Targeting Breathing Limitations to Improve Functional Outcomes in Heart Failure With Preserved Ejection Fraction (HFpEF)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 78
- Locations
- 2
- Primary Endpoint
- O2 cost of breathing (Objective 1)
Study Overview
Brief Summary
The overall purpose of this study is to investigate whether pulmonary limitations that increase the oxygen (O2) cost of breathing impact dyspnea on exertion (DOE) and peak exercise capacity in patients with HFpEF and obesity. As per investigator's hypothesis, obesity is likely a significant contributor to DOE and exercise intolerance in patients with HFpEF.
Detailed Description
Clinical screening tests including cardiopulmonary exercise testing (CPET), pulmonary function testing, and dual-energy x-ray absorptiometry (DEXA) scans will be performed on all subjects. Investigator's approach will be to undertake the following objectives:
Objective 1: (Observational) is a cross-sectional study designed to test the interaction of HFpEF (underlying changes in pulmonary function) and obesity (obesity-related changes in pulmonary function) on the O2 cost of breathing, and its association with DOE and peak exercise capacity. The specific hypotheses proposed to test as part of this objective are:
Hypothesis 1.1: Due to the presence of obesity-related mechanical ventilatory constraints, the O2 cost of breathing will be greater in obese HFpEF patients and obese controls vs. nonobese HFpEF patients and nonobese controls, but will be similar between obese HFpEF patients vs. obese controls.
Hypothesis 1.2: The association between the O2 cost of breathing and DOE and the association between the O2 cost of breathing and peak exercise capacity will be stronger in obese HFpEF patients and obese controls vs. nonobese HFpEF patients and nonobese controls, but will be similar between obese HFpEF patients vs. obese controls.
Objective 2: (Interventional) is a single-blind, randomized, placebo-controlled, cross-over trial designed to investigate the effects of reducing obesity-related mechanical ventilatory constraints by breathing a HeO2 gas mixture (HeO2: 21% O2 and 79% He) on DOE and peak exercise capacity. The specific hypotheses proposed to test as part of this objective are:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Single (Participant)
Masking Description
The order of the room air and HeO2 tests will be randomized and the subjects will not be told what gas mixture they will be breathing.
Eligibility Criteria
- Ages
- 55 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •signs and symptoms of heart failure
- •an ejection fraction > 0.50;
- •objective evidence of diastolic dysfunction. elevated biomarkers (NT-proBNP >300 ng/dl) or HF hospitalization
- •healthy volunteers
Exclusion Criteria
- •age < 55 years
- •BMI > 50 kg/m2
- •Atrial fibrillation with poorly controlled heart rate
- •phosphodiesterase type 5 (PDE5) inhibitor use
- •severe valvular disease
- •severe Chronic obstructive pulmonary disease (COPD)
- •Chronic kidney disease (CKD) 4 or higher
- •any restriction of ambulation and mobility.
Outcomes
Primary Outcomes
O2 cost of breathing (Objective 1)
Time Frame: Day 2
O2 cost of breathing measured during eucapnic voluntary hyperventilation, and calculated using oxygen uptake and ventilation variables.
Change in DOE during HeO2 breathing (Objective 2)
Time Frame: Day 3 or 4
Dyspnea on Exertion (DOE) will be assessed via ratings of perceived breathlessness (RPB) using a 0-10 Borg Scale, and will be compared with that measured during room air breathing.
Change in peak exercise capacity during HeO2 breathing (Objective 2)
Time Frame: Day 3 or 4
Peak exercise capacity will be assessed by measuring peak oxygen uptake (in L/min, measured via a breath-by-breath metabolic measurement system), peak power output recorded from a cycle ergometer (Watts), and/or total exercise duration (minutes).
Secondary Outcomes
No secondary outcomes reported
Investigators
Bryce Balmain
Principal Investigator
University of Texas Southwestern Medical Center