title: Detection of muscle wasting in patients with chronic heart failure using C-terminal agrin fragment: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).
abstract: OBJECTIVE
  Skeletal muscle wasting affects 20% of patients with chronic heart failure and has serious implications for their activities of daily living. Assessment of muscle wasting is technically challenging. C-terminal agrin-fragment (CAF), a breakdown product of the synaptically located protein agrin, has shown early promise as biomarker of muscle wasting. We sought to investigate the diagnostic properties of CAF in muscle wasting among patients with heart failure.
  
  
  RESULTS
  We assessed serum CAF levels in 196 patients who participated in the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Muscle wasting was identified using dual-energy X-ray absorptiometry (DEXA) in 38 patients (19.4%). Patients with muscle wasting demonstrated higher CAF values than those without (125.1 ± 59.5 pmol/L vs. 103.8 ± 42.9 pmol/L, P = 0.01). Using receiver operating characteristics (ROC), we calculated the optimal CAF value to identify patients with muscle wasting as >87.5 pmol/L, which had a sensitivity of 78.9% and a specificity of 43.7%. The area under the ROC curve was 0.63 (95% confidence interval 0.56-0.70). Using simple regression, we found that serum CAF was associated with handgrip (R = - 0.17, P = 0.03) and quadriceps strength (R = - 0.31, P < 0.0001), peak oxygen consumption (R = - 0.5, P < 0.0001), 6-min walk distance (R = - 0.32, P < 0.0001), and gait speed (R = - 0.2, P = 0.001), as well as with parameters of kidney and liver function, iron metabolism and storage.
  
  
  CONCLUSIONS
  CAF shows good sensitivity for the detection of skeletal muscle wasting in patients with heart failure. Its assessment may be useful to identify patients who should undergo additional testing, such as detailed body composition analysis. As no other biomarker is currently available, further investigation is warranted.
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Steinbeck
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ebner
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Valentova
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Tarek
authors.initials: T
authors.lastname: Bekfani
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Elsner
authors.affiliation: Neurotune AG, Schlieren, Switzerland.
authors.forename: Pius
authors.initials: P
authors.lastname: Dahinden
authors.affiliation: Neurotune AG, Schlieren, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hettwer
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.|Centre for Stroke Research Berlin, Charité Medical School, Berlin, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Scherbakov
authors.affiliation: Department of Nephrology and Intensive Care, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Schefold
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Sandek
authors.affiliation: Department of Cardiology and Pneumology, University of Göttingen Medical School, Göttingen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.|Centre for Stroke Research Berlin, Charité Medical School, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.|Department of Cardiology and Pneumology, University of Göttingen Medical School, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany.|Department of Cardiology and Pneumology, University of Göttingen Medical School, Göttingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D018171:Agrin / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D008297:Male; D009133:Muscular Atrophy / Q000175:diagnosis* / Q000209:etiology; D010446:Peptide Fragments / Q000097:blood*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D018171:Agrin; D015415:Biomarkers; C000602450:C-terminal agrin fragment; D010446:Peptide Fragments
keywords: Agrin; Biomarker; Heart Failure; Muscle wasting; Sarcopenia