|Principal Investigator: Markus Amann|
|Keywords: Muscle , Afferent , Heart Failure||Department: Internal Medicine|
|IRB Number: 00062889||Co Investigator: Markus Amann|
|Recruitment Status: Recruiting|
To better understand the impact the aging process has on vascular function and improve methods of treatment for patients with heart Failure
Participant Selection Criteria:
All participants will be accepted without regard to ethnic origin. Individuals with medical contraindications to exercise will be identified by Drs. Morgan, Jessop, Bledsoe, Buys and Stehlik using a questionnaire, a focused medical history and physical examination, and these individuals will be excluded from the study. No project personnel will receive compensation for participant enrollment or any other purpose directly related to the study. Minors, mentally disabled patients and prisoners will be excluded from this study.
Patients with HF and Healthy Control Participants
Cardiologist Dr. Stehlik will assist with the identification and recruitment of the HF patients. Healthy control participants will go through the selection criteria as described above and the additional procedures outlined below under the section "Control Participant" below.
HF Patients: The study group will include participants treated for heart failure ages 20-89 and on stable medications. We will exclude morbidly obese patients (BMI >45), patients with uncontrolled hypertension (>160/100), anemia (Hgb<9), severe renal insufficiency (individuals with creatinine clearance <30 by the Cockcroft-Gault formula), history of orthostatic intolerance, and patients who are current smokers. Patients with significant non-cardiac co-morbidities, which if present could alter the study results, will be excluded. Candidates must have no orthopedic limitations that would prohibit them from performing elbow-flexor or knee extensor exercise. Due to the typical age of patients with heart failure, all women will be postmenopausal (either natural or surgical) defined as a cessation of menses for at least 2 years. Women currently taking hormone replacement therapy (HRT) will be excluded from the proposed studies due to the direct vascular effects of HRT.
Control Participants: Healthy controls will consist of young (18-35 years old) and age (within 5 years), gender, activity, and BMI matched participants (frequency matched) with no history of cardiovascular related abnormalities (i.e., shortness of breath, chest discomfort, abnormal rest or exercise ECG), or pulmonary abnormalities, not morbidly obese (BMI <36) and no or minimal smoking history (<15 pk yr). Initial personal interviews will facilitate participant screening. Suitable volunteers will undergo a series of preliminary studies, including, in the presence of a licensed physician, a conventional maximum VO2 test on a cycle ergometer with EKG monitoring and forehead pulse oxymetry. Participants will be sedentary, defined here as no regular physical activity for at least the prior 6 months and current activity level will be documented by an activity questionnaire. Human participant safety during these studies will be at the forefront of all of our experiments. A subset of controls who are hypertensive, with a resting systolic blood pressure in the high normal or stage I hypertensive range (i.e. 130-159 mmHg), will also be included in this research.
Patient Management / Cardiac Medications: Prior to entry into the study, all heart failure patients will undergo a formal evaluation with our clinical heart failure expert, Dr. Josef Stehlik. These patients will need to be on standardized, state of the art, optimized therapy. This was the approach taken by the large, successful, NIH-supported HF Action Trial (94). Any potential participant that has not been on state of the art therapy will be put on optimized therapy and subsequently maintained on this for a minimum of 30 days prior to study entry. Changes to the management for whatever reason after “optimization” will require an additional 30 days prior to entry. The standard of care for patients with stable class II - III heart failure due to systolic dysfunction generally includes the use of ACE inhibitors, diuretics, digoxin and beta-blockers. A-II receptor blockers are frequently used for patients who cannot tolerate ACE inhibitors, usually due to cough. Although these medications may influence cardiopulmonary interactions in various ways, we feel it is important, practical and safe to study these patients under conditions of optimal care. All standard pharmacotherapeutic agents for heart failure have effects on the neurohormonal modulation of this disorder. However, concurrent withdrawal of ACE-inhibitor, beta-blocker, digoxin and diuretic would likely be associated with modest decompensation in a high proportion of patients. Accordingly, the impact of our studies will be applicable to a heart failure population receiving standard optimized therapy.
Pregnancy testing will be performed on all women of child bearing age and potential. Any pregnant participants will be excluded from the study.
Patients with a pacemaker and/or defibrilator will be excluded from the fatigue studies (hypothesis 3, 4 & 5) due to the use of a magnetic nerve stimulator, from MRI/MRS (hypothesis 7). Hypertensive participants will be excluded if 1) their body mass index is less than 19.0 or 40.0 kg/m2 or greater (because underweight and morbid obesity are known to influence glucose metabolism and sympathetic nervous system function), 2) they use medication that interferes with glucose metabolism or sympathetic nervous system function, 3) their systolic blood pressure is 180 mmHg or greater, their diastolic blood pressure is 110 mmHg or greater, 4) their anti-hypertensive treatment consists of two or more drugs, 5) they have type 2 diabetes mellitus (fasting plasma glucose of > 126 mg/dL or glucose value >200 mg/dL or Hb A1C > 6.5%). Participants will be excluded from the Neck Pressure/Neck Suction procedure if they have any of the following conditions: carotid bruit, known carotid stenosis > 50%, history of myocardial infarction or stroke within the preceding 3 months, or as-yet undiagnosed carotid stenosis, bruits and any significant plaque identified during the preliminary visit. Participants will be excluded from the Indocyanine Green (ICG) procedure if they are allergic to iodide or iodide containing substances.