BASEL IX: PE Uncommon in Patients Presenting With Syncope

Patrice Wendling

August 06, 2019

The diagnosis of pulmonary embolism (PE) — a potentially fatal oversight if missed — is uncommon in patients presenting with syncope, according to results of the ongoing Basel Syncope Evaluation Study (BASEL IX).

"I think the systematic screening for patients with syncope presenting to the emergency department is not warranted and that a tailored approach to look for PE is recommended," Patrick Badertscher, MD, Cardiovascular Research Institute Basel and the University of Basel, Switzerland, told | Medscape Cardiology.

An understanding of the prevalence of PE is necessary to make a decision on the merits of systematic PE screening of all patients with syncope, but previous studies have produced conflicting estimates. In addition, uncertainty exists over the clinical significance of incidentally detected small perfusion defects on computed tomographic pulmonary angiography (CTPA), with a recent study reporting false-positive results in 42% of patients with a low probability for PE who underwent CTPA.

To examine PE prevalence, the investigators prospectively enrolled 1895 consecutive patients presenting with syncope to the emergency department (ED) at 13 centers in Europe, North America, and Oceania from May 2010 to February 2017. Of these, 1397 were included in the analysis and 1156 had complete 2-year follow-up. Their median age was 69 years and 42% were women.

Syncope was defined according to current European Society of Cardiology guidelines. PE presence or absence was centrally adjudicated on the basis of  the combination of pretest clinical probability and D-dimer testing and CTPA or ventilation/perfusion (V/Q) scanning when clinically indicated. Imaging criteria for PE were an intraluminal filling defect on CTPA or a perfusion defect of at least 75% of a segment with corresponding normal ventilation.

PE was ruled out in 612 patients (44%) because of a low clinical pretest probability (Wells score ≤4) and negative D-dimer test. Among the remaining patients, imaging with CTPA or V/Q scan ruled out PE at presentation in 88 (6.3%) and documented PE in 19 (1.4%; 95% CI, 0.87 - 2.11).

Among the subgroup of patients hospitalized for syncope and patients hospitalized for a first syncope, PE prevalence increased slightly to 2.3% and 4.3%, respectively. This is substantially lower than the rate reported in the Pulmonary Embolism in Syncope Italian Trial (PESIT), in which PE occurred in 17.3% of 560 patients hospitalized with a first episode of syncope, observed Badertscher.

During 2 years of clinical follow-up, a new PE or cardiovascular death occurred in only 12 patients (0.9%), none of whom had PE ruled out by a low clinical pretest probability and negative D-dimer test during the initial workup, the investigators report in the August 13 issue of the Journal of the American College of Cardiology.

"We show now the prevalence is lower than the other papers that came out after the PESIT trial," Badertscher said. "I think there are now four or even five other cohorts showing that the prevalence is slightly lower. So I think it's fair to assume that systematic screening in patients, even in hospitalized patients with the first evidence of syncope, is not warranted if they don't have any other signs for pulmonary embolism. If we do so, I think we still need more follow-up data to see if we have benefit if we anticoagulate those patients because there I'm not convinced."

Between a Zebra and a Horse

From the viewpoint of PESIT, "PE is as common as a horse," and from the viewpoint of BASEL IX, "PE as a cause of syncope is as rare as a zebra," Samuel Z. Goldhaber, MD, Brigham and Women's Hospital, Harvard Medical School, Boston, writes in an accompanying editorial. "How does a cardiovascular medicine clinician reconcile the extremely different findings from the PESIT and BASEL IX studies? Which study got it right and which is totally off base?"

He noted several fundamental differences between the two studies, including a high risk for PE in PESIT patients because of a median age of 80 years, their admission to hospital, and a first episode of syncope. In contrast, BASEL IX patients were younger, had first time or multiple episodes of syncope, and were included regardless of whether or not they were hospitalized. Workup for PE was not required in these patients and, "perhaps most startling," most (n = 678) did not undergo CT or lung scan imaging, even if they had a high pretest probability, a positive D-dimer assay, or both, he said.

"The third side of the PESIT versus BASEL IX story might involve applying the best attributes of each study in our daily clinical practice," Goldhaber suggests. "For patients with first-time syncope, minimal workup for PE with a clinical probability assessment and D-dimer makes sense. If this workup points to a high probability for PE, imaging should be obtained.

"In the current era, where the threshold for being hospitalized is high, first-time syncope patients should be worked up for PE even if they are going to be discharged home after ED evaluation," he said. "Perhaps the relation between syncope and PE is best described as the 'progeny of a horse and a zebra'."

Both Goldhaber and Badertscher said a main strength of BASEL IX is that all patients were followed for 2 years. However, because the study recruited patients presenting with syncope to the ED within 12 hours of symptom onset, it is unknown whether the results can be extrapolated to patients presenting to primary care or those presenting later than 12 hours after syncope. Another limitation is that the use of venous thromboembolism and cardiovascular death during long-term follow-up as part of the assessment of PE may have led to over- or underestimation of its true prevalence.

Notably, hospitalization rates at the 13 BASEL IX centers varied widely, from 28% to 87%.

"I think this is just reflecting the lack of consensus of how we should evaluate patients; it's very nonstandardized," Badertscher said. "For PE, it's clearly evident that it's difficult to establish the diagnosis in syncope patients. So very often, they end up being admitted and they run the same tests with very low diagnostic yield."

The yield for tailored diagnostic imaging was low, at 16%, and much lower than the 41% yield reported for the systematic use of imaging in PESIT.

Going forward, Badertscher said there may be a "huge potential role in the future for syncope units where doctors from different specialties — maybe cardiologists, virologists, emergency physicians — work closely together and have a predefined pathway for syncope patients," Badertscher said. "I think there are some studies showing this might be the most efficient approach."

The team's recent study, showing moderate to good diagnostic yield using B-type natriuretic peptide, N-terminal proBNP, and high-sensitivity cardiac troponin in patients presenting to the ED with syncope, also suggests there's still some diagnostic room to see how biomarkers should be applied in this patient population, he said.

The study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel (Switzerland), the University of Basel, Abbott, BRAHMS, Singulex, University Hospital Basel, and the Emergency Medicine Foundation (Australia). Badertscher has received research funding from the University of Basel . Goldhaber reported having no relevant relationships.

J Am Coll Cardiol. 2019;74:744-54 and 755-758. Abstract, Editorial

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