Carvedilol as therapy in pediatric heart failure: An initial multicenter experience

doi:10.1067/mpd.2001.113045

The Journal of Pediatrics

Volume 138, Issue 4, April 2001, Pages 505-511

https://doi.org/10.1067/mpd.2001.113045 Get rights and content

Abstract

Objective: The objective was to determine the dosing, efficacy, and side effects of the nonselective β-blocker carvedilol for the management of heart failure in children. Study design: Carvedilol use in addition to standard medical therapy for pediatric heart failure was reviewed at 6 centers. Results: Children with dilated cardiomyopathy (80%) and congenital heart disease (20%), age 3 months to 19 years (n = 46), were treated with carvedilol. The average initial dose was 0.08 mg/kg, uptitrated over a mean of 11.3 weeks to an average maintenance dose of 0.46 mg/kg. After 3 months on carvedilol, there were improvements in modified New York Heart Association class in 67% of patients (P = .0005, χ² analysis) and improvement in mean shortening fraction from 16.2% to 19.0% (P = .005, paired t test). Side effects, mainly dizziness, hypotension, and headache, occurred in 54% of patients but were well tolerated. Adverse outcomes (death, cardiac transplantation, and ventricular-assist device placement) occurred in 30% of patients. Conclusions: Carvedilol as an adjunct to standard therapy for pediatric heart failure improves symptoms and left ventricular function. Side effects are common but well tolerated. Further prospective study is required to determine the effect of carvedilol on survival and to clearly define its role in pediatric heart failure therapy. (J Pediatr 2001;138:505-11)

Section snippets

Patients and Dosing

Investigators from 6 medical centers were asked to review the medical records of pediatric patients with heart failure, age 0 to 19 years, who received carvedilol in addition to standard therapy of digoxin, diuretics, and ACE inhibitors. Underlying diagnoses, morphologic ventricle types (left ventricle or right ventricle), details of the standard heart failure therapy (initial doses and any changes of digoxin, diuretics, ACE inhibitors, or other vasodilator therapy), and details of carvedilol

Patient Population and Diagnoses

Children from 6 medical centers, ranging in age from 3 months to 19 years (n = 46), were treated with carvedilol from January 1998 through February 2000 (Table II).All patients had undergone medical treatment for at least 3 months before the initiation of carvedilol, and no patients had received previous β-blocker therapy. Thirty-seven (80%) patients had a dilated cardiomyopathy, which included 24 with “idiopathic” cardiomyopathy, 5 with chemotherapy-related cardiomyopathy, 2 with mitochondrial

Discussion

β-Blocking agents for chronic heart failure have been studied in adults for >20 years.1, 16, 17 Carvedilol and other β-blockers have been shown in adult clinical trials to improve survival, decrease symptoms, improve ventricular function, decrease hospitalizations,1, 5, 6, 7, 8, 9, 16, 17 enhance ventricular remodeling,¹⁸ decrease free radicals and adverse neurohumoral factors,15, 19, 20 decrease arrhythmias,²¹ and slow progression of heart failure.7, 9 The neurohumoral mechanisms of chronic,

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Cited by (193)

