Prospective diagnostic accuracy study of plasma soluble ST2 for diagnosis of acute aortic syndromes

Abstract

Acute aortic syndromes (AASs) are difficult to diagnose emergencies. Plasma soluble ST2 (sST2), a prognostic biomarker for heart failure, has been proposed as a diagnostic biomarker of AASs outperforming D-dimer, the current diagnostic standard. We performed a prospective diagnostic accuracy study of sST2 for AASs in the Emergency Department (ED). In 2017-2018, patients were enrolled if they had ≥1 red-flag symptoms (chest/abdominal/back pain, syncope, perfusion deficit) and a clinical suspicion of AAS. sST2 was detected with the Presage® assay. Adjudication was based on computed tomography angiography (CTA) or on diagnostic outcome inclusive of 30-day follow-up. 297 patients were enrolled, including 88 with AASs. The median age was 67 years. In 162 patients with CTA, the median sST2 level was 41.7 ng/mL (IQR 29.4-103.2) in AASs and 34.6 ng/mL (IQR 21.4-51.5) in alternative diagnoses (P = 0.005). In ROC analysis, the AUC of sST2 was 0.63, as compared to 0.82 of D-dimer (P < 0.001). Sensitivity and specificity values of sST2 associated with different cutoffs were: 95.5% and 10.8% (≥12 ng/mL), 84.1% and 29.7% (≥23.7 ng/mL), 35.2% and 85.1% (≥66.5 ng/mL). Results were similar in the full cohort. In conclusion, in patients from a European ED, plasma sST2 provided modest accuracy for diagnosis of AASs.

Figure 1

Data used for diagnostic outcome adjudication. Cath: coronary angiography (cardiac catheterization laboratory); CR: chest X-ray; CTA: contrast-enhanced computed tomography angiography of the chest and abdomen; FoCUS: focused cardiac ultrasound; FU: follow-up; hosp. adm.: hospital admission; n.a.: not available; TEE: transesophageal echocardiography.

Figure 2

Dot-plot and box-whisker representation of plasma sST2 levels in study patients, classified by: (a) dichotomic final diagnosis (adjudication based on CTA), (b) subtype of acute aortic syndrome, (c) dichotomic final diagnosis (adjudication based on diagnostic outcome). A-AAD: type A acute aortic dissection; AAS: acute aortic syndrome; ACS: acute coronary syndrome; alt. diag.: alternative diagnosis; B-AAD: type B AAD; IMH: intramural aortic hematoma; PAU: penetrating aortic ulcer; SAR: spontaneous aortic rupture.

Figure 3

Scatter plots evaluating the correlation and linear regression between plasma sST2 and (a) white blood cell count, (b) creatinine, (c) troponin T and (d) D-dimer, in patients with acute aortic syndromes. Linear regression analysis data are presented as inset.

Figure 4

Receiver operating characteristic (ROC) curves of plasma sST2 and D-dimer for diagnosis of acute aortic syndromes in (a,b) patients subjected to CTA and (c,d) in all study patients classified according to diagnostic outcome. AUC values are reported with their 95%CI in brackets.