Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

Lewis MJ, Reardon LC, Aboulhosn J, Haeffele C, Chen S, Kim Y, Fuller S, Forbess L, Alshawabkeh L, Urey MA, Book WM, Rodriguez F 3rd, Menachem JN, Clark DE, Valente AM, Carazo M, Egbe A, Connolly HM, Krieger EV, Angiulo J, Cedars A, Ko J, Jacobsen RM, Earing MG, Cramer JW, Ermis P, Broda C, Nugaeva N, Ross H, Awerbach JD, Krasuski RA, Rosenbaum M.J Am Coll Cardiol. 2023 Jun 6;81(22):2149-2160. doi: 10.1016/j.jacc.2023.03.421.PMID: 37257950

Take Home Points

  • Retrospective cohort study of 131 patients undergoing heart transplant (HT) or combined heart liver transplant (CHLT) across 15 centres that comprise the FOSTER registry (Fontan Outcomes Study to improve Transplant Experience and Results).
  • 91 patients underwent HT and 40 CHLT (between years 1995-2021)
  • Post-match, patients undergoing CHLT trended towards improved survival at 1 year (93% vs 74%, P=0.097) and at 5 years (86% vs 52%, P=0.041) compared to HT alone.
  • Patients with a FALD score >2, CHLT was associated with better survival (1 year: 85% vs 62%; p=0.0044; 5 years; 77% vs 42%; p=0.019)
  • In a model incorporating transplant decade and FALD score, CHLT was associated with improved survival (HR:0.33; p=0.044) and higher FALD score was associated with higher mortality (FALD score 2 [HR:14.6; p=0.015], 3[HR:22.2; p=0.007], and 4[HR:27.8; p=0.011]).
  • Higher FALD scores were associated with higher post-transplant mortality.
  • In this cohort, patients undergoing CHLT were older with higher FALD score but had similar overall survival and better survival than patients with a FALD score >2
  • This is the largest observational study to compare HT and CHLT in adult Fontan patients.
Dr Damien Cullington

Commentary by Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:

The purpose of this analysis was to try to explore further how FALD affects post-transplant outcomes and when a CHLT should be selected over HT alone. The patient characteristics are shown in Table 1.

The Fontan procedure is a palliative one and as most of us reading will appreciate, has limited durability. Over the life course, some patients fare much better than others and this is dependent on a variety of interwoven factors. Some of these are immovable e.g. cardiac anatomy (LV vs RV dominance) and PA size; type of Fontan procedure and era of completion and others are modifiable such as lifestyle choices (e.g. smoking; diet; exercise) and the resultant effects. It is universal that all patients with a Fontan develop FALD from an early age owing to high systemic venous pressures. For the patient with a failing Fontan who requires cardiac transplantation, the extent and severity of FALD is a major defining issue as the treating team must decide if HT alone will suffice or if CHLT is needed – subjectively, the latter is viewed as a higher risk procedure associated with higher mortality – something one would perhaps rather avoid if not absolutely necessary. This study also shows if this subjective opinion is valid or if risk can be mitigated by careful selection of candidates for HT or CHLT.

Table 1 – Patient Characteristics

Results

144 patients from 15 ACHD/transplant centres were enrolled. The median time follow up for HT and CHLT was similar (1.57 years vs 1.53 years). CHLT was commoner in more recent decades and in in centres which had performing >10 Fontan HT/CHLT. There was no observable difference between HT and CHLT patients in terms of the native anatomy, type of Fontan, degree of ventricular or valvular dysfunction, time from diagnosis of Fontan failure to transplant evaluation or prior Fontan revision.

Pre-operative characteristics

Compared to HT recipients, CHLT recipients were more likely to be on multiple inotropes pre-transplant (38% vs 25%; p=0.014) and with longer bypass times (310 mins vs 251 mins; p=0.008). There was no difference in the cardiac allograft ischaemic time (237 mins vs 225 mins; p=0.4).

FALD Score

 A comprehensive dataset relating to degree of FALD was collected for each patient. Using this data, a Fontan associated liver disease score was constructed based on prior studies which examined FALD-specific predictors of outcomes and markers of advanced liver disease.

Survival

The authors performed a subgroup analysis of recipients undergoing CHLT and HT from 2000 which represents a ‘contemporary’ dataset. Survival at 1 year was not statistically different between HT and CHLT recipients – 78% vs 89%; p=0.17. At 5 years, survival was 62% vs 85%; p=0.096. A higher FALD score was associated with worse survival and survival post CHLT was not worse compared to HT alone. Cause of death in HT/CHLT recipients is shown in Table 3.

Conclusions

The subjective view of CHLT being associated with worse survival than HT may well be an ‘old fashioned’ conception in the modern era. Logically, CHLT may the best choice for patients with significant FALD (a FALD score > 2) with the caveat that it is performed in experienced/high volume centres. Prospective data is required and the authors accept that there are numerous confounding factors which bias the data – centre transplant volume; patient selection; surgical technique

The authors succinctly point out: “balancing the increased procedural risk of CHLT with the potential post-transplant benefits remains a central problem in defining the risk-benefit ratio of dual organ transplantation in this population.”