Update of Pediatric Heart Failure
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Improvement of the outcome in patients with infantile dilated cardiomyopathy over three decades – The usefulness of long-term gradually medical supportive care
2019, Journal of Cardiology
Citation Excerpt :
Therefore, the medical therapy for severe heart failure is important to avoid a heart transplantation. The use of ACEIs and beta-blockers appears to have some impact on the pediatric outcomes [7–9]. We reviewed the outcome in infants with DCM within 24 months over the three decades before treatment by devices in our institution.
The treatment of heart failure has changed with the use of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers since the middle of the 1990s. However, the outcome in infantile dilated cardiomyopathy (DCM) when treated with them remains poorly understood.
We reviewed the medical records of infants with DCM within 24 months old in our hospital between 1979 and 2012, and compared the outcome in the later group (1997–2012) with that in the early group (1979–1996). The survival and cardiac event (CE)-free survival rates were calculated by the Kaplan–Meier method.
There were 20 patients in the early group and 24 patients in the later group. The median left ventricular fractional shortening at the onset of disease in the early and later groups were 11% (range 4–17%) and 12% (range 4–25%), respectively. In the later group, ACEIs and beta-blockers were administered in 22 and 21 patients, respectively. An usual low-dose induction of carvedilol therapy (0.01–0.02 mg/kg/day) sometimes worsened the heart failure in 9 patients (43%) after the successful initial conventional treatment for acute heart failure. Nineteen patients died and 25 survived. The CEs were as follows: heart transplantation 4, mitral valvuloplasty 1, Batista operation with mitral valve replacement 1, and cardiac resynchronization therapy in the late period 1. The 20-year survival rate in the early and later groups were 5% (95% CI 0.7–28) and 100%, respectively (p < 0.001). The 2-year CE-free survival rate in the early and later groups were 5% (95% CI 0.7–28) and 83% (95% CI 59–91), respectively (p < 0.001).
The outcome in patients with infantile DCM has significantly improved with careful acute and chronic treatments using ACEIs and beta-blockers since the 2000s. Adopting a long-term supportive treatment during a period of low ventricular function and the use of beta-blockers corresponding to each patient's condition were key to survival.
Essentials of Cardiology
2019, A Practice of Anesthesia for Infants and Children
Congenital heart disease (CHD) is the most common birth defect affecting approximately 1% of live births. Although CHD is the leading cause of neonatal mortality, advances over the last several decades including significant contributions related to anesthesia care, now allow for survival of most affected infants. The wide spectrum of congenital cardiovascular anomalies and the various types of acquired heart disease in the pediatric age group presents a challenge to the clinician who does not specialize in the care of these children. Even for those with a focus or interest in cardiovascular disease, the range of structural defects, myocardial disorders, and other conditions, and the varied associated hemodynamic perturbations can be overwhelming. The ability to provide optimal perioperative care to affected children heavily relies on a clear understanding of the basic pathophysiology of the congenital anomalies and acquired diseases, familiarity with the commonly used diagnostic modalities in cardiology and their clinical applications, and medical and surgical treatment options available to affected individuals. In this chapter, we present essential concepts in cardiology to enhance the overall knowledge of the practicing anesthesiologist in pediatric cardiovascular disease.
Cardiac Physiology and Pharmacology
2019, A Practice of Anesthesia for Infants and Children
This chapter describes important features of the fetal circulation, essential changes at birth and other age-specific developments of the cardiovascular system. The incidence, prevalence and basic pathophysiological principles of congenital heart defects are presented. Several special situations are discussed in more detail: the exercise physiology of patients with repaired congenital heart disease, the Fontan physiology and the transplanted heart. Indications and practical considerations for the use of various vasoactive and antiarrhythmic drugs are reviewed.
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2018, Progress in Pediatric Cardiology
Citation Excerpt :
While the treatment of children with heart failure has come to include the use of ACE inhibitors, aldosterone antagonist, and beta-blockers, studies have failed to demonstrate the robust morbidity and mortality benefit that was seen in adults. There have been some small studies in children that support the use of beta blockers [14–19] and ACE inhibitors [20–22] in pediatric patients with ventricular dysfunction. However, the findings from these limited studies were not observed in larger trials.
The history of the clinical approach to heart failure has been notable for a series of evolving conceptual paradigms, each in an effort to explain the clinical syndrome that presents. With the recent emphasis on a neurohormonal model of heart failure, we have seen the development of new therapeutic options that target biologically active molecules to preserve myocardial function. Sacubitril-valsartan, a combined angiotensin-neprilysin inhibitor shows the greatest clinical promise, while there is less evidence to support the use of recombinant relaxin-2 or vasopressin antagonists. This article will review the history of posited mechanisms of heart failure and the impact on treatment, novel therapeutic options with neurohormonal targets, and the challenges of developing therapies for the pediatric heart failure population.
Essentials of Cardiology
2018, A Practice of Anesthesia for Infants and Children
Congenital heart disease (CHD) is the most common birth defect affecting approximately 1% of live births. Although CHD is the leading cause of neonatal mortality, advances over the last several decades including significant contributions related to anesthesia care, now allow for survival of most affected infants. The wide spectrum of congenital cardiovascular anomalies and the various types of acquired heart disease in the pediatric age group presents a challenge to the clinician who does not specialize in the care of these children. Even for those with a focus or interest in cardiovascular disease, the range of structural defects, myocardial disorders, and other conditions, and the varied associated hemodynamic perturbations can be overwhelming. The ability to provide optimal perioperative care to affected children heavily relies on a clear understanding of the basic pathophysiology of the congenital anomalies and acquired diseases, familiarity with the commonly used diagnostic modalities in cardiology and their clinical applications, and medical and surgical treatment options available to affected individuals. In this chapter, we present essential concepts in cardiology to enhance the overall knowledge of the practicing anesthesiologist in pediatric cardiovascular disease.

View all citing articles on Scopus

^☆: Reprint requests: Luke A. Bruns, MD, Division of Cardiology, 3S30, St Louis Children’s Hospital, One Children’s Pl, St Louis, MO 63110.

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Original ArticlesCarvedilol as therapy in pediatric heart failure: An initial multicenter experience☆

Abstract

Section snippets

Patients and Dosing

Patient Population and Diagnoses

Discussion

Clinical effects of beta-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials

Circulation

Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes

Clin Invest Med

Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger

J Pharmacol Exp Ther

Ischemic and nonischemic heart failure do not require different treatment strategies

J Cardiovasc Pharmacol

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

N Engl J Med

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure

Circulation

Double-blind, placebo controlled study of the effects of carvedilol in patients with moderate to severe heart failure

Circulation

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart

Circulation

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

Circulation

A management trial for Duchenne cardiomyopathy

Am J Phys Med Rehabil

Cardioprotection for Duchenne’s muscular dystrophy

Am Heart J

Beta-blocker therapy of severe congestive heart failure in infants with left to right shunts

Am J Cardiol

Beta-blocker treatment of dilated cardiomyopathy with congestive heart failure in children: a multi-institutional experience

J Heart Lung Transplant

Recommendations regarding quantitation in M-mode echocardiographic measurements

Circulation

Beta-blockers for chronic heart failure: from prejudice to enlightenment

J Cardiovasc Pharmacol

Beta-blockers in heart failure. The “new wave” of clinical trials

Drugs

Beta-adrenergic blocking agents: past, present, and future perspectives

Coron Artery Dis

Original Articles
Carvedilol as therapy in pediatric heart failure: An initial multicenter experience☆