Donor Heart Offer
There are many factors to consider when a potential heart offer is made - ABO group, size, cause of death, distance from transplant center, immunological compatibility etc. in addition to recipient factors e.g. NYHA class. Often the decision is very difficult, especially if the donor is suboptimal and the transplant candidate is either extremely sick and may well die if not transplanted, or "well" at home in which case a poor outcome would curtail their life prematurely. These decisions should therefore always be shared with the team and recorded so the decision can be reviewed retrospective and increase the institutional experience.
These guidelines below are limited by the quality of evidence. Unfortunately the evidence, with perhaps the exception of ischemic time, is weak and the majority of statements are based on "expert opinion". Donor quality is also only one determinant of outcome - recipient status is undoubtedly more important. The evidence is clear that implanting a so called "marginal donor" into a recipient in relatively good condition is likely to result in a good outcome, in contrast to a poor outcome if the same organ is implanted into a recipient in poor condition. The scientific evidence can thus only guide us so much and as always multiple factors need to be taken into account in any individual decision.
Excellent resources are the “ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation” Kirk R, Dipchand AI, Davies RR et al. J Heart Lung Transplant. 2020;39:331-41. PMID: 32088108 doi: 10.1016/j.healun.2020.01.1345 and a special edition of Pediatric Transplantation (Volume 24, Issue 3, May 2020) which provides an in depth review of the evidence utilized in writing the consensus statement. The International Society for Heart and Lung Transplantation (ISHLT) Guidelines for the Care of Heart Transplant Recipients by Velleca et al. was published in 2022 and makes recommendations for adult recipients https://www.jhltonline.org/article/S1053-2498(22)02166-0/fulltext
ABO matching & HLA Antibodies
ABO Matching: It is critical that the ABO group of the donor is matched to the recipient, otherwise hyperacute rejection will occur in the operating room and be unrecoverable. Acceptable matches are shown in Table 1. Matching of Rhesus type is not necessary.ABO mismatches are possible in exceptional circumstances. See the section in immunology for more details.
HLA Antibodies: Around 10-20% of recipients have preformed HLA antibodies. If the titres are high and depending on the HLA class they may cause hyperacute rejection. Virtual cross matching can now be performed in advance - if the recipient has preformed HLA antibodies they can be assess against the donor HLA type prior to transplant and if a strong reaction is predicted the donor used for a different recipient. More details are in the immunology section
Size and Age Matching
- Weight: The donor/recipient weight difference is important as this is a reasonable indicator of the difference between the donor and recipient heart size. As a generally accepted rule the D:R ratio should be between 0.7 to 2.0. However, as with all recommendations this "rule" may be broken depending on other circumstances. For example some children with cardiomyopathy present with a huge heart and the pericardial space will accept a larger donor heart. At the time of listing it is usual to specify the acceptable donor weight range.
- Height: For cardiac transplant, unlike lung transplants, height disparity is not an issue.
- Age Difference: Guidelines recommend that for children, the age difference is 5 years or less between the donor and recipient. Donors for older teenagers should be less than 25 years of age. Adult donors less than 45 years old may be readily utilized but donors older than 50 years of age should be avoided unless there are exceptional circumstances and the ischemic time will be short. An angiogram should be requested if the donor is more than 40 years of age or has risk factors for coronary disease but it is often not possible to obtain. The long term outcomes are somewhat better if these donor guidelines are observed, however they are harder to follow in Europe than in North America, as donors are scarcer thus constraining choice.
Cause of Death, Resuscitation and Inotropes
- Cause of Death: It is important to note the cause of death. Traumatic deaths (principally road traffic accidents in Europe) may result in chest trauma and significant myocardial contusion. Trauma to the head or cerebral vascular accidents (especially intracranial haemorrhage) usually results in a massive catecholamine surge causing subendocardial ischemia, which is reflected in ECG and echocardiogram abnormalities (see cardiac function section). If known, then donation from those with a channelopathy should not be used, likewise from donors from non bacterial meningoencephalitis are not accepted. In SIDS a small study showed comparable post transplant outcomes provided the ejection fraction was normal. Causes of death from infections and other donor morbidity are dealt with in the relevant sections
- Resuscitation: Prolonged resuscitation may result in poor cardiac function however if the function recovers then it is unlikely to cause problems and a history of CPR should not preclude donation
- Inotropes: Large adult and pediatric studies have shown that neither high or low inotrope usage in the donor influenced transplant outcome
Donor Cardiac Function
- Echocardiogram: It is well known that assessing echocardiogram function is an inexact science and where possible the transplant center should have access to the donor echocardiogram. The ejection fraction or fractional shortening may well be reduced in catastrophic brain injuries from what ever cause. Over time almost all resolve so the time interval from the event causing death and the echocardiogram should be assessed. Most reversible abnormalities will resolve in 2-3 days. Retrieval should be delayed until resolution has occurred. Often however delay is not possible and then whether the heart is accepted or not depends upon the degree of dysfunction, and whether a further insult to the heart will occur e.g. a long ischemic time due to the donor distance. Left ventricular hypertrophy maybe a cause for concern in donors when LV septal or posterior wall thickness is greater than 13mm, especially in conjunction with other high risk characteristics such as age ≥ 55 years or an allograft ischemic time >4 hours or a family history of hypertrophic cardiomyopathy.
