TY - JOUR
T1 - Levels of Trimethylamine N-Oxide Remain Elevated Long Term after Left Ventricular Assist Device and Heart Transplantation and Are Independent from Measures of Inflammation and Gut Dysbiosis
AU - Yuzefpolskaya, Melana
AU - Bohn, Bruno
AU - Javaid, Azka
AU - Mondellini, Giulio M.
AU - Braghieri, Lorenzo
AU - Pinsino, Alberto
AU - Onat, Duygu
AU - Cagliostro, Barbara
AU - Kim, Andrea
AU - Takeda, Koji
AU - Naka, Yoshifumi
AU - Farr, Maryjane
AU - Sayer, Gabriel T.
AU - Uriel, Nir
AU - Nandakumar, Renu
AU - Mohan, Sumit
AU - Colombo, Paolo C.
AU - Demmer, Ryan T.
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Background: Trimethylamine N-oxide (TMAO) - a gut-derived metabolite - is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF- (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] M) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] M, respectively; all P<0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] M) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] M). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] M) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] M) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.
AB - Background: Trimethylamine N-oxide (TMAO) - a gut-derived metabolite - is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis. Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF- (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity. Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] M) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] M, respectively; all P<0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] M) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] M). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] M) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] M) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity. Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.
KW - endothelin-1
KW - heart failure
KW - heart transplantation
KW - inflammation
KW - interleukin-6
UR - https://www.scopus.com/pages/publications/85108076792
UR - https://www.scopus.com/pages/publications/85108076792#tab=citedBy
U2 - 10.1161/CIRCHEARTFAILURE.120.007909
DO - 10.1161/CIRCHEARTFAILURE.120.007909
M3 - Article
C2 - 34129361
AN - SCOPUS:85108076792
SN - 1941-3289
VL - 14
SP - E007909
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 6
ER -
