Novel Troponin Test May Safely Rule Out Stress Testing in Stable CAD

by Nicole Lou, Staff Writer, MedPage Today November 5, 2018

This article is a collaboration between MedPage Today and:

Results from a novel high-sensitivity cardiac troponin I (hs-cTnI) assay may identify stable coronary artery disease (CAD) patients who are very unlikely to develop myocardial ischemia or cardiovascular events in the next 3 years, investigators reported.

A 2.5 pg/mL threshold on the Architect STAT Troponin-I assay from Abbott ruled out inducible myocardial ischemia that would have been detected in routine stress testing with a negative predictive value of 90% and sensitivity of at least 90%, reported Arshed Quyyumi, MD, of Emory University School of Medicine in Atlanta, and colleagues in a study published online in Annals of Internal Medicine.

Among the 17% patients in the derivation cohort with an hs-cTnI level below the cutoff, 10% had any inducible ischemic defect and just 3% had clinically-relevant ischemia involving 10% or more of the myocardium. None of those with hs-cTnI <2.5 pg/mL experienced cardiovascular death or MI over 3 years, compared with 7% among those with higher troponin levels.

"Very low hs-cTnI levels may be useful in excluding inducible myocardial ischemia in patients with stable CAD," the authors concluded, suggesting that this may help reduce overuse of cardiac stress testing in patients with stable CAD.

However, the hs-cTnI threshold suffered from a low specificity (24%) and positive predictive value (40%) for diagnosing inducible myocardial ischemia.

"Thus, hs-cTnI levels are not useful for determining whether inducible myocardial ischemia is present, and if clinical suspicion exists, the patient should probably still have conventional stress testing," according to Quyyumi's group.

Yet if the authors had explored higher hs-cTnI values instead of staying within the 1.5-3.0 pg/mL range, they might have ended up with better positive predictive values and specificities, suggested P.J. Devereaux, MD, PhD, of McMaster University and Population Health Research Institute in Hamilton, Ontario, in an accompanying editorial.

"Taken together, these data suggest that hs-cTn assays may be more accurate, convenient, quick, and cost-effective than MPS [myocardial perfusion single-photon emission CT] in predicting the course of stable CAD," he concluded.

The assay used was recently cleared for use on the European market but is not approved by the FDA.

The 2.5 pg/mL cutoff was derived from a 589-person cohort, all recruited from Emory's hospital network, comprised of 76% men and 36% with a prior MI. The average age was 63.

Participants underwent myocardial perfusion imaging during treadmill or pharmacologic stress testing to see if they had inducible myocardial ischemia. This group also had blood drawn in the days before or after their stress test for the plasma hs-cTnI assay.

Troponin I was detected in all patients (median 4.3 pg/mL, IQR 2.8-7.2 pg/mL). Patients with inducible myocardial ischemia had higher hs-cTnI levels (5.4 versus 3.9 pg/mL, P<0.001). The higher the ischemic burden, the higher the troponin.

Quyyumi and colleagues had their findings supported by a separate validation group of 118 MI survivors from the Mental Stress and Myocardial Ischemia After MI: Sex Differences and Mechanisms study. This cohort was younger and included fewer men than did the derivation group.

In this case, 27% had hs-cTnI levels fall below 2.5 pg/mL.

"Our data suggest that in patients with CAD without known myocardial scar, an hs-cTnI level below 2.5 pg/mL, which is present in approximately a quarter of this population, identifies a group with a 99% chance of having no clinically significant ischemia (≥10% of the myocardium)," the investigators said.

The study should be not generalized to a population without known CAD or to those with unstable angina, they cautioned.

Further evaluation in a large observational study of the optimal thresholds of several hs-cTn assays to identify patients at low and high risk for cardiovascular death and nonfatal MI would be valuable, according to Devereaux.

But, he noted, the results are in line with data from the HOPE trial, in which a substudy showed that patients with stable CAD and a low hs-cTnI level (under 6 pg/mL on the Beckman Coulter assay) had a low risk for major cardiovascular events during 4.5-year follow-up.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by the National Institutes of Health.

Quyyumi disclosed no relevant conflicts of interest.

Devereaux reported grants from Abbott Diagnostics, Boehringer Ingelheim, Covidien, Philips Healthcare, and Roche Diagnostics.

Primary Source

Annals of Internal Medicine

Source Reference: Hammadah M, et al "Use of high-sensitivity cardiac troponin for the exclusion of inducible myocardial ischemia: a cohort study" Ann Intern Med 2o18; DOI: 10.7326/M18-0670.

Secondary Source

Annals of Internal Medicine

Source Reference: Devereaux PJ "The potential for troponin to inform prognosis in patients with stable coronary artery disease" Ann Intern Med 2018; DOI: 10.7326/M18-2984.