Risk factors

Doubts over troponin thresholds for diagnosing perioperative MI

Cardiology researchers have cast doubt on the appropriateness of recommended high-sensitivity cardiac troponin I thresholds after finding the cut-offs were too low to diagnose perioperative myocardial infarction or significant injury with their assay.

Their prospective study, which used Abbott Laboratories’ ARCHITECT STAT assay showed myocardial injury was ‘ubiquitous’ among patients post-cardiac surgery and “only extremely large elevations are associated with the 30-day risk of death”, US cardiologists wrote in an accompanying editorial.

While requiring validation in other cohorts and data from alternative assays, the finding may inform future recommendations, as the current ones have little supporting data, they and the study authors wrote.

Published in the New England Journal of Medicine, the study assessed perioperative cardiac troponin I levels in 13,862 patients who underwent cardiac surgery at one of 24 hospitals across 12 countries, and their association with 30-day mortality risk.

It found 296 people died within a month of surgery, with patients being higher risk (hazard ratio greater than 1) if their cardiac troponin levels were 5,67o ng/L (95% CI: 1,045 to 8,260) within 24 hours of isolated coronary-artery bypass grafting (CABG) or aortic valve replacement or repair, or 12,981 ng/L (95% CI: 2,673 to 16,591) after other cardiac surgeries.

These levels are 218 and 499 times the assay’s upper reference limit (26 ng/L), respectively, the study authors noted.

For context, the recommended levels for diagnosing perioperative myocardial infarction and clinically important injury range from 10 to more than 70 times the upper reference limit.

The recommendations set in the Fourth Universal Definition of Myocardial Infarction and Academic Research Consortium-2 consensus documents are based largely on expert opinion, with the latter stating that although there was “no evidence-based threshold for cardiac troponin levels after CABG, it endorsed a threshold for the diagnosis of myocardial infarction of 35 times the upper reference limit together with new evidence of ischemia”, the authors wrote.

For patients who have normal concentrations of cardiac troponin at baseline, a concentration of more than 10 times the upper reference limit within the first 48 hours, together with evidence of new myocardial ischaemia should be used in the diagnosis of myocardial infarction.

Meanwhile, a threshold over 70 times the upper reference limit is a stand-alone criterion for clinically important periprocedural myocardial injury, the study authors explained.

“The recommended troponin thresholds in these consensus statements (>10, ≥35, and ≥70 times the upper reference limit) were exceeded in 97.5%, 89.4%, and 74.7% of patients, respectively, within the first day after surgery,” they said.

The abundance of patients with high cardiac troponin I levels makes defining prognostically important myocardial injury challenging and suggests recommended thresholds may need a dramatic increase if they’re going to influence patient care.

Validation needed

Before any changes can be made, however, the findings need to be independently validated, the researchers and editorialists wrote.

Even then, these results only apply to the ARCHITECT STAT assays used in this study.

“Sites using other assays will need to await additional assay-specific data before drawing any conclusions,” the editorial authors warned.

The study authors also noted that their thresholds are based on increased risk of death at 30 days and that longer-term outcomes, such as heart failure development, “may be influenced by the extent of myocardial injury” and may occur at lower thresholds than they’ve just identified.

Further, more work needs to go into distinguishing perioperative myocardial infarction from injury. This study failed to account for new evidence of ischaemia or “provide any insight into the mechanisms of perioperative cardiac injury”.

“Such a distinction is critical, since evaluation and treatment approaches would differ notably.”

“Indeed, until more is understood about underlying mechanisms and strategies for prevention or treatment, the diagnosis of perioperative injury (without infarction) arguably has limited value, other than perhaps suggesting careful review of the surgical and postoperative course for unrecognized complications and closer follow-up with consideration of echocardiography.”

“The current findings provide limited help for clinicians evaluating patients after cardiac surgery” and reinforce the “impression that large troponin elevations are expected after routine cardiac surgery, correlate poorly with clinically evident complications, and remain difficult to interpret and use in determining patient care”.

However, they may also lead to more research that can help narrow down clinically important thresholds and improve patient care.

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