Peripheral Metabolic Function in Chronic Heart Failure Patients

Peripheral Metabolic Function in Chronic Heart Failure Patients: Key to Lessen the Cardiac Load

Exercise intolerance is a major limiting symptom in patients with CHF. However the poor correlation between the hemodynamic parameters of left ventricular performance at rest and exercise performance has led to the concept that peripheral factors such as muscle perfusion and muscle metabolism play a role as determinants of exercise capacity.

Study Overview

• Status: Unknown
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Behavioral: Exercise training

Detailed Description

The pathophysiology behind the breathlessness and fatigue experienced by CHF patients during exercise remains unclear. Recent evidence suggests that the peripheral skeletal muscle, which becomes abnormal in heart failure, is the source of afferent signals which disrupt normal patterns of cardiorespiratory control. When CHF patients exercise, an inappropriately strong sympathetic response further limits exercise tolerance by evoking larger than normal increases in peripheral sympathetic activation at a faster rate than in healthy individuals. A consequence of this exacerbated sympathetic response may be the further sympathetic restraint of blood flow to the active skeletal muscles resulting in hypoperfusion of the muscle vascular bed and fatigue. Small muscle mass exercise training increases muscle oxidative capacity and improves aerobic work capacity in CHF patients. A range of studies is proposed here that will provide an integrative view of the mechanistic basis behind exercise intolerance in CHF and relate the intramuscular metabolic status to the autonomic control of hemodynamics during exercise. An understanding of the mechanistic basis of the improved exercise tolerance with training, independent of improved resting cardiac function, will yield important information regarding the integrated control of blood flow and metabolic demand in CHF and highlight the importance of maintaining the integrity of the peripheral musculature in CHF.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gregers W Munch, MSc PhD; Phone Number: +45 35459574; Email: gregers.munch@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Centre of Inflammation and Metabolism (CIM), Centre for Physical Activity Research
    • Contact: Gregers W Munch, MSc PhD; Phone Number: +45 35459574; Email: gregers.munch@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• New York Heart Association (NYHA) Class II - III
• Ejection fraction <35%
• Heart failure as a result of previous myocardial infarction
• Optimal treatment (ACE-inhibitors, beta-blockers)
• Stable heart failure
• Patients with and without implantable cardioverter defibrillator (ICD)

Exclusion Criteria:

• Peripheral vascular disease with symptoms of atherosclerosis (intermittent claudication)
• Aneurysm in a. femoral
• Moderate to severe heart valve disease
• Moderate to severe Chronic Obstructive Pulmonary Disease (COPD) with FEV1 <60%
• Heart Failure Patients with Biventricular pacemaker (BVP)
• Serious heart rhythm disturbances (arrhythmias such as atrial fibrillation and frequent premature ventricular contractions)
• Myocardial infarction within the last month
• Unstable angina (angina pectoris)
• Renal failure (creatinine greater than 2.5 mg / dL)
• Severe systemic disease of the nervous system, pulmonary or other severe organ involvement
• BMI> 30
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise training - Whole body exercise; Control subjects will train 2-legged cycling (whole body exercise) for 6 weeks	Behavioral: Exercise training; All gruoups will undergo 6 weeks of training intervention either with a small musclemass (one-legged exercise) or whole body exercise (two-legged cycling)
Experimental: Exercise training - One-legged exercise; Control subjects will train high intense one-legged exercise for 6 weeks	Behavioral: Exercise training; All gruoups will undergo 6 weeks of training intervention either with a small musclemass (one-legged exercise) or whole body exercise (two-legged cycling)
Experimental: Exercise training - 2-legged cycling CHF; CHF patients will train 2-legged cycling (whole body exercise) for 6 weeks	Behavioral: Exercise training; All gruoups will undergo 6 weeks of training intervention either with a small musclemass (one-legged exercise) or whole body exercise (two-legged cycling)
Experimental: Exercise training - CHF; CHF Patients will train high intense one-legged exercise for 6 weeks	Behavioral: Exercise training; All gruoups will undergo 6 weeks of training intervention either with a small musclemass (one-legged exercise) or whole body exercise (two-legged cycling)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline sympathetic nerve activity after 6 weeks of training	Sympathetic nerve activity, measured in plasma and dialysat with reference to nor-adrenaline.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of exercise training on exercise capacity in regards to oxygen uptake	Exercise capacity in regards to oxygen uptake (VO2peak) will be evaluated before and after the training intervention	6 weeks
The effect of exercise training on exercise capacity in regards to maximal workload	Exercise capacity in regards to Workload during 2-legged cycling (Wattpeak) will be evaluated before and after the training intervention	6 weeks
The effect of exercise training on exercise capacity in regards to a 6 min walk test	Exercise capacity in regards to a 6 min walk test (meters) will be evaluated before and after the training intervention	6 weeks

Collaborators and Investigators

• Sponsor: Anders Rasmussen Rinnov
• Investigators: Study Chair: Stefan P Mortensen, Dr. Med, IMM - Department of Cardiovascular and Renal Research

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: November 6, 2014
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 11, 2016

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: April 4, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Training; Cardiac function; Peripheral blood flow; One-legged exercise; Muscle metaboreflex
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: VEK-H-3-2013-048