The most severe form of congenital heart disease includes patients with single right ventricle (SRV) physiology who exhibit 40% mortality by 5 years of age. These patients are all at very high risk for heart failure. Clinical drug trials in these patients show that therapies proven to be efficacious in adults do not appear to improve heart failure in patients with SRV physiology. There exist numerous hypotheses to potentially explain these differences, all of which revolve around the theoretical differences in cardiac mechanics between biventricular and single ventricle physiology. However, none of these hypotheses can currently be tested because 1) the pathophysiologic mechanisms behind the development of heart failure in patients with SRV have not been comprehensively studied, 2) there are currently no reliable methods to non-invasively assess cardiac mechanics in patients with SRV, and 3) the associations between these measures and patient outcomes has not been studied. My long term goal is to become an independent scientist in the evaluation of heart failure in patients with single ventricle physiology so that I may investigate novel heart failure therapies by leading clinical trials in these patients and use serum/non-invasive heart failure biomarkers to gain insight into the results of such trials. To reach this goal, complete the following aims: 1) Investigate pathophysiologic mechanisms that lead to the development of heart failure in patients with SRV, 2) assess the accuracy of echocardiographic measures of cardiac mechanics by assessing their correlation with reference-standard measures, and 3) investigate the clinical utility of these serum and non-invasive measures of myocardial function by assessing their association with short-term outcomes. The resultant understanding of SRV physiology will lead to new and innovative therapies, and ideally, improve outcomes in this vulnerable population. The skills gained from the execution of this career development plan and research protocol will uniquely qualify me to be a leader in the fields of myocardial mechanics, single ventricle physiology, and clinical drug and interventional trials in the pediatric population.

Public Health Relevance

Patients with only a single functional right ventricle undergo a series of surgeries that result in blood flowing passively from the veins in their body to the arteries that lead to the lungs without the need for a second ventricle; abnormalities in cardiac muscle contraction, relaxation, or its interaction with the arterial system lead to many complications that result in significant morbidity and mortality in these patients. The reasons for the development of heart failure are unknown in these patients; as such, there are no known effective heart failure therapies in these children. Therefore, the goals of this study are to understand the mechanisms behind the development of heart failure in this population.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
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Scott, Jane
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Medical University of South Carolina
Schools of Medicine
United States
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Chowdhury, Shahryar M; Butts, Ryan J; Hlavacek, Anthony M et al. (2018) Echocardiographic Detection of Increased Ventricular Diastolic Stiffness in Pediatric Heart Transplant Recipients: A Pilot Study. J Am Soc Echocardiogr 31:342-348.e1