Right Ventricular Response to Exercise Among Patients with Chronic Obstructive Pulmonary Disease - PROJECT SUMMARY/ABSTRACT Pulmonary hypertension (PH) commonly affects patients with chronic obstructive pulmonary disease (COPD), and associated right ventricular (RV) dysfunction increases exercise limitation, healthcare costs, and mortality. There are no established treatments for PH or RV dysfunction in COPD. Exercise training is a low-risk, cost- effective therapy that improves symptoms and exercise capacity. Exercise training can improve RV dysfunction in some patients, but the lack of personalized, pathophysiology-targeted recommendations is a barrier to effectively using exercise training to improve RV dysfunction in COPD. The proposed K23 training program will address this need by training the candidate in mechanistic clinical trial design and implementation, applying and analyzing multimodal methods to investigate RV dysfunction, and designing and evaluating mechanism- targeted exercise interventions. To support the training plan, the proposed research will investigate patterns of RV response to aerobic exercise and establish the feasibility of an exercise intervention targeted to improve RV contractile response in patients with COPD. Aim 1 is to identify patterns of acute RV response to aerobic exercise. Patients with COPD (n=60) will complete transthoracic echocardiography (TTE) including assessment of RV global longitudinal strain at rest, moderate- and high-intensity exercise. To validate TTE metrics of contractility, a subset (n=16) undergoing clinical right heart catheterization will complete pressure- volume analysis. To identify non-invasive surrogates of RV contractility to apply in future clinical trials, cardiopulmonary exercise testing (CPET) and six-minute walk test (6MWT) metrics will be assessed. Based on the candidate's preliminary data, it is hypothesized that three patterns of RV contractile response will be observed, with one pattern being increase in RV contractility during moderate-intensity exercise but decrease (“contractile exhaustion”) during high-intensity exercise. Aim 2 will assess the feasibility of an exercise training intervention targeted to RV contractile response. Twelve participants from Aim 1 with RV contractility increase during only moderate-intensity exercise will complete a 12-week moderate-intensity interval training program to establish safety and feasibility (adherence). Repeat Aim 1 assessments will assess preliminary efficacy in improving RV contractility. This proposal will lead to multiple peer-reviewed manuscripts and a strong R01 proposal investigating the efficacy of an exercise intervention targeted to RV contractile response to improve RV dysfunction in patients with COPD. The goals of this K23 align with the NHLBI strategic goal of identifying factors that account for individual differences in pathobiology and responses to treatments. The results will tailor exercise training treatments to the individual patient to optimize outcomes. The structured training, expert mentorship, and integrated research aims will prepare the candidate to become an independent physician scientist optimizing exercise prescriptions to prevent and treat RV dysfunction in patients with lung disease.
