Focused Cardiac Ultrasound for Acute Aortic Syndromes

Aorta graphic

Integration of transthoracic focused cardiac ultrasound in the diagnostic algorithm for suspected acute aortic syndromes

Eur Heart J June 2019 - Pubmed Link

Accompanying editorial (endorses use of this evidence)


Take Home Points

1. In this secondary endpoint prospective observational study, the combination of a risk score, d-dimer, and focused cardiac ultrasound was very sensitive for acute aortic syndromes (AAS).

2. Direct signs of AAS on focused cardiac ultrasound were very specific for the diagnosis.

3. More studies are needed for validation of these findings.


Background

Acute aortic syndromes such as aortic dissection have long plagued the acute care community with fear. These pathologies are often deadly and unfortunately, do not always present like the textbooks tell us. Therefore, many are stuck in the quagmire between overtesting low risk patients and missing atypical patients who have the disease. Much has been done to try to aid in this dilemma - decision scores, d-dimers, so far nothing has been terribly helpful. But then...ultrasound. This group had an idea - take everything we know so far about categorizing risk and then add the additional data point of ultrasound findings. We know that ultrasound can visualize much of the aorta, but it is notoriously insensitive for finding dissection flaps. Perhaps by combining a decision instrument, a serum d-dimer, and a focused echo - we can create a diagnostic pathway that doesn’t miss a lot of badness and doesn’t have us testing everybody.

Of note, the 2014 European Society of Cardiology Guidelines are referenced often in this article.

  • Recommends TTE in all cases (figure 6 in guidelines), Leve 1 C recommendation (high recommendation with low evidence) for initial imaging. In fact, some times does not require follow up imaging.


Check out The Evidence Atlas - Aorta for a review of prior evidence on point of care ultrasound in aortic diseases.


Questions

In patients with low pre-test probability for acute aortic syndrome, can a focused cardiac ultrasound (FoCUS) identify patients that would require further confirmatory imaging?

In patients with low pre-test probability for acute aortic syndrome, can a negative focused echo in conjunction with a negative serum D-dimer, safely rule-out acute aortic syndrome?


Population

This was from the ADvISED group (Aortic Dissection Detection Risk Score Plus D-dimer in Suspected Acute Aortic Dissection)

Included tertiary hospitals from four countries (Italy, Brazil, Germany, Switzerland)

This was a prespecified analysis of the original study where the primary outcome was to see if the aortic dissection detection score + D-dimer to evaluate for aortic dissection.

The original study (Nazerian et al 2018) found that an ADD-RS ≤1 with a negative D-dimer had a sensitivity of 98.8%, LR- 0.02.


Inclusion:

  • > 18 years

  • ≥ 1 of the following in ≤ 14 days: chest/abdominal/back pain, Syncope, Signs/symptoms of perfusion deficits (nervous system, myocardium, abdominal organs, limbs)

  • Acute aortic syndromes (AAS) considered in differential. Defined as the treating attending felt the need to rule it out

  • FoCUS performed in ED prior to advanced imaging or surgery


Exclusion:

  • Primary trauma

  • Did not consent to participate


Design

As mentioned above, this was a pre-specified secondary sub-analysis of a prior prospective study. This is consistent with what is on the Clinical Trials entry with the exception that they did not evaluate chest xray as they said they would originally. “Pre-specified secondary sub-analysis will evaluate accuracy of FoCUS and chest xray for suspected aortic dissection.”

ClinicalTrials.gov, No. NCT02086136


Here is how it worked (based on the prior publication):

  1. Patients enrolled from emergency departments if they met criteria above (24/7)

  2. A D-dimer was ordered. D-dimer cutoff was <500 ng/mL.

  3. Aortic Dissection Detection Risk Score was calculated. Basically asks: A) High risk condition (Marfan, family hx, known aortic problems or aneurysm), B) High risk pain feature (abrupt, ripping, tearing), C) High risk exam (pulse def, BP differential, focal neuro deficit plus pain, aortic insufficiency murmur, shock)

  4. All other tests were up to the treating physician who was not blinded to the study information (such as echo or risk score).

  5. Focused cardiac ultrasound (FoCUS) performed immediately after enrollment (and prior to advanced imaging or surgery). It seems this was performed by someone other than the treating physician.

  6. Immediately afterwards, whoever did the echo completed a form which included if windows were good or bad and what the findings were

  7. Reference standards for diagnosis was CT Angiography, Transesophageal echo, MR Angiography, surgery, or autopsy. If these were not done in the ED, then 14 day telephone interview was performed or there was an outpatient visit. If there was none of these, there was a clinical adjudication between two reviewers based on chart review.

