Magnitude of Soluble ST2 as a Novel Biomarker for Acute Aortic Dissection
Background—Misdiagnosis of acute aortic dissection (AAD) can lead to significant morbidity and death. Soluble ST2 (sST2) is a cardiovascular injury-related biomarker. The extent to which sST2 is elevated in AAD and whether sST2 can discriminate AAD from other causes of sudden-onset severe chest pain is unknown.
Methods—We measured plasma concentrations of sST2 (R&D systems assay) in 1360 patients, including 1027 participants in the retrospective discovery set and 333 patients with initial suspicion of AAD enrolled in the prospective validation cohort. Measures of discrimination for differentiating AAD from other causes of chest pain were calculated.
Results—In the acute phase, sST2 levels were higher in patients with AAD than those with either acute myocardial infarction (AMI) in the first case-control discovery set within 24h symptom onset or pulmonary embolism (PE) patients in the second discovery set (medians of 129.2 ng/mL vs. 14.7 with p<0.001 for AAD vs. AMI and 88.6 vs. 9.3 with p<0.001 for AAD vs. PE). In the prospective validation set, sST2 was most elevated in AAD patients (median [25, 75 percentile]: 76.4 [49.6, 130.3]) and modestly elevated in AMI (25.0 [15.5, 37.2]), PE (14.9 [10.2, 30.1]) and angina patients (21.5 [13.1, 27.6], all p<0.001 vs. AAD). The area under ROC curve for AAD patients versus all control patients within 24h presenting in emergency department were 0.97 (0.95, 0.98) for sST2, 0.91 (0.88, 0.94) for D-dimer, 0.50 (0.44, 0.56) for cTnI respectively. At a cutoff level of 34.6 ng/mL, sST2 had the sensitivity of 99.1%, specificity of 84.9%, positive predictive value of 68.7%, negative predictive value of 99.7%, positive likelihood ratio of 6.6 and negative likelihood ratio of 0.01.
Conclusions—Among patients with suspected aortic dissection in the emergency department, sST2 showed superior overall diagnostic performance than D-dimer or cTnI. Additional study is needed to determine if sST2 might be a useful "rule-out" marker for AAD in the emergency room.
- Received July 11, 2017.
- Revision received October 19, 2017.
- Accepted October 30, 2017.