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-α (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] µM) 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] µM, 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] µM) 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] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76–2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66–2.05] µM) 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.

中文翻译：

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左心室辅助装置和心脏移植后，三甲胺 N-氧化物水平长期保持升高，并且与炎症和肠道菌群失调的测量无关

背景：三甲胺 N-氧化物 (TMAO) - 一种肠道衍生代谢物 - 在心力衰竭 (HF) 中升高并与预后不良有关。我们调查了 HF、左心室辅助装置 (LVAD) 和心脏移植 (HT) 中 TMAO 的变化，并评估了其与炎症、内毒素血症、氧化应激和肠道菌群失调的关系。方法：我们招募了 341 名患者。对 611 例血液中的 TMAO、CRP（C 反应蛋白）、IL（白细胞介素）-6、TNF-α（肿瘤坏死因子 α）、ET-1（内皮素-1）、脂联素、脂多糖、可溶性 CD14 和异前列腺素进行了测量HF（纽约心脏协会 I-IV 级）和 LVAD 后和 HT 后多个时间点的样本。通过 16S rRNA 测序在 327 个粪便样本中评估肠道微生物群。多变量回归模型用于评估TMAO与（1）纽约心脏协会等级之间的关系；(2) LVAD 前后或 HT 后；(3) 炎症、内毒素血症、氧化应激和微生物多样性的生物标志物。结果：在 HF 纽约心脏协会 I 级 (1.23 [95% CI, 0.52–1.94] µM) 中 ln-TMAO 低于 II、III 级, 或 IV (1.99 [95% CI, 1.68–2.30], 1.97 [95% CI, 1.71–2.24], 和 2.09 [95% CI, 1.83–2.34] µM；所有P <0.05）。与 II-IV 类相比，ln-TMAO 在 LVAD 后 1 个月（1.58 [95% CI，1.32-1.83] µM）和 HT 后 1 周和 1 个月（0.97 [95% CI，0.60-1.35 ] 和 1.36 [95% CI, 1.01–1.70] µM)。长期 LVAD（>6 个月：1.99 [95% CI，1.76–2.22] µM）和 HT（>6 个月：1.86 [95% CI，1.66–2.05] µM）中的 ln-TMAO 水平与症状无差异高频。经过多变量调整后，TMAO 与炎症、内毒素血症、氧化应激或微生物多样性的生物标志物无关。结论：TMAO 水平在有症状的 HF 患者中升高，并且在 LVAD 和 HT 后长期保持升高。TMAO 水平独立于炎症、内毒素血症、氧化应激和肠道菌群失调的测量。