Discussion

Provided that a bi-ventricular physiology is not achievable, Fontan surgery is regarded as a palliative strategy in certain uni-ventricular conditions. Even though surgical techniques have evolved since the original reports, attrition was close to 26% at 5 years in Fontan’s own words. ^{Reference Fontan, Kirklin and Fernández1} Whether the causes of eventual deterioration are due to left or right single ventricle anatomy, or ventricle dysfunction versus Fontan circuit failure are beyond the scope of this paper. ^{Reference Backer, Russell and Pahl12,Reference Michielon, vanMelle and Wolff13} The authors focus their attention in the surgical strategy.

Transplant after Fontan completion is actually a surgical challenge. Besides the hurdles of a re-do surgery (fourth sternotomy in HLHS patients), uni-ventricular physiology adds unique requirements. The lack of a sub-pulmonary pump makes both systemic and pulmonary circuits to be in serial connection. Preload, chronically diminished, enhances diastolic dysfunction. Afterload changes, either pulmonary or systemic, drive to systolic dysfunction. Non-modifiable causes such as ventricle morphology, heterotaxy, PLE, or plastic bronchitis (PB) increase morbidity. Adult Fontan patients need to have their liver and kidney function assessed ^{Reference Mauchley and Mitchell14,Reference Rychik, Atz and Celermajer22} to check a Fontan-associated-liver disease (FALD) either to contraindicate the heart transplant or to indicate a combined liver-heart transplant.

Before evaluating transplant candidacy in Fontan patients, catheter-based and surgical options must be optimised. Aorta and pulmonary branches angioplasty (or stenting) to release afterload, valvular regurgitation repair (or replacement), anti-arrhythmia measures (including pacemaker and resyncrhonisation), extracardiac Fontan conversion, ^{Reference Mavroudis, Backer, Deal, Johnsrude and Strasburger23} etc., should be scrutinised. In comparison to bi-ventricular hearts, uni-ventricular patients are considered as suboptimal candidates for mechanical circulatory support. A review shows more than twofold mortality (57.7 versus 24.4%) in uni- as opposed to bi-ventricular patients, ^{Reference Home, Conway, Rebeyka and Buchholz24} inasmuch several improvements are in progress. ^{Reference Adachi, Burki and Fraser25}

Pre-transplant assessment is paramount. This cohort of patients have undergone many catheter-based and surgical procedures, including transfusions, and lymphocytic reactivity must be checked. Neck and groin vessels might not be patent any longer. Pulmonary arteries pressure and resistance should be considered as slightly elevated, and it proves that a reliable method to assess it has not been yet defined. ^{Reference Mitchell, Campbell and Ivy26}

Several papers report a comprehensive approach to these complex operations. ^{Reference Mauchley and Mitchell14,Reference Gil-Jaurena, Pérez-Caballero and Pita21,Reference Hosseinpour, González-Calle and Adsuar27,Reference Iyengar, Sharma and Weintraub28} Close coordination between procurement and transplant teams are key, in order to keep at a minimum ischaemia (in a scenario where a spare hour is needed between cardiectomy and proper graft stitching). As previously stated, extra tissue from the donor is harvested to patch the recipient with “autologous” material. The rationale is trying to avoid foreign pieces, which might be more prone to endocarditis in the setting of a immunodeficiency post-transplant. We routinely evaluate the “5 sutures” to be carried out, in a sort of algorithm (Fig 1), and anticipate any modifications. Peripheral vessel patency beforehand information allows quick and safe anaesthetic monitoring and groin preparedness for cannulation. The more information and setup, the less improvisation at transplant time.

Table 2 displays the changes carried out for the 5 anastomoses in the 20 patients enrolled. Every structure has been modified at least once. Although previously reported on isolation, ^{Reference Doty, Renlund, Caputo, Burton and Jones15–Reference Gil-Jaurena, Pérez-Caballero and Pita21} few papers actually consider it a strategy (Fig 2b) facing complex procedures. ^{Reference Mauchley and Mitchell14,Reference Gil-Jaurena, Pérez-Caballero and Pita21,Reference Hosseinpour, González-Calle and Adsuar27,Reference Iyengar, Sharma and Weintraub28}

1. 1. The size mismatch between left atria was sorted out leaving a “bi-atrial” cuff in the recipient (No. 2).

