PE risk in severe exertional dyspnea – First10EM

I think the article’s conclusions are incredibly obvious, and therefore impractical to change them, but I fear a cursory reading could lead to misinterpretations, and therefore the article is probably worth covering. (This is the same research group that published the infamous PESIT study and all subsequent misinformation about the risk of PE in syncope, so it seems reasonable to be cautious.) The question: What is the prevalence of PE in patients with acute onset, severe exertional dyspnea?

The paper

Prandoni P, Lensing AWA, Prins MH, et al. Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study. J Thromb Haemost. 2023 Jan;21(1):68-75. doi: 10.1016/j.jtha.2022.09.007. Epub 2022 December 22nd. PMID: 36695397

The methods

This is a multicenter, prospective, cross-sectional study of 14 hospitals in Italy.

patients

Adult patients (18-75 years) with less than one month of marked dyspnoea during previously well tolerated physical activity.

Marked dyspnea was defined as a severity of 3 or greater on the Medical Research Council’s modified dyspnea scale. This is defined as having to stop for breath after 100 yards or a few minutes of walking on level ground. For comparison, a severity of 2 is walking slower than people of the same age due to shortness of breath or having to stop for breath when walking at their own pace on the grade, and these patients were excluded from the study.

Exclusions: Previous DVT or PE, anticoagulant therapy, CTPA contraindications, or pregnancy.

Intervention/Confrontation

All patients were processed using a validated standard PE algorithm, using the simplified Wells score and an age-adjusted D-Dimer.

Result

The primary outcome was the prevalence of PE.

The results

Of the 683 patients screened, 266 were excluded (primarily due to lack of sufficiently severe dyspnea), leaving 417 patients in the overall study cohort. Of these, 213 had additional manifestations indicative of PE and 94 (44%) of them pronounced themselves as PE. Of the 204 who had no further manifestations of PE, 40 (19.6%) diagnosed with PE. Of these 204, 96 had apparent alternative explanations for the dyspnea (although details are somewhat limited), and the rate rule was still 14.6% in this subgroup.

Interestingly, they stopped the study based on a predefined endpoint, but then decided to run a second validation study because the rate rule was higher than expected. They looked at 61 other patients with the same inclusion criteria, but this time excluding anyone with signs or symptoms of PE or clear alternative explanations, and in this cohort the rate was 30%.

My thoughts

I don’t find these findings surprising at all, but perhaps PE diagnosis is taught differently around the world. The main symptom of PE is shortness of breath. People spend a lot of time talking about PE in the context of pleuritic chest pain, but the PE experts who have taught me have always emphasized that the primary symptom of PE is shortness of breath. Thus, if a young patient suddenly develops severe exertional dyspnea, with no obvious cause, pulmonary embolism is near the maximum differential, whether or not she has the classic risk factors for VTE. If that surprises you, this study may be a game changer, but for the rest of us, I think this just confirms usual practice.

The big risk of this study is that it is over-applied, forgetting the inclusion criteria. There are many reasons patients develop mild dyspnea on exertion, and working on any patient with a viral illness or seasonal PE allergies could do a lot of harm. However, in a patient with severe acute onset dyspnea on exertion, there is no doubt that pulmonary embolism should be considered.

Based on previous rule rates in Italy, we can anticipate that the rule rate will be lower in other contexts. However, looking at the 20-30% rate rule here, even though the rate rule is half that in Canada, these patients are still well above the test threshold and justify the work.

Bottom line

In what shouldn’t be a surprise to anyone if a patient has acute exertional dyspnea, PE is on the differential diagnosis. Just be careful not to extrapolate these findings to less severe or more vague symptoms.

References

Prandoni P, Lensing AWA, Prins MH, Ciammaichella M, Pirillo S, Pace F, Zalunardo B, Bottino F, Ageno W, Muiesan ML, Forlin M, Depietri L, Bova C, Costantini N, Caviglioli C, Migliaccio L, Noventa F , Levi M, Davidson BL, Palareti G; Pulmonary Embolism Dyspnoea Italian Study (PEDIS) Investigators. Prevalence of pulmonary embolism among patients with recent onset of dyspnea on exertion. A cross-sectional study. J Thromb Haemost. 2023 Jan;21(1):68-75. doi: 10.1016/j.jtha.2022.09.007. Epub 2022 December 22nd. PMID: 36695397