Considering Pulmonary Embolism for Unexplained Syncope Is ‘Absolutely Mandatory,’ Investigators Say

Approximately one in six patients hospitalized for a first episode of syncope have a pulmonary embolism, a new study shows, with the prevalence of pulmonary embolism highest among individuals without an alternative explanation for the transient loss of consciousness.

Although most causes of syncope can be “quite trivial,” the researchers say the findings highlight the importance of a diagnostic workup when the patient with syncope is admitted to hospital, to consider whether pulmonary embolism might be an underlying cause of the condition.

“It is absolutely mandatory to think about pulmonary embolism in patients with unexplained syncope,” lead investigator Paolo Prandoni, MD (University of Padua, Italy), told TCTMD. “The diagnostic algorithm we used was quite easy. Pulmonary embolism can be safely and effectively treated with antithrombotic medications and there is a high probability of impacting favorably on the prognosis of patients with a prompt diagnosis. This is crucial.”

Published in the October 20, 2016, issue of the New England Journal of Medicine, the Pulmonary Embolism in Syncope Italian Trial (PESIT) included 560 patients admitted to the emergency department at 11 hospitals. The presence or absence of pulmonary embolism was based on pretest clinical probability using the simplified Wells score and the result of the D-dimer assay. Pulmonary embolism was ruled out as the cause of syncope in 330 of the 560 patients on the basis of the diagnostic algorithm.

Of the remaining 230 patients, 58.7% had a positive D-dimer assay, 1.3% had a high pretest clinical probability of pulmonary embolism only, and 40.0% of patients had both a high pretest probability and a positive D-dimer test. These patients were sent for further testing with CT pulmonary angiography or ventilation-perfusion lung scanning, with pulmonary embolism was identified in 42.2%.

“If the pretest probability is high or the D-dimer test is positive, in these cases it is necessary to proceed with either CT angiography or ventilation perfusion scanning,” said Prandoni. “In these patients, pulmonary embolism accounts for 40% to 45% of syncope cases. It’s an extremely high proportion and you have to consider it a possibility.”

In the entire cohort of 560 patients, the prevalence of pulmonary embolism was 17.3%, ranging from 15% to 20% across the participating hospitals. Pulmonary embolism was detected in one-quarter of patients with syncope of an undetermined origin and in 12.7% of patients who had a possible alternative explanation for the loss of consciousness. 

To TCTMD, Prandoni said syncope can be neutrally mediated, can be caused by orthostatic hypotension, or can be the result of a cardiovascular disorder, such as an arrhythmia, structural cardiovascular disease, or pulmonary embolism. In approximately 30% to 40% of cases, there is no clear explanation for the transient loss of consciousness, and first-episode patients are typically admitted to hospital for a diagnostic workup. However, clinical guidelines, including those from the American Heart Association and European Society of Cardiology, pay scant attention to pulmonary embolism as a potential cause of syncope.

“It’s not considered,” said Prandoni. “If you look at the clinical guidelines, including the most recent American and European guidelines, pulmonary embolism is considered a rare cause of syncope and that’s probably why physicians are not inclined to search for it. There is a tremendous need for reconsidering these guidelines.”

He added that pulmonary embolism is also overlooked in patients who present to the hospital for a variety of conditions, including chest pain, dyspnea, tachyarrhythmia, heart failure, pneumonia, and pleural effusion, among others. The PESIT researchers selected syncope as the condition as it is well characterized and there are national guidelines for treatment, but it is only one example where pulmonary embolism might be overlooked.

In terms of recommendations, Prandoni suggested patients with either a high pretest clinical probability or a positive D-dimer assay receive the first injection of low-molecular-weight heparin or fondaparinux prior to CT angiography or the ventilation-perfusion scan, as early treatment “might be lifesaving.” If the test comes back negative, then physicians can halt antithrombotic therapy, he said.