Remember they were looking for any Acute Aortic Syndrome (AAS) which included aortic dissection, intramural aortic hematoma, penetrating aortic ulcer, and spontaneous aortic rupture


Power analysis = need 222 participants with negative exams, total of 740 patients included in study.


Who did the ultrasounds?

Cardiologist, Internal medicine, or Emergency Medicine physicians with ≥ 1 year of experience in FoCUS


The Scan

Phased array transducer

Phased

Patient supine or left lateral decubitus

Needed ≥1 of these views:

  • Left/right parasternal

  • Apical

  • Suprasternal

  • Subcostal

  • Abdominal aorta

  • Carotid arteries


This is important for understanding the results:

The following were considered direct signs of a positive FoCUS:

  • Intimal flap

  • Intramural aortic hematoma (>5mm)

  • Penetrating aortic ulcer (crater-like outpouching with jagged edges in the aortic wall)


These were Indirect signs:

  • Thoracic aorta dilation ≥4 cm

  • Pericardial effusion or tamponade

  • Aortic valve regurgitation on color doppler


Learn how to do Ultrasound for Aortic Dissection from 5 Minute Sono!

5minsono


Check out Aorta Pathology on the POCUS Atlas!

thePOCUSAtlas


Results

Study marked as completed December 2016. First publication had 1850 patients.

Of the patients with ultrasound before other imaging - 864 patients eligible, 17 excluded because no FoCUS before imaging, a few for non consenting or lost to follow up


N = 839

  • 17.4% of patients had AAS

  • 10.1% Type A AAD

  • 3.2% Type B AAD

  • 2.4% Intramural Hematoma

  • 1.3% Spontaneous Aortic Rupture

  • 0.4% Penetrating Aortic Ulcer

  • 168 (20%) had ADD > 1

  • 10% had direct signs, 26.6% had indirect signs on FoCUS (of those with AAS)

  • Only 5.2% of the original 839 had direct signs present.

Patients that did not have AAS had

  • Musculoskeletal chest pain (26.3%)

  • GI disease (12%)

  • ACS (10.8%)

  • Syncope (6.2%)

  • Pericarditis, pneumonia, aortic aneurysm, PE, Stroke, limb, ischemia, others


Remember, this whole article is technically a secondary outcome of the first study.

Main Outcomes

1. Overall Accuracy of FoCUS for AAS

Take away - Direct signs are very specific. Having any direct or indirect sign is fairly sensitive.

Table 1


2. Does FoCUS increase accuracy compared to using only ADD-RS?

Take away: Yes

AUC improved when adding FoCUS to ADD-RS alone. 0.77 → 0.88 for ADD-RS + and FoCUS of Any Sign


3. How accurate is the combination of ADD-RS and FoCUS?

Take home: Direct findings are specific; any finding is not that sensitive.

Table 2

If pretest probability of 10% (that is the incidence in their low risk group), after a negative FoCUS, post test probability would be ~2%.

There is some conflict in numbers here between the manuscript and supplemental figures. Supplementary table 4 is listed above. N = 671 here.

Then they list additional data for the diagnostic performance of the rule out strategy of ADD-RS ≤1 and a negative FoCUS. This time there are only 476 patients that meet criteria (not sure what happened to the other 200 patients). Now this rule out strategy has a 93.8% sensitivity and 67.4% specificity. This is also quoted in abstract.


FoCUS + ADD-RS ≤1 Rule Out Strategy:

Sensitivity 93.8%, -LR 0.09. Failure rate 1.9% (0.9-3.6), Efficiency 56.7%.

(Efficiency = number of patients satisfying rule-out criteria/number of enrolled patients)


4. Now what happens when we add in D-dimer?

Take home: It is even more sensitive

ADD-RS ≤1 + Direct FoCUS Signs Absent + D-dimer Negative

Sens 100% (97.3-100%)

Specificity 58.7% (55-62.4%)

+LR 2.42 (2.2-2.64)

-LR 0 (0-0.1)

Failure rate 0

Efficiency 48.9%

Using FoCUS negative (not just direct signs) was still 100% sensitive but specificity dropped to 48.4%.


Other Findings

Cardiologist vs Non-cardiologist - Cardiologists performed 20.3% of scans

Cardiologists more sensitive for direct signs (70% vs 41.3%). No statistically significant difference in sensitivity when considering Any Sign.

No statistically significant difference in specificity for direct or any signs.


Multivariable Logistic Regression Analysis - Odds Ratios for Aortic Dissection

  • Hypertension 2.881

  • Cancer 0.016

  • History of ischemic cardiac disease 0.287

  • Abrupt onset of pain 4.159

  • Positive D-dimer 86.82

  • Direct signs on FoCUS 38.262

  • Thoracic Enlargement on FoCUS 6.556

  • Pericardial Effusion on FoCUS 9.071

  • Note that aortic valve regurg was not significant predictor


FoCUS more sensitive and specific for Type A AAD (for both direct and any sign)


Authors Proposed Diagnostic Algorithm (labeled as Take home figure in manuscript):

If low risk and FoCUS negative → D-dimer → If negative, consider it ruled out. If positive, get other imaging.


