Coronary Artery Disease in Hearts Donated for Transplantation
NCT Number: NCT06528834
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Heart Failure
Sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 10
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-09
Completion Date: 2027-09
Locations: Royal Brompton and Harefield Hospital NHS Trust, London, Middlesex, UB9 6JH, United Kingdom

Summary:
In spite of recent initiatives, in particular, the introduction into clinical practice of donation after circulatory death (DCD), there is a persistent mismatch between the demand for donor hearts for transplantation and their supply \[1\]. This mismatch is accentuated by the relatively low rate of utilisation of hearts donated for transplantation, i.e. the proportion of organs transplanted divided by the number of donations. In the UK between 2016 and 2018 this ranged from 25.7 to 30.8% \[2\]. For the year 2022/23, a total of 207 heart transplants (DBD and DCD) were performed out of 1429 donations giving a utilisation rate of 14.5% \[3\].

The rigorous assessment of donor heart quality prior to, and during donor organ retrieval, which is a crucial determinant of recipient outcome, accounts for the low utilisation rate. In both the donation after brain(stem) death (DBD) and DCD settings, pre-retrieval echocardiography is the principal method of anatomical and functional assessment. In the DCD setting, where normothermic organ perfusion (either in situ or ex situ) is mandatory to restore myocardial function, additional functional and biochemical assessments are available.

In addition to recipient risk factors, donor age and comorbidity burden continue to limit the applicability and effectiveness of heart transplantation. Older donors are both associated with an increased comorbidity burden and prevalence of coronary artery disease (CAD). Donor-transmitted CAD is of particular concern due to the significant association with early graft dysfunction when multi-vessel disease is present \[4,5\]. Guidelines recommend that donor hearts with obstructive CAD in any major coronary artery be declined for transplantation \[4\]. However, there is evidence that single vessel CAD neither alters short- nor long term recipient prognosis \[6\]. The short and long term risks to the recipient of donor heart CAD needs to be carefully evaluated in relation to the risk of a transplant candidate remaining on the waiting list \[7,8\].

None of the methods currently available in the UK for the assessment of potential heart donors allows adequate characterisation of coronary artery disease (CAD). Instead, retrieval surgeons place a heavy reliance on an indirect assessment of CAD, i.e. direct visualisation and palpation of the large epicardial coronary arteries with the aim of identifying occlusive lesions. The discovery of such lesions is the justification for declining a donor organ otherwise deemed to be suitable for transplantation.

In other countries, access to coronary artery imaging prior to heart donation is an established option, where indicated. Indeed, the Association of Organ Procurement Organizations Consensus Statement, supported by the Society of Critical Care Medicine and the American College of Chest Physicians recommends coronary angiography in all older donors (\>40 years) and in younger patients with risk factors for CAD.

In the proposed study we seek to perform coronary angiography at Harefield Hospital on donated hearts where our retrieval team has declined the organ solely on the grounds of visible/palpable CAD. In so doing we aim to better understand the diagnostic utility of the assessment method. An internal audit of heart retrieval has revealed that of the donated hearts offered to Harefield since 2020 between 8 to 13 are declined per annum on the grounds of visible/palpable coronary artery disease, i.e. approx. 10 per annum. Assuming a study enrolment rate of 1:3 of donated hearts with CAD identified at the time of retrieval, we therefore anticipate that this study will take 36 months to complete. This investigation forms part of a broader research/service improvement initiative which aims to not only enhance the assessment of CAD in potential donors but also to better understand the pathogenesis of CAD in heart transplant recipients. The ultimate goals are to reduce the risks associated with transplantation and increasing donor organ availability. We propose to initiate this investigation as a single centre study but would welcome the participation of other UK centres who would like to collaborate.

We believe this research initiative is well aligned with the strategic objectives of the NHS BT Business Plan 2022-23 \[9\].

1. Hsich E. Circ. Heart. Fail. 2016 Apr. 9(4) e002679.
2. Rushton and Hogg March 2019 NHSBT/CAG, CHARH(19)25.
3. NHS-BT Annual Activity Report:Section 7, Cardiothoracic activity. 2022-23.
4. Ivanes F et al. Int J Cardiol. 2019 277;71-8.
5. Kotloff RM et al. Crit Care med. 2015;43:1291-325.
6. Dorent et al. Arch. Cardiovasc. Dis. 2018;111:126-39.
7. Kilic A et al. J Thorac Dis. 2014;6:1097-104.
8. Estevz-Loureiro R et al. Transplant. Proc. 2010;42:2987-91.
9. NHS BT Business Plan 2022-23, July 2022.

Primary Outcome Measures: Discordance, The goal of this study is perform coronary angiography on hearts which were retrieved by our transplant team and were declined for transplantation solely on the grounds of visible/palpable (i.e. manual examination) coronary artery disease. In so doing, we aim to better understand whether the current assessment method is reliable. Thus the primary endpoint is discordance between the two diagnostic methods., 3 years