New directions in basic research in hypertrophy and heart failure: Relevance for pediatric cardiology

Tremendous advances have been made in understanding the basic cellular mechanisms of hypertrophy and heart failure. Powerful new tools, such as targeted gene manipulation in the mouse, have provided great insight into the complex cross-talk between different signaling pathways regulating cardiac function and remodeling. New levels of complexity are being uncovered, e.g. regulation of gene expression by micro-RNAs and histone modification. However, many of the models used to study these processes may not accurately recapitulate the cardiac stresses experienced by patients with congenital heart disease. There has been a very "left ventricular-centric" bias in this field, whereas many congenital heart disease patients have abnormal hemodynamics affecting the right ventricle (e.g. tetralogy of Fallot, L-TGA, hypoplastic left heart). Developing a better understanding of the similarities and differences between left and right ventricular hypertrophy and failure will be critically important, as common therapeutics which are effective in left ventricular failure are often not effective in the failing right ventricle.