Background

  • Acute aortic syndromes (AAS) are rare causes in patients presenting with chest/abdominal/back pain or syncope. 
  • Types of AAS include aortic dissection, intramural aortic hematoma, and penetrating aortic ulcer. 
  • Diagnosis of AAS requires urgent advanced aortic imaging (AAI), such as computed tomography angiography (CTA).  
    • We don’t have a great tool for deciding who to perform AAI on for patients with these complaints, which can lead to misdiagnosis and overtesting in this patient population. 
  • The main pre-test probability (PTP) assessment tool is the aortic dissection detection (ADD) risk score, which is unsuitable for ruling out AAS. 
  • TTE via point-of-care ultrasound (POCUS) could improve our diagnostic accuracy. 
  • D-dimer levels also increase in AAS; therefore, a low D-dimer level argues against AAS, most strongly in patients with a low PTP. 
    • Unfortunately, D-dimer lacks specificity, as the levels increase with age, though the age-adjusted interpretation of D-dimer may increase specificity without compromising sensitivity. 
  • This prospective study evaluates the outcomes of implementing a diagnostic protocol for AAS based on POCUS-integrated PTP (iPTP) and D-dimer.

 

Clinical Question

Does the diagnostic protocol of assessing POCUS and D-dimer for those with possible AAS improve the safety and efficiency of selecting patients for AAI?

Population

  • Outpatients enrolled before decisions were made on advanced imaging
    • 3022 patients screened, 1979 enrolled
  • Inclusion criteria:
    • Presence of at least one AAS-compatible symptoms (thoracic/back/abdominal pain, syncope, organ perfusion deficit) lasting for up to 14 days
    • AAS is considered a meaningful diagnostic concern

Intervention

  • History and physical, followed by ADD score calculation
    • ADD score:
      • If you have 0-1 points, proceed with D-dimer
      • If you have 2+ points, proceed with AAI
      • You gain one point for each of these features:
        • Any high-risk condition: Marfan syndrome, family history of aortic disease, known aortic valve disease, recent aortic manipulation, or known thoracic aortic aneurysm
        • Any high-risk pain feature: chest, back, or abdominal pain described as abrupt onset, severe intensity, or ripping/tearing
        • Any high-risk exam feature: evidence of perfusion deficit (pulse deficit, systolic BP differential, or focal neuro deficit plus pain), new aortic insufficiency murmur (with pain), hypotension/shock
  • Emergency medicine attending physician (or another physician, i.e., cardiology consultant), an expert in POCUS, performed a focused POCUS exam
    • POCUS protocol: thoracic aorta and heart were scanned from left parasternal long-axis and supra-sternal notch views with the patient in supine or left lateral decubitus position
      • The physician could use additional cardiac views at their discretion (including parasternal, subcostal, and apical) and views for neck arteries, abdominal aorta, and limb arteries
    • Identified direct signs of AAS, including:
      • The presence of an intimal flap separating two aortic lumens
      • The presence of circular or crescentic thickening (>5mm) of the aortic wall
      • The presence of a crater-like outpouching with jagged edges in the aortic wall
    • Indirect signs of AAS:
      • Thoracic aortic dilatation (diameter ≥40mm measured from the outer edges of the largest portion of the thoracic aorta)
      • Pericardial effusion
      • Aortic valve regurgitation is at least moderate at color Doppler
  • Calculating iPTP (POCUS-integrated pre-test probability) 
    • Low iPTP if POCUS signs were absent and ADD score 0-1
    • High iPTP score if any direct POCUS sign was present or if ADD score 2-3
    • High iPTP if only indirect POCUS signs were present and the ADD score was 0-1, but the patient was unstable or if the alternative diagnosis was unlikely
  • D-dimer
    • Blood sampled before AAI
    • Positive if D-dimer ≥500 ng/mL
    • Negative if D-dimer <500 ng/mL
    • Secondary analysis with age-adjusted D-dimer cutoff, calculated as patient’s age in years multiplied by 10, with a minimum value of 500 ng/mL
  • Advanced aortic imaging
    • Preferred AAI was ECG-synchronized contrast-enhanced CTA of the chest and abdomen, extending to the skull in the presence of neurologic symptoms
      • TEE and MRA were additional reference standard methods
    • Study protocol indicated to perform urgent AAI in patients with:
      • High iPTP, irrespective of D-dimer levels
      • Low iPTP with D-dimer >500 ng/mL
    • Rule out of AAS without AAI indicated in patients with:
      • Low iPTP with D-dimer <500 ng/mL

Outcomes

  • The primary outcome of interest was protocol safety, measured as the cumulative 30-day incident of AAS in rule-out patients
  • Secondary outcomes of interest were:
    • Protocol efficiency – the proportion of rule-out patients avoiding advanced imaging
    • Protocol feasibility – the adherence of advanced imaging requests to protocol indications
    • Difference in safety and efficiency using age-adjusted D-dimer interpretation

Design

  • Prospective management outcome study
  • 12 EDs from 5 countries, mean census 60,000 visits/year, and 83% were aortic hub centers

Excluded

  • <18 years old
  • Evident alternative diagnosis
  • Primary trauma
  • History of previous AAS
  • Patient’s inaccessibility for follow-up
  • Patient’s refusal to participate

Primary Results

  • 3022 patients screened, 1979 patients enrolled 
  • 398 (20%) patients were high iPTP of AAS 
    • AAS incidence was 35% (140 patients)
  • 1581 (80%) patients were low iPTP of AAS
    • Tested with D-dimer 
      • Turn around time of d-dimer result 1hr 17min
    • Those with negative D-dimer, low iPTP of AAS = 
      • One lost to follow up 
      • NONE had AAS, and none died within 30 days
    • Those with positive D-dimer, low iPTP of AAS = 
      • One lost to follow up
      • Incidence of AAS was 6% (36 patients)
      • 12 died within 30 days of follow-up 
  • The protocol improved the triage of patients towards advanced imaging and allowed safe/efficient AAS rule out with a failure of 0.41% (1 miss in 244 patients ruled out)
    • Acceptable miss rate in general for EM physicians of <1%

Strengths

  • The protocol is feasible, with the majority of EM physicians ultrasound-trained 
  • A low protocol failure rate that is acceptable to the EM community

Limitations

  • Prospective study 
  • Not everyone was scanned, so there might have been minor AAS missed 
  • Generalizability in places without POCUS-trained physicians 
  • Generalizability in places with different d-dimer cutoffs or longer turnaround time for results

Author's Conclusions

Using iPTP and dimer can safely and efficiently rule out AAS in certain patients. 

Our Conclusions

  • This study is well done and has a protocol that is generally attainable and easy to follow. Based on the statistics, it is safe and efficient.
  • Ultrasound-trained physicians may start integrating this into their clinical practice when they have a patient with AAS on the differential, as it is shown to be safe in determining when to pursue or not pursue AAI. 
  • Future studies incorporating this protocol will be important to validate prior to switching to it, given the importance of timely AAS diagnosis.
  • Depending on your ultrasound training, you may or may not feel confident in your ability to rule assess for AAS on POCUS. Therefore this protocol might not be for everyone.