Coll, E., Fernández-Pérez, C., et al. Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion. Am J Transplant 21:11 (2021), 3618–3628.
Oniscu, G.C., Mehew, J., Butler, A.J., et al. Improved organ utilization and better transplant outcomes with in situ normothermic regional perfusion in controlled donation after circulatory death. Transplantation 107 (2022), 10–97.
Nistal, J.F., Cobo, M., Larraz, E., Juárez, C., Ballesteros, M.Á., Heart transplantation from controlled donation after circulatory death using thoracoabdominal normothermic regional perfusion and cold storage. J Card Surg 36:9 (2021), 3421–3424.
Pérez Redondo, M., Alcántara Carmona, S., Villar García, S., et al. Transplantation of a heart donated after circulatory death via thoraco-abdominal normothermic regional perfusion and results from the first Spanish case. J Cardiothorac Surg 15:1 (2020), 1–6.
Messer, S., Cernic, S., Page, A., et al. A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors. J Heart Lung Transplant 39:12 (2020), 1463–1475.
Hoffman, J.R., McMaster, W.G., Rali, A.S., et al. Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion. J Heart Lung Transplant 40:11 (2021), 1408–1418.
Miñambres, E., Royo-Villanova, M., Pérez-Redondo, M., et al. Spanish experience with heart transplants from controlled donation after the circulatory determination of death using thoraco-abdominal normothermic regional perfusion and cold storage. Am J Transplant 21:4 (2021), 1597–1602.
Vandendriessche, K., Tchana-Sato, V., Ledoux, D., et al. Transplantation of donor hearts after circulatory death using normothermic regional perfusion and cold storage preservation. Eur J Cardiothorac Surg 60:4 (2021), 813–819.
Smith, D.E., Kon, Z.N., Carillo, J.A., et al. Early experience with donation after circulatory death heart transplantation using normothermic regional perfusion in the United States. J Thorac Cardiovasc Surg 164:2 (2022), 557–568.
McKinney, W., Data structures for statistical computing in python. In proceedings of the 9th python in science conference, 2010 (Vol. 445, No. 1, pp. 51-56).
Therneau, T., A package for survival analysis in R. R package version 3.4-0. 2022 https://CRAN.R-project.org/package=survival.
Davidson-Pilon, C., Lifelines: survival analysis in Python. J Open Source Software, 4(40), 2019, 1317.
Berman, M., Ali, A., Ashley, E., et al. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death?. J Heart Lung Transplant 29:9 (2010), 957–965.
Al-Adhami, A., Singh, S.S., De, S.D., et al. Primary graft dysfunction after heart transplantation–unravelling the enigma. Curr Probl Cardiol, 47, 2021, 100941.
Olkowicz, M., Ribeiro, R., Yu, F., et al. Dynamic metabolic changes during prolonged ex situ heart perfusion are associated with myocardial functional decline. Front Immunol, 13, 2022, 859506.
Ardehali, A., Esmailian, F., Deng, M., et al. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet 385:9987 (2015), 2577–2584.
Hamed, A., Tsui, S., Huber, J., Lin, R., Poggio, E.C., Ardehali, A., 19: serum lactate is a highly sensitive and specific predictor of post cardiac transplant outcomes using the organ care system. J Heart Lung Transplant, 28(2), 2009, S71.
Cernic, S., Page, A., Messer, S., et al. Lactate during ex-situ heart perfusion does not predict the requirement for mechanical circulatory support following donation after circulatory death (DCD) heart transplants. J Heart Lung Transplant 41:9 (2022), 1294–1302.
Gomes, B., Ribeiro, R., Alvarez, J., et al. Normothermic regional perfusion (NRP) during heart DCD recovery: is lung quality impacted? A pre-clinical study. J Heart Lung Transplant 39:4 (2020), S353–S354.
Manara, A., Shemie, S.D., Large, S., et al. Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: a United Kingdom and Canadian proposal. Am J Transplant 20:8 (2020), 2017–2025.
