High-Sensitivity Troponins May Overestimate PE Severity

High-sensitivity cardiac troponin I (hs-cTnI) may overestimate risk in patients with hemodynamically stable pulmonary embolism (PE), which could translate into unnecessary monitoring, treatment, and longer hospital stays, new research suggests.

In the post hoc analysis, patients who had abnormally elevated levels on a hs-cTnI, but not on a conventional cardiac troponin I assay, were not more likely to have PE-related adverse events or to die, either from PE or any cause, over 30-day follow-up.

The finding is “somewhat discomforting,” given the widespread use of the more sensitive test for noncoronary conditions in many centers, lead study author Behnood Bikdeli, MD (Brigham and Women’s Hospital, Boston, MA), told TCTMD.

“We hope this study generates more interest among other colleagues to validate these [findings] in their own centers,” he said. “If the results are replicated in subsequent studies, what it means is that we are potentially overtreating some patients.”

Until further validation is forthcoming, standard troponin I assays should probably remain the fail-safe, Bikdeli added, noting that the ability of high-sensitivity troponin assays to risk stratify patients with PE hasn’t been rigorously assessed.

The data raise concern that the threshold of hs-cTnI that is acceptable for MI may not be translatable to PE, say Vinay Guduguntla, MD, and Robert O. Bonow, MD (both Northwestern University Feinberg School of Medicine, Chicago, IL), in an accompanying editorial.

“In this instance, appropriately classifying low- and intermediate-risk patients with PE is highly relevant as catheter-based therapies, such as mechanical thrombectomy, become more common in treating patients deemed to be at intermediate risk,” they write.

PROTECT Analysis

Published in JAMA Cardiology, the study looked at 834 hemodynamically stable patients (mean age 67.5 years; 51% female) with PE who were included in the multicenter PROTECT study.

Approximately twice as many patients had a positive test result using hs-cTnI versus conventional assay (31.7% vs 16.7%). While the latter was predictive of a complicated course—defined as death from any cause, hemodynamic collapse, or adjudicated recurrent PE within 30 days of follow-up—hs-cTnI was not. In fact, none of those with a positive hs-cTnI and negative conventional assay developed a complicated course.

Estimates of low risk, intermediate-low risk, and intermediate-high risk were 29.6%, 63.5%, and 6.8%, respectively with the conventional assay and 20.3%, 71.0%, and 8.8%, respectively with the high-sensitivity assay.

The authors also looked at how the results of both assays correlated with the European Society of Cardiology (ESC) 2019 acute PE guidelines’ risk-stratification scores for stable patients. With the ESC classifications, 29.6% of patients were low risk based on having a negative troponin result on standard cardiac troponin I testing, a simplified pulmonary embolism severity index of 0, and no echocardiographic evidence of RV dysfunction. However, nearly one-third of this group had a positive test result when using hs-cTnI—a finding that would move them into a higher risk category.

Similarly, 6.8% of patients were classified by the ESC metrics as intermediate-high risk based on the conventional assay, a proportion that increased to 8.8% with hs-cTnI. With this shift between assays, the rate of a complicated 30-day course among those considered intermediate-high risk decreased from 17.5% to 13.7%.

The main study results were consistent in male versus female patients, in younger versus older patients, and in several sensitivity analyses.

Toward Better Risk Stratification

Guduguntla and Bonow note that while the study is limited by its small sample size and low event rates, it raises questions about other assays like N-terminal pro-brain natriuretic peptide (NT-proBNP), which has shown poor specificity in PE.

“Ultimately, biomarkers alone should be interpreted with caution and always be used within the broader context of a comprehensive patient evaluation,” they conclude.

To TCTMD, Bikdeli added that the only way to really leverage better risk stratification for PE is to change the current paradigm that puts patients into one of just three categories.

“I think it’s more complicated than that,” he noted. “If you read all the guidelines, they don't even talk about respiratory decompensation as a clear category for severity. But all of us know that sometimes PE presents with respiratory failure, and those cases are considered a severe form of PE. The point being, there are many factors we should consider in risk stratification . . . biomarkers being an important one.”