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Challenges and Opportunities in Pediatric Heart Failure and Transplantation

Update on Pharmacological Heart Failure Therapies in Children

Do Adult Medications Work in Children and if Not, Why Not?

Joseph W. Rossano, Robert E. Shaddy
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https://doi.org/10.1161/CIRCULATIONAHA.113.003615
Circulation. 2014;129:607-612
Originally published February 3, 2014
Joseph W. Rossano
From the Cardiac Center, Children’s Hospital of Philadelphia, Philadelphia, PA; and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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Robert E. Shaddy
From the Cardiac Center, Children’s Hospital of Philadelphia, Philadelphia, PA; and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
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  • heart failure
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Heart failure is a serious problem in children with acquired and congenital heart disease (CHD). In 2006, there were nearly 14 000 hospitalizations related to heart failure in pediatric patients.1 The disease is also costly, not only in terms of lives lost with a 20-fold increase in hospital mortality compared with children without heart failure but also in terms of morbidities, prolonged hospitalizations, and dramatically high hospital charges.1–3 However, it is not clear that there has been an overall improvement in the outcomes of children with heart failure. Although the risk-adjusted hospital mortality has declined, several single-center and multicenter studies of dilated cardiomyopathy (DCM) failed to demonstrate any change in survival over several decades.4–7

Multiple large, prospective, multicenter, randomized, controlled trials in adult heart failure patients have demonstrated the survival advantage of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists.8–12 However, many drugs shown to be beneficial in the treatment of heart failure in adults have not been proven to be effective in children.4,13–17 There are many potential reasons for this. One potential reason is that the medications are actually beneficial, but the design and populations included in prior studies were not sufficient to demonstrate the benefit. However, there are other problems that may have more to do with the potential differences between adults and children with heart failure and their response to medications that treat heart failure. These issues are the focus of this review.

Challenges in Study Design in Pediatric Heart Failure

One potential explanation for the negative findings of many pediatric heart failure studies is that the medications actually work, but the challenges in study design and study implementation make it difficult, if not impossible, to see the beneficial treatment effect. Prospective pediatric heart failure drug trials are …

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Circulation
February 4, 2014, Volume 129, Issue 5
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    Update on Pharmacological Heart Failure Therapies in Children
    Joseph W. Rossano and Robert E. Shaddy
    Circulation. 2014;129:607-612, originally published February 3, 2014
    https://doi.org/10.1161/CIRCULATIONAHA.113.003615

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    Update on Pharmacological Heart Failure Therapies in Children
    Joseph W. Rossano and Robert E. Shaddy
    Circulation. 2014;129:607-612, originally published February 3, 2014
    https://doi.org/10.1161/CIRCULATIONAHA.113.003615
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