New Mechanistic and Therapeutic Targets for Pediatric Heart Failure

Pediatric heart failure (HF) is the inability of the heart of an infant, child, or adolescent to meet the body’s metabolic demands. It involves circulatory, neurohumoral, and molecular abnormalities that manifest as edema, respiratory distress, growth failure, and exercise intolerance. The myriad causes include inherited and acquired myocardial anomalies (cardiomyopathy [CM]), volume overload (intracardiac shunts, valvular regurgitation), and the unique hemodynamics predicated by a functional single ventricle (palliated complex congenital heart disease [CHD]).Although the societal and financial costs of adult HF are well known, the burden of pediatric HF is less familiar, but no less onerous. New-onset HF requiring hospital admission occurs in 0.87 per 100 000 children,1 yet that does not include the growing population with CHD-related HF. In 2006, there were nearly 14 000 pediatric hospitalizations for HF from all causes in the United States.2 The rate of HF-related admissions was nearly 18 per 100 000 children,2 which is comparable to severe sepsis.3The mortality for pediatric HF hospitalizations is significant. The 7% overall hospital mortality rate exceeds the 4% mortality of adult HF admissions4 and represents a 20-fold increase over children without HF.2 With comorbidities like renal failure, sepsis, or stroke, hospital mortality in pediatric HF can exceed 20%,2 yet the risk does not end with discharge. After an initial HF hospitalization, only 21% of children in 1 study avoided readmission, death, or transplantation.5Pediatric HF treatment is resource intensive. Although the total healthcare costs for pediatric HF are lower than for adults, per-patient costs are higher. The estimated hospital charge per pediatric HF admission in 2006 was >$135 000, with aggregate charges exceeding $1.8 billion.6 Certain subpopulations of pediatric HF incurred disproportionally higher costs. For example, single-ventricle CHD averaged >$200 000 per hospitalization,7 whereas adult …