Sensitive troponin assay and the classification of myocardial infarction

Abstract

Background: Lowering the diagnostic threshold for troponin is controversial because it may disproportionately increase the diagnosis of myocardial infarction in patients without acute coronary syndrome. We assessed the impact of lowering the diagnostic threshold of troponin on the incidence, management, and outcome of patients with type 2 myocardial infarction or myocardial injury.

Methods: Consecutive patients with elevated plasma troponin I concentrations (≥50 ng/L; n = 2929) were classified with type 1 (50%) myocardial infarction, type 2 myocardial infarction or myocardial injury (48%), and type 3 to 5 myocardial infarction (2%) before and after lowering the diagnostic threshold from 200 to 50 ng/L with a sensitive assay. Event-free survival from death and recurrent myocardial infarction was recorded at 1 year.

Results: Lowering the threshold increased the diagnosis of type 2 myocardial infarction or myocardial injury more than type 1 myocardial infarction (672 vs 257 additional patients, P < .001). Patients with myocardial injury or type 2 myocardial infarction were at higher risk of death compared with those with type 1 myocardial infarction (37% vs 16%; relative risk [RR], 2.31; 95% confidence interval [CI], 1.98-2.69) but had fewer recurrent myocardial infarctions (4% vs 12%; RR, 0.35; 95% CI, 0.26-0.49). In patients with troponin concentrations 50 to 199 ng/L, lowering the diagnostic threshold was associated with increased healthcare resource use (P < .05) that reduced recurrent myocardial infarction and death for patients with type 1 myocardial infarction (31% vs 20%; RR, 0.64; 95% CI, 0.41-0.99), but not type 2 myocardial infarction or myocardial injury (36% vs 33%; RR, 0.93; 95% CI, 0.75-1.15).

Conclusions: After implementation of a sensitive troponin assay, the incidence of type 2 myocardial infarction or myocardial injury disproportionately increased and is now as frequent as type 1 myocardial infarction. Outcomes of patients with type 2 myocardial infarction or myocardial injury are poor and do not seem to be modifiable after reclassification despite substantial increases in healthcare resource use.

Keywords: Myocardial infarction; Outcomes; Troponin; Type 2.

Online Figure 1

CONSORT diagram of study population stratified by infarct type and study phase. Consecutive patients with plasma troponin I concentrations ≥50 ng/L were identified irrespective of clinical presentation during the validation (February 1, 2008, to July 31, 2008) and implementation (February 1, 2009, to July 31, 2009) of a contemporary sensitive troponin I assay (n = 2929). Exclusion criteria were limited to patients admitted for elective nonemergency procedures, patients who were resident outside of Lothian, and patients with incomplete hospital records. The remaining 2165 patients were classified with type 1 to 5 myocardial infarction or myocardial injury. Although plasma troponin was measured using a reformulated sensitive assay throughout both phases, only concentrations above a diagnostic threshold of 200 ng/L were reported in the validation phase, whereas concentrations above a revised diagnostic threshold of 50 ng/mL were reported during the implementation phase. MI = myocardial infarction.

Online Figure 2

Primary diagnosis of patients with type 2 myocardial infarction and myocardial injury. Patients classified with (A) type 2 myocardial infarction or (B) myocardial injury were a heterogeneous group presenting to a wide range of medical and surgical specialties. Most patients with type 2 myocardial infarction had a cardiac or respiratory diagnosis, with heart failure and arrhythmias the most common cause of elevated troponin concentrations.

Figure 1

Incidence rate of type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury per 100,000 persons in Lothian stratified by age. The incidence rate was estimated as the number of events during the total 12-month period divided by the mid-year population estimates for that age-specific stratum. Patients aged <75 years had a higher incidence of type 1 than type 2 myocardial infarction or myocardial injury (124 vs 60 per 100,000 persons), whereas the reverse was true for patients aged ≥75 years (750 vs 1008 per 100,000 persons).

Figure 2

Cumulative incidence of (A) recurrent myocardial infarction and (B) death in patients with type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury. Compared with patients with type 1 myocardial infarction, patients with type 2 myocardial infarction or myocardial injury were less likely to be readmitted with myocardial infarction, but were more likely to die at 1 year. In comparison with patients with type 1 myocardial infarction, more patients with type 2 myocardial infarction (16% vs 31%; hazard ratio [HR], 1.62; 95% CI, 1.30-2.04) and myocardial injury (16% vs 37%; HR, 1.87, 95% CI, 1.52-2.30) were dead, but fewer had recurrent myocardial infarction (12% vs 6%; HR, 0.40, 95% CI, 0.26-0.62 and 12% vs 3%; HR, 0.24; 95% CI, 0.15-0.40, respectively) at 1 year. HR presented after adjustment for age and sex with type 1 myocardial infarction as referent.

Figure 3

Change in the investigation, management, and clinical outcomes of patients with type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury after implementation of a sensitive troponin assay. In patients with troponin concentrations of 50 to 199 ng/L and type 1 myocardial infarction, lowering the diagnostic threshold increased referrals for a specialist opinion, further investigation, and treatments for myocardial infarction (P < .01 for all). For patients with type 2 myocardial infarction and myocardial injury, similar patterns were seen, although the absolute magnitude was smaller. In patients with type 1 myocardial infarction, lowering the diagnostic threshold was associated with a significant reduction in recurrent myocardial infarction (absolute risk reduction, 12%; 95% CI, 3-23), whereas outcomes in patients with type 2 myocardial infarction and myocardial injury remained unchanged. DAPT = dual antiplatelet therapy; MI = myocardial infarction; PCI = percutaneous coronary intervention. *P < .05. ** P < .01. ***P < .001.