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Nazerian P, Mueller C, Soeiro AM, et al. Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study. Circulation. 2018;137:250-258. PMID 29030346

One-paragraph summary

Between 2014 and 2016, six hospitals in four countries prospectively enrolled 1,850 consecutive emergency department outpatients who had at least one of chest, abdominal or back pain, syncope, or a perfusion deficit, and in whom acute aortic syndrome (AAS) was in the differential diagnosis. Pretest probability was assessed with the guideline-endorsed aortic dissection detection risk score (ADD-RS, range 0–3) and D-dimer was dichotomised at 500 ng/mL. Final adjudication used conclusive imaging, autopsy, surgery, or 14-day follow-up. AAS was present in 241 patients (13%): 125 type A dissection, 53 type B dissection, 35 intramural haematoma, 18 aortic rupture, 10 penetrating aortic ulcer. ADD-RS was 0 in 438 patients (24%), 1 in 1,071 (58%), and >1 in 341 (18%). D-dimer alone had a sensitivity of 96.7% (95% CI 93.6–98.6) and a specificity of 64.0% (61.6–66.4); eight patients with confirmed AAS had a negative D-dimer. Combining ADD-RS = 0 with a negative D-dimer produced a failure rate of 0.3% (0.1–1.9) and ruled out 15.9% of the cohort; the more permissive ADD-RS ≤1 with a negative D-dimer also produced a failure rate of 0.3% (0.1–1.0) while ruling out 49.9% (47.7–52.2). The trial was registered as NCT02086136.

Key findings

  • D-dimer <500 ng/mL alone: sensitivity 96.7%, specificity 64.0% for AAS — high sensitivity, but with 8 false negatives among 241 AAS cases, insufficient as a stand-alone rule-out.
  • ADD-RS ≤1 plus negative D-dimer: failure rate 0.3% (3 AAS among 924 patients), efficiency 49.9% — i.e. half of suspected patients can be dismissed at a miss rate comparable to accepted rule-out strategies in pulmonary embolism.
  • ADD-RS = 0 plus negative D-dimer: failure rate 0.3% (1 AAS among 294), efficiency only 15.9% — safer per patient but far less useful operationally.
  • Prevalence of AAS in this enriched ED population was 13%, an order of magnitude above unselected chest pain, which drives the post-test probabilities.
  • The AAS case mix included 45 non-dissection entities (35 IMH, 10 PAU) — subtypes with less fibrin turnover and therefore the likely locus of D-dimer false negatives.

Limitations

  • Observational, not a management trial. No patient was managed by the rule; failure rates are estimated retrospectively from the adjudicated cohort, so they are best-case estimates of what a prospective implementation would achieve.
  • Enriched population. Enrolment required a clinician to have AAS in the differential. Transporting the 0.3% failure rate to an unselected chest-pain population is unwarranted.
  • Single fixed cutoff. D-dimer was dichotomised at 500 ng/mL with no age adjustment; specificity of 64% means the rule increases rather than decreases imaging in the D-dimer-positive majority.
  • 8 false negatives is not zero. In absolute terms, one AAS was missed by the ADD-RS = 0 strategy and three by ADD-RS ≤1. For a condition with hourly mortality, the tolerance for that failure rate is a value judgement, not a statistical one — a point contested in published correspondence (PMID 30571366).
  • No information on aneurysm. The study says nothing about detecting or monitoring non-acute thoracic aortic aneurysm, which is the larger clinical problem.

Why it matters

ADvISED is the only study that put a circulating biomarker into a validated aortic diagnostic algorithm, and it did so by demonstrating what a biomarker in this disease actually is: one term in a bundle, never a test. Its structure — pretest probability score, then biomarker, with a prespecified failure rate and efficiency reported as a pair — became the template for the field, and the FoCUS subanalysis (PMID 31226214) extended it to three terms, reaching a 0% failure rate (95% CI 0–1.2%). It also sets the performance bar any future aortic biomarker must clear: beat 0.3% failure at 49.9% efficiency. Fifteen years after Suzuki's review of candidate acute-dissection markers (PMID 20717014), ADvISED remains the only one of them that changed practice.

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