Spot Urinary Creatinine Concentration in Patients with Chronic Heart Failure Identifies a Distinct Muscle-Wasting Phenotype with a Strikingly Different Risk of Mortality

Background: There is a raising awareness that heart failure (HF) is a highly heterogeneous, multiorgan syndrome with an increasing global prevalence and still poor prognosis. The comorbidities of HF are one of the key reasons for presence of various phenotypes with different clinical profile and outcome. Heterogeneity of skeletal muscles (SMs) quantity and function may have an impact on patient's phenotype.Aim: We intended to compare clinical characteristics of phenotypes defined by a combination of various SM mass taken as a fat-free compartment from DEXA scans and different levels of SUCR (Spot Urinary Creatinine). All-cause mortality with mortality predicted by MAGGIC in such phenotypes were compared.Methods: In 720 HF patients with reduced ejection fraction (age: 52.3 +/- 10 years, female: 14%, NYHA: 2.7 +/- 0.7, LVEF: 24.3 +/- 7.3%), admitted to the hospital for heart transplantation candidacy assessment, morning SUCR along with body composition scanning (DEXA) was performed. All study participants were dichotomized twice, first by low or normal appendicular muscle mass index (ASMI) and second by SUCR (Spot Urinary Creatinine) < and >= of 1.34 g/L. Four study groups (phenotypes) were created as combinations of lower or higher SUCR and low or normal ASMI.Results: Low ASMI was found in 242 (33.6%) patients, while the remaining 478 had normal muscle mass. In 446 patients (61.9%), SUCR was <1.34 g/L. During 3 years of follow-up, 223 (31.0%) patients died (all-cause). The phenotype of lower both ASMI and SUCR was associated with the highest mortality. The death rate in phenotype with both low ASMI and SUCR exceeded by 70% the risk estimated by MAGGIC. This difference was significant as judged by the 95% confidence interval for MAGGIC estimation. In Cox regression analysis adjusted for MAGGIC and parameters known to increase risk, the relative risk of patients with phenotype of low both ASMI and SUCR was elevated by 45-55% as compared to patients with all other phenotypes. The protective role of higher SUCR in patients with muscle wasting was, therefore, confirmed in Cox analysis.Conclusions: Measurement of SUCR in HF patients can identify clinical phenotypes with skeletal muscle wasting but strikingly different risk of death that is actually not captured by MAGGIC score. The higher level of SUCR was associated with similar risk independently of presence of muscle wasting. As the analysis of SUCR is cheap and easy to perform, it should be further tested as a potentially useful biomarker, which may precisely phenotype HF patients independently of their skeletal muscle status.

Automated summary

Heart failure is a highly heterogeneous syndrome, and the heterogeneity of skeletal muscle quantity and function may have an impact on patient's phenotype. In this study, clinical characteristics of different phenotypes defined by a combination of skeletal muscle mass and urinary creatinine levels were compared. The phenotype with low skeletal muscle mass and low urinary creatinine levels was associated with the highest mortality, and this risk was not captured by the MAGGIC score. Measurement of urinary creatinine can serve as a potentially useful biomarker to phenotype heart failure patients independently of their skeletal muscle status.