If low risk, if only indirect signs are present, the patient is stable and another diagnosis is more likely, they suggest a D-dimer could also rule out AAS.


If High risk or Low risk + Direct signs → get further imaging.


Limitations

All of this data was a secondary end point of the prior study. Therefore, it should be taken in the context of being hypothesis generating. Further, this is only a single study and would require external validation. Not all populations would be similar to the 13% of AAS they saw in their original population.

This was only about half of the original population. Presumably this is because many patients did not receive a FoCUS prior to advanced imaging. The problem is that there were no specific rules regarding who went straight to imaging and who received an ultrasound (at least none stated). Therefore, this introduces a significant selection bias in the patients included in this study - perhaps they were all more stable than the rest of the population allowing for time to do the scan? Or perhaps they were more critically ill and the physicians needed answers quickly? It would have been nice to see a table comparing the populations who received FoCUS and those who did not.

Only about half of patients received aortic imaging, rest were adjudicated - may not be the perfect reference standard. There certainly could have been cases that were missed after the 14 day follow up.

Most people are not familiar with some of the intricacies of this scan. Looking for a penetrating ulcer?! Good luck. These were skilled operators and therefore less experienced users may not have this degree of accuracy. On the other hand, thoracic aortic dilation and pericardial effusions, well within the scope and ability of many who perform focused echo, did have significant positive likelihood ratios. This is useful information, another tool in the diagnostic work up.


Discussion

How does this change what we do? Authors think the biggest impact of FoCUS is to identify patients who are low probability but have positive FoCUS, and therefore obtain further imaging. Authors also suggest that if low risk and only having indirect signs (or no signs) on FoCUS, with a negative d-dimer, perhaps could avoid further work up. This is a fairly large, well done study and the results are compelling; however, we still have to maintain some caution here. This is an extremely high risk diagnosis, and therefore most people would likely err on the side of caution. In my opinion, this rule out strategy appears very promising, but I do not think I will be using it routinely. Regarding the rule in component - I am not sure that this is going to change my management either. If I have a patient that is low risk - the ultrasound is just a single data point. If I chose to perform an ultrasound and it had a direct sign on it, yes I would get further imaging. However, your pre-test probability prior to that ultrasound is likely more important. For example - were they high risk because their pain was sudden and severe (common in my population) or were they high risk because they had a pulse deficit and a neuro deficit with a new aortic murmur? Prevalence of disease in this study was 17.4% vs 13% in original study. The point is that “low risk” by the ADD-RS is not a homogenous population. Therefore, you have other factors to consider in determining the need for further work up. POCUS is just one tool you can use to help determine your risk.

It is interesting the distinctions between the accuracies of direct and indirect signs. It seems that for ruling in we should use only direct signs, but for ruling out we should use any of those signs. This is going to lead to a lot of false positives when ruling out. One unexpected finding is that in looking at the High risk group (ADD-RS ≥2), it is weird that the specificity goes down in the high probability group. You would think that the opposite would occur.

Lastly, we should just briefly mention that we will need to decide how sensitive we need this algorithm to be. Remember that the original study with ADD-RS and D-dimer alone only missed 0.3%. Similarly, the ADD-RS and FoCUS alone only missed 1.9%. Do we really need both? Sure this is a high risk diagnosis but we know from other ventures that if we make it too sensitive we risk over testing leading to potential negative consequences for a portion of the population.


Take Home Points

1. In this secondary endpoint prospective observational study, the combination of a risk score, d-dimer, and focused cardiac ultrasound was very sensitive for acute aortic syndromes (AAS).

2. Direct signs of AAS on focused cardiac ultrasound were very specific for the diagnosis.

3. More studies are needed for validation of these findings.


More Great FOAMed on this Topic

REBEL EM on original trial

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Our score

5 Probes


Expert Reviewer for this Post

Pare

Joseph Pare, MD MHS @jrpare29

Dr. Pare is an attending physician at Boston Medical Center and Director of Ultrasound Research in the Department of Emergency Medicine at Boston University School of Medicine


Cite this post as

Michael Prats. Focused Cardiac Ultrasound for Acute Aortic Syndromes. Ultrasound G.E.L. Podcast Blog. Published on January 20, 2020. Accessed on February 17, 2020. Available at https://www.ultrasoundgel.org/84.
Published on 01/20/20 06:00 AM
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