Abstract
Dear Editor,
The study by Ceylan et al 1 explored plasma trimethylamine N-oxide (TMAO) levels in patients with acute decompensated heart failure (ADHF) and stable heart failure (SHF). The authors should be congratulated for addressing an increasingly relevant biomarker question and for showing that TMAO was higher in ADHF, correlated with B-type natriuretic peptide (BNP) and renal indices, and showed moderate discriminatory performance alongside established natriuretic peptide testing. Some additional comments may be useful.
First, the interpretation of TMAO as a marker of decompensation may benefit from more granular consideration of renal and hematologic status. TMAO is closely related to kidney function,2,3 and in this cohort estimated glomerular filtration rate (eGFR), creatinine, hemoglobin, and hematocrit differed markedly between ADHF and SHF patients. Because acute congestion may impair renal clearance and contribute to hemodilution, stratified analyses by eGFR category and anemia status, together with interaction testing with BNP, could help clarify whether TMAO reflects ADHF-related biology or the accompanying cardiorenal-anemia milieu.
Second, circulating TMAO concentrations are influenced by diet and gut microbial metabolism and have been linked to cardiovascular risk.4,5 Although fasting blood collection is a strength, recent intake of red meat, fish, eggs, or L-carnitine-containing supplements, as well as exposure to antibiotics, probiotics, or microbiota-directed therapies, may still affect circulating TMAO.4,5 Incorporating a brief dietary and medication exposure assessment in future studies would make the biological interpretation of elevated TMAO in ADHF more precise.
Third, the proposed diagnostic cut-off should be interpreted cautiously. The study measured TMAO using an enzyme-linked immunosorbent assay (ELISA), whereas many mechanistic and clinical studies have used isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). 6 Before the 406 ng/mL threshold is considered for clinical use, cross-platform calibration, external validation, and reporting of net reclassification, calibration, and decision-curve analyses would help determine whether TMAO meaningfully changes diagnostic decisions beyond BNP.
Overall, this study represents an important step toward linking gut-derived metabolites with acute heart failure presentation. At present, TMAO appears best viewed not as a replacement for natriuretic peptides, but as a promising context-dependent adjunct whose value may become clearer when renal function, anemia, diet, assay method, and contemporary heart failure therapy 7 are considered together.
