Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction

Abstract

Background: Whilst the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule-in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. Methods: In a secondary analysis of a multi-centre randomized controlled trial, we identified 46,092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value (PPV) and specificity were determined at the sex-specific 99th percentile upper reference limit (URL), and rule-in thresholds of 64 ng/L and 5-fold of the URL for a diagnosis of type 1 myocardial infarction. Results: Troponin was above the 99th percentile in 8,188 (18%) patients. The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14%, and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th percentile - 75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction, and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold URL gave a PPV of 57% (95% confidence interval [CI] 56-58%), 59% (58-61%) and 62% (60-64%), and a specificity of 96% (96-96%), 96% (96-96%) and 98% (97-98%), respectively. The absolute, relative and rate of change in troponin concentration was highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared to troponin concentration at presentation alone (area under curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123

Validation of the myocardial-ischaemic-injury-index machine learning algorithm to guide the diagnosis of myocardial infarction in a heterogenous population: a prespecified exploratory analysis

“…Second, although performance of the low-probability threshold was consistent across important patient subgroups, we observed heterogeneity in the PPV of the high-probability threshold, particularly when stratified according to the primary presenting symptom. This finding is consistent with our previous research 29 , 30 and probably reflects the greater prevalence of non-ischaemic myocardial injury and type 2 myocardial infarction in our consecutive patient population as compared with the cohorts used to train the algorithm whereby some patient selection was inevitable. It is possible that an algorithm that incorporates other clinical features might perform more consistently across these subgroups when identifying patients at high probability of type 1 myocardial infarction.…”

Clinical and prognostic implications of high-sensitivity cardiac troponin T concentrations in type 2 non-ST elevation myocardial infarction

“…First, the magnitude of hs-cTnT release appeared to be similar as in type 1 NSTEMI. This contrasts to data reported elsewhere [3] , [4] , [5] and likely depends on the exclusion of patients with ST-elevation MI from our cohort. Even differences in blood sampling strategies may have contributed.…”

“…Our data however, also highlight the difficulties to distinguish type 2 from type 1 NSTEMI, and hs-cTnT concentrations provide no clue in this regard. Even previous data demonstrated that cTn only provides limited discriminative value [4] , [5] , [8] , [9] . Some studies have suggested that this could be enhanced by the consideration of clinical findings and/or other biomarkers [10] , [11] , [12] , [13] .…”

“…Compared to patients with type 1 MI, those with type 2 MI tend to be older and suffer more frequently from comorbidities, both cardiovascular and non-cardiovascular [2] . Cardiac troponin (cTn) concentrations however, tend to be lower in type 2 MI [3] , [4] , [5] indicating less severe myocardial injury. Still, type 2 MI patients have similar or even higher risk of adverse outcome as those with type 1 MI when taking into account differences in risk panorama [2] , [6] .…”

Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI)

“…Since then, cTns continue to represent the gold standard for MI diagnosis. However, even if they are still among the most widely used cardiac biomarkers, their low positive predictive power and low disease specificity can lead to incorrect diagnosis, as they are not completely specific to MI [8][9][10]. Additionally, the improved sensitivity of high analysis assay cTns (hs-Tns) is associated with prolonged time to correct diagnosis, undue interventions, and has diminished value in the first era of disease development, and its prognostic role is less well-established.…”