Effect of Cardiac Resynchronization Therapy (CRT) on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Cardiac Resynchronization Therapy on Skeletal Muscle Histology, Neuroendocrine Activation and Inflammatory Response

Conditions
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Skeletal Muscle Changes After Crt

Intervention / Treatment
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* Device: CRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart failure, left bundle branch block Exclusion Criteria: serious comorbidity including systemic inflammatory disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Heart failure patients. Intervention CRT<br>CRT implantation in heart failure. Effect of intervention after 6 months of treatment. | Device: CRT<br>* Insertion of CRT in patients with left bundle branch block. Assessment of skeletal muscle and infalmmatory profile<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| capillary density | To assess if CRT improves skeletal muscle cappillary density | finnished | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRT, heart failure, left bundle branch block, skeletal muscle, cytokines, VO2, pgc1alpha