Landmark innovations in the management of complex congenital heart diseases (CHD) have transformed survival over the past 40 years. The growing population of survivors are at risk for heart failure, rhythm disturbances and early mortality. Despite the magnitude of the clinical problem, the cellular mechanisms of heart failure are poorly understood. To further support the poor understanding of the cellular mechanisms of heart failure, standard heart failure therapies (β-blockers, angiotensin converting enzyme inhibitors) lack efficacy in the CHD population. In addition, current clinical decision-making using echocardiography and cardiac MRI can only detect late structural changes, are insensitive to detect the early stages of fibrosis, and are still imperfect measures to predict whether a dilated and hypertrophied ventricle will recover function or progress to heart failure. Therefore, there is a need to develop noninvasive biomarkers to provide clinicians a window into the remodeling events occurring in the heart, to detect the early, reversible stages of failure, and to predict which patients are at greatest risk of Fontan failure. Our lab uses a high throughput proteomics approach using cardiac tissue, plasma and circulating microvesicles to understand the mechanisms of disease progression.