The ADvISED Trial: A Novel Clinical Algorithm for the Diagnosis of Acute Aortic Syndromes

Written by Salim Rezaie REBEL EM Medical Category: Cardiovascular

Background: Acute Aortic Syndromes (AAS) are life threatening cardiovascular emergencies that are the bane of every emergency physician’s existence. They are diagnostic challenges due to the clinical presentation being highly non-specific. Computed tomography angiography (CTA), Transesophageal Echocardiography (TEE), and Magnetic Resonance Angiography (MRA) can help accurately diagnose AAS. CTA exposes patients to radiation and large doses of intravenous contrast, neither of which is a good enough reason to skip the test in patients you think may have a dissection, but certainly not something we want to do to all patients coming to the ED with chest pain. TEE and MRA may not be available or able to be performed in a timely manner. Having a clinical algorithm that can help physicians reduce misdiagnosis and at the same time avoid over-testing are lacking.

What They Did:

Multicenter, prospective observational study

6 Hospitals in 4 countries

Use of the Aortic Dissection Detection Risk Score (ADD-RS) of ≤1 + Negative D-Dimer (DD) for ruling out AAS

Outcomes:

Primary: Failure rate of ADD-RS and D-Dimer neg strategy for ruling out AAS Calculation: AAS diagnoses/ Number of Patients with Negative DD Within in a Risk Category

Failure rate of ADD-RS and D-Dimer neg strategy for ruling out AAS Secondary: Efficiency in Ruling-Out AAS Calculation: Number of Patients with Negative DD Within a Risk Category/Number of Enrolled Patients

Efficiency in Ruling-Out AAS

Inclusion:

Consecutive patients ≥18 years of age, with any 1 or more of the following symptoms, dating ≤14 days: Chest/Abdominal/Back Pain Syncope Perfusion Deficit Acute Aortic syndrome in Differential Diagnosis



Exclusion:

Primary trauma

Unwillingness or inadequacy to participate in the study

Definitions:



Pre-Test Probability Assessment (ADD-RS): Based on 12 risk markers classified in 3 categories Calculated by number of categories (0 – 3) where at least one risk marker was present



D-Dimer (DD): Defined as negative if <500ng/mL fibrinogen equivalent units

Conclusive Imaging Used for Diagnosis of AAS: CTA, TEE, and/or MRA

Results:

1850 patients analyzed 438 (24%) patients had ADD-RS = 0 1071 (58%) patients had ADD-RS = 1 341 (18%) patients had ADD-RS > 1 241 (13%) patients had AAS

Positive DD (≥500 mg/mL) for Diagnosis for AAS 813 (43.9%) of patients 585 (38.8%) patients had ADD-RS≤1 228 (66.9%) patients had ADD-RS>1



8 patients with AAS had a negative DD

Critical Results:

Strengths:

Asks an important clinical question

Multicenter study increases generalizability

First study to really look at how to implement d-dimer into a diagnostic algorithm

Addresses the need issue from ACEP to not incorporate d-dimer until a risk stratification tool had been developed

Limitations:

Observational study with many confounders

Physicians not blinded to items for pre-test probability assessment or the DD test results, potentially causing bias in this study

Although symptoms triggering screening were pre-specified, entry criterion were provider determined

Half the patients in this study did not have conclusive imaging and their case follow up was based on 14-day clinical follow up data only

Unclear if 14 day follow up is an adequate time period

There is no comparison to clinical gestalt

Rate of AAD is pretty high (i.e. 13%), making it unclear how this would work in lower risk groups

Only use one d-dimer assay, that may not be available at all institutions

No discussion of age-adjustment of d-dimer

Discussion:

In this paper, the authors suggest the following algorithm: ADD-RS>1, regardless of DD should proceed to CTA ADD-RS = 0 or ≤ 1 + DD neg are potentially ruled out for AAS



This strategy will miss around 1 in 300 cases of AAS

Author Conclusion: “Integration of ADD-RS (both = 0 or ≤ 1) with DD may be considered to standardize diagnostic rule-out of AAS.”

Clinical Take Home Point:

This is a novel clinical strategy in evaluating patients with the potential of Acute Aortic Syndromes (AAS), but still requires external validation, for reproducibility and comparison to overall clinical gestalt before implementation into clinical practice.

References:

Nazerian et al. Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study. Circulation 2017. PMID: 29030346

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)