Effects of Exercise Training on Fluid Instability in Heart Failure Patients

Background: Heart Failure (HF) is a significant healthcare concern in the US, with a 120%
rise in mortality rates over 15 years costing the country an estimated $37.2 billion in
2009. Veterans are currently impacted at a rate of 5.2%, and cost an average of
$14,959/individual/year for those utilizing the VA's Healthcare services. Research has shown
that exercise training (ET) improves aerobic capacity, endothelial dysfunction, quality of
life, and the ability to tolerate activity within the overall HF population. Animal models
have emerged to explain some of the underlying mechanisms for the pathologic expression of
symptoms and the links to ET. A translational link has not yet been explored between the
animal models and human symptom expression.

Objectives: The long-term goal of this research program is to develop an exercise training
(ET) program that effectively decreases fluid shift variability in HF patients, while being
safely implemented in the home environment and remotely monitored by a healthcare provider
within a nurse-lead HF Clinic. The purpose of the proposed research project is to determine
if ET alters fluid status of patients with HF as compared to those under standard treatment
of care. The central hypothesis is that a combined weight-bearing aerobic and resistance ET
protocol will reduce (stabilize) 24-hour weight and bioelectrical impedance patterns of
variability, as evaluated via mixed-effects regression modeling, greater than any other form
of ET protocol.

Methods: Design: Using established experimental design techniques implemented in an
innovative manner, a between-group design is used within the experimental arm employing a
single subject, multiple-baseline design. The use of such technique allows for the subjects
to be their own controls, while also allowing for statistical between group comparisons.

Subjects and Setting: 60 subjects meeting inclusion/exclusion criteria will be enrolled from
the VA HF Clinic and outpatient VA cardiology clinics within 50 miles of Columbia, South
Carolina. Subjects will be randomized to the exercise or usual care groups.

Procedures: The exercise protocol lasts 12 weeks, with subjects being randomized to order of
ET. Weight-bearing aerobic ET will be walking on a treadmill; non-weight-bearing aerobic ET
will be stationary bicycling; and resistance ET will be lower body isolation ET. Fluid
stability is the concept of day-to-day variability of movement of intra-cellular fluid to
extra-cellular space. Fluid stability will be assessed using 24-hour weight and
bioelectrical impedance and quantified statistically using mixed effect modeling.

Data Analysis: Statistical analysis will utilize a longitudinal mixed-effects regression
model, modeling variability over time for the subjects individually, as well as within
groups. Additionally, main effects (time and group) and interaction effects (time by group)
will be assessed.

Status: Funding began September 1, 2010. The study was transferred to Dorn VAMC in Columbia,
SC in March of 2011 and is currently recruiting subjects.

Inclusion Criteria:

- Advanced Heart Failure

- Ability to Walk

- Over 21

Exclusion Criteria:

- Renal Failure

- Inability to walk

- Physician exclusion