High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction

Andrew R Chapman, Philip D Adamson, Anoop S V Shah, Atul Anand, Fiona E Strachan, Amy V Ferry, Kuan Ken Lee, Colin Berry, Iain Findlay, Anne Cruikshank, Alan Reid, Alasdair Gray, Paul O Collinson, Fred Apple, David A McAllister, Donogh Maguire, Keith A A Fox, Catalina A Vallejos, Catriona Keerie, Christopher J Weir, David E Newby, Nicholas L Mills, High-STEACS Investigators, Christopher Tuck, Anda Bularga, Ryan Wereski, Dennis Sandeman, Catherine L Stables, Athanasios Tsanasis, Lucy Marshall, Stacey D Stewart, Takeshi Fujisawa, Mischa Hautvast, Jean McPherson, Lynn McKinlay, Simon Walker, Ian Ford, Simon Walker, Shannon Amoils, Jennifer Stevens, John Norrie, Jack Andrews, Phil Adamson, Alastair Moss, Mohamed Anwar, John Hung, Simon Walker, Jonathan Malo, Colin Fischbacher, Bernard Croal, Stephen J Leslie, Richard Parker, Allan Walker, Ronnie Harkess, Chris Tuck, Tony Wackett, Roma Armstrong, Marion Flood, Laura Stirling, Claire MacDonald, Imran Sadat, Frank Finlay, Heather Charles, Pamela Linksted, Stephen Young, Bill Alexander, Chris Duncan, Andrew R Chapman, Philip D Adamson, Anoop S V Shah, Atul Anand, Fiona E Strachan, Amy V Ferry, Kuan Ken Lee, Colin Berry, Iain Findlay, Anne Cruikshank, Alan Reid, Alasdair Gray, Paul O Collinson, Fred Apple, David A McAllister, Donogh Maguire, Keith A A Fox, Catalina A Vallejos, Catriona Keerie, Christopher J Weir, David E Newby, Nicholas L Mills, High-STEACS Investigators, Christopher Tuck, Anda Bularga, Ryan Wereski, Dennis Sandeman, Catherine L Stables, Athanasios Tsanasis, Lucy Marshall, Stacey D Stewart, Takeshi Fujisawa, Mischa Hautvast, Jean McPherson, Lynn McKinlay, Simon Walker, Ian Ford, Simon Walker, Shannon Amoils, Jennifer Stevens, John Norrie, Jack Andrews, Phil Adamson, Alastair Moss, Mohamed Anwar, John Hung, Simon Walker, Jonathan Malo, Colin Fischbacher, Bernard Croal, Stephen J Leslie, Richard Parker, Allan Walker, Ronnie Harkess, Chris Tuck, Tony Wackett, Roma Armstrong, Marion Flood, Laura Stirling, Claire MacDonald, Imran Sadat, Frank Finlay, Heather Charles, Pamela Linksted, Stephen Young, Bill Alexander, Chris Duncan

Abstract

Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood.

Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories.

Results: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes.

Conclusions: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction.

Clinical trial registration: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Keywords: myocardial infarction; troponin.

Figures

Figure 1.
Figure 1.
Consort diagram with identification of the study population by classification, and proportion identified by the contemporary troponin assay (cTnI) or reclassified by the high-sensitivity assay (hs-cTnI). Serial cardiac troponin concentrations were available in 77% (6983 of 9115) of patients with myocardial injury. MI indicates myocardial infarction.
Figure 2.
Figure 2.
Cumulative incidence curves for the primary outcome of type 1 or 4b myocardial infarction or cardiovascular death, and competing risk of noncardiovascular death, stratified by type 1 myocardial infarction (red), type 2 myocardial infarction (gold), acute myocardial injury (dark blue), chronic myocardial injury (light blue), and no myocardial injury (green) with table of number at risk. Estimates obtained from a cumulative incidence function. MI indicates myocardial infarction.
Figure 3.
Figure 3.
Forest plot of the primary outcome (type 1 or 4b myocardial infarction or cardiovascular death) and noncardiovascular death in the trial population stratified by index diagnosis; type 1 myocardial infarction (red), type 2 myocardial infarction (gold), acute myocardial injury (dark blue) and chronic myocardial injury (light blue), relative to those with no myocardial injury. Adjusted cause-specific hazard ratios (csHR) obtained from multivariable cox regression models including adjustment for age, sex, a history of ischemic heart disease or diabetes mellitus, renal function, time of presentation from the start date of the trial, season, phase of the trial, and site of recruitment (as a random effect). In this model the competing event or time of censor are both considered as independent outcomes. MI indicates myocardial infarction.
Figure 4.
Figure 4.
Flow diagram (alluvial plot) illustrating the frequency of cause of death grouped by classification of myocardial infarction and cardiovascular or noncardiovascular causes. Type 1 myocardial infarction (red), type 2 myocardial infarction (gold), acute myocardial injury (dark blue), and chronic myocardial injury (light blue). All causes of death which occurred in 5 or more patients are included, with the width of the band indicating the relative size of the population. COPD indicates chronic obstructive pulmonary disease; and MI, myocardial infarction.

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