Alterations in the sarcopenia index are associated with inflammation, gut, and oral microbiota among heart failure, left ventricular assist device, and heart transplant patients

BACKGROUND: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. METHODS: We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. RESULTS: Median (interquartile range) natural logarithm (ln)-SI was -0.13 (-0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r r = -0.28, p < 0.01), gut (r r = 0.28, p < 0.01) , oral microbial diversity (r r = 0.24, p < 0.01). These associations remained significant after multi- variable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. CONCLUSIONS: SI levels decreased in symptomatic HF , remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa com- positional changes. J Heart Lung Transplant 2024;43:1395-1408 (c) Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation.