Any Troponin Bump in Suspected ACS—MI or Not—Signals High CV Risk: High-STEACS

The risk of MI/CV death was similar regardless of whether the final diagnosis was type 1 MI, type 2 MI, or myocardial injury.

Any Troponin Bump in Suspected ACS—MI or Not—Signals High CV Risk: High-STEACS

Implementing high-sensitivity troponin testing and categorizing based on the fourth universal definition of MI in the evaluation of suspected ACS uncovers more patients who have an increased risk of poor outcomes no matter how their myocardial injury is defined, a secondary analysis of the High-STEACS trial shows.

Though the 1-year rate of MI or CV death was highest in patients diagnosed with type 1 MI (17%), it was not much lower in patients with type 2 MI (14%) or acute or chronic myocardial injury (16%). Risk was greater in all of those groups compared with patients without troponin elevations (2%), with cause-specific hazard ratios ranging from 3.50 to 5.64.

The findings were reported by lead author Andrew Chapman, MD (University of Edinburgh, Scotland), and colleagues in a study published online October 7, 2019, ahead of print in Circulation.

“What we demonstrate is that even if you a type 2 myocardial infarction secondary to another illness you are still at an increased risk of a future cardiovascular event, be that a future MI or death from a cardiac cause,” Chapman told TCTMD, adding that that’s “slightly surprising” because these patients are older, have more comorbidities, and are more likely to die from noncardiovascular causes than are patients with type 1 MI. “And at the moment,” he noted, “these patients are treated in a very, very different way to patients with type 1 myocardial infarction.”

There are clear systems in place to treat type 1 MI, Chapman said, but for type 2 MI or myocardial injury that doesn’t reach the threshold of MI, “we’ve got no randomized trials whatsoever to guide our management of these patients.”

He suggested that in these groups, it’s possible “we should be doing more, whether that is considering investigations for underlying coronary or structural heart disease or even moving one step further and just pragmatically recommending an antiplatelet agent and a statin agent as secondary prevention.”

Ideally, Chapman said, “what we really need to do now is take the information from this study and design a randomized controlled trial to test this hypothesis, because a clinician might well reasonably argue that these patients may not have a modifiable cardiovascular risk and it may simply reflect the fact that they are older and they have other comorbidities.”

Commenting for TCTMD, L. Kristin Newby, MD (Duke University Medical Center, Durham, NC), said the study highlights some areas in which further research is needed, particularly regarding what is driving the prognostic importance of elevated troponins levels detected by high-sensitivity assays outside of type 1 MI and what should be done about it.

Type 2 MIs can be detected even with conventional troponin tests, so cardiologists have learned how to manage them, Newby said. “Now I think the surprising thing there is how many more type 2 myocardial infarctions we’re picking up.”

Acute and chronic myocardial injuries are trickier, she indicated, saying, “That’s where I think we need a better understanding of what’s causing the injury, and we will have to have more refined understanding to be able to target a treatment to that group because it’s such a heterogeneous group.”

High-STEACS

Use of high-sensitivity cardiac troponin assays has enhanced the detection of myocardial injury outside of the setting of ACS, and the latest iteration of the universal definition of MI—the fourth—recommends both use of such testing and classification of patients based on the etiology of myocardial injury.

The High-STEACS trial, conducted at 10 Scottish hospitals, evaluated the impact of implementing this approach in more than 48,000 consecutive patients with suspected ACS (mean age 61 years; 47% women). The main results reported last year showed one out of every six patients with myocardial injury missed by conventional troponin assays were reclassified using the new approach, but that clinical outcomes were unchanged.

In this prespecified secondary analysis, the researchers classified patients with troponin elevations according to the fourth universal definition of MI (the third version was used in High-STEACS) and examined their management and outcomes.

Overall, 21.5% of patients in the trial had some degree of myocardial injury detected. Of those, more than half (55%) were diagnosed with type 1 MI, 12% with type 2 MI, and 18% and 14% with acute or chronic myocardial injury, respectively. Implementation of high-sensitivity troponin testing and the recommendations of the universal definition of MI increased detection of each condition, although a greater impact was seen for type 2 MI (increased by 22%) and acute or chronic myocardial injury (increased by 36% and 43%) than for type 1 MI (increased by 11%).

Compared with patients without myocardial injury, the rate of subsequent MI or CV death in the first year of follow-up was increased in all diagnostic categories:

  • Type 1 MI: cause-specific HR 5.64; 95% CI 5.12-6.22
  • Type 2 MI: cause-specific HR 3.50; 95% CI 2.94-4.15
  • Acute myocardial injury: cause-specific HR 4.38; 95% CI 3.80-5.05
  • Chronic myocardial injury: cause-specific HR 3.88; 95% CI 3.31-4.55

The rate of all-cause death was highest in patients with acute myocardial injury (33%), followed by chronic myocardial injury (29%), type 2 MI (23%), type 1 MI (14%), and no myocardial injury (5%). A similar pattern was seen for noncardiovascular death.

“We found all patients with myocardial injury and infarction are at increased future cardiovascular risk, irrespective of etiology, despite an excess in noncardiovascular death in patients with type 2 myocardial infarction and myocardial injury,” the authors note.

Changes in investigation or treatment during the trial were seen only in the type 1 MI group, in which there were increases in antiplatelet therapy and coronary revascularization. The rate of MI or CV death, however, remained unchanged across all diagnostic categories.

Clinical Uncertainty

The investigators suggest the lack of change in outcomes could be related to uncertainty about the best way to evaluate and treat patients with troponin elevations but not type 1 MI.

It’s reasonable to conclude that these groups need to be managed more aggressively, Chapman said, “but the difficulty is . . . that we don’t have evidence to show that intervening will make a difference. And that’s where I think there is a need for a clinical trial.

“So at the moment, what we’d recommend in practice . . . [is] that what we should be doing is being pragmatic, trying to assess the individual’s cardiovascular risk using all the information that we have available, and then determining whether or not we should give them treatment on an individual patient basis,” he advised.

Chapman is the principal investigator for DEMAND-MI, which is a prospective study of patients with type 2 MI that includes various tests, including invasive coronary angiography with optical coherence tomography and fractional flow reserve (FFR), coronary CT angiography, CT-derived FFR, cardiac magnetic resonance imaging.

“These patients’ outcomes are poor. I think they’re understudied. I think they’re undertreated. And I think one of the reasons for that is that clinicians just don’t really know what to do with them at the moment because we don’t have the evidence,” Chapman said. “And I’m hoping the DEMAND-MI study and a future randomized controlled trial will be able to provide that evidence.”

In terms of next steps, Newby said the main focus should be on refining the acute and chronic myocardial injury groups and determining which treatments will improve outcomes. She said, for example, that it’s possible a diabetic patient with chronic myocardial injury might benefit from intensified glucose management or treatment with one of the antidiabetic medications shown to reduce CV risk.

“So,” Newby asked, “can we leverage troponin and the knowledge of that injury to help us better treat these people?” She agreed, however, that prospective studies are needed to determine whether such an approach will help.

Sources
Disclosures
  • High-STEACS was funded by a Special Project Grant from the British Heart Foundation, with additional support from a British Heart Foundation-Turing Cardiovascular Data Science Award and British Heart Foundation Research Excellence Award. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge.
  • Chapman reports receiving support from a Clinical Research Training Fellowship, a Butler Senior Clinical Research Fellowship, Chair awards from the British Heart Foundation, and a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences; and honoraria from Abbott Diagnostics.
  • Newby reports receiving consulting honoraria from Roche Diagnostics, Ortho Clinical Diagnostics, and Quidel.

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