Modulation of neurohormonal activity after treatment of children in heart failure with carvedilol

Background: In adults with heart failure, neurohormonal overstimulation is related to the progression of the disease, and influences prognosis. beta-blockers, which modulate neurohormonal activation, now play an essential role in the pharmacological management of heart failure in adults, but their use in children is very limited. Patients and Methods: To investigate the effects of carvedilol administration on neurohormonal activation and left ventricular function, carvedilol was added to standard treatment for heart failure in 9 patients with dilated cardiomyopathy due to heart muscle disease. Standard treatment has been in place for at least 1 month. The protocol consisted in a baseline evaluation to assess neurohormonal activation, and echocardiographic evaluation of left ventricular function. This was followed by a final evaluation at 12 months from carvedilol loading. Carvedilol was started at 0.05 mg/kg/day, and increased every two weeks until the target dose of 0.8mg/kg/day was reached. Results: Carvedilol administration was associated with a significant reduction in plasma norepinephrine (p = 0.00001), dopamine (p = 0.0001), aldosterone (p = 0.00001) and activation of the renin-angiotensin system (p = 0.0006). Similar reductions in vanilmandelic and homovanillic acid were noted. After 12 months, a positive remodeling took place, with significant reductions in end-diastolic (p = 0.004) and end-systolic diameters (p = 0.009), and an increase in left ventricular ejection fraction (p = 0.001). No adverse effects needing reduction or interruption in the dosage were noted in the run-in phase, nor in the period of maintenance. Conclusion: Carvedilol is a safe complement to standard therapy for heart failure in children, allowing a significant reduction of neurohormonal activation with evident benefits on both ventricular function and the clinical condition.