OBJECTIVES: This study aimed to assess the outcomes of heterotaxy patients who underwent the Fontan operation, focusing on morphological features and surgical techniques. METHODS: Eighty-two consecutive heterotaxy patients who underwent the Fontan operation from 1985 to 2021 were compared to 150 patients with tricuspid atresia (TA) and 144 patients with hypoplastic left heart syndrome (HLHS). The Kaplan-Meier method and Cox proportional hazard model were used to analyse transplant-free survival and predictor of outcomes. RESULTS: The 20-year transplant-free survival rates were comparable between right atrial isomerism (RAI, n = 45) and left atrial isomerism (LAI, n = 37) [RAI versus LAI, 76% (95% confidence interval, 57-87%) vs 68% (47-82%), P = 0.22], although more pulmonary vein interventions at Fontan were needed in RAI. Surgical techniques included extracardiac conduit in 66%, intra-atrial conduit in 9% and lateral tunnel in 18% of the cases. Cardiac position and apicocaval juxtaposition did not influence outcomes, but the inferior vena cava (IVC)-contralateral pulmonary artery (PA) Fontan was associated with 100% survival, while the IVC-ipsilateral PA Fontan at the cardiac apex showed a 67% (34-87%) survival rate at 20 years. In-hospital mortality was higher in heterotaxy [9.8% (5-19%)] compared to TA [1.3% (0.3-5.3%), P<
0.01) and HLHS [2.8% (1.1-7.3%), P = 0.02], with no early death after 2000 in any group. The 20-year transplant-free survival in heterotaxy [72% (59-82%)] was similar to that in HLHS [80% (69-87%), P = 0.11]. CONCLUSIONS: Various routing techniques can be successfully applied to overcome anatomical challenges in heterotaxy. Despite higher in-hospital mortality, overall survival was similar to HLHS. RAI had comparable survival to LAI with more pulmonary vein interventions at Fontan.