Understanding Bias in Acute Aortic Syndrome Research

Reference: McLatchie et al and DAShED investigators. Diagnosis of Acute Aortic Syndrome in the Emergency Department (DAShED) study: an observational cohort study of people attending the emergency department with symptoms consistent with acute aortic syndrome. EMJ Nov 2023. Date: February 11, 2024 Guest Skeptic: Nirdosh Ashok Kumar, Emergency Medicine Specialist – Aga Khan University Hospital, Karachi, Pakistan. Case: A 66-year-old female with a history of smoking, hypertension, and type-2 diabetes presents to the emergency department (ED) with syncope while walking her dog. She complains of retrosternal chest pain radiating to her jaw. She is bradycardic, hypotensive, and tachypneic. She is received in the resuscitation room. Monitors have been attached, and intravenous (IV) access has been achieved and IV analgesia has been given. The ECG shows sinus tachycardia with non-specific ST-T changes. The chest x-ray is unremarkable. However, she is still in severe pain. A post-graduate year 2 (PGY-2) resident asks you if it could be a ruptured abdominal aortic aneurysm, aortic dissection, or angina. Background: The diagnosis of acute aortic syndrome (AAS) is commonly delayed or missed in the ED. AAS has been referred to as the “lethal triad” that incorporates aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU) [1].  It is a rare condition with a high mortality rate and can present in atypical ways. It affects approximately 4,000 people per year in the United Kingdom [2] and 43,000 to 47,000 people per year in the USA [3]. The annual incidence rate of AD ranges between 2.9 and 7.2 per 100,000. [4-8] The misdiagnosis rate is estimated to be between 16% and 38%6,[9-19] with a diagnostic delay of up to 24 hours for 25% of cases, and mortality follows a linear increase of 0.5% per hour in the first 48 hours. [20] A retrospective observational study from Canadian researcher, Dr. Robert Ohle was published in CJEM in 2023. This study found that between 2003 and 2018, there were 1,299 cases of AAS in Ontario, the largest province in the country. It reported an overall annual incidence rate of 0.61 per 100,000 people which is much lower than previously reported rates. The study also highlighted the significant mortality rate associated with AAS, with a one-year mortality rate decreasing from 47.4% to 29.1%, and ED mortality at 14.9%​​. [21] When looking specifically at atraumatic chest pain presentations to the ED, it is estimated the incidence of AAS is one in 980. [22] It can be like looking for a needle in a haystack of chest pain patients. The gold standard for diagnosing AAS is to perform a CT aorta angiogram (CTA). However, scanning everyone chest pain patient would have a very low diagnostic yield [23,24], expose many patients to unnecessary ionizing radiation and end up being very costly. It would be great if there was a validated clinical decision tool (CDT) to help clinicians be more selective in using CTA to diagnose AAS. Some CDTs have been devised and tested for diagnosing AAS. [25,26] The Aortic Dissection Detection Risk Score (ADD-RS) is one CDT that has been derived and tested. Four studies with methodologic limitations were included in an SRMA of the ADD-RS and published in AEM 2020. [27] The authors concluded that patients with an ADD-RS score of ≤ 1 with d-dimer < 500 ng/mL have high sensitivity for ruling out AASs. However, it is unclear if it is good enough for clinicians to use, better than clinical gestalt [28,29], and an impact analysis has not been done to determine if it would lead to fewer CTAs and d-dimers being performed. Clinical Questions: What are the characteristics of ED attendances with possible AAS, how effective are existing clinical decision tools (ADD-RS, Canadian Guideline, Sheffield, AORTAs) and the use of CTA in an undifferentiated cohort of ED patients? Reference: McLatchie et al and DAShED investigators.