Abstract
<h3>Purpose</h3> Sarcopenia is common in advanced heart failure (HF). Multiple mechanisms thought to contribute, including inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Serum creatinine to Cystatin C ratio (sCr/CysC) is a validated marker of sarcopenia. We investigated the association of sCr/CysC with: i) biomarkers of inflammation, endotoxemia and oxidative stress, and ii) gut microbial diversity, across a broad spectrum of HF categories (HF, LVAD, Heart Transplant (HT)). <h3>Methods</h3> Concomitant blood and stool samples were prospectively collected in a cohort of advanced HF pts. LVAD and HT pts were longitudinally sampled at serial time points. Biomarkers of inflammation (IL-6), endotoxemia (LPS) and oxidative stress (isoprostane) were measured in serum. Stool samples were analyzed using 16S rRNA sequencing. Alpha diversity (number and distribution of bacterial taxa within samples) was defined using Shannon Index. Linear mixed models were used to regress sCr/CysC on Shannon Index and serum biomarkers, adjusting for age, sex, race and HF categories. <h3>Results</h3> Among 183 pts (57±13 y,18% F) 253 blood and 253 stool samples were collected (HF=77, LVAD=89, HT=87). sCr/CysC decreased with worsened HF class and improved over time after LVAD and HT (Fig 1A, <i>p</i> <.0001). In separate adjusted models, a decrease in Shannon Index and an increase in IL-6 were associated with a decline in sCr/CysC (β=.08 <i>p</i> < 0.001, and β= -.07 <i>p</i> < .001, respectively), while isoprostane and LPS were not. When combined in a single model, the association of Shannon Index and IL-6 with sCr/CysC remained significant (Shannon Index β=.05 <i>p</i> = .01, and IL-6 β= -.06 <i>p</i> < .001; R<sup>2</sup>=.29). The lowest sCr/CysC was found in pts with the lowest tertile of Shannon index and highest tertile of IL-6 (Fig 1B). <h3>Conclusion</h3> Sarcopenia is independently associated with gut dysbiosis and inflammation across a broad spectrum of HF categories. These observations might help identify novel therapeutic targets to prevent and/or reverse sarcopenia in HF.
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