Clinical correlation and prognostic predictive value of neurohumoral factors in patients late after the Fontan operation

Aims We tested the hypothesis that neurohumoral activation could correlate with exercise tolerance and have a prognostic value in patients late after Fontan operation. Methods and Results We studied 50 consecutive patients after the Fontan operation and 10 age-matched normal controls. We measured brain and atrial natriuretic peptides, norepinephrine (NE), plasma rennin activity, aldosterone, angiotensin II, and endothelin and investigated the relationship of neurohumoral factors with exercise tolerance and central hemodynamics. We also evaluated the prognostic predictive value of these factors. All factors were significantly higher in the patients than in controls, but no factor correlated with peak oxygen consumption (peak VO2). There were significant correlations of atrial natriuretic peptide with cardiac index, NE with left ventricular ejection fraction (LVEF), and pulmonary arterial wedge pressure. After 4 yearsʹ follow-up, univariate Cox proportional hazards analysis showed that peak VO2 and LVEF could significantly predict the long-term event-free ratio. In multivariate analysis, LVEF and NE have a significant predictive value. In Kaplan-Meier event-free curves, NE combined with peak VO2 showed a significant predictive value. Conclusions Activated neurohumoral factors are not determinants of exercise tolerance in patients late after the Fontan operation. The plasma level of NE combined with peak VO2 has a prognostic predictive value in these patients.