RILEY SYMPOSIUM 2008 Riley Heart Center Symposium on Cardiac Development: Growth and Morphogenesis of the Ventricular Wall Loren J. Field Weinian Shou Randall L. Caldwell Received: 5 February 2009 / Accepted: 26 February 2009 / Published online: 2 April 2009 Ó Springer Science+Business Media, LLC 2009 Heart failure in the young is a common clinical entity that has significant morbidity and mortality and carries sub- stantial long-term social and financial costs. The leading cause is congenital heart disease, which is the most com- mon birth defect and is also the fifth ranked cause of years of potential life lost, at 2 per 1000 population [1, 2, 6, 21]. Well over 450,000 children [21] and over 1 million adults [12] in the United States have a congenital heart defect, emphasizing its impact on public health. Despite the importance of heart failure in children and infants, it has been less well studied when compared with the rich liter- ature and basic understanding of heart failure in adults. As a result, therapy for children with heart failure has advanced more slowly. Indeed, most new concepts for management of heart failure in children today are based on the translation of adult treatment strategies with little pre- clinical evidence supporting their use in the young [7, 9]. However, recent and exciting discoveries in the molecular regulation of cardiac morphogenesis, as well as in the cellular and molecular response of the heart to injury, have provided new tools to understand heart failure in the young. At its most basic definition, heart failure is simply the inability of the heart to meet the metabolic demands of the body. Not surprisingly, the origins of heart failure in infants and children are strikingly different from those in adults [9, 26], and in most instances, they can be traced to congenital or acquired myocardial injuries as outlined in Fig. 1. Congenital injuries frequently result from abnormal heart morphogenesis, which in turn gives rise to structural defects in utero. Inappropriate gene expression [5, 11], expression of mutant genes [4, 10], and exposure to car- diotoxic chemicals [8] or drugs [28] are known to promote abnormal morphogenesis. The resulting structural defects (exemplified by atrial and ventricular septal defects, aortic coarctation or valve stenosis, and complex heart disease) render heart pump function tremendously inadequate. In turn, this causes prolonged work overload and a progres- sive loss of cardiomyocyte function and viability worsening the clinical disease [13, 29]. Nearly 1% of all newborns will have a structural heart defect [14], and the majority of these is severe enough to cause heart failure and death in the absence of surgical and/or other inter- vention. Inherited cardiomyopathies constitute another important class of congenital heart defects (i.e., abnor- malities of the sarcomere) [25, 27]. Patients with familial hypertrophic cardiomyopathy often develop severe cardiac hypertrophy characterized by overt cardiomyocyte disarray as juveniles or young adults, and they succumb to sudden cardiac death. In contrast, dilated cardiomyopathy might result from defects in contractile proteins [16] or in the transmission of mechanical force to the surface of the cardiomyocyte (i.e., cytoskeletal defects [19, 23]). Thoughtful ongoing investigations have provided a detailed understanding of the contractile apparatus and their mutations that cause impaired heart function [3]. Acquired injuries are also a major source of childhood heart failure and are associated with cardiomyocyte loss; for example, although surgery can frequently reduce the impact of congenital structural defects resulting in pro- nounced functional recovery, ischemia/reperfusion (I/R) injury from the surgical intervention itself can lead to myocardial damage [22] and subsequent cardiomyopathies later in juvenile patients [24]. Additionally, inability to completely correct structural defects leads to chronic L. J. Field (&) Á W. Shou Á R. L. Caldwell The Riley Heart Center, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA e-mail: ljfield@iupui.edu 123 Pediatr Cardiol (2009) 30:577–579 DOI 10.1007/s00246-009-9407-4