Abstract 13507: Aldosterone Regulation by Angiotensin-converting Enzyme in Congenital Heart Disease: The Clinical Importance of Blocking Angiotensin-converting Enzyme in a Single Ventricular Heart
Background: Aldosterone(Aldo) is known to accelerate cardiovascular fibrogenesis that causes ventricular diastolic dysfunction and vascular stiffening. However, serum Aldo levels are considerably different among pediatric patients with various congenital heart defects. The regulatory mechanism for Aldo in this population remains poorly understood. We hypothesized that hemodynamic-related angiotensin-converting enzyme (ACE) activity has strong effects on Aldo modulation.
Methods: Serum levels of renin, Aldo, and ACE were measured in 246 children, particularly focusing on the repaired coarctation of the aorta (CoA, n = 56), and Fontan (n = 38) and Glenn (n = 47) circulation. Data were compared to those of control patients who had small ASD or VSD (n = 105).
Results: Serum renin and Aldo levels were significantly higher in CoA, Glenn, and Fontan patients than in controls (both, p < 0.001 vs. controls). Although renin levels were similar among the groups, Aldo levels were significantly lower in the CoA (406 ± 679 pg/mL) than in the Glenn (1230 ± 1217 pg/mL, p < 0.001) and Fontan (838 ± 1085 pg/mL, p = 0.04) groups, resulting in a significantly lower Aldo/renin ratio in the CoA group compared to the other groups (p < 0.001). Importantly, serum ACE levels were significantly lower in the CoA than in the other groups (p = 0.02), suggesting ACE-modulated Aldo production in these patients. Multiple regression analysis revealed that the serum ACE level was positively correlated with end diastolic pressure and negatively correlated with mean pulmonary arterial pressure (p = 0.001 and 0.004, respectively). Moreover, the serum ACE level was significantly correlated with the ventricular diastolic parameters of logistic tau and stiffness β in Fontan circulation.
Conclusions: ACE activity, which was enhanced by ventricular diastolic dysfunction and reduced by the increased pulmonary pressure, modulated serum Aldo levels in this study. Because of the low pulmonary pressure in right ventricular bypass surgery, serum Aldo levels in Glenn/Fontan circulation can easily be increased by ACE activation. This may partly explain the mechanism for the progression of heart failure after the Fontan procedure, and may support the use of ACE inhibitors in Fontan patients.
- © 2013 by American Heart Association, Inc.