High Extracellular-to-Intracellular Water Ratio in Limb Muscles is Associated with Low Muscle Strength in Patients with Heart Failure

Background A high extracellular water (ECW) to intracellular water (ICW) ratio of skeletal muscle as assessed by bioelectrical impedance analysis is reportedly associated with loss of muscle strength. However, the validity of this index for heart failure (HF), which is likely associated with changes in the water distribution, is unclear. Methods This study involved 190 patients with HF. The total ECW and ICW of both upper and lower extremities were measured, and a high ECW/ICW ratio was defined as an ECW/ICW ratio higher than the median (≥0.636 for men, ≥0.652 for women). Low muscle strength was defined as reduced handgrip strength according to the criteria established by the Asian Working Group for Sarcopenia. Results Patients with a high ECW/ICW ratio were older, had a higher left ventricular ejection fraction and B-type natriuretic peptide level, and had a lower body mass index, hemoglobin level, albumin level, estimated glomerular filtration rate, handgrip strength, and 6-minute walk distance than patients with a low ECW/ICW ratio (p < 0.05). An increasing ECW and/or decreasing ICW was associated with a higher ECW/ICW ratio (p < 0.05). In the multivariate logistic regression analysis, a high ECW/ICW ratio and low skeletal muscle mass were independently associated with low muscle strength (p < 0.05). Conclusion A high ECW/ICW ratio in limb muscles (i.e., an increasing ECW and/or decreasing ICW) is independently associated with muscle weakness regardless of skeletal muscle mass in patients with HF. What Is New? What Are the Clinical Implications? ### Competing Interest Statement KY received research grants from Abbott Co., Ltd.; Otsuka Pharmaceutical Co., Ltd.; Biotronik Japan Inc.; Japan Lifeline Co., Ltd.; and Fukuda Denshi. KY received speakers? bureau fees from Otsuka Pharmaceutical Co., Ltd.; Novartis; and Daiichi-Sankyo Co. Ltd. Tottori university department of cardiovascular medicine reciived scholarship fund: Abbott?Otsuka Pharmaceutical Co. Ltd., Biotronik Japan Inc., Japan Lifeline Co. Ltd., Fukuda Denshi, ### Funding Statement This study was supported by a grant from the Japan Society for the Promotion of Science (JSPS KAKENHI Grant No. 19K08582). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research ethics committee of Tottori University approved the study. (No.2418) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The research data will not be shared.