The Left and Right Ventricles in Sleep Apnea with COPD

Abstract Dr. Janna Raphelson is a Pulmonary Critical Care fellow at UCSD and she is applying for this F32 grant to further her development as an academic physician scientist. Throughout the time period of this award she hopes to develop an expertise in heart/lung/sleep physiology that will be the foundation of her path to

independence as a clinician researcher. She will also pursue proficiency in biostatistical methods and trial design through formal coursework and direct mentoring, and gain exposure to the field of control of breathing. Her specific project for this period will focus on cardiovascular outcomes in patients with comorbid obstructive

sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to as overlap syndrome (OVS). To our knowledge, no randomized trials have been performed in OVS leaving a major void regarding how best to treat >1% of the adult US population. The proposed work is a mechanistic study to evaluate the

underlying mechanisms behind increased cardiovascular risk in patients with OVS compared to patients with COPD or OSA alone. The central hypothesis is that poor outcomes in OVS vs. COPD or OSA alone are driven by right and left heart remodeling which is more pronounced when exposed to both sustained and intermittent

hypoxia in OVS as determined by cardiac MRI imaging metrics. Aim 1 will test the hypothesis that RV remodeling (as measured by RV mass index, primary outcome) will be more elevated in patients with OVS compared to patients with COPD or OSA alone. Given the high vascular risk among afflicted patients, the very

high population prevalence of disease, and the lack of current data, further mechanistic research is imperative. Aim 2 will assess the ability of the BODE index, a commonly used clinical tool to predict mortality in COPD, to predict cardiac changes as seen on cardiac MRI. Exercise capacity limitations (an important component of the

BODE index) have been linked to myocardial fibrosis and LV remodeling, thus in Aim 2 we hypothesize that high BODE index scores will predict a greater degree of myocardial fibrosis (primary outcome) and increased LV remodeling index (secondary outcome) by cardiac MRI in patients with COPD. This grant period will help

launch Janna’s academic career as she is highly focused and deeply committed to making a scientific impact on patients afflicted with pulmonary and sleep related disease. She is working in a highly supportive environment with a mentoring team with a proven track record, and she is passionate about her vision of

becoming a leading physician scientist running an NIH funded laboratory in the coming years.