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TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).

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Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Basel Cardiovascular Research Foundation, and B Braun Medical AG.

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NCT02158468.

Background-Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance. Methods and Results-Sixty CHF patients (30 patients aged Յ55 years, mean age 46Ϯ5 years; 30 patients aged Ն65 years, mean age 72Ϯ5 years) and 60 healthy controls (30 subjects aged Յ55 years, mean age 50Ϯ5 years; 30 subjects aged Ն65 years, mean age 72Ϯ4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624Ϯ59 versus 401Ϯ25 relative units; Pϭ0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by Ϫ32.8% (Pϭ0.02) in CHF patients aged Յ55 years and by Ϫ37.0% (PϽ0.05) in CHF patients aged Ն65 years. Conclusions-MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00176319.