Skeletal Muscle Plasticity Following LVAD Support

Project: Research project

Project Details


Chronic heart failure (CHF) is the leading discharge diagnosis among Medicare patients in the United States.
Although pharmacologic therapies have resulted in dramatic reductions in mortality in patients with heart
failure, exercise intolerance remains a major cause of disability, morbidity, and decreased quality of life.
Exertional fatigue often prevents regular physical activity and this may contribute to several co-morbid
diseases and the poor outcome from CHF. The mechanisms that account for limitations in exercise tolerance
in CHF are not completely understood. The hallmark feature of exercise intolerance in heart failure is early
lactate production that is linked with a skeletal muscle myopathy. A large number of questions remain
unanswered. Perhaps the most basic of these questions is whether there is a direct link between the heart
and skeletal muscle? The central hypothesis in this proposal is that there is a direct interplay between central
hemodynamics and peripheral skeletal muscle in CHF, and that this interaction will be evident through a
sustained normalization of central hemodynamic abnormalities. We will study humanswith heart failure where
abnormalities in central hemodynamics are corrected by the placement of a left ventricular assist device
(LVAD). Patients will be studied before, and at time points following LVAD placement. Predictions of the
central hypothesis will be tested in a minimum of 60 patients undergoing LVAD placement at Duke University
Medical Center. An equal number of patients, currently in the hospital for non-oral pharmacological
management of CHF will serve as the comparison (control) group. The Specific Aims are: I. Establish that
alterations in central hemodynamics are sufficient to induce changes in peripheral skeletal muscle in patients
with CHF. II. Establish the extent, type, and time course, of peripheral skeletal muscle plasticity from entry to
9-weeks post, LVAD support or, medical therapy. Determine which, and to what extent, changes in peripheral
skeletal muscle contribute to changes in exercise tolerance from 2-weeks to 9-weeks following LVAD
placement? III. A) Examine potential circulating mediators (i.e. tumor necrosis factor-Q)of the skeletal muscle
myopathy before, and at serial time points after, LVAD placement. B) Examine changes in rectus abdominus
muscle pre-LVAD to heart transplantation, using selected measures from Specific Aim 1, and compare those
to changes in leg (vastus lateralus) muscle over a comparable time period.
StatusNot started


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