Troponin Elevations Only Detected With a High‐sensitivity Assay: Clinical Correlations and Prognostic Significance

Abstract

Objectives With clinical use of high‐sensitivity troponin I (hsTnI), more frequent troponin elevations will occur. However, the burden and implications of these elevations are not well understood. The authors quantified the prevalence of elevated hsTnI in patients presenting with possible acute coronary syndrome (ACS) who do not have elevated troponin with a current generation assay (cardiac troponin I [cTnI]) and determined the association of these newly detected elevations with a composite of all‐cause mortality and subsequent cardiac hospitalization. Methods This was a prospective observational study of 808 subjects evaluated for possible ACS and followed for up to 1 year. Troponin values were measured with hsTnI (Abbott Laboratories) and cTnI (Abbott and Beckman Coulter). Cardiac hospitalization was defined as hospitalization for ACS, revascularization, acute heart failure (AHF), or tachy/brady arrhythmia that occurred after the index emergency department (ED) visit or hospital discharge. Results Forty subjects (5%) were diagnosed with ACS (26 myocardial infarction and 14 unstable angina). On the initial sample, the prevalence of elevated hsTnI among subjects with nonelevated cTnI was 9.2% using a gender‐neutral cutoff (95% confidence interval [CI] = 7.1% to 11.4%) and 11.1% using a gender‐specific cutoff (95% CI = 8.8% to 13.4%). Adjudicated diagnoses for subjects whose initial samples had elevated hsTnI but nonelevated cTnI (gender‐neutral cutoff) were as follows: three (4.6%) ACS, 15 (23.1%) AHF, three (4.6%) volume overload etiology unclear/noncardiac, three (4.6%) cardiac (non‐ACS), and 41 (63.1%) other. Of the 65 patients whose initial samples had hsTnI but nonelevated cTnI, eight developed cTnI elevation on subsequent serial sampling. After traditional cardiovascular risk factors and renal function were adjusted for, subjects with elevated initial hsTnI but nonelevated cTnI (initial and serial sampling) had a higher risk of all‐cause mortality and subsequent cardiac hospitalization than subjects with both nonelevated hsTnI and nonelevated cTnI (hazard ratio [HR] = 1.91, 95% CI = 1.14 to 3.19). Conclusions On the initial sample, 9% to 11% of subjects without cTnI elevation had hsTnI elevation. Although the majority of the patients with these newly detected hsTnI elevations did not have ACS, they had a higher risk for all‐cause mortality and subsequent cardiac hospitalization.

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

“…It is important to note that troponin levels may also be elevated in the blood of patients with a wide variety of other medical disorders. 84 Although these elevations reflect myocardial damage that is associated with poorer prognosis, the underlying mechanism for myonecrosis is not believed to be ischemic and varies by illness. It has also been recognized that even when MI has been excluded among patients who present to the emergency room with chest pain, low levels of troponin in blood, as detected by high-sensitivity assays, predict higher all-cause mortality and cardiac hospitalization in the months ahead.…”

“…It has also been recognized that even when MI has been excluded among patients who present to the emergency room with chest pain, low levels of troponin in blood, as detected by high-sensitivity assays, predict higher all-cause mortality and cardiac hospitalization in the months ahead. 84 Although immunoassays are the method used in current troponin assays, extension to even more sensitive MS technologies may emerge in clinical practice. This could provide the opportunity to measure not only troponin levels but also protein modifications of sarcomere proteins that may correlate with disease.…”

Impact on Patient Management and Outcome of Switching between 2 Contemporary Sensitive Cardiac Troponin Assays

“…Both cardiac troponin I (cTnI) and cTnT assays are widely used and are considered diagnostically equivalent (1 ). In addition to diagnostic utility, cardiac troponin has prognostic value in both cardiac and noncardiac settings, including individuals with exacerbation of chronic obstructive pulmonary disease, sepsis, pulmonary embolism, and major noncardiac surgery (3)(4)(5)(6).…”

Improving the 510(k) FDA Process for Cardiac Troponin Assays: In Search of Common Ground

“…It was indicated that with high-sensitivity cardiac troponin assays, a rising cardiac troponin pattern would likely be seen in about 20% of ED patients (7 ). Thus, the number of patients needed to give a study the appropriate statistical power might be reduced.…”

“…The FDA pointed out that they do not dictate the number of study participants, but rather that manufacturers need to substantiate their enrollment protocols with appropriately powered statistics to demonstrate equivalence to previously cleared assays. The FDA acknowledged that with high-sensitivity cardiac troponin assays, a larger number of patients with non-acute coronary syndrome myocardial injury will be detected, thereby decreasing the clinical specificity of these assays for AMI (7,10 ). We were of the impression that often the FDA expects all patients to be categorized as either having AMI or not having AMI despite the ambiguities described above.…”