cardiovascular members papercut lit review

The PROFUNDUS Study

Aug 28, 2024

A 62 yo patient with a previously diagnosed spontaneous coronary artery dissection (SCAD) presents with sudden onset 10/10 central severe chest pain. Examination is normal, with no pulse deficit and no murmur. The ECG is normal, the initial troponin is normal. Cardiology are not interested unless the followup 3 hour troponin is raised. (40 minutes read)

Could this be a thoracic aortic dissection? You may expect a troponin rise in a proximal dissection (as the proximal aorta contains troponin), but a normal troponin doesn't rule it out.

The patient scores a 1 in the aortic dissection detection (ADD) risk score due to the pain features. Would you send this patient home if the D-dimer were normal? Does the fact that the patient have SCAD, increase her risks of a thoracic dissection? Would you perform a CT angiogram? Is there something more we can do to define a lower risk group?

Perhaps the new PROFUNDUS Study can help.

Acute Aortic Syndromes(AAS) have a significant, time dependent...

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Could this be a thoracic aortic dissection? You may expect a troponin rise in a proximal dissection (as the proximal aorta contains troponin), but a normal troponin doesn't rule it out.

Perhaps the new PROFUNDUS Study can help.

Acute Aortic Syndromes(AAS) have a significant, time dependent mortality, which can approach 1-2% mortality per hour. We investigate many patients with suspected AAS in the emergency department, with a low yield of true positives. The imaging of choice is CT angiography.

The clinical scoring system we use to determine high versus low risk for AAS is the ADD. There is now a move to using a score of 0-1 with a normal D-dimer to rule out AAS. Although this is not standard of care at present.

We need to beware as the ADD score has a low specificity and has been derived from a register of AAS patients. We are not sure if using the ADD score provides any advantage in terms of ordering tests such as a CT angiogram.

Can the use of ADD with a D-dimer and ultrasound improve our diagnostic ability for AAS?

The aim of this study was to assess "the safety and efficiency of a diagnostic protocol integrating clinical data with point-of- care ultrasound (POCUS) and D-dimer (single/age-adjusted cutoff), to select patients for" aortic imaging.

What They Did

This was a prospective management outcome study in 12 emergency departments in 5 countries, evaluating application of POCUS-enhanced clinical assessment plus D-dimer, to rule-in/out AASs.

.Primary Outcome: The cumulative 30-day incidence of AAS in rule-out patients.

Secondary Outcomes:

protocol efficiency: the proportion of rule-out patients avoiding advanced imaging,
protocol feasibility: the adherence of advanced imaging requests to protocol indications, and
difference in safety and efficiency using age- adjusted D-dimer interpretation.

Inclusion criteria were presence of at least one AAS symptoms for up to 14 days, and AAS was considered a potential diagnosis:

thoracic/back/abdominal pain
syncope,
organ perfusion deficit
- focal neurologic deficit
- limb ischemia

Patients were excluded if:

18 years,
alternative diagnosis evident,
primary trauma,
history of previous AAS,
patient’s inaccessibility for follow-up and
patient’s refusal to participate.

An expert physician in POCUS (Emergency Physician or Cardiologist) performed a focused bedside exam.

The POCUS examination consisted of the patient in the supine or left lateral decubitus position and the thoracic aorta and the heart being scanned with two views (although the physician could use other views at their discretion):

left parasternal long-axis and
supra-sternal notch

Signs of AAS on POCUS included:

intimal flap separating two aortic lumens (B and C in figure above),
circular / crescentic thickening (>5 mm) of the aortic wall (D)
presence of a crater-like outpouching with jagged edges in the aortic wall (E)

Indirect Signs included:

thoracic aortic dilatation (diameter ≥40 mm) ( F,G), measured from leading edge to leading edge at the largest portion of thoracic aorta),
pericardial effusion (H)
> moderate aortic valve regurgitation on colour Doppler (I)

Patients were classified as follows:

low risk if no POCUS Signs were present and the ADD score was 0-1.
High risk
- if a direct POCUS sign was present or if the ADD score was 2–3
- If only indirect POCUS signs were present and the ADD score was 0–1, and the patient was unstable or if an alternative diagnosis was unlikely.

D-dimer was considered positive if ≥500 ng/mL. In secondary analysis, an age-ajusted cutoff was calculated as patient’s age in years multiplied by 10, with a minimum value of 500 ng/mL.

Patients being discharged, were instructed to return to the ED if symptoms did not improve or if new symptoms developed. All patients were followed for 30 days, through hospital data check and telephone contact.

What They Found

N= 1979

ADD score

≤1 in 1690 (85%) patients
≥2 in 289 (15%).

398 (20 %) patients were classified at high risk of AAS.

109 (6%) patients with ADD score ≤1, were classified as high risk due to POCUS findings
- 53 patients with any direct sign,
- 56 with any indirect sign coupled to clinical instability or unlikelihood of an alternative diagnosis.

1581 (80%) patients were classified at low risk were tested for D-dimer

941 (48%) patients had a normal D-dimer <500 ng/mL.

Primary Outcome:

Of the 941 patients classified as low risk with a D-dimer <500 ng/mL, within 30 days of followup:

1 was lost to follow-up
- If it was assumed that the patient lost to follow-up had AAS, it would make the incidence of the incidence of AAS 0.11 % (95 % CI, 0.01–0.60 %; 1 of 941 patients).
0 had AAS and none died

Secondary outcome

The diagnostic protocol indicated to rule out AAS in 41 % (95 % CI, 39–43 %; 812 of 1979), given that 129 patients underwent angiography.

Discussion

Some of the results included:

Protocol failure rate of 0.41 %, i.e. 1 miss in 244 rule-outs
The protocol could avert 2 in 5 CTAs
The lowest efficiency was in patients aged >70 years and those with known aortic aneurysm.

Limitations of this Study

Advanced imaging was not performed on all patients, so that the study may underestimate the risk of overlooking milder AAS forms
POCUS has lower specificity for tears in type B forms, so patients may have been missed.
There were significant protocol violations included both an excess (6.5 %) and lack (13 %) of advanced imaging.

The authors' conclusion was: "A diagnostic strategy using POCUS-integrated PTP plus D-dimer safely ruled out AAS. POCUS improved identification of patients requiring urgent CTA. The protocol averted advanced imaging in 41 % of patients. A modified protocol using age-adjusted D-dimer could increase this percentage to 54 %, further reducing the need for advanced aortic imaging, without compromising safety."

My Take on This

We struggle to minimise the number of investigations we perform in the emergency department. The use of D-Dimer testing in pulmonary embolism and the introduction of Wells and PERC, have changed the way we practice.

I think we're headed in the same direction for AAS, but we may not be there yet. The concerns that I have with this approach is that POCUS is an operator dependant procedure and we can get it wrong. Looking for flaps is far more difficult than looking for a pericardial effusion. The expertise needed does not extend to all physicians. The use of D-dimer, when used with ADD score is also promising, however in the spectrum of AAS, some of its variants, may not result in a high D-dimer.

I would like to see a study like this done in multiple centres where there are varying degrees of capacity in POCUS and where all patients in the rule out arm get imaging. An intramural haematoma or aortic ulcer can progress to aortic dissection, but may not be picked up by POCUS as easily.

I will consider the use POCUS at present, but I'm not sure that it's prime time before further studies are done.

References

Morello F et al. Diagnosis of acute aortic syndromes with ultrasound and D-dimer: the PROFUNDUS Study. European Journal of Internal Medicine, In print. https://doi.org/10.1016/j.ejim.2024.05.029