Association of gut-related metabolites with outcome in acute heart failure.

BACKGROUND: Trimethylamine N-oxide (TMAO), a gut-related metabolite, is associated with heart failure (HF) outcomes. However, TMAO is the final product of a complex metabolic pathway (ie, choline/carnitine) that has never been entirely investigated in HF. The present study investigates a panel of metabolites involved in the TMAO-choline/carnitine metabolic pathway for their associations with outcome in acute HF patients. METHODS: In total, 806 plasma samples from acute HF patients were analyzed for TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, γ-butyrobetaine, crotonobetaine, trimethylamine, betaine aldehyde, choline, and betaine using a developed liquid chromatography-tandem mass spectrometry method. Associations with outcome of all-cause mortality (death) and a composite of all-cause mortality and/or rehospitalization caused by HF (death/HF) at 30 days and 1 year were investigated. RESULTS: TMAO, trimethyllysine, L-carnitine, acetyl-L-carnitine, and γ-butyrobetaine were associated with death and death/HF at 30 days (short term; hazard ratio 1.30-1.49, P≤ .021) and at 1 year (long term; hazard ratio 1.15-1.25, P≤ .026) when adjusted for cardiac risk factors. L-carnitine and acetyl-L-carnitine were superior for short-term outcomes whereas TMAO was the superior metabolite for association with long-term outcomes. Furthermore, acetyl-L-carnitine and L-carnitine were superior for in-hospital mortality and improved risk stratification when combined with current clinical risk scores (ie, Acute Decompensated HEart Failure National REgistry, Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure, and Get With The Guidelines-Heart Failure; odds ratio (OR) ≥ 1.52, P≤ .020). CONCLUSIONS: Carnitine-related metabolites show associations with adverse outcomes in acute HF, in particular L-carnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes. Further studies are warranted to investigate the role and implications of carnitine metabolites including intervention in the pathogenesis of HF.

Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS): basics and clinical applications.

Background Matrix-assisted laser desorption ionisation (MALDI) mass spectrometry (MS) has been used for more than 30 years. Compared with other analytical techniques, it offers ease of use, high throughput, robustness, cost-effectiveness, rapid analysis and sensitivity. As advantages, current clinical techniques (e.g. immunoassays) are unable to directly measure the biomarker; rather, they measure secondary signals. MALDI-MS has been extensively researched for clinical applications, and it is set for a breakthrough as a routine tool for clinical diagnostics. Content This review reports on the principles of MALDI-MS and discusses current clinical applications and the future clinical prospects for MALDI-MS. Furthermore, the review assesses the limitations currently experienced in clinical assays, the advantages and the impact of MALDI-MS to transform clinical laboratories. Summary MALDI-MS is widely used in clinical microbiology for the screening of microbial isolates; however, there is scope to apply MALDI-MS in the diagnosis, prognosis, therapeutic drug monitoring and biopsy imaging in many diseases. Outlook There is considerable potential for MALDI-MS in clinic as a tool for screening, profiling and imaging because of its high sensitivity and specificity over alternative techniques.

Relationship between renal function stage and clinical outcomes after paclitaxel-eluting stent implantation.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). This study aimed to evaluate the relationship between the degree of renal function at baseline and long-term clinical outcomes in coronary artery disease patients who underwent paclitaxel-eluting stent implantation. METHODS: A total of 336 patients with 400 de-novo lesions underwent PCI between May 2007 and March 2009. The patients were divided into 4 groups: control (glomerular filtration rate (GFR) ≧ 90 ml/min; n = 132); mild CKD (GFR 60-89 ml/min; n = 112); moderate CKD (GFR < 60 ml/min; n = 51); and dialysis (n = 41). All lesions were treated using a paclitaxel-eluting stent. The primary and secondary endpoints were incidences of mortality and major adverse cardiovascular events (MACE) during 2 years after PCI and target vessel revascularization (TVR), respectively. RESULTS: Two-year MACE incidence rates were 9.7%, 15.2%, 30%, and 31% in control, mild CKD, moderate CKD, and dialysis groups, respectively. TVR trended upward with increasing renal impairment (8.3%, 12.5%, 18%, and 21.4% for the 4 groups, respectively, p = 0.09). Mild CKD, moderate CKD, and dialysis patients had adjusted hazard ratios of 2.51 (95% CI, 1.01-6.24); 3.20 (95% CI, 1.07-9.60); and 4.19 (95% CI, 1.30-13.51), respectively, for 2-year MACE. CONCLUSIONS: A graded relationship was observed between lower renal function and increased TVR, although it did not reach statistical significance. Cardiac death and TVR rates were significantly higher in moderate CKD and dialysis patients after paclitaxel-eluting stent implantation. Patients with reduced renal function, even mild CKD, were independent predictors of MACE.