Prelisting

Within the ACHD and HTx community, there is the belief that we often ‘miss the window’ to transplant patients as the onset of symptoms is often closely coupled with end-organ dysfunction, significantly increasing the risk of transplantation. Recognising cardiac decompensation, however, is challenging as patients with ACHD differ pathophysiologically from those with normal cardiac anatomy. Typical prognostic indicators such as exercise intolerance, progressive cyanosis and peak VO₂ have not been validated in order to signal appropriate timing.6 As we have yet to identify predictors of impending mortality, our institution has moved towards a proactive multidisciplinary approach to the evaluation of patients with ACHD in this ‘grey zone’—those who are momentarily too healthy for transplant but in whom we anticipate a future need for transplantation or mechanical circulatory support.

Our ACHD team, comprised both paediatric and adult medical and surgical specialists, holds bimonthly meetings to discuss medical and surgical management of complicated patients with ACHD. We have HTx specialists who jointly manage these patients and participate in the meetings as well. We have found that this provides a unique perspective and earlier HTx consideration, in line with current recommendations from the American Heart Association.5 Anecdotally, we believe this early involvement has led to improvements in prediction strategies and appropriate patient selection.

Listing

Transplant listing for our patients without CHD starts with a formal presentation by the HTx team to a committee of medical and surgical transplant physicians, social workers and nurses similar to many institutions. Our patients with ACHD are presented to the committee jointly by the HTx and ACHD teams. We believe our multidisciplinary approach to transplant listing has unique advantages in this population. First, it enhances our understanding of these patients’ unique pathophysiology and the associated medical risks such as PLE, complex collateral circulation and early hepatic congestion. Second, it allows for a preliminary discussion of the surgical considerations given these patients’ unique anatomy.

There is a perception of increased post-transplant morbidity and mortality in patients with ACHD which often delays or discourages listing of patients.7 Our prelisting collaboration has enhanced both our medical and surgical understanding of ACHD, allowing us to be confident in successful outcomes for the patients who have been listed. Since 2010, we have formally evaluated 41 patients with CHD for transplantation (table 3). Twenty-six patients have been listed with 20 proceedings to transplantation. Of the 15 who were turned down, the largest proportion was patients with single ventricle physiology. As with patients without CHD, the main reasons for ineligibility were surgical risk, additional medical comorbidities, and social non-compliance or lack of social support. The surgical risks were most commonly due to a high burden of collateral circulation. Medical comorbidities were mainly due to multisystem organ dysfunction. Not captured in the 41 patients evaluated are those patients who were followed by ACHD who were never formally presented to the joint team due to medical issues or patient preference not to be considered for transplant. A description of the 20 consecutive patients transplanted is shown in table 4.

Methods for listing

Since 1996, the number of patients who are listed status 2 has not changed for patients with CHD, but that percentage has fallen from 66% to 40% in patients without CHD. In the era from 2006 to 2010, there was a significantly higher percentage of patients without CHD upgraded to status 1 than patients with CHD (55% vs 43%).8 While multifactorial, this shift has been driven by multiple changes in the organ allocation policy, including a provision stating that patients with a ventricular assist device (VAD) are listed as status 1B. In addition, patients with VAD receive UNOS status 1A for 30 days to be used at their physician’s discretion or additional status 1A time for any VAD complication. This places patients with ACHD at a disadvantage as use of VAD support is rare in these patients. Additionally, typical metrics such as inotrope dependence or use of mechanical circulatory support do not apply to these patients. A study by Everitt et al 9 based on evaluation of the UNOS database from 2005 to 2009, showed that 36% of patients with ACHD were listed 1A/B compared with 55% of patients without ACHD.9 Fourteen per cent of exemptions requested between July 2009 and 2011 were for patients with ACHD.10

Eight-five per cent (n=17) of our patients were listed 1A/B. Five of the 1A patients were listed by exception and six of the nine 1B patients were listed by exception. While our patients with CHD often do not meet standard criteria for status 1A or 1B listing, we have successfully petitioned UNOS for exception listing in critical circumstances, citing our large body of anecdotal evidence. In our experience, more than 50% of listed patients with ACHD have required an exception in order to undergo transplantation.

Surgical planning

It is standard for both transplant and CHD surgeons to attend and participate in our listing meetings. Pretransplant anatomic considerations include the presence of anomalous pulmonary venous or systemic venous return, abnormal atrial situs or connexions and alterations of pulmonary arteries or aortas that often require reconstruction.11 Prior discussions associated with organ procurement and perioperative implantation unique to the CHD population are essential to minimising complications and reducing ischaemic time. As these patients have undergone multiple procedures and modifications, increased length of donor vessels may be necessary to correct abnormalities of the atria, great vessels, or systemic or pulmonary venous return.7

There are a variety of opinions regarding which specific surgeons should implant the donor heart in the complex congenital adult patient. In regard to patients with ACHD, it has been shown that in-hospital mortality is lower when the congenital operations are performed by specialised paediatric heart surgeons with outcomes correlated with the annual percentage of paediatric heart operations performed.12 Recently, data from Mori et al 11 detailed successful transplantation in an ACHD population undergoing surgery by an adult congenital cardiac surgeon. In contrast, Goldberg et al 6 have suggested that survival is improved if the transplant is performed at a high-volume centre that performs paediatric transplant with access to paediatric heart transplant teams. Our transplants were performed at a high-volume adult transplant centre by adult transplant surgeons with consultation and surgical assistance of our CHD surgeons. The patients recovered in the adult cardiothoracic intensive care unit and adult surgical/medical wards. We feel this is the best method of treatment for these patients. However, we agree with Mori et al that meticulous care and cooperation are essential to success and believe that there are significant benefits postoperatively if the surgery is completed at an adult hospital.

