Functional Characterization of Children with Chronic Venous Thromboembolic Disease

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PROJECT SUMMARY Venous thrombosis affects approximately 1 in 200 hospitalized children. Important symptoms after deep venous thrombosis (DVT) involving lower extremities and pulmonary embolism (PE) include shortness of breath and exercise intolerance resulting in a decreased quality of life. The mechanisms of these symptoms are unknown. Although patients with venous thrombosis with excise intolerance and exertional dyspnea are generally considered to be deconditioned, our preliminary data challenge this conventional wisdom. Thus, it is presently unclear if exercise intolerance or exertional dyspnea are due to cardiovascular, pulmonary, or limb- muscle dysfunction and whether acquired risk-factors such as deconditioning or obesity contribute to these problems. If we find evidence of deconditioning causing or complicating exercise intolerance or dyspnea, exercise training would be dramatically beneficial; for obesity-related changes in respiratory mechanics, aggressive weight loss measures may be necessary before exercise training can be tolerated. In this application, we will utilize state-of-the-art measures, including 7 Tesla magnetic resonance imaging, at rest and during exercise to investigate central and peripheral mechanisms of these common symptoms. Aim 1 will characterize cardiac limitations; Aim 2, pulmonary and Aim 3, skeletal muscle metabolic aberrations following DVT and PE at 3 and 12 months post-diagnosis in pediatric patients following diagnosis. Our long-term objective is to provide novel and clinically relevant results that could potentially alter approaches for preventing and treating exercise intolerance and dyspnea and improving the quality of life for pediatric patients with VTE.