Right Ventricular Response to Exercise Among Patients With Chronic Obstructive Pulmonary Disease

This study will determine patterns of right ventricular (RV) response to aerobic exercise in patients with chronic obstructive pulmonary disease (COPD) and will design a targeted exercise intervention to improve RV response. We will study 60 patients with COPD. Participants will complete cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) during rest, moderate- and high-intensity exercise. A subset of participants (n=16) who have been recommended to undergo clinical right heart catheterization will be recruited for the primary study with additional invasive pressure-volume analysis during the CPET. This testing will be used to validate measures of RV function obtained through noninvasive testing. The sample size was selected based upon our preliminary data and statistical analysis plans.

To test whether an exercise intervention targeted to RV response to exercise is feasible for patients, 12 participants will complete a targeted exercise training intervention based on their RV contractile response during baseline testing. This intervention will include participants who demonstrate RV contractility increase to moderate- but not high-intensity exercise. We will test the feasibility of a moderate-intensity interval training program. Participants will complete exercise training sessions 3x/week for 12 weeks. Exercise training will be performed on an upright stationary bicycle. Following the exercise training intervention, participants will repeat CPET and TTE. They will also complete a health-related quality of life questionnaire before and after the exercise training intervention.

Inclusion criteria

• COPD (determined by ratio of forced expiratory volume in 1 second to forced vital capacity [FEV1/FVC] <0.7)
• Age >= 40 years

Exclusion criteria

• Exacerbation of COPD in the 3 months prior to enrollment
• Change in COPD therapy in the 3 weeks prior to enrollment
• Requirement of >6 LPM supplemental oxygen at rest
• Requirement of >10 LPM supplemental oxygen with exertion
• Active/uncontrolled cardiovascular disease (e.g. hypertension with blood pressure >150/100 despite antihypertensives; coronary artery disease with angina; left ventricular ejection fraction ≤40%; uncontrolled arrhythmia; pulmonic, mitral or aortic valvular abnormality greater than mild in severity; tricuspid regurgitation greater than moderate in severity)
• Volume overload (jugular vascular distension or greater than trace peripheral edema)
• World Health Organization Functional Class IV
• Known pulmonary hypertension with mean pulmonary artery pressure >45 mmHg
• Untreated severe obstructive sleep apnea and/or obesity hypoventilation syndrome
• Active malignancy (other than skin)
• Medical conditions that limit exercise on an upright stationary bicycle (e.g. severe osteoarthritis, imbalance/gait instability, etc.)
• Pregnancy
• Body mass index <18 or >35
• Hematocrit <25% or >55%
• For subset undergoing right heart catheterization, chronic anticoagulation that is unable to be held for the study visit
• For subset undergoing right heart catheterization or exercise training, forced expiratory volume in 1 second of <20%
• For exercise training, already engaged in routine exercise training (>30 minutes at >3 METs 3 times/week or more)
• For exercise training, inability to complete initial in-person exercise training sessions for approximately 35 minutes 3x/week for 3 weeks (followed by exercise training sessions with an option for hybrid remote/in-person participation)
• For exercise training with an option for hybrid remote exercise training, any medical conditions which threaten the safety of remote exercise training (e.g. imbalance/gait instability, etc.).