Clinical Investigations: Congestive Heart Failure
Carvedilol therapy in pediatric patients with congestive heart failure: A study investigating clinical and pharmacokinetic parameters*,**,★

https://doi.org/10.1067/mhj.2002.121265Get rights and content

Abstract

Objective Our purpose was to evaluate the clinical effect of carvedilol among pediatric patients with congestive heart failure (CHF) who did not respond to standard therapy and to assess the pharmacokinetics of carvedilol among these children. Methods In this prospective, open intervention trial with blinded interpretation of selected end points, patients with CHF who did not improve on standard therapy, including digoxin, angiotensin-converting enzyme inhibitors, and diuretics, were treated with oral carvedilol in a ramped dosing scheme. Clinical parameters (ejection fraction, fractional shortening, and modified Ross score) were assessed before initiation of treatment and monthly for 6 months. Pharmacokinetic profiles of carvedilol were determined over the first 12-hour period after the initial dose in study patients, and for comparison, in 9 healthy adult volunteers. Results Fifteen patients (aged 6 weeks to 19 years) were enrolled in the study, including 10 patients with dilated cardiomyopathy and 5 with CHF secondary to congenital heart disease. All 15 patients tolerated carvedilol for the duration of the trial, and all achieved maximum target dosing. After 6 months of carvedilol therapy, ejection fraction increased (36% vs 54%; P <.05) and modified Ross Score improved (5 ± 2 vs 3 ± 3; P <.05). Elimination half-life was about 50% shorter in pediatric CHF patients compared with healthy adult volunteers (2.9 vs 5.2 hours; P <.05). Conclusions Pediatric patients with CHF not responding to standard therapy may benefit from oral carvedilol treatment. The observed increased elimination of carvedilol in children suggests that optimal dosing strategies need to be further defined among the pediatric population. (Am Heart J 2002;143:916-22.)

Section snippets

Study organization

This study was a prospective, open intervention involving pediatric patients with CHF. The local ethics committee gave approval, and the patients or their parents gave informed consent. In addition, healthy adult volunteers participated in a pharmacokinetic investigation after approval was given by the local ethics committee and informed consent was obtained from each volunteer.

Patients

Between 1997 and 1999, all pediatric patients admitted to our hospital with CHF resulting from dilated cardiomyopathy

Patient characteristics

Fifteen patients participated in the study, and their baseline demographic and clinical characteristics are summarized in Tables II and III.

. Baseline characteristics of patients

Patients (n)15
Age (y)0.12-19.3
Sex (female/male)4/11
Body weight (kg)3.1-98.2
CHF etiology
 Dilated cardiomyopathy (n)10
 Congenital heart disease (n)5
  Ventricular septal defect (n)1
  Hypoplastic left heart syndrome (n)2
  Mitral insufficiency (n)1
  Double outlet right ventricle (n)1
CHF was the result of dilated cardiomyopathy in 10

Discussion

The novel findings of this study include that oral carvedilol added to standard drug therapy in pediatric patients with CHF is well tolerated and associated with an improvement in ventricular function and clinical symptom scores. Children eliminated carvedilol faster than adults, which could result in a different dosing regimen for pediatric patients with CHF to optimize the therapeutic response.

CHF in children is a rare disease with a prevalence of about 3 cases per million. The prognosis of

Acknowledgements

We are indebted to Dr Lise M. Bjerre and Dr Martin Hulpke-Wette (Göttingen, Germany) and Dr Darren McQuire (Dallas, Tex) for helpful comments and for critically reviewing the manuscript.

References (28)

  • M Packer et al.

    The effect of carvedilol on morbidity and mortality in patients with chronic heart failure

    N Engl J Med

    (1996)
  • WH. Frishman

    Carvedilol. Drug therapy

    N Engl J Med

    (1998)
  • MERIT-HF

    Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF)

    Lancet

    (1999)
  • CIBIS et al.

    The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial

    Lancet

    (1999)

    • Cited by (130)

    • Update of Pediatric Heart Failure

      2020, Pediatric Clinics of North America
      Citation Excerpt :

      In 1987, Ross developed a score tailored to symptoms of infants and younger children (see Table 1).9 In 2002, Laer and colleagues10 developed their own model based on age and 6 variables. By 2012, Ross11 modified his own score to include age-based symptoms.

    • Growth differentiation factor 15 as a useful biomarker of heart failure in young patients with unrepaired congenital heart disease of left to right shunt

      2020, Journal of Cardiology
      Citation Excerpt :

      In addition to arterial oxygen content (CaO2 = 1.36 × Hb x SaO2 × 10), oxygen delivery (DO2), and oxygen extraction ratio (OER) were calculated as the following equation: DO2 = CO × CaO2, OER = (SaO2 – SvO2) / SaO2. In order to evaluate clinical symptoms of HF, modified Ross score was calculated for all patients [13]. In brief, the modified Ross score consisted of patient’s symptoms (diaphoresis, tachypnea) and findings of physical examination (breathing style, respiratory rate, heart rate, and hepatomegaly), assigning 0 to +2 points for each parameter with a distribution of 0–12 points.

    • Heart failure in paediatric patients: pathophysiology and treatment. Part II

      2018, Revista Colombiana de Cardiologia

    • Heart failure in paediatric patients. Pathophysiology and management. Part 1

      2018, Revista Colombiana de Cardiologia

    • Relationship between heart failure and intestinal inflammation in infants with congenital heart disease

      2024, BMC Microbiology

    • Influence of Age, Heart Failure and ACE Inhibitor Treatment on Plasma Renin Activity in Children: Insights from a Systematic Review and the European LENA Project

      2023, Frontiers in Bioscience - Landmark
    View all citing articles on Scopus
    *

    This study was supported by the Deutsche Stiftung für Herzforschung, Frankfurt, Germany.

    **

    Reprint requests: Stephanie Läer, MD, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Abteilung für Pharmakologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Martinistrasse 52, Germany.

    ★

    E-mail: [email protected]

    View full text
    Copyright © 2002 Mosby, Inc. All rights reserved.