A laboratory score that incorporates high-sensitivity cardiac troponin (hs-cTn) and glucose results along with estimated glomerular filtration rate (eGFR) is more sensitive and specific than hs-cTn results alone in stratifying risk in patients who present to emergency departments with suspected acute coronary syndrome (ACS) (CMAJ 2018; 190:3974-84).
Adopting this clinical chemistry score (CCS) could improve lab reporting and analytics in the context of an ACS workup, according to the authors. Doing so “would standardize reporting of hs-cTn test results, how the tests are interpreted in the normal range, and represent an option less susceptible to both analytical and preanalytical errors,” they wrote. “This could result in the safest laboratory approach for physicians to use at presentation in the emergency department.”
Analytical variation and interferences in hs-cTn assays can lead physicians to misclassify patients’ risk when using existing algorithms, according to the authors. This makes it imperative for improved lab services to assist doctors in evaluating patients with suspected ACS, they contend.
High glucose levels may identify patients who are more hemodynamically unstable, who have a larger infarct size, and who have higher 30-day mortality risk. Evidence also suggests that eGFR is an independent predictor of major adverse cardiac outcomes in patients with ACS, according to the authors.
The investigators validated the CCS performance as a predictor of myocardial infarction (MI) or death within 30 days in a post hoc analysis of 4,245 patients seen in emergency departments in Canada, Australia, Germany, and New Zealand. They assigned a total of 0 to 5 points for the overall CCS based on established cutoffs and either 0 or 1 point each for glucose levels and eGFR and from 0 to 3 points for hs-cTn results. They created separate CCSes incorporating hs-cTn I and hs-cTn T results. A CCS of 0 indicates a patient’s lab results all are normal; a CCS of 5 indicates they all are abnormal.
Overall, 17.1% of participants died or had an MI within 30 days. Considering all four study populations, a CCS based on hs-cTn I with 0 points had a 100% sensitivity while a CCS based on hs-cTn T with 0 points had a 99.9% sensitivity and 1 false negative, with 8.9% of hs-cTn I and 10.5% of hs-cTn T populations classified as low risk for MI or death within 30 days. In contrast, hs-cTn I results alone with a cutoff <5 ng/L had a sensitivity of 96.6% while hs-cTn T results alone with a cutoff of <6 ng/L had a sensitivity of 98.2%.
A CCS with 5 points also performed better than hs-cTn results alone in identifying patients at high risk, with specificity of 96.6% and 94.0% for the hs-cTn I and hs-cTn T CCSes, respectively, versus 93.2% and 73.8% specificity for hs-cTn I and hs-cTn T results alone, respectively.
These findings suggest that a CCS of 0 “would classify close to 10% of the population in the emergency department who present with symptoms of [ACS] as being at low risk for unstable angina, MI, revascularization procedures and death,” wrote the researchers, thereby reassuring physicians that such patients are at low risk after their first blood draw.
Gene Expression Signature Distinguishes Kawasaki Disease From Other Infectious Diseases; Could Become Diagnostic Test
A 13-transcript gene expression signature distinguished patients with Kawasaki disease (KD) from those with bacterial, viral, or inflammatory disease and shows promise as a blood-based test that might aid in rapidly diagnosing KD (JAMA Pediatrics 2018; doi:10.1001/jamapediatrics.2018.2293). In a separate statement, the authors report being in discussions with biotech companies to develop a clinical test from the signature.
The researchers developed the signature in the hopes that it would help identify KD early in the disease process to facilitate prompt treatment and to prevent of one of the most serious sequelae of KD, coronary artery aneurism. KD diagnosis currently relies on the presence of four out of five clinical criteria, and symptoms of the disease are very similar to other infectious diseases.
Researchers in four countries conducted a case-control study involving 606 children, including 404 in a discovery and testing cohort and 202 in a validation cohort, with 78 and 102 KD patients, respectively. They identified 1,600 transcripts significantly expressed differentially in patients with KD versus those with other diseases and healthy controls. After subsequent modeling, the investigators identified 13 genes that when implemented as a disease risk score (DRS) distinguished patients with KD from other infectious and inflammatory conditions.
The DRS combines the fluorescence intensity of upregulated transcripts and subtracts the combined fluorescence intensity of down-regulated transcripts. In all, eight of the genes show increased expression in KD in comparison to other diseases, while five show decreased expression.
This 13-gene DRS had an area under the receiver operator characteristic (AUC), sensitivity, and specificity in the discovery test set and in the validation set of 96.2%, 81.7%, 92.1%, and 94.6%, 85.9%, and 89.1%, respectively.
To test how well the KD DRS corresponded with levels of diagnostic certainty the investigators also characterized patients in the validation set as having possible, highly probable, or definitive KD based on independent review of clinical data collected as part of the study. AUCs for the KD DRS tracked with these groups, rising from 70.0%. to 96.3% and 98.1%, respectively.