TrimethylamineN-oxide and prognosis in acute heart failure

Abstract

Objective Acute heart failure (AHF) is associated with high mortality and morbidity. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, has reported association with mortality risk in chronic HF but this association in AHF is still unknown. The present study investigated TMAO in patients admitted to hospital with AHF, and association of circulating levels with prognosis. Methods In total, 972 plasma samples were analysed for TMAO concentration by liquid chromatography-mass spectrometry. Associations with in-hospital mortality (72 events), all-cause mortality (death, 268 events) and a composite of death or rehospitalisation due to HF (death/HF, 384 events) at 1 year were examined. Results TMAO improved risk stratification for inhospital mortality in combination with current clinical scorings (OR≥1.13, p≤0.014). TMAO tertile analyses reported a graded risk in adverse outcome within 1 year (OR≥1.61, p≤0.004) and improved outcome prediction when stratified as none, one or both biomarker(s) elevated in combination with N-terminal pro B-type natriuretic peptide (NT-proBNP) (OR≥2.15, p≤0.007). TMAO was independently predictive for death and death/ HF when corrected for cardiac risk factors (HR≥1.16, p≤0.037); however, this ability was weakened when indices of renal function were included, possibly due to multicollinearity. Conclusions TMAO contributed additional information on patient stratification for in-hospital mortality of AHF admissions using available clinical scores that include renal indices. Furthermore, elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders.

Trimethylamine N-oxide and Risk Stratification after Acute Myocardial Infarction

“…Collectively, with beneficial prognostic information available for heart failure, [17,18] chronic kidney disease [19,20] and now acute MI, TMAO is proving to be an applicable biomarker across a range of cardio-renal pathological states.…”

Heart failure is associated with depletion of core intestinal microbiota

“…However, a functional relevance of an impaired and/or altered bacterial profile as a primary risk factor or early disease marker for the initial onset of heart failure seems to be conceivable as well. Of note, recent studies have shown that intestinal bacterial‐dependent generated trimethylamine‐N‐oxide (TMAO) levels in blood are a prognostic factor for long‐term mortality risk in HF patients independent of traditional risk factors and indices 43, 44. In our study we focused on HF patients mostly in an acute state of decompensation.…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…However, changes in metabolite profiles seem not to be disease specific, because similar differences were observed in serum samples of patients with diseases such as nonHodgkin lymphoma, congestive HF, and communityacquired pneumonia (CAP) [182]. In separate studies, the levels of the metabolite, trimethylamine N-oxide (TMAO), were shown to be associated with the outcome in both acute HF and CAP patients [183,184]. This is not surprising because systemic metabolic dysfunction is a general process that can be observed in other diseases.…”