High-Sensitivity Troponin Test May Overestimate Risk in PE

For patients with hemodynamically stable pulmonary embolism (PE), there was no prognostic value found for the mild elevations in cardiac troponin captured only on high-sensitivity assays at the emergency room, based on an exploratory analysis of the PROTECT cohort study.

Whereas a finding of conventional cardiac troponin I (cTnI) elevation was associated with a complicated course (OR 2.84, 95% CI 1.62-4.98) — defined as hemodynamic collapse, recurrent PE, or all-cause death within 30 days after PE — a positive high-sensitivity cardiac troponin I (hs-cTnI) test had no significant relationship with these poor outcomes (OR 1.12, 95% CI 0.65-1.93).

Compared with conventional cTnI, hs-cTnI classified fewer patients as low risk. However, none of the patients who had elevated hs-cTnI but normal cTnI wound up suffering a complicated course of disease, reported David Jiménez, MD, PhD, of Hospital Ramón y Cajal in Madrid, Spain, and colleagues in JAMA Cardiology.

The implication is that relying on hs-cTnI may result in clinicians overestimating risk in patients with stable PE.

“Although we are unaware of other comparative studies for cTn vs hs-cTn for patients with PE, our study raises concern about use of hs-cTnI for risk-stratification of patients with PE. If our data are confirmed by other studies, the use of hs-cTn instead of cTn would increase resource utilization and hospital stay without any counterbalancing gain for patient safety or better outcomes. Therefore, it is likely that a higher cutoff is required to consider hs-cTn results as clinically relevant for risk stratification of patients with PE,” Jiménez’s group wrote.

European guidelines currently endorse cardiac troponin levels for risk stratification in acute PE, but they do not specify which type of troponin assay is preferred.

Meanwhile, health systems now favor high-sensitivity tests over conventional ones — despite the lack of proven clinical benefit — for people presenting with coronary artery disease and chest pain. “Considering the ongoing replacement of cTn with hs-cTn in many health systems, testing for other noncoronary conditions, such as PE, is being frequently moved from cTn to hs-cTn, as well,” Jiménez and colleagues noted.

“Therefore, our results raise concern about misclassification of actual risk when cTnI is replaced with hs-cTnI,” they emphasized. “The falsely elevated risk identified with hs-cTnI may also translate into additional unnecessary diagnostic tests and treatments, such as fibrinolysis or catheter-based therapies, with excess costs and serious treatment-related complications.”

Although it appears that the standard thresholds of hs-cTnI for acute myocardial infarction diagnosis may not apply to the acute PE population, study authors acknowledged they were unable to suggest better cutoffs for hs-cTn tests that would flag adverse PE outcomes.

“The editors hope that this analysis will stimulate future investigation, and for this reason considered these preliminary data worthy of publication. Further attention should also be given to other tests like NT-proBNP, which has shown poor specificity in this context,” wrote Vinay Guduguntla, MD, and Robert Bonow, MD, MS, both of Northwestern University Feinberg School of Medicine in Chicago, in an accompanying editor’s note.

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

Relying on the sex-specific 99th percentile upper reference limit of cardiac troponin may incorrectly suggest myocardial infarction (MI) in older adults with suspected heart attacks, though no diagnostic approach emerged as a better alternative.

The main finding of the prospective PROTECT cohort study was that RV dysfunction, assessed by multidetector CT pulmonary angiography, was no predictor of outcomes for the 848 patients with acute PE enrolled from 12 hospital emergency departments in Spain.

In this post hoc analysis, Jiménez and colleagues included the 98.3% of PROTECT participants (mean age 67.5 years, roughly split between sexes) who had hs-cTnI and cTnI values available from blood testing.

A positive cTnI result was flagged for 16.7% (based on a threshold of >0.05 ng/mL) and a positive hs-cTnI result for 31.7% (threshold of >0.029 ng/mL). Based on the conventional troponin results, 29.6% of PE patients were considered low-risk vs 20.3% with hs-cTnI under the 2019 European Society of Cardiology PE risk category classification scheme.

That hs-cTnI took more people out of the low-risk group likely has clinical implications.

“The non-low-risk status, according to the guidelines, will likely translate into closer monitoring, a longer hospital stay, and potentially additional tests or treatments, particularly in the subgroup of patients who were designated as intermediate-high risk when hs-cTnI was used,” Jiménez’s group said.

In PROTECT, none of the 78 patients designated as ESC low risk with cTnI but not hs-cTnI wound up with a complicated course.

“We recognize, however, the preliminary nature of these data as they are based on a small patient sample with only 62 events,” the investigators cautioned.

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