Identifying Right Ventricular Dysfunction in COPD Through Right Heart Catheterization, Imaging and Exercise

Study Overview
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Brief Summary
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This study plans to learn more about heart function among individuals with chronic obstructive pulmonary disease (COPD). In particular, the investigators want to understand the different patterns of right ventricular response to pulmonary hypertension (high pressure in the lungs) during rest and exercise. By identifying patterns of right ventricular dysfunction, this study will help identify better treatments for patients with COPD in the future.

Official Title
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Identifying Patterns of Resting and Exertional Right Ventricular Dysfunction Among Patients With Chronic Obstructive Pulmonary Disease and Pulmonary Artery Enlargement

Conditions
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COPD, Pulmonary Hypertension, Right Ventricular Dysfunction

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD (determined by ratio of forced expiratory volume in 1 second to forced vital capacity [FEV1/FVC] <0.7) • Pulmonary artery enlargement determined by pulmonary artery-to-aorta ratio >1 or >30 mm obtained within 3 years of enrollment and not during an acute exacerbation of COPD Exclusion Criteria: Exacerbation of COPD or use of systemic corticosteroids 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 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 ≤45%; arrhythmia; pulmonic, mitral or aortic valvular abnormality greater than trace in severity; tricuspid regurgitation greater than mild in severity; diabetes with HbA1c >7.5%) Volume overload (jugular vascular distension or greater than trace peripheral edema) Interstitial lung disease Untreated obstructive sleep apnea Active malignancy Medical conditions that limit exercise on an upright stationary bicycle (e.g. osteoarthritis, etc.) Pregnancy Body mass index <18.5 or >35 Hematocrit <32% or >55% For optional Part 2 i.e. exercise training and Visit 2, residence >90 miles from University of Colorado Anschutz Medical Campus or unwillingness/inability to attend exercise training sessions for approximately 35 minutes 3x/week for 12 weeks For optional Part 2 i.e. exercise training and Visit 2, already engaged in routine exercise training (>30 minutes at >3 METs 3 times/week or more)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: Study participants will undergo testing to identify patterns of right ventricular dysfunction. If a study participant decides to participate in exercise training, the participant will complete an exercise training intervention followed by repeat testing to determine impact of exercise training on right ventricular dysfunction.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COPD with pulmonary artery enlargement<br>Participants will complete testing to identify patterns of right ventricular dysfunction. If a participant decides to participate in the optional exercise training program, the participant will complete exercise training followed by repeat testing to determine the impact of exercise training on right ventricular dysfunction. | Behavioral: Exercise training<br>* Exercise training will include supervised high-intensity interval training for  35 minutes 3x/week on an upright stationary bicycle and unsupervised continuous aerobic exercise for  30 minutes 2x/week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right ventricular-arterial coupling measured by conductance catheter | Ratio of end-systolic elastance to effective arterial elastance (Ees/EA) | Up to 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean pulmonary artery pressure measured by pulmonary artery catheter | In mmHg | Up to 1 hour | 
| Cardiac output measured by pulmonary artery catheter | In L/min, calculated by Fick equation | Up to 1 hour | 
| Right ventricular contractility measured by conductance catheter | Maximum rate of pressure change, dP/dtmax in mmHg/sec | Up to 1 hour | 
| Right ventricular lusitropy measured by conductance catheter | Minimum rate of pressure change, dP/dtmin in mmHg/sec | Up to 1 hour | 
| Right ventricular energetics, measured by conductance catheter | Stroke work in mmHg*mL | Up to 1 hour | 
| Maximum oxygen consumption (VO2max) | In L/min | Up to 1 hour | 
| Red blood cell acylcarnitine 10:0 measured by peripheral venous metabolomics(ultra-high performance liquid chromatography coupled to mass spectrometry) | Relative ion count | Up to 1 hour | 
| Plasma acylcarnitine 10:0 measured by peripheral venous metabolomics (ultra-high performance liquid chromatography coupled to mass spectrometry) | Relative ion count | Up to 1 hour | 
| Health-related quality of life by Short Form 36 (SF-36) questionnaire | Units, range 0-100 with greater scores indicating a more favorable health state | Up to 1 hour | 
| Right to left ventricle diameter ratio measured by computed tomography | Ratio of right ventricle diameter to left ventricle diameter | Up to 1 hour | 
| Distal pulmonary vascular pruning measured by computed tomography | Ratio of total volume of small pulmonary blood vessels defined by cross-sectional area <5 mm2 to total volume of all pulmonary blood vessels | Up to 1 hour |