Skeletal Muscle Changes After Crt Clinical Trial
Official title:
Effect of Cardiac Resynchronization Therapy on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response
Heart failure patients with left bundle branch block have a poor prognosis. Biventricular pacing which synchronize the heart pump action is associated with improved functional capacity. This study aims to evaluate the basic changes in skeletal muscle functioning after a period of biventricular pacing in 21 patients with heart failure.
Congestive heart failure (CHF) is the most common hospital discharge diagnosis in elderly
patients . Fatigue and dyspnea with exercise intolerance and a poor quality of life are the
main characteristics of this syndrome , and it is associated with substantial mortality and
morbidity , .
Although the systolic dysfunction has been recognized as the primum movens of CHF, it is now
generally accepted that the progression of the syndrome is not solely related to the pump
failure.
The neuro-endocrine model has reached a wide consensus as one of the basic mechanisms for
progressive heart failure based on the good results obtained by ACE-inhibitor therapy . A
decade ago the cytokine model was added to explain the syndrome of heart failure . The
cytokines are highly potent endogenous peptides produced by different cell types . Elevated
levels might be markers for cardiac cachexia, but they may also play an important role in
the mechanism of CHF progression . Subsequently, the muscle hypothesis was proposed as an
explanation for the deconditioning in CHF patients . In skeletal muscle from healthy
individuals there is a balanced distribution between type I fibres (aerobic), type IIA
fibres (both aerobic and anaerobic) and type IIB fibres (mostly anaerobic). In CHF a shift
to type II fibres and a reduced capillary density as well as a reduced cytochrome oxidase
activity is observed, but the mechanisms leading to such a shift have not been clarified .
Deconditioning may be an important factor aggravating the underlying pathophysiology in CHF
and exercise training has been shown to improve exercise performance and to reduce symptoms
in this population . This is partly mediated by activation of the Protein PGC-1, a critical
factor coordinating the activation of metabolic genes required for substrate utilization and
mitochondrial biogenesis . The increase in this enzyme has been highly correlated to
increase in peak VO2 after a aerobic interval training program in heart failure .
One would expect that an improvement in exercise performance following improvement in
central hemodynamics with cardiac resynchronization therapy (CRT) would be associated with
improved muscular blood flow and energy metabolism. However, so far no reports have been
published on the skeletal muscle response to CRT. The purpose of this study was to evaluate
the effect of 6 months CRT pacing on skeletal muscle histology and mitochondrial mass and
the association of these changes to alterations in functional capacity as measured with peak
VO2. Moreover, we also sought to assess the relationship between changes in skeletal muscle
and alterations in the inflammatory response in serum and in skeletal muscle.
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Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment