Adverse pulmonary vascular remodeling in the Fontan circulation

Background: The Fontan circulation is a palliation for patients with a functionally univentricular heart. It is characterized by gradual attrition over time. An increase in pulmonary vascular resistance could be a key factor in the long-term failure of the Fontan circulation. In this study we aimed to identify pulmonary vascular remodeling in patients with a Fontan circulation.

Methods: Pulmonary vascular histomorphometric analysis and immunohistochemistry were performed in lung tissue obtained at autopsy from 12 Fontan patients. These patients had died either peri-operatively (Group A: death during or <15 days after Fontan completion; n = 5) or in mid to long-term follow-up (Group B: death >5 years after Fontan completion; n = 7). Two age-matched control groups (n = 10 and n = 14, respectively) were included.

Results: Intra-acinar pulmonary vessels in the Fontan Group B patients showed decreased medial thickness (p = 0.028) compared with age-matched controls, whereas intimal thickness was increased (p = 0.002). Intimal thickness in the Fontan Group B patients correlated with age at death (r = 0.964, p < 0.001) and with the length of time that the Fontan circulation had been in place (r = 0.714, p = 0.036). Immunohistochemistry revealed a reduction of vascular smooth muscles cells in the medial layer of the intra-acinar pulmonary vessels. The eccentric intimal thickening was composed of mainly acellular fibrosis with collagen deposition.

Conclusions: We observed a unique pattern of adverse pulmonary vascular remodeling in patients with a long-standing Fontan circulation who had died during follow-up. This remodeling pattern may play a major role in long-term attrition of the Fontan circulation.