Carvedilol in children with cardiomyopathy: 3-year experience at a single institution

doi:10.1016/j.healun.2003.07.025

The Journal of Heart and Lung Transplantation

Volume 23, Issue 7, July 2004, Pages 832-838

Presented at the 23rd annual meeting of the International Society for Heart and Lung Transplantation, Vienna, Austria, April 2003.

https://doi.org/10.1016/j.healun.2003.07.025 Get rights and content

Abstract

Background

Carvedilol reduces mortality and hospitalization in adults with congestive heart failure. Limited information is available about its use in children.

Methods

We reviewed the medical records of 24 children with dilated cardiomyopathy and left ventricular ejection fraction of ≤40%, who were treated with carvedilol as adjunct therapy to angiotensin-converting enzyme inhibitors, digoxin and diuretics.

Results

Carvedilol was initiated 14.3 ± 23.3 (mean ± SD) months after the diagnosis of cardiomyopathy. Mean age at initiation of therapy was 7.2 ± 6.4 years. The mean initial and maximum doses were 0.15 ± 0.09 and 0.98 ± 0.26 mg/kg/day. Adverse effects occurred in 5 patients (21%). Two patients (8%) required discontinuation of the drug within 5 weeks of the initial dose. The remaining 22 patients tolerated carvedilol for a mean follow-up period of 26.6 ± 14.7 months. Among these 22 patients, mean left ventricular ejection fraction improved from 24.6 ± 7.6% to 42.2 ± 14.2% (p < 0.001), and mean sphericity index from 0.86 ± 0.11 to 0.74 ± 0.10 (p < 0.001). New York Heart Association functional class improved in 15 patients (68%). One patient (4%) died and 3 (14%) were transplanted.

Conclusions

Carvedilol, in addition to standard therapy for dilated cardiomyopathy in children improves cardiac function and symptoms; it is well tolerated, with minimal adverse effects, but close monitoring is necessary as it might worsen congestive heart failure and precipitate asthma. Control studies are necessary to assess the effect of carvedilol on mortality and hospitalization rates.

Section snippets

Methods

A systematic approach for the treatment of dilated CMP was established at our institution in 1998. Since then, patients with left ventricular ejection fraction (LVEF) ≤40% have been referred to our pediatric heart failure program where a single designated physician evaluates and follows the referred children. At each follow-up visit, symptoms, level of physical activity, growth and development are assessed and documented. Pharmacologic treatment with digoxin, ACE inhibitors and diuretics are

Study population

The study population consisted of 24 pediatric patients, 12 girls and 12 boys, and included 15 children who had been referred for cardiac transplant evaluation. Age at diagnosis ranged from 1 day to 16.5 years, with a mean (± SD) of 6.0 ± 6.3 (median 3.0) years.

All patients had idiopathic dilated cardiomyopathy and LVEF ≤40%; in 16 patients (67%) LVEF was <30%. Carvedilol was added as adjunct therapy to digoxin, ACE inhibitors and diuretics. After carvedilol initiation, all patients remained on

Discussion

One of the most deleterious effects of congestive heart failure is activation of the sympathetic system.25 Stimulation of β1-receptors by cathecolamines leads to increases in heart rate and contractility.26 Stimulation of α1-receptors causes peripheral and coronary vasoconstriction,27 increases oxygen consumption of the myocardium by increasing the afterload,25 and contributes to remodeling of the heart with fibrosis and hypertrophy.28 Norepinephrine stimulation of β1-receptors results in

References (30)

A.B. Lewis et al.
Outcome of infants and children with dilated cardiomyopathy
Am J Cardiol
(1991)
A.B. Lewis
Prognostic value of echocardiography in children with dilated cardiomyopathy
Am Heart J
(1994)
T. Akagi et al.
Natural history of dilated cardiomyopathy in children
Am Heart J
(1991)
A.B. Lewis
Late recovery of ventricular function in children with idiopathic dilated cardiomyopathy
Am Heart J
(1999)
R. Doughty et al.
Left ventricular remodeling with carvedilol in patients with congestive heart failure due to ischemic heart disease
J Am Coll Cardiol
(1997)
D.W. Wahr et al.
Left ventricular volumes determined by two-dimensional echocardiography in a normal adult population
J Am Coll Cardiol
(1983)
L.A. Bruns et al.
Carvedilol as therapy in pediatric heart failurean initial multicenter experience
J Pediatr
(2001)
M. Packer
Pathophysiology of chronic heart failure
Lancet
(1992)
M. Simons et al.
Coronary vasoconstriction and catecholamine cardiomyopathy
Am Heart J
(1985)
M.A. Grenier et al.
Design and implementation of the North American Pediatric Cardiomyopathy Registry
Am Heart J
(2000)

A. Arola et al.

Idiopathic dilated cardiomyopathy in childrenprognostic indicators and outcome

Pediatrics

(1998)

S.A. Webber

15 years of pediatric heart transplantation at the University of Pittsburghlessons learned and future prospects

Pediatr Transplant

(1997)

M. Packer et al.

The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group

N Engl J Med

(1996)

W.S. Colucci et al.

Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure

Circulation

(1996)

M. Packer et al.

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective randomized evaluation of carvedilol on symptoms and exercise

Circulation

(1996)

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Failing heart—medical aspectsCarvedilol in children with cardiomyopathy: 3-year experience at a single institution

Abstract

Background

Methods

Results

Conclusions

Section snippets

Methods

Study population

Discussion

Am J Cardiol

Am Heart J

Am Heart J

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Pediatr

Lancet

Am Heart J

Design and implementation of the North American Pediatric Cardiomyopathy Registry

Am Heart J

Idiopathic dilated cardiomyopathy in childrenprognostic indicators and outcome

Pediatrics

15 years of pediatric heart transplantation at the University of Pittsburghlessons learned and future prospects

Pediatr Transplant

The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group

N Engl J Med

Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure

Circulation

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective randomized evaluation of carvedilol on symptoms and exercise

Circulation

Failing heart—medical aspects
Carvedilol in children with cardiomyopathy: 3-year experience at a single institution