Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.

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There is intense interest in the identification of novel biomarkers which improve the diagnosis of heart failure. Serum samples from 52 patients with systolic heart failure (EF < 40% plus signs and symptoms of failure) and 57 controls were analyzed by gas chromatography -time of flight -mass spectrometry and the raw data reduced to 272 statistically robust metabolite peaks. 38 peaks showed a significant difference between case and control (p < 5·10 )5 ). Two such metabolites were pseudouridine, a modified nucleotide present in t-and rRNA and a marker of cell turnover, as well as the tricarboxylic acid cycle intermediate 2-oxoglutarate. Furthermore, 3 further new compounds were also excellent discriminators between patients and controls: 2-hydroxy, 2-methylpropanoic acid, erythritol and 2,4,6-trihydroxypyrimidine. Although renal disease may be associated with heart failure, and metabolites associated with renal disease and other markers were also elevated (e.g. urea, creatinine and uric acid), there was no correlation within the patient group between these metabolites and our heart failure biomarkers, indicating that these were indeed biomarkers of heart failure and not renal disease per se. These findings demonstrate the power of data-driven metabolomics approaches to identify such markers of disease.

ObjectiveWe aimed to derive and validate a clinical decision rule (CDR) for suspected cardiac chest pain in the emergency department (ED). Incorporating information available at the time of first presentation, this CDR would effectively risk-stratify patients and immediately identify: (A) patients for whom hospitalisation may be safely avoided; and (B) high-risk patients, facilitating judicious use of resources.MethodsIn two sequential prospective observational cohort studies at heterogeneous centres, we included ED patients with suspected cardiac chest pain. We recorded clinical features and drew blood on arrival. The primary outcome was major adverse cardiac events (MACE) (death, prevalent or incident acute myocardial infarction, coronary revascularisation or new coronary stenosis >50%) within 30 days. The CDR was derived by logistic regression, considering reliable (κ>0.6) univariate predictors (p<0.05) for inclusion.ResultsIn the derivation study (n=698) we derived a CDR including eight variables (high sensitivity troponin T; heart-type fatty acid binding protein; ECG ischaemia; diaphoresis observed; vomiting; pain radiation to right arm/shoulder; worsening angina; hypotension), which had a C-statistic of 0.95 (95% CI 0.93 to 0.97) implying near perfect diagnostic performance. On external validation (n=463) the CDR identified 27.0% of patients as ‘very low risk’ and potentially suitable for discharge from the ED. 0.0% of these patients had prevalent acute myocardial infarction and 1.6% developed MACE (n=2; both coronary stenoses without revascularisation). 9.9% of patients were classified as ‘high-risk’, 95.7% of whom developed MACE.ConclusionsThe Manchester Acute Coronary Syndromes (MACS) rule has the potential to safely reduce unnecessary hospital admissions and facilitate judicious use of high dependency resources.