001 High sensitivity troponin: validation and subsequent audit of a novel “rule out” cut-off: Abstract 001 Table 1
Authors: Body R , Burrows G , Cook G , Carley S D , France M , Jarvis J , Haves B , Lewis P S 
Published: September 2011

Objectives and Backgrounds

High sensitivity troponin (hs-Tn) has been shown to improve early diagnosis of acute myocardial infarction (AMI). We recently reported that levels below the limit of blank (LoB, <3 ng/l) of the Roche assay had 100.0% negative predictive value (NPV). Now, we aim to validate that finding in (i) a cohort study and (ii) routine clinical use following implementation.

Methods

Initially, we included adult emergency department (ED) patients with suspected cardiac chest pain in a prospective diagnostic cohort study. Standard troponin T (TnT) and hs-TnT (Roche) were tested at presentation. The primary outcome was a diagnosis of AMI, adjudicated by two independent investigators based on reference standard ≥12 h TnT testing. Secondary outcomes included AMI defined by ≥12 h hs-TnT. After clinically implementing hs-TnT at a different institution, we identified all patients undergoing ≥2 hs-TnT tests within 24 h and evaluated initial hs-TnT level for predicting any subsequent rise.

Results

477 patients were included in the cohort study. 475 (99.6%) underwent reference standard testing. 82 (17.3%) had AMI. The area under the ROC curve was 0.95 (95% CI 0.92 to 0.97) for hs-TnT compared to 0.84 (0.78 to 0.90) for TnT (p=0.001). At the 99th percentile, sensitivity was 93.9% (86.3% to 98.0%) for hs-TnT and 70.7% (59.7% to 80.3%) for TnT (p<0.0001; Abstract 001 table 1). At the LoB (<3 ng/l) cut-off, sensitivity of hs-TnT was 98.8% (93.4% to 100.0%) with NPV 99.2% (95.5% to 100.0%). Using ≥12 h hs-TnT to define AMI, sensitivity of initial hs-TnT<3 ng/l was 99.4% (96.5% to 100.0%). On subsequently appraising hs-TnT in 915 patients in clinical practice, sensitivity (at the LoB) was 99.8% (99.1% to 100.0%) with NPV 99.4% (96.6% to 100.0%).

Abstract 001 Table 1

Diagnostic performance of hs-TnT (at each cut-off) and cTnT in the cohort study and subsequent audit in clinical practice

Assay and cut-offSensitivitySpecificityPPVNPVLR+LR−cTnT (cohort study)70.7 (59.7 to 80.3)92.8 (89.8 to 95.2)67.4 (56.5 to 77.2)93.8 (90.0 to 96.0)9.88 (6.73 to 14.49)0.32 (0.22 to 0.44)hs-TnT (14 ng/l, cohort study)93.9 (86.3 to 98.0)77.8 (73.3 to 81.8)47.0 (39.1 to 54.9)98.4 (96.3 to 99.5)4.22 (3.48 to 5.12)0.08 (0.03 to 0.18)hs-TnT (3 ng/l, cohort study)98.8 (93.4 to 100.0)30.7 (26.2 to 35.5)23.0 (18.7 to 27.8)99.2 (95.5 to 100.0)1.43 (1.33 to 1.53)0.04 (0.01 to 0.28)hs-TnT (14 ng/l, audit)92.8 (90.4 to 94.7)97.2 (94.7 to 98.7)98.4 (97.0 to 99.3)87.9 (84.0 to 91.1)33.1 (17.4 to 63.0)0.07 (0.06 to 0.10)hs-TnT (3 ng/l, audit)99.8 (99.1 to 100.0)49.5 (43.9 to 55.1)78.5 (75.4 to 81.4)99.4 (96.6 to 100.0)1.98 (1.77 to 2.20)0.00 (0.00 to 0.02)

95% CIs in parentheses. 14 ng/l is the 99th percentile of the hs-TnT assay.

LR−, negative likelihood ratio; LR+, positive likelihood ratio; NPV, negative predictive value; PPV, positive predictive value.

Conclusions

This work again demonstrates that hs-TnT improves sensitivity for AMI in the ED. Undetectable hs-TnT (<3 ng/l) levels have very high NPV, a strategy that has now been prospectively validated in both research and clinical practice populations. A randomised controlled trial of early discharge using hs-TnT is being planned.