2. 2. Our aortic anastomoses have evolved since one of our early patients had his/her anastomoses stented in the postop (No. 3). Currently, we advocate for a more aggressive “hemi-arch” procedure when a size mismatch is anticipated, particularly in HLHS patients with a short and bizarre new aorta. ^{Reference Kanter, Mahle, Vincent and Berg29} Thus, we have recently cannulated the brachiocephalic artery interposing a PTFE conduit to avoid deep hypothermia and circulatory arrest. As an alternative, axillary cannulation can be applied (not used yet in our experience). Nevertheless, unexpected findings can lead us to cool down and arrest the pump to fix the aortic anastomoses. That was the case of a patient whose (fragile) aorta torn apart when trying to release a scar in a former Waterston shunt (No. 19).

3. 3. Pulmonary arteries plasty has been already reported, ^{Reference Mauchley and Mitchell14} choosing synthetic material. ^{Reference Iyengar, Sharma and Weintraub28} As abovementioned, an autologous (recipient/donor) patch is preferred when available. Donor aorta was selected in our first patient, but we then switched to donor pericardium in order to spare the graft aorta (arch) for hemi-arch techniques. Previously implanted stents are completely removed, ^{Reference Gil-Jaurena, Zunzunegui and Pérez-Caballero30} mainly in the left branch, before patching from hilum to hilum.

4. 4. A short sleeve is left in situ for the suture of the inferior vena cavae after removing the extracardiac conduit. We found this maneuver helpful in avoiding tearing and deep cannulation close to the diaphragm. Again, stents were removed ^{Reference Gil-Jaurena, Zunzunegui and Pérez-Caballero30} in 4 patients in a low flow setting (2) or femoral cannulation and circulatory arrest (2).

5. 5. Superior vena cavae suture changes were anticipated in the preoperative screening. Cannulation sites were modified and suturing was carried out under cross-clamp, instead of on a beating-heart as routinely.

Generally speaking, short period of deep hypothermia and circulatory arrest were scheduled as we earned experience, particularly for profound structures (left pulmonary artery, inferior vena cava) and when stents were deemed to be removed. Interestingly, some patients underwent three intermittent periods of circulatory arrest at 18 °C to address LPA, IVC, and aortic arch. We have learned to cool the patients down slowly, anticipating any such low-flow (or even arrest) safe periods. Owing to the complexity and changes in the five anastomoses, plus the average long-distance procurement, ischaemia was longer than 4 hours in 15 patients (Table 2). Not surprisingly, on average one hour is necessary to “prepare” the field after cardiectomy and before graft stitching begins (Fig 2). Only two patients in our series (No. 5 and No. 10) did not undergo any changes in their sutures: both were atrio-pulmonary Fontan-type (assuming that detachment of atrium from the pulmonary artery is not a modification).

Post-operative complications are to be expected in this subset of patients. Four patients returned to theatre because early postop bleeding. Re-do surgery and plenty of collateral vessels have been blamed for that. ^{Reference Iyengar, Winlaw and Galati6,Reference Kanter11,Reference Backer, Russell and Pahl12,Reference Mauchley and Mitchell14} Even worse, one of the patients died in the operation theatre because of massive and uncontrollable bleeding, as reported elsewhere ^{Reference Michielon, vanMelle and Wolff13} particularly in caquectic and coagulopathic patients. Right ventricular dysfunction, likely caused by subtle pulmonary hypertension, lead to ECMO in six patients (successfully removed before 72 hours). Interestingly, patient No. 13 was on a systemic assist device for 3 weeks before transplant and on a sub-pulmonary assist device (ECMO) after transplant for 2 days. Not surprisingly, the right atrial appendage and aorta were cannulated in both instances (same structures, different ventricles). Collateral vessels required closure in the cath lab in four patients. Step up on inotropes with good bi-ventricular function should give the clue in such circumstances. ^{Reference Krishnan, Lamour, Hsu, Kichuk, Donnelly and Addonizio31} PLE resolved in five out of the six patients (sixth one died in theatre), as has been reported. ^{Reference Backer, Russell and Pahl12} Whether PLE is a predisposing factor for post-operative infection in a immunodepression setting ^{Reference Michielon, vanMelle and Wolff13} cannot be ascertained in our short experience.

Patients over 18 years deserve further attention. ^{Reference Murtuza, Hermuzi and Crossland32,Reference Hernández, Lemor and Clark33} Most of them were morphologically left single-ventricle and atrio-pulmonary Fontan type connection. “Old-fashioned” techniques like thoracic and Waterston shunts were found in this subgroup. One has to be prepared for more surprises (if any) amongst older patients who encompass the evolution of Fontan-type surgical techniques. On the contrary, most young single-ventricle transplant candidates belong to the HLHS category and have been stepwise and uniformly operated on.