Preoperative management

It would be incorrect to assume that patients with ACHD awaiting transplant are like our patients without CHD. Prior to transplant, these patients similarly require close haemodynamic monitoring and laboratory evaluation, which we have found is best managed jointly by the HTx and ACHD teams. Most heart failure specialists lack a full appreciation of the complex congenital physiology and pretransplant haemodynamics. In non-CHD transplants, accurately evaluating, interpreting and treating elevated pulmonary vascular resistance (PVR) is challenging. In patients with ACHD, this is further complicated by anatomic alterations. Accuracy of calculations is often impossible due to anomalies of the pulmonary vasculature or dual supplies of pulmonary blood flow. Furthermore, sluggish blood flow to the two pulmonary arteries or loss of hepatic blood flow places patients at risk for microemboli or arteriovenous malformations that may alter the distribution between the right and left lungs, making the PVR variable between the lungs.13

PVR is often measured or interpreted incorrectly in the ACHD population which has the potential for either missed transplant opportunities or postoperative right heart failure.1 While paediatric transplanted hearts may be able to handle elevated PVR, in the adult this has not been replicated.14 One study found a preoperative PVR greater than 4 Wood units was associated with a perioperative mortality of 21%, but with no significant difference in long-term survival based on pretransplantation PVR.15 The average PVR for our patients with ACHD awaiting transplantation was 1.6 Wood units with two patients on pulmonary vasodilators. This excludes the three patients who underwent heart–lung transplantation. None of the patients developed right heart failure necessitating mechanical support. Two of three patients who required postoperative mechanical support were heart–lung transplants. These outcomes support our belief that with collaborative evaluation of PVR, the risk of right heart failure can be mitigated.

Donor selection/ischaemic time

Irving et al 7 have described their practice of using oversized donors in the setting of elevated PVR. This is especially useful in the setting of technically complicated evaluation of PVR. On average, the body surface areaof our donors was 13% above our recipients and the donors were on average 9 years younger. Of the 20 transplants, seven were male donors to female recipients and three were female donors to male recipient transplants.

Additional studies have demonstrated worse outcomes with longer ischaemic times. Lamour found that there was an increase in 1 year mortality from 15% to 40% in a 40-year-old ACHD recipient of a heart from a 50-year-old simply by increasing the ischaemic time from 3 hours to >5 hours.13 Again, the preoperative surgical planning including our harvest team has kept our median ischaemic time to 211 min.

Bystander organ dysfunction

As in non-CHD transplants, thorough evaluation of end-organ dysfunction is essential. With the input of our hepatology team, we plan on a heart and liver transplant for all patients with Fontan physiology who have evidence of liver dysfunction and fibrosis/cirrhosis. While the decision is finalised after visual inspection and pathologic diagnosis of cirrhosis at the time of OHT, all of the patients with Fontan physiology have required combined heart and liver transplantation.

It has been previously documented that post-transplant outcomes in patients who underwent Fontan are worse than their non-Fontan counterparts. One study by Lamour et al 13 reports a 71% 1-year survival of patients who underwent Fontan and 83% in patients who did not undergo Fontan. Five-year survival was 60% in patients who underwent Fontan and 74% in patients who did not undergo Fontan. While 5-year data are not yet available, our 1-year survival was 100%. In addition to PVR, bleeding risk is also a concern in patients with Fontan physiology. It has been postulated that the addition of liver transplant reduces the risk of postoperative hepatic dysfunction and reduces bleeding risk as Fontan-associated liver disease often causes thrombocytopenia, mild elevation in the international normalised ratio and clotting factor abnormalities.16 Furthermore, there is growing evidence that cardiac cellular and antibody-mediated rejection is less frequent after heart–liver transplantation possibly allowing for reduced immunosuppression when necessary.17

Perioperative management

Beyond the complicated nature of the haemodynamic management and surgical preparation, the immediate perioperative period is perhaps the most tenuous and potentially morbid. The benefits of transplant at large centres are often underappreciated. These include the care patients receive from cardiac intensivists (cardiac anaesthesia) as well as from cardiac nurses who have been exposed to hundreds of cardiac surgeries, specifically cardiac transplants. Since 2010, our institution has completed >300 cardiac transplants. The experience our team has with perioperative complications is challenging to quantify though has undeniably led to positive outcomes when it comes to patients with ACHD undergoing transplant.

Postoperative management

In the postoperative setting, the ACHD team is available for consultative input but does not typically follow these patients. The management falls most heavily on HTx physicians and nurse practitioners. At our institution, this team is responsible for managing approximately 850 active patients from the time of transplant evaluation to the early perioperative phase through the remainder of their lifespan post-transplant. The coordination of consultative teams, immunosuppressive management as well as treatment of comorbidities is led by the HTx group as this is the group with the greatest experience in this area.

Limitations

This study is limited by its observational, retrospective single-centre nature. It is further limited by the small number of patients who underwent cardiac transplantation.