- Electrocardiogram: If the cause of death is a brain injury (trauma, haemorrhage or asphyxia including drowning) the ECG may well be abnormal. Q wave and T wave abnormalities typical of ischemia may be seen and there is often prolongation of the QT interval. The latter can be especially worrying as channelopathies are well know as a cause of sudden cardiac death or drowning and would be a contraindication for donation. Usually abnormalities resolve within a day or two and, if so then donation can go ahead. If a delay is not possible then the likelihood of it being a channelopathy should be assessed in conjunction with other factors e.g. the transplant candidate status.
- Biomarkers: Troponin-I, troponin-T and CK-MB are commonly elevated for several days after brain death due either to cardiopulmonary resuscitation or the catecholamine surge in traumatic brain injury. There is no evidence that either influence transplant outcomes. Likewise donor BNP or NT-proBNP are not predictive of outcome.
This is really the only donor parameter to be shown to directly relate to outcomes, especially primary graft failure. If possible it should be within 4 hours. However successful outcomes with much longer ischemic times are well recorded - particularly with young donors in whom other factors e.g. cardiac function are normal. Ischemic time may be broken down into warm ischemic time (time taken to explant and implant the heart) and cold ischemic time - time when the heart is cooled for transport and whilst awaiting implant in the OR - the so called "bucket time". The ischemic time thus depends upon the proximity of the donor to the recipient hospital, the coordination between the retrieval and implant teams, especially when the explant is likely to be prolonged e.g. due to multiple previous sternotomies, necessity for pulmonary artery reconstruction, explant of a VAD etc.
Transmission of donor infections is well recognized but uncommon (< 1%) due to screening techniques. Conway et al published a comprehensive review of the implications of donor infections.
- Covid-19: Emerging evidence in adults and case reports in children suggest that there is no additional short term risk for recipients of Covid-19 positive heart donors
- Bacterial Infections: These may be the primary cause of death e.g. meningococcal septicemia or nosocomial acquired. By the time donation is considered usually the bacterium and antibiotic sensitivity has been determined and treatment given. Even if this is not the case, no deaths have ben reported from blood culture positive donors. Although there are no reports in the literature, donors with multi-drug resistant organisms should be used with caution. Tuberculosis has been transmitted in adults but responds to treatment. Bacterial infections are not a contraindication to donation and transplant can proceed provided the recipient is covered with appropriate antibiotics.
- Virology: Nucleic Acid Amplification Testing (NAT) is a quick and reliable method of detecting viruses. There is however a short window between acquiring an infection and a NAT positive test so occasionally despite negative testing, transmission can occur. Infectivologists should be consulted before utilizing donor with Hepatitis B or C. For HBV there is limited data on whether recipient prophylaxis can prevent infection and it is not recommended. For HCV adult recipients, donation is not contraindicated as treatment is effective. In children treatment for HCV is available for those 11 years of age or more and case reports have shown success in utilizing HCV donors. HIV is an absolute contraindication although there are now increasing numbers of HIV positive recipients receiving HIV positive donor organ.
- Congenital Heart Disease: Minor CHD e.g. ASD, mild subaortic stenosis etc. is not a contraindication as they can be repaired at time of transplant
- Hypertension: There is no evidence that donor hypertension compromises transplant outcomes
- Diabetes: Neither type I or type II diabetes is associated with adverse outcomes, however they may be a risk factor for donor coronary disease
- Anaphylaxis: This is a rare cause of death but while the allergy can be transferred to the recipient it is not a contraindication
- Malignancy: There is very little data on the transmissibility of malignancy and none in pediatric donors. Those donors whose primary malignancy is confined to the cranium can certainly be used. For other malignancies it is reasonable to expect a low risk in those who are cancer free for 5 years with an expectation of a high cure rate. It should be born in mind that some cancer treatments, notably radiotherapy to mediastinum and anthracyclines may cause late cardiac dysfunction
- Genetic syndromes e.g. trisomy, are not contraindicated, although considerations should be given to those with severe mobility or nutritional deficiencies as they likely will be deconditioned and theoretically additional post transplant cardiac support may be required
- Addiction: Concern has been expressed for donations from drug and or alcohol abuse. Cocaine for example is known to cause coronary spasm. Additionally there are concerns regarding the lifestyle of addicts and their exposure to viral infections e.g. HIV and Hepatitis. Despite these concerns post transplant outcomes have been demonstrated to be unaffected by donation from addicts