High-Sensitivity Troponin Assay More Precisely Calibrates Mortality Risk in Suspected ACS Patients

Use of a new high-sensitivity (hs) cardiac troponin T assay in patients with suspected ACS detects minor troponin elevations in many that may not have been identified by previous tests, according to a registry study published in the April 28, 2015, issue of the Journal of the American College of Cardiology. Although only about one-fifth of these patients turn out to have ACS, they are at higher mortality risk than their counterparts with no detectable troponin.
A Different Take - High-Sensitivity Troponin Assay More Precisely Calibrates Mortality Risk in Suspected ACS Patients

Investigators led by Dina Melki, MD, PhD, of Karolinska University Hospital (Stockholm, Sweden), analyzed data from 48,594 patients with suspected ACS who were admitted to Swedish hospitals that used an hs cardiac troponin T assay (Elecsys; Roche Diagnostics) between 2009 and 2012. All were enrolled in the nationwide SWEDEHEART registry.

Patients were divided into 4 groups based on maximal troponin level:

  • Group 1 (n = 5,790): < 6 ng/L                                                                                         
  • Group 2 (n = 6,491): 6-13 ng/L                                                                                                
  • Group 3 (n = 10,476): 14-49 ng/L                                                                                        
  • Group 4 (n = 25,837): 50 ng/L                                                                                                      

Groups 3 and 4 were similar with regard to age (about 72 years), sex (about 64% male), and the presence of risk factors. However, patients in group 3 had more previous cardiac disease and A-fib and were more often treated with antiplatelet therapy, beta-blockers, statins, and ACE inhibitors or angiotensin receptor blockers. The proportion of patients presenting with ST-segment deviation rose with the maximal troponin level.

During hospitalization, the likelihood of receiving angiography and echocardiography increased in a stepwise fashion from group 1 through group 4. Likewise, among those who underwent angiography, the presence of significant stenosis rose with troponin level (43.0%, 60.6%, 71.0%, and 87.7%, respectively, for groups 1 through 4) as did the incidence of LV systolic dysfunction among those who had echocardiography (9.9%, 15.6%, 29.7%, 45.0%, respectively). Use of various intravenous treatments, continuous positive airway pressure, coronary interventions, complications, and post-ACS medications at discharge also rose with troponin level.

ACS Likelihood, Mortality Risk Rise With Troponin Level

The most common diagnoses varied with troponin level, with the proportion of ACS diagnoses rising steadily with troponin values (table 1).

 Table 1. Discharge Diagnoses by Troponin Group

At 1 year, all-cause mortality ranged from 1.6% in group 1 to 17.1% in group 4. Compared with group 1, the adjusted risk rose steadily and was more than 4-fold higher for those in group 4 (table 2).
 

Table 2. Adjusted Risk of 1-Year All-Cause Mortality vs Group 1
 

When the study population was divided into 20 groups by maximal troponin level, adjusted mortality started to increase at the 14-18 ng/L level (HR 1.94; 95% CI 1.47-2.56) and rose continuously above that threshold. The pattern was similar regardless of sex or age ( 65 years vs > 65 years), although crude mortality rates were somewhat higher in women and markedly higher in the elderly. 

With maximal hs troponin of < 6 ng/L as a reference, the adjusted relative effect of higher levels was most pronounced among patients with other noncardiac causes of their symptoms.

“More studies are needed to characterize the heterogeneity of patients with minor [hs-troponin] increases, to expose underlying pathophysiological mechanisms responsible for low-level troponin release, and to enhance treatment strategies to improve long-term clinical outcomes,” the authors write.

Balancing Sensitivity, Specificity

In an accompanying editorial, James L. Januzzi Jr, MD, of Massachusetts General Hospital (Boston, MA), notes that in patients experiencing an acute MI, an hs cardiac tropoin T assay may pick up an abnormal value earlier than a conventional troponin test would, thereby enabling more rapid diagnosis. Moreover, he writes, these assays “detect acute MI in up to 25% of ACS patients with normal conventional [cardiac troponin] values who are thought to have unstable angina.”

However, he observes, the enhanced sensitivity is counterbalanced by a loss of specificity. The hs assays “now detect previously unrecognized myocardial necrosis in many acute and chronic cardiovascular conditions, confounding interpretation and confusing clinicians.”

The fact that most patients with abnormal troponin levels did not have an acute MI in this study raises “justifiable concerns about the ramifications of lower specificity for the diagnosis,” Dr. Januzzi writes, adding that regardless of diagnosis, patients with higher troponin levels “are indeed at higher risk.”

Physicians must remember that an abnormal troponin level only signals myocardial necrosis, not its mechanism, he observes. Thus, they “must carefully consider the differential diagnosis… and only make a diagnosis of acute MI if evidence of myocardial ischemia is present.” This also entails determining the appropriate workup for patients with different abnormal hs-troponin levels.

There will be a learning curve as clinicians gain experience with hs troponins, Dr. Januzzi says, but “more rapid and sensitive detection of acute MI coupled with greater prognostic value from [this] testing makes it worth the effort.”

More Harm Than Good

However, in a telephone with TCTMD, Sorin J. Brener, MD, of New York Methodist Hospital (New York, NY), suggested that introduction of the more sensitive test may do more harm than good.

The new assay is “an excellent tool to detect myocardial injury, but it doesn’t help us in deciding whether [a particular elevation] is an MI and certainly not an ACS that leads to an MI,” Dr. Brener said. “All this [study] tells us is if we keep looking with more granularity, we will find further gradations of risk.”

The problem is not with the test, he asserted, but the likelihood that it will “induce a set of actions that are inappropriate in the majority of cases.”

Many clinicians already complain that troponin is too sensitive, making it difficult to ignore an enzyme elevation and forgo catheterization and antiplatelet therapy when good clinical judgment suggests they should. “This will just make things worse; you will worry about people that before you didn’t worry about,” he lamented.

The highest mortality was in patients with heart failure as the principal diagnosis, Dr. Brener pointed out. And in this group, inexperienced clinicians seeing a troponin elevation often suspect an acute MI and call for a cardiology consult, which in turn triggers unnecessary and potentially harmful treatment, he said.

“It’s nice to know a patient is at increased risk,” Dr. Brener acknowledged. “Maybe he is not receiving the right medications or is not taking them and should be monitored more closely. But if you find increased risk and react inappropriately [with revascularization], you may actually enhance the risk rather than diminish it,” he warned.

 

Sources:

1. Melki D, Lugnegård J, Alfredsson J, et al. Implications of introducing high-sensitivity cardiac troponin T into clinical practice: data from the SWEDEHEART registry. J Am Coll Cardiol. 2015;65:1655-1664.

2. Januzzi JL Jr. What to expect when measuring high-sensitivity troponin: practical advice for clinicians [editorial]. J Am Coll Cardiol. 2015;65:1665-1667.

  • Dr. Januzzi reports receiving grant support from Siemens, Singulex, and Thermo Fisher; consulting income from Critical Diagnostics, Novartis, Roche Diagnostics, and Sphingotec; and research payments for clinical endpoint committees from Amgen, Boehringer Ingelheim, and Novartis.
  • Dr. Brener reports no relevant conflicts of interest.

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Disclosures
  • Dr. Melki reports receiving honoraria from Roche Diagnostics.

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