Hyponatremia and Its Association with the Neurohormonal Activity and Adverse Clinical Events in Children and Young Adult Patients after the Fontan Operation

Background.  Hyponatremia (HN) is relatively common in adults with congenital heart disease and is a powerful predictor of mortality. However, the precise relationship of HN to the Fontan pathophysiology remains unknown. Purpose.  Our study aimed to clarify the association of HN to the Fontan pathophysiology. Methods and Results.  We measured the plasma sodium (Na) level in 169 consecutive Fontan patients (78 children) and HN (≤137 mEq/L) was observed in 50 patients (30% of the total patients, 31% of the children). The HN patients showed a lower peak oxygen uptake (VO2) with a greater New York Heart Association class (P < .0001). The plasma level of norepinephrine (NE), rennin activity (PRA), arginine vasopressin, central venous pressure (CVP) and medications were associated with the Na levels and the NE, PRA, and diuretic use were the independent determinants (P < .01−.0001). The plasma B-type natriuretic peptide was not correlated with the Na levels. In the children, diuretic use and the PRA independently determined the Na levels without any association to the CVP or peak VO2. During a median follow-up of 2.1 years, the HN in addition to the CVP and peak VO2 independently predicted the unscheduled hospitalizations in all patients, while the HN was the only independent predictor of the hospitalizations in the adult patients (hazard ratio: 3.1, 95% confidence interval 1.2–8.0, P= .021). Conclusions.  Child and adult Fontan patients exhibited a high prevalence for HN that closely reflected some neurohumoral activation and predicted adverse clinical events, especially in adult Fontan patients.