Background: Fontan circulatory failure (FCF) is a chronic state in palliated single ventricle heart disease with high morbidity and mortality including heart failure, multisystem end-organ disease, and need for heart transplant. Specific FCF morbidities have not been rigorously defined, limiting study of how FCF morbidities impact pre- and post-HT outcomes. We hypothesized that FCF-related morbidities affect survival from heart transplant waitlisting through 1-year post-heart transplant. Methods: This 20-center, retrospective cohort study collected demographic, medical/surgical history, waitlist data, and peri- and post-heart transplant data, and a priori defined FCF-specific morbidities in Fontan patients who were listed for heart transplant from 2008-2022. Univariate 2-group statistics compared surviving individuals with those who 1) died anytime from waitlisting to 1-year post-heart transplant, 2) died on the waitlist, 3) underwent transplant and died within 1-year post-transplant. Using covariates from both univariate analyses, multivariable logistic regression determined the primary study outcome of independent FCF risk factors for mortality between waitlist and 1-year post-heart transplant Results: Of 409 waitlisted patients, 24 (5.9%) died on the waitlist. Of the 341 (83.4%) who underwent HT, 27 (8.5%) did not survive to 1-year. Univariate risk factors for waitlist death included higher aortopulmonary collateral burden, > 1 hospitalization in prior year, younger age, sleep apnea, higher NYHA class, non-enrollment in school or work, and single-parent home. Risk factors for 1-year post-heart transplant mortality included hypoplastic left heart syndrome diagnosis, patent fenestration, anatomic Fontan obstruction, clinical cyanosis (pulse oximetry < 90%), polycythemia, portal variceal disease, mental health condition requiring treatment, and higher HLA class II PRA. Of the patients not surviving from waitlisting to 1-year post-heart transplant, independent risk factors for mortality included >1 hospitalization in the year prior to waitlisting (adjusted odds ratio 2.0, p=0.05) and clinical cyanosis (adjusted odds ratio 5.0, p=0.002). Conclusions: Patients with Fontan palliation selected for heart transplant have significant mortality from waitlisting through transplant. Among FCF specific morbidities, cyanosis is associated with worsened survival and necessitates further study. Clinical morbidity of any type requiring repeated hospital admission also should prompt consideration of heart transplant.

The authors have declared no competing interest.

This research was supported by a grant from the Additional Ventures and Enduring Hearts organizations and a gift from the Van Hooser family.

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