Replacement of cTnI With hs-cTnI for Evaluation of Pulmonary Embolism May Misclassify Risk

Many health systems have replaced conventional cardiac troponin I (cTnI) with high-sensitivity cardiac troponin I (hs-cTnI) because of the excellent negative predictive value of hs-cTnI in assessing patients with coronary artery disease (CAD) and chest pain. Testing of non-coronary conditions is frequently being moved to hs-cTnI as well.

Behnood Bikdeli, MD, MS, a cardiologist in the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, David Jiménez, MD, PhD, of the Respiratory Department at Hospital Ramón y Cajal in Madrid, and colleagues recently conducted the first study to compare the prognostic relevance of cTnI with hs-cTnI in patients with pulmonary embolism (PE).

In JAMA Cardiology, they raise concerns about falsely elevated risk in patients with stable PE when hs-cTnI is substituted for cTnI.


The researchers conducted a post hoc analysis of the prospective multicenter PROTECT study, which evaluated the ability of multidetector CT pulmonary angiography to assess the prognostic value of right ventricular (RV) dysfunction in patients with hemodynamically stable PE. The 848 participants had blood collected around the time of PE diagnosis.

834 participants (98%) had both cTnI and hs-cTnI troponin values available and were included in the post hoc analysis. The PROTECT laboratory defined a cTnI positive result as >0.05 ng/mL, indicative of myocardial injury. For the current analysis, the researchers used a different hs-cTnI assay (ARCHITECT STAT High Sensitivity Troponin-I, Abbott) and defined a hs-cTnI positive result as >0.029 ng/mL.

139 patients (17%) had a cTnI positive result, and 264 (32%) had a hs-cTnI positive result.

Troponin Values and Outcomes

The primary outcome in the current analysis was a complicated course, defined as death from any cause, hemodynamic collapse, or recurrent PE within 30 days of follow-up. Hemodynamic collapse was defined as new systolic hypotension <90 mm Hg for longer than 15 minutes or the need for a vasopressor, fibrinolytic therapy, or cardiopulmonary resuscitation within 30 days.

A complicated course was observed in 62 patients (7%). The researchers made several observations about positive troponin results:

  • Positive cTnI was associated with significantly increased odds of a complicated course—OR, 2.84 (95% CI, 1.62–4.98)
  • Positive hs-cTnI was not associated with a complicated course—OR, 1.12 (95% CI, 0.65–1.93)
  • None of the 125 patients who had positive hs-cTnI but negative cTnI developed a complicated course

Troponin Values and Risk Stratification

Using the European Society of Cardiology 2019 criteria, the researchers classified PROTECT participants as:

  • Intermediate-high risk—hemodynamically stability, sPESI score >0, evidence of RV dysfunction, and positive cardiac troponin

All other participants were considered to be at intermediate-low risk, since PROTECT did not enroll patients with hemodynamic instability, the high-risk category.

Risk classification varied substantially depending on which troponin value was used:

  • Low risk—30% of participants using cTnI vs. 20% using hs-cTnI
  • Intermediate-high risk—7% of participants using cTnI vs. 9% using hs-cTnI
  • Intermediate-low risk—63% of participants using cTnI vs. 71% using hs-cTnI

Caution Warranted

Using hs-cTnI to classify a patient as being at intermediate risk, particularly intermediate-high risk, is likely to result in closer monitoring, a longer hospital stay, additional diagnostic tests and treatments such as fibrinolysis or catheter-based therapies, with excess costs and the potential for serious complications. Yet in this cohort, patients with positive hs-cTnI but negative cTnI did not develop PE-related adverse outcomes.

A higher cutoff is likely required to consider hs-cTnI results as clinically relevant for risk stratification of patients with PE.

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