Pathophysiological Mechanisms of Activity-Related Dyspnea in Heart Failure: A Pilot Study

Dyspnea (breathlessness) on exertion is the most prevalent and distressing symptom of heart failure (HF). Nevertheless, the mechanisms of dyspnea in HF remain poorly understood. Thus, the general aim of this pilot study is to advance our understanding of the mechanisms of activity-related dyspnea in patients with HF. Studies will be performed in patients with mild, moderate and severe HF (n=24) as well as in healthy, age- and sex-matched control subjects (n=8). We will test the hypothesis that the increased prevalence and severity of activity-related dyspnea in HF reflects the interaction between an exaggerated drive to breathe and the inability of the respiratory system to meet this increased demand. Detailed physiological and perceptual responses to bicycle exercise will be examined and compared, first, between HF patients and healthy control subjects and, second, across patients with varying degrees of HF severity. The results from this preliminary study will be used to help design future studies in this patient population.

Study Overview

• Status: Unknown
• Conditions: Heart Failure
• Intervention / Treatment: Other: Cardiopulmonary Exercise Testing

• Study Type: Observational
• Enrollment (Anticipated): 32

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McConnell Centre for Innovative Medicine, Research Institute of the McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Ambulatory, male and female heart failure patients (n=24) will be recruited from the Heart Failure and Heart Transplant Centre of the Royal Victoria Hospital, McGill University Health Centre. Healthy, sedentary, non-smoking, asymptomatic, control subjects (n=8) will be recruited through advertisement in the Montréal and surrounding area

Description

Inclusion Criteria for Heart Failure Patients:

• Male or Female
• Greater than or equal to 40 years
• Greater than or equal to 6 month history of Heart Failure due to ischemic or idiopathic causes
• New York Heart Association Functional Class I (n=8), II (n=8) and III (n=8)
• Ambulatory
• Clinically Stable, as evidenced by no change in medication dosage or frequency of administration and no exacerbations or hospitalizations due to Heart Failure in the preceding 3-months
• Left Ventricular Ejection Fraction on echocardiography of less than or equal to 45% determined in the preceding 12-months.

Exclusion Criteria for Heart Failure Patients:

• Chronic obstructive lung disease and/or active disease other than Heart Failure (e.g., bronchial asthma; pulmonary arterial hypertension that is not considered secondary to left heart failure; peripheral artery disease; primary valvular disease; neurological, cognitive, neuromuscular, endocrine, kidney, metabolic and/or musculoskeletal disease)
• Unstable angina
• Intermittent claudication
• History of dangerous cardiac arrhythmias
• Myocardial infarction and/or stroke in the preceding 6-months
• Use of a pacemaker or cardiac resynchronization device
• Use of domiciliary oxygen and/or exercise-induced arterial oxyhemoglobin desaturation to <80% on room air
• Current and/or ex-smoker with a cigarette smoking history of greater than or equal to 10 pack years
• Body mass index less than 18.5 or greater than or equal to 35.0 kg/m2
• Use of antidepressant, opioid and/or anti-coagulant drugs in the preceding 4-weeks
• Evidence of periodic breathing (or oscillatory ventilation) on initial exercise testing
• Evidence of significant sleep-disordered breathing (i.e., apnea-hypopnea index >15 events/hour of sleep) based on overnight polysomnography performed within preceding 12-months.

Inclusion Criteria for Healthy Control Subjects:

• Male or Female
• Greater than or equal to 40 years
• Non-smoker

Exclusion Criteria for Healthy Control Subjects:

• History of cardiovascular, cerebrovascular, pulmonary, musculoskeletal, neuromuscular, renal, endocrine, metabolic, neurologic and/or cognitive disease/dysfunction.
• Evidence of exercise-induced myocardial ischemia on ECG
• Evidence of exercise-induced oxyhemoglobin desaturation to <80% on room air
• Taking regular medication(s)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Heart Failure: NYHA functional class I; Ambulatory and clinically-stable patients with New York Heart Association Functional Class I heart failure and a left ventricular ejection fraction (LVEF) on echocardiography of <45%.	Other: Cardiopulmonary Exercise Testing; Symptom-limited incremental exercise testing (10 watts/min) on an electronically braked cycle ergometer
Heart Failure: NYHA functional class II; Ambulatory and clinically-stable patients with New York Heart Association Functional Class II heart failure and a left ventricular ejection fraction (LVEF) on echocardiography of <45%.	Other: Cardiopulmonary Exercise Testing; Symptom-limited incremental exercise testing (10 watts/min) on an electronically braked cycle ergometer
Heart Failure: NYHA functional class III; Ambulatory and clinically-stable patients with New York Heart Association Functional Class III heart failure and a left ventricular ejection fraction (LVEF) on echocardiography of <45%.	Other: Cardiopulmonary Exercise Testing; Symptom-limited incremental exercise testing (10 watts/min) on an electronically braked cycle ergometer
Healthy Control Subjects; Healthy, sedentary, non-smoking, age- and sex-matched control subjects.	Other: Cardiopulmonary Exercise Testing; Symptom-limited incremental exercise testing (10 watts/min) on an electronically braked cycle ergometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sensory intensity (Borg 0-10 scale) ratings of dyspnea at a standardized sub-maximal work rate during exercise	Patients will be followed until all study visits are complete, an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Esophageal electrode catheter-derived measurements of the diaphragm EMG at a standardized sub-maximal work rate during exercise.		Patients will be followed until all study visits are complete, an expected average of 2 weeks
Power output (measured in watts) at the symptom-limited peak of incremental cycle ergometer exercise testing	The highest power output (measured in watts) that the study participants are able to sustain for greater than or equal to 30 seconds will be defined as the "symptom-limited peak power output" and used as a secondary outcome measure in this study.	Patients will be followed until all study visits are complete, an expected average of 2 weeks.

Collaborators and Investigators

• Sponsor: McGill University

Publications and helpful links

Helpful Links

• Clinical Exercise & Respiratory Physiology Laboratory (CERPL) of McGill University

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ANTICIPATED): December 1, 2017
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: November 28, 2013
• First Submitted That Met QC Criteria: December 5, 2013
• First Posted (ESTIMATE): December 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Heart Failure; Exercise; Respiratory mechanics; Dyspnea; Diaphragm electromyogram
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Heart Failure; Dyspnea
• Other Study ID Numbers: MCRDF 2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No