Bernstein et al ^{Reference Bernstein, Naftel and Chin10} published in 2006 the first multicentric study about transplant in failed Fontan. Since several groups have reported papers with series including more than 10 patients. ^{Reference Backer, Russell and Pahl12–Reference Mauchley and Mitchell14} They all agree that surgical mortality is far worse than in other-than-Fontan transplants, approaching 20%. Interestingly, the group in Emory ^{Reference Kanter11} (Atlanta, United States of America) shows astonishing low rates such as 4%. A European multicentric study in 2015 gathers 61 patients from 11 institutions along 20 years, ^{Reference Michielon, vanMelle and Wolff13} mirroring the scattering of data and the hurdles on accumulating experience on Fontan-transplanted patients in any given centre. In this paper, ^{Reference Michielon, vanMelle and Wolff13} 26% of the patients come from HLHS morphology, whilst 72% are extracardiac connection type. Most of the authors underline pre-operative assessment of utmost importance, including vessel patency and image techniques (MRI) to precisely define adherence to the sternum. ^{Reference Mauchley and Mitchell14} Conventional interventionism and surgery to delay or improve pre-transplant status are strongly advised. ^{Reference Michielon, vanMelle and Wolff13} Amongst these procedures are: collaterals closure/embolisation, vessel angioplasty/stenting, valve repair/replacement, Fontan conversion plus Maze procedure, etc. Data collection will provide insight into Fontan failure mechanisms such as: single-ventricle dysfunction or sub-pulmonary failure (even both), right versus left morphological single ventricle, late versus early failure. Backer et al ^{Reference Backer, Russell and Pahl12} stated that late failure (ventricle dysfunction) yields better prognosis (82% survival at 5 years post-transplant) compared to early deterioration for Fontan sub-pulmonary circuit failure – with good ventricle function – (33% survival at 5 years). PLE has been recently accepted as an indication for transplant listing, ^{Reference Michielon, vanMelle and Wolff13,Reference Mauchley and Mitchell14} provided it is a surrogate of Fontan circuit failure. Accordingly, Fontan takedown is considered a truly early Fontan failure, with a 25% mortality rate after transplant in the European study. ^{Reference Michielon, vanMelle and Wolff13}

From a surgical standpoint, most papers agree that transplant after Fontan is actually a challenge. Re-do surgery, collateral circulation, coagulation disorders, caquexia, etc., increase complexity. Venous system (both and, occasionally, three cavae), pulmonary branches (from hilum to hilum), and aorta (aortic arch) reconstruction are routine in this setting (Fig 2). Exquisite coordination between procurement and implanting teams is of paramount importance, foreseeing 3–4-hour headstart prior to graft arrival. Extra donor tissue is suggested. Bypass and ischaemia times are longer than usual. Deep hypothermia plus circulatory arrest (intermittent periods) are becoming familiar. Altogether, these are ingredients for a morbidity and mortality higher than average. Bleeding and post-operative right ventricular failure (ECMO included) are to be expected in the postop, as well as a hyperdynamic state caused by residual collateral circulation (needing cath lab transfer for vessels closure ^{Reference Mauchley and Mitchell14,Reference Krishnan, Lamour, Hsu, Kichuk, Donnelly and Addonizio31} ).

Our series enrolled 20 consecutive transplants (kids and adults) in a 7-year lapse, performed by the same team of congenital surgeons, with a follow-up of nearly 4 years. 13 patients were under 18 years (mostly HLHS, extracardiac Fontan) and 7 of them, over 18 years (mainly morphologically left single ventricle and mixture of Fontan-type procedures). A sequential analysis focused on the five proposed anastomoses is carried out, planning in advance any change pertaining to them all (Fig 1). This rationale includes lowering temperature and pump flows (anticipating arrest periods), as well as stents removal. The goal is to avoid improvisation as much as possible. Morbidity and mortality results are similar to other groups, ^{Reference Bernstein, Naftel and Chin10} assuming our low figures and follow-up as a limitation. Interestingly, mortality rate is not worse than non-Fontan transplants in our own Institution.

Refinements in surgical technique and post-operative care yield good results nowadays, allowing more children to reach adulthood. Conversely, more palliated patients (e.g., Fontan) are likely to become transplant candidates according to their attrition rate. Michielon et al ^{Reference Michielon, Carotti, Pongiglione, Cogo and Marino34} foresee that 70% of congenital heart transplants will belong to uni-ventricular conditions in the future. A likely mismatch between the increase of candidates and donors enhances us either to exhaust conventional approaches, either to develop surgical expertise in the transplant. ^{Reference McCormick and Schumacher35} Encouraging reports with good results should consider allocation ^{Reference Rychik, Atz and Celermajer22,Reference Murtuza, Hermuzi and Crossland32} and resources for this emerging and demanding cohort of patients.