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.


Eligibility Criteria:
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)