DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide. Significantly, COPD carries a 2-5 fold increased risk of cardiovascular disease (CVD). This association persists even after accounting for shared risk factors, such as tobacco smoking. However, few studies have evaluated distinct pathophysiological mechanisms contributing to poor cardiovascular outcomes in individuals with COPD and CVD. Our hypothesis is that lung hyperinflation from COPD influences this cardiopulmonary relationship. In support of this hypothesis, studies of lung volume reduction surgery have suggested improvement in cardiovascular performance after surgical deflation. However, the mediators of this relationship are still generally unclear and essentially unknown in patients with both COPD and CVD. Given the frequent co-morbidity of COPD and CVD, an understanding of this complex relationship is critical to: 1) identifying COPD patients at risk for poor cardiovascular outcomes and 2) developing novel treatments to address this additional CVD risk in COPD patients. The purpose of this project is to identify structural, hemodynamic, and functional cardiac alterations unique to subjects with hyperinflation from a population of individuals with both COPD and CVD. We hypothesize that amongst individuals with COPD and CVD, lung hyperinflation leads to decreased cardiac chamber sizes, diminished cardiac filling, and, consequently, reduced cardiac output which can be reversed with lung deflation strategies. We will first investigate these questions using a local cohort of 8,000 subjects who have undergone cardiac MRIs, the current gold standard for cardiac chamber quantification, and analyze CMR- derived measures of cardiac structure and function in subjects with COPD and CVD, with and without hyperinflation. To understand the relationship of cardiac geometry to cardiac physiology, we will analyze previously ascertained invasive hemodynamic parameters from right heart catheterization, the gold standard for such measurements, in the same subjects. To help discern causal effects, we will use a novel reversible, non-invasive lung deflation device prospectively on ten subjects with hyperinflation and evaluate the hemodynamic effects of acute deflation with non-invasive impedance cardiography. As part of the research training program, the principle investigator will complete a Masters in Medical Sciences at Harvard Medical School through the Harvard Master's Program in Clinical and Translational Investigation in order to master the needed skills in biostatistics, advanced cardiopulmonary physiology, and translational human investigation. This research project will be performed under the complementary guidance of well-established investigators in pulmonary bioengineering and advanced cardiothoracic imaging with advice from experts in COPD therapeutics and cardiopulmonary physiology.

PUBLIC HEALTH RELEVANCE: COPD is a prevalent disease with increasing morbidity and mortality, in large part related to concurrent cardiovascular disease. This study aims to better understand the mechanisms by which lung volumes affect cardiac performance in patients with COPD and cardiovascular disease. The results of this work have the potential to inform therapies for COPD patients.