249High-sensitivity cardiac troponin and the universal definition of myocardial infarction: a randomised controlled trial
Authors: Chapman A R , Adamson P D , Anand A , Shah A S V , Lee K K , Strachan F E , Ferry A S V , Sandeman D E , Berry C , Gray A J , Tuck C , Fox K A A , Newby D E , Weir C , Mills N L 
Published: October 2019

Abstract

Background
The Universal Definition of Myocardial Infarction recommends the 99th centile diagnostic threshold using a high-sensitivity cardiac troponin (hs-cTn) assay and the classification of patients by the etiology of myocardial injury. Whether implementation of this definition improves risk stratification, treatment or outcomes is unknown.

Methods
In a stepped-wedge cluster randomized controlled trial, we implemented a high-sensitivity troponin assay and the recommendations of the Universal Definition in 48,282 consecutive patients with suspected acute coronary syndrome across ten hospitals. In a pre-specified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death, and secondary outcome of non-cardiovascular death at one year across diagnostic categories as per the Fourth Universal Definition. We applied competing risks methodology in all analyses, using a cumulative incidence function and determining the cause-specific hazard ratio (csHR) for competing outcomes.

Results
Cardiac troponin concentrations were elevated in 21.5% (10,360/48,282) of all trial participants. Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4,471), type 2 myocardial infarction by 22% (205/916), acute myocardial injury by 36% (443/1,233) and chronic myocardial injury by 43% (389/898). The risk and rate of the primary outcome was highest in those with type 1 myocardial infarction, whereas the risk and rate of non-cardiovascular death was highest in those with acute myocardial injury (Table, Figure). Despite increases in anti-platelet therapy and coronary revascularization after implementation, the primary outcome was unchanged in patients with type 1 myocardial infarction (csHR 1.00, 95% CI 0.82 to 1.21), or in any other category.
Adjusted csHR for competing outcomes Myocardial infarction or cardiovascular death Non-cardiovascular death Adjusted csHR (95% CI) Adjusted csHR (95% CI) Type 1 myocardial infarction 5.64 (5.12 to 6.22) 0.83 (0.72 to 0.96) Type 2 myocardial infarction 3.50 (2.94 to 4.15) 1.72 (1.44 to 2.06) Acute myocardial injury 4.38 (3.80 to 5.05) 2.65 (2.33 to 3.00) Chronic myocardial injury 3.88 (3.31 to 4.55) 2.06 (1.77 to 2.40) Cox regression models adjusted for age, sex, diabetes, ischaemic heart disease, season, days since trial onset and site of recruitment (as a random effect).
Cumulative incidence and number at risk

Conclusions
Implementation of the recommendations of the Universal Definition identified patients with different risks of future cardiovascular and non-cardiovascular events, but did not improve outcomes. Greater understanding of the underlying mechanisms and effective strategies for the investigation and treatment of patients with myocardial injury and infarction are required if we are to improve outcomes.

Acknowledgement/Funding
British Heart Foundation