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By Michael H. Crawford, MD, Editor
SYNOPSIS: A prospective study of patients with suspected acute aortic syndromes showed that a clinical risk score plus D-dimer testing carried a positive predictive value of 99.7% and a 0.3% incidence of false-negative studies. The authors recommended that this approach become the standard method for triage to imaging in patients with suspected acute aortic syndromes.
SOURCE: Nazerian P, Mueller C, Soeiro AM, et al. Diagnostic accuracy of the aortic dissection detection risk score plus D-dimer for acute aortic syndromes. Circulation 2018;137:250-258.
Aortic dissection, intramural hematoma, and penetrating ulcer are life-threatening acute aortic syndromes (AAS), with a concerning misdiagnosis rate of up to 40%. Although CT angiography can diagnose AAS accurately, < 3% of such studies conducted in patients suspected of experiencing AAS were positive in an ED-based study. Clearly, clinicians need something to increase the accuracy of diagnosis and reduce unnecessary testing.
Thus, this prospective observational study conducted in six centers in three countries in Europe and one in Brazil that tested an AAS risk score (RS) plus D-dimer testing (DD) is of interest. Adult patients presenting to the ED in whom AAS was in the differential diagnosis were assessed. Only those who refused participation or experienced significant trauma were excluded. The RS included 12 risk markers and has been published previously.1 Confirmation of AAS was by CT angiography, MR angiography, transesophageal echocardiography, surgery, or autopsy. If these tests were not performed, researchers confirmed using a 14-day follow-up observation period. The primary outcome was the failure rate of two diagnostic strategies for excluding AAS: 1) RS = 0 and DD negative (< 500 ng/mL); and 2) RS < 1 and DD negative.
Over three years, researchers enrolled 1,850 patients in the study. Of these, 24% demonstrated RS = 0 and 58% exhibited RS = 1; thus, 82% were classified as low risk for AAS. DD was positive in 44%, 33% with RS = 0 and 41% with RS = 1. Therefore, the DD was positive in 39% of patients with RS < 1 and in 67% with RS > 1. A conclusive diagnosis of AAS was made in 13% of the patients. A positive DD had a sensitivity of 97% and a specificity of 64% for the diagnosis of AAS. In the 294 patients with an RS = 0 and who were DD-negative, only one case of AAS was observed for a failure rate of 0.3%. The authors concluded that either RS = 0 or < 1 plus DD negative should be adopted as the standard to exclude the diagnosis of AAS.
This risk score for AAS was evaluated against the International Registry of Acute Aortic Dissection (IRAD) database from 1996 to 2009, which included 2,538 patients with confirmed AAS. The score is based on identifying risk markers from three groups. If one or more are discovered from a group, that equals 1 point; one or more from another group is another point and so on for a total possible score of 3. The three groups are pain features, such as abrupt, severe, or tearing; predisposition features, such as known aneurysm or aortic valve disease; and physical examination features, such as a new aortic regurgitation murmur or pulse deficits. In the IRAD database of confirmed AAS cases, 88% exhibited more than one pain feature; 28% more than one predisposition feature; and 51% one or more exam features. This resulted in a sensitivity of 96% and a false-negative rate of 4%. Given that only 1/10,000 ED visits are confirmed AAS, this is a rare condition that precludes performing a prospective study, according to the authors. Thus, the authors did not know the specificity or false-positive rates. Accordingly, the RS-DD muliticenter study is of interest, since it is prospective and includes the DD test, which is reported to carry a very high negative predictive value. The main findings of this study were that the RS-DD combination carried a very high positive predictive value of 99.7% and a failure rate of 0.3% (false-negatives). If those with a negative DD but a RS > 1 were examined, 4% had an AAS, which is similar to the false-negative rate of RS alone in the older study. Clearly, this false-negative rate is unacceptable for this condition, and the RS-DD doesn’t work well in those at clinically high risk, even in those with a negative DD. Thus, these patients should undergo imaging despite the negative DD. A high clinical suspicion trumps DD.
There are limitations to this study. The clinical entry criteria were prespecified but determined by each provider. This is hard to standardize. The study was conducted in urban teaching hospitals and may not be generalizable. It was non-blinded, which likely affected the decision to perform imaging, but would it have been ethical to blind the study? Finally, about half the subjects did not undergo imaging, surgery, or autopsy, but received an AAS confirmation or denial by a two-week follow-up period under the assumption that untreated AAS would lead to early adverse events. This approach identified seven patients with AAS (0.4% of all patients), but may have missed some mild cases. These were probably not type A dissections, but could have been type B, intramural hematoma or penetrating ulcers that healed on their own.
At this point, the RS plus DD evaluation is the best tool at our disposal for the initial triage of suspected AAS cases. Those with a RS > 1 should go right to imaging. Those with RS < 1 should undergo a DD and imaging only if it is positive.
Financial Disclosure: Clinical Cardiology Alert’s Physician Editor Michael H. Crawford, MD, Peer Reviewer Susan Zhao, MD, Nurse Planner Amy Johnson, MSN, RN, Editor Jonathan Springston, Executive Editor Leslie Coplin, and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.