Bekfani, T. et al. (2016) Sarcopenia in patients with heart failure with preserved ejection fraction: impact on muscle strength, exercise capacity and quality of life. International Journal of Cardiology, 222, pp. 41-46. (doi:10.1016Cardiology, 222, pp. 41-46. (doi:10. /j.ijcard.2016 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/129510/ AbstractBackground: To describe the prevalence of sarcopenia in ambulatory patients with heart failure with preserved ejection fraction (HFpEF) and its relation to reduced exercise capacity, muscle strength, and quality of life (QoL). Methods and Results:A total of 117 symptomatic outpatients with HFpEF were prospectively enrolled in Germany, England, and Slovenia as part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). Appendicular skeletal muscle (ASM) mass (the sum of muscle mass in both arms and legs) was assessed by DEXA.Echocardiography, 6-minute walk testing (6-MWT), muscle strength assessment, spiroergometry and QoL evaluation using EQ-5D Questionnaire were performed. Sarcopenia was defined as ASM 2 standard deviations below the mean of a healthy reference group aged 18-40 years. Patients were divided into 3 groups according to the E/e' value: ≤8, 9-14, and ≥15. Sarcopenia was detected in 19.7% of all patients. These patients performed worse during 6-MWT (404±116 vs. 307±145 meters, p=0.003) and showed lower absolute peak oxygen consumption (1579±474 vs. 1211±442 ml/min, P<0.05). Both ASM and muscle strength were lowest in patients with E/e'>15 (P<0.05). Higher values of muscle strength/ASM were associated with a better QoL (r=0.5, p<0.0005). Logistic regression showed ASM to be independently associated with reduced distance walked during the 6-MWT adjusted for NYHA, height, left atrium diameter, ferritin and forced expiratory volume in 1 second (FEV1) (odds ratio 1.2, p=0.02). Conclusion:Sarcopenia affects a clinically relevant proportion of patients with HFpEF. Low ASM is strongly linked to reduced muscle strength, exercise capacity and QoL in these patients. 4 KeywordsHeart failure with preserved ejection fraction -muscle wasting -sarcopenia -exercise capacity -quality of life.5

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This article highlights preclinical and clinical studies in the field of wasting disorders that were presented at the 7th Cachexia Conference held in Kobe, Japan, in December 2013. This year, the main topics were the development of new methods and new biomarkers in the field of cachexia and wasting disorders with particular focus on inflammatory pathways, growth differentiation factor-15, myostatin, the ubiquitin proteasome-dependent pathway, valosin and the regulation of ubiquitin-specific protease 19 that is involved in the differentiation of myogenin and myosin heavy chain. This article presents highlights from the development of drugs that have shown potential in the treatment of wasting disorders, particularly the ghrelin receptor agonist anamorelin, the myostatin antagonist REGN1033, the selective androgen receptor modulators enobosarm and TEI-E0001, and the anabolic catabolic transforming agent espindolol. In addition, novel data on the prevalence and detection methods of muscle wasting/sarcopenia are presented, including the D3-creatine dilution method and several new biomarkers.

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.