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.


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 0.8 mg/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.


CONCLUSIONS
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.
Giardini
Alessandro
A
Pediatric Cardiology, Policlinico "S. Orsola", University of Bologna, Italy. alessandro5574@iol.it
Formigari
Roberto
R
Bronzetti
Gabriele
G
Prandstraller
Daniela
D
Donti
Andrea
A
Bonvicini
Marco
M
Picchio
Fernando M
FM
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D000077261:Carvedilol; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D018377:Neurotransmitter Agents / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D018377:Neurotransmitter Agents; D011412:Propanolamines; D000077261:Carvedilol