We read with great interest the article by Karlinski Vizentin et al.1 The authors conducted a systematic review of combined heart-liver transplants (CHLTs) in post-Fontan patients. The pooled analysis of 67 patients showed a 1-y survival rate of 88% with very low graft rejection rates, although complication rates from acute kidney injury and temporary dialysis were high. We have a few concerns regarding this article. First, there is likely a significant overlap in the study population. The study by Lewis et al2 was a retrospective analysis of 40 CHLT cases between 1995 and 2021 enrolled in the FOSTER (Fontan Outcomes Study to improve Transplant Experience and Results) registry, which involved 17 centers, including Stanford University, the University of Pennsylvania, and Vanderbilt University. The pooled analysis combined these 40 patients with single-center reports from Stanford University, the University of Pennsylvania, and Vanderbilt University. Indeed, the last authors of the studies from Stanford and the University of Pennsylvania, and 1 author of the Vanderbilt study, were included as authors in the study by Lewis et al. Therefore, there is a significant likelihood of patient overlap in the pooled analysis for 1-y survival and liver rejection.1 Patient overlap inflates the sample size and underestimates the variance, leading to biased estimates. Removing Lewis et al from these analyses will reduce the cohort size to 27 patients, which is smaller than their study and thus provides limited incremental value beyond it. Second, the reported outcomes may not reflect real-world data. Recent analyses of the Organ Procurement and Transplantation Network data showed much lower 1-y survival (73%) in CHLT for adult patients with congenital heart disease, which was much worse than CHLT for other indications.3,4 Although these studies used the Organ Procurement and Transplantation Network registry and the exact number of post-Fontan patients within the studies could not be identified, it is likely that many of them were post-Fontan. These recent reports are concerning, especially given improved access to CHLT after the heart allocation policy change in 2018 and the increasing number of CHLTs.5 The promising 1-y survival rate of 88% in the pooled analysis might reflect expertise at select centers, and might not reflect expected outcomes at a national level. Further research is needed to investigate this discrepancy in short-term survival and clarify whether it stems from superior management at expert centers, stricter patient selection criteria, or differing outcomes in post-Fontan versus non-Fontan patients with congenital heart disease. In conclusion, the pooled analysis performed by Karlinski Vizentin et al is likely biased by significant patient overlap.
Nakayama et al. (Wed,) studied this question.