Life After Surviving Fontan Surgery: A Meta-Analysis of the Incidence and Predictors of Late Death

Aim We now know that 20-40% of patients with a single ventricle will develop heart failure after the second decade post-Fontan surgery. However, we remain unable to risk-stratify the cohort to identify patients at highest risk of late failure and death. We conducted a systematic review of all reported late outcomes for patients with a Fontan circulation to identify predictors of late death. Methods We searched MEDLINE, Embase and PubMed with subject terms ("single ventricle", "Hypoplastic left heart syndrome", "congenital heart defects" or "Fontan procedure") AND ("heart failure", "post-operative complications", "death", "cause of death", "transplantation" or "follow-up studies") for relevant studies between January 1990 and December 2015. Variables identified as significant predictors of late death on multivariate analysis were collated for metaanalysis. Survival data was extrapolated from Kaplan-Meier survival curves to generate a distribution-free summary survival curve. Results Thirty-four relevant publications were identified, with a total of 7536 patients included in the analysis. Mean follow-up duration was 114 months (range 24-269 months). There were 688 (11%) late deaths. Predominant causes of death were late Fontan failure (34%), sudden death (19%) and perioperative death (16%). Estimated mean survival at 5, 10 and 20 years post Fontan surgery were 95% (95% CI 93-96), 91% (95% CI 89-93) and 82% (95% CI 77-85). Significant predictors of late death include prolonged pleural effusions post Fontan surgery (HR1.18, 95% CI 1.09-1.29, p < 0.001), protein losing enteropathy (HR2.19, 95% CI 1.69-2.84, p < 0.001), increased ventricular end diastolic volume (HR1.03 per 10 ml/BSA increase, 95% CI 1.02-1.05, p < 0.001) and having a permanent pacemaker (HR12.63, 95% CI 6.17-25.86, p < 0.001). Conclusions Over 80% of patients who survive Fontan surgery will be alive at 20 years. Developing late sequelae including protein losing enteropathy, ventricular dysfunction or requiring a pacemaker predict a higher risk of late death.