Optimum Troponin Cutoffs for ACS in the ED

Myocardial ischemia is a reduction in coronary blood flow insufficient for heart cell (myocardiocyte) demand. Prolonged ischemia results in myocardiocyte injury, death and necrosis i.e., myocardial infarction (MI). Cardiovascular disease resulting in myocardial ischemia is a major cause of morbidity and mortality worldwide. Acute coronary syndrome (ACS) is a spectrum of clinical presentations of acute myocardial ischemia ranging from ST-elevation MI (STEMI) to non-STEMI (NSTEMI) and unstable angina (UA). Because ACS portends a high-risk of death, treatment is time sensitive and delays to diagnosis and definitive care may decrease survival. However, the treatment-associated risk of bleeding, stroke and death also necessitate an accurate diagnosis of ACS.

Chest pain is the most common symptom of ACS and is the main cause of emergency department (ED) visits by the middle-aged and the second most common presenting complaint in other age groups accounting for up to 500,000 ED visits in Canada and 5 million in the United States of America (USA) each year. In 2005, the number of ED visits for chest pain increased by 20% over the previous decade and, as the median age of the western world's population increases over the next decade, EDs will assess more chest pain patients for ACS than ever before.

Because chest pain is a common presenting complaint and a symptom of many non-ACS conditions, the diagnosis of ACS is challenging. STEMI is diagnosed by specific electrocardiogram (ECG) findings whereas NSTEMI and UA are clinically indistinguishable because of the similarity in symptoms and transient or non-specific ECG findings at presentation. Differentiation of NSTEMI from the less severe UA is based on whether the ischemic myocardial injury is severe enough to release detectable concentrations of a myocardiocyte-specific protein, cardiac troponin (cTn). Therefore, patients with ACS symptoms and a non-diagnostic ECG are diagnosed with NSTEMI if their troponin level is above the cutoff concentration while similar patients with troponin levels below the cutoff are diagnosed with UA but both are admitted for treatment. However, patients with atypical symptoms with cTn concentrations below the cutoff represent a clinical dilemma and are usually discharged from the ED without any treatment or understanding of their risk of an ACS-related event within the next days, weeks or months.

Within the next year, many Canadian laboratories will replace their current cTn tests with the new high-sensitivity cardiac troponin assays (hs-cTn) that are analytically more sensitive and more precise at lower concentrations. This change could have a significant impact on EDs and the healthcare system in general. First and foremost, application of the current cutoff definition for NSTEMI to the newer hs-cTn assays will produce an increase in the prevalence of NSTEMI that may or may not be a true increase. This will result in more patients admitted to hospital and given high-risk therapies but with unknown overall changes in morbidity and mortality. Second, recent evidence suggests that the newer assays can help diagnose MI earlier and incremental hs-cTn measurements are potentially prognostic for future cardiovascular events (CVE) including death. Therefore, this inevitable change in assays has the potential to stress current healthcare resources or significantly improve ACS diagnosis and subsequent outcomes. The primary barrier to achieving optimum clinical benefit from the implementation of hs-cTn is the current lack of information. Specifically, the studies on hs-cTn assay cutoffs for early MI diagnosis in North American populations are limited and published research on hs-cTn assays for risk stratification in the ED is non-existent.

The investigators primary objective is to determine which hs-cTn concentration(s) are most predictive of a composite outcome of CVE over time in ED patients presenting with ACS symptoms. In the same population, the investigators also will determine if an early change in cTn and hs-cTn concentrations is more predictive than the peak cTn and hs-cTn concentrations of the composite outcome over time. The investigators intention is that physicians will be able to apply the prognostic cTn and hs-cTn cutoffs from their study results to prescribe the most time-appropriate interventions for their patients. The expected effect of generalized application of the investigators results being positive changes in patient safety, survival, secondary ACS prevention and even ED overcrowding.