Elsevier

American Heart Journal

Volume 150, Issue 3, September 2005, Pages 588-594
American Heart Journal

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

https://doi.org/10.1016/j.ahj.2004.10.030Get rights and content

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 years' 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.

Section snippets

Patients

Fifty consecutive patients after the Fontan operation who were hospitalized in our institution for long-term cardiac evaluation, including catheterization from 1999 to 2002, were enrolled in this study. The patients, 26 males and 24 females, ranged in age from 13 to 41 years (mean age 22.7 ± 3.6 years). Forty-one patients were in New York Heart Association functional class I and 9 patients were in class II. The cardiac anomalies were single ventricle in 21 patients, tricuspid atresia in 17

Results

All neurohumoral factors were significantly higher in the patients than that in the controls (Table II) but did not correlate with peak oxygen consumption (peak VO2) (Table III).

Figure 1 summarizes the relationship of the neurohumoral factors with the central hemodynamic variables obtained by cardiac catheterization. There was a negative correlation between the ANP and the cardiac index (r = 0.42, P = .0095), the NE and the left ventricular ejection fraction (LVEF) (r = 0.35, P = .026), and the

Discussion

Congestive heart failure is characterized by the progressive activation of several neurohumoral factors; and specifically, increased levels of NE and natriuretic peptides, as well as activation of the RAAS, have been described and associated with a poor prognosis.1, 2, 3, 4, 5, 6, 7, 8 We hypothesized that neurohumoral activation is present in patients after the Fontan operation, despite the absence of marked ventricular systolic dysfunction, and contributes to an adverse prognosis.

We have

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