The Impact of Positive Airway Pressure (PAP) Therapy on Myocardial Blood Flow in Adults with Obstructive Sleep Apnea at High-Risk of Cardiovascular Disease: The PAP-Flow Study - ABSTRACT New and innovative approaches to studying modifiable mechanisms of heart failure are crucial. Heart failure impacts approximately 7 million adults in the United States and has a 5-year mortality rate of 42%. Obstructive sleep apnea (OSA), traditionally assessed by the apnea-hypopnea index (AHI), increases the risk of heart failure. OSA-specific measures of hypoxia (hypoxic burden) and autonomic response (∆heart rate) are associated with heart failure and adverse cardiovascular disease (CVD) outcomes, independent of the AHI. Abnormal left ventricular (LV) myocardial flow reserve, measured by cardiac PET stress test, is a marker of coronary microvascular dysfunction and is implicated in heart failure with preserved ejection fraction (HFpEF) development. Right ventricular (RV) myocardial blood flow is also emerging as a measure of CVD prognosis. Hypotheses: Some patients with OSA experience an immediate (one-week) increase in LV myocardial flow reserve after PAP initiation. Hypoxic burden and ∆heart rate are associated with abnormal LV myocardial flow reserve and predict immediate LV myocardial flow reserve increase with PAP therapy. LV myocardial flow reserve increase is associated with improvement in myocardial function. PAP use also improves abnormal RV myocardial blood flow. We will recruit 60 individuals with ≥ moderate PAP-naïve OSA (AHI ≥15/hour) to test these hypotheses. Those with abnormal LV myocardial flow reserve (n=40) will have repeat testing at one week and four months after initiating PAP. The specific aims are: 1. To determine if OSA-specific hypoxic burden and ∆heart rate (the peak minus nadir heart rate associated with an obstructive episode on a sleep test) are associated with abnormal LV myocardial flow reserve at baseline 2: Among persons with abnormal LV myocardial flow reserve, we will determine if: A) LV myocardial flow reserve increases after one week and four months of PAP use, and if baseline hypoxic burden and ∆heart rate predicts immediate (one-week) flow reserve increase, B) LV myocardial flow reserve increase after one week and four months of PAP therapy is associated with improvements in measures of myocardial function at four months. AIM 3 (Exploratory): Focusing on the RV, we will explore A) the baseline association between the hypoxic burden, ∆heart rate, and RV myocardial blood flow and B) changes in RV myocardial blood flow with PAP therapy and their association with LV and RV myocardial function. An enhanced understanding of OSA physiology, mastery of translational cardiac imaging, and clinical research skills gained during this award will strategically position me to become an independent investigator focused on CVD mechanisms and therapeutics in persons with sleep-disordered breathing, including OSA. Our study findings should inform current heart failure risk assessment practices and guide management decisions for patients with OSA. It will form the basis of cardiac imaging-based mechanistic clinical trials of OSA- specific therapies and their impact on the heart. Such studies will form the foundation of my R-01 application.
