Association of stromal cell derived factor 1α and interferon-γ induced protein 10 with Fontan pathophysiology.

BACKGROUND Despite restoration of systemic and pulmonary circulation and normalized oxygen saturation, patients with Fontan circulation experience frailty, exercise intolerance, and impaired exercise hemodynamics. Altered cytokine-chemokine profiles have been reported, but their relationship with Fontan pathophysiology remains poorly defined.

METHODS Adult Fontan patients and matched controls were assessed for frailty, cardiopulmonary exercise capacity, and resting/exercise-augmented hemodynamics. Plasma cytokine-chemokine concentrations were measured using multiplex ELISA.

RESULTS Twenty Fontan patients (mean age 28.8 ± 9.8 years; 35% female) and 20 controls (29.7 ± 6.0 years; 30% female) were studied. Fontan patients had slower 5× sit-to-stand times (9.6 ± 3.1 vs. 5.7 ± 1.3 sec; p<0.0001), lower VO₂max (% predicted), and reduced stroke index, cardiac index, and cardiac power index. TNF-α, IL-1β, IL-6, IFN-γ, IL-8, IP-10, MCP-1, and SDF-1α were elevated in Fontan patients, while IL-10 and MIP-1α were not different. SDF-1α and IP-10 correlated with frailty, impaired oxygen uptake, and hemodynamic parameters.

CONCLUSION Elevated SDF-1α and IP-10 are associated with frailty and impaired exercise hemodynamics in Fontan patients. These novel findings suggest a role for inflammation in Fontan-associated dysfunction and warrant further investigation.