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

Aims 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. Methods and 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. Conclusion 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.

Morphological Regeneration and Functional Recovery of Neuromuscular Junctions after Tourniquet-Induced Injuries in Mouse Hindlimb

“…Both morphological alterations of NMJs (motor nerve terminals and nAChR clusters) and resulting of sciatic nerve stimulated-EPPs during the TR suggest that motor nerve denervation could be mainly involved in disability of NMJ transmission during early stage of TR, while fragmentation of nAChR clusters possibly is the key factor that causes inefficiency of NMJ transmission during late-stage of TR. Some previous studies have shown that fragmentation of an individual nAChR cluster might correlate with a decline in efficacy of the neuromuscular transmission in pathophysiological states (Maselli et al, 1995; Gonzalez-Freire et al, 2014; Steinbeck et al, 2015; Vescovo, 2015; Willadt et al, 2016). Our current study further demonstrates that dysfunction of NMJ transmission is mediated by both motor nerve denervation and the fragmentation of nAChR clusters during TR.…”

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure ― Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) ―

“…8- 10 The Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) was a multi-national, pathophysiological observation study into HF and its comorbidities. 11, 12 August 2013. During that period we recruited 275 patients and 52 controls.…”

Heart–brain interactions in patients with heart failure, including takotsubo syndrome: a need to monitor autonomic sympathetic activity: reply

“…The same problem applies to other mechanistic pathways that have been identified as principle pathologic mechanisms in the progression of HF. Metabolic failure in HF is recognized to account for impaired energy metabolism as well as for impaired structural metabolism leading to muscle wasting and eventually cardiac cachexia . Insulin resistance is a key characteristic feature in HF underlying metabolic failure .…”