Implementation of a highly sensitive cardiac troponin I assay: Test volumes, positivity rates and interpretation of results

Abstract

Background

While more sensitive cardiac troponin (cTn) assays may overcome current limitations in diagnosing acute coronary syndrome (ACS), clinicians and laboratorians are concerned about the clinical impact of higher rates of cTn positivity.

Methods

We collected statistics on test volume and positivity rates before and after the implementation of a more sensitive assay. We divided patients into 6 groups based on their cardiac troponin I (cTnI) results and utilized additional laboratory test results to determine the impact of the new assay. In addition, we assessed the clinical significance of low-positive cTnI results (0.05–0.10 µg/l).

Results

Lowering the diagnostic cutoff from 0.10 to 0.04 µg/l increased the number of positive test results by 44.2% hospital-wide and 114.4% in the emergency department without significantly changing test volume. In some patients, low-positive results were part of the typical rise and fall of cTnI consistent with myocardial damage. Diagnosis was more challenging in patients with consistently low-positive results. Patients in this group were significantly more likely to have impaired renal function than those with cTnI elevations > 0.10 µg/l.

Conclusions

More sensitive cTn assays will increase the number of positive results and allow for earlier detection of cardiac injury while also detecting non-ACS related pathologies.

Introduction

The ability to rapidly determine the presence of myocardial ischemia is crucial for patients presenting with chest pain or other signs and symptoms suggestive of acute coronary syndrome (ACS). Cardiac troponin has become the gold standard among biochemical markers used for both the diagnosis and prognosis of such patients [1], [2], [3]. However, until recently, cardiac troponin testing has had various limitations including suboptimal analytical sensitivities and low-end imprecision. As a result of assay performance and the kinetics of cardiac troponin release from damaged cardiac myocytes, patients presenting hours after the onset of symptoms may still have undetectable cardiac troponin concentrations. Typically, patients will have measurable cardiac troponin within 4 to 6 h of symptoms [4], but the opportunity for rapid triage and early intervention may be lost by that time. Thus, improvements in the performance of cardiac troponin assays can potentially overcome the current limitations and benefit patients presenting early in the course of myocardial ischemia.

The American College of Cardiology (ACC) and the European Society of Cardiology (ESC) both recommend using a diagnostic cutpoint at the 99th percentile of the reference population with a coefficient of variation (CV) of ≤ 10% for the diagnosis of ACS [1], [2], [3], [5], [6], [7], [8]. Some of the currently available cardiac troponin assays do not meet these requirements [9].

Siemens Healthcare Diagnostics recently replaced their older cTnI assay with an improved assay, TnI-Ultra, which offers both enhanced sensitivity and precision. We have previously compared the characteristics of cTnI to TnI-Ultra and confirmed that TnI-Ultra offers improved analytical and clinical performance, consistent with the ACC/ESC guidelines [10]. TnI-Ultra achieved a 10% CV at the manufacturer's 99th percentile resulting in a diagnostic decision point of 0.04 µg/l. Because of the improved analytical performance of the TnI-Ultra assay and the decision by the manufacturer to discontinue their cTnI assay, we implemented TnI-Ultra testing in our clinical laboratory.

We expected and previously confirmed that the enhanced performance characteristics of the TnI-Ultra assay would have anticipated benefits such as the earlier diagnosis of ACS in a subset of patients [10]. At the same time, both the clinicians and laboratorians were concerned about the clinical utility of cardiac troponin assays with increased sensitivity in other patients. It was clear that the number of positive cardiac troponin I results would increase due to the new low-positive range of 0.05–0.10 µg/l. However, we did not know whether or not this would translate into an increase in the volume and cost of cardiac troponin I testing for the clinical laboratory or how these low-positive test results would affect diagnostic decisions of our clinicians and subsequent treatment of our patients.

Data on the clinical significance of low-positive cardiac troponins is limited. It is known that cardiac troponin can be increased in conditions other than ACS [4], [11] such as renal disease [12], [13], [14] and congestive heart failure [4], [15]. Sommerer et al. [14] have shown that plasma concentrations of cTnT are increased in approximately 40% of asymptomatic chronic haemodialysis patients. Latini et al. [15] reported detectable cTnT in patients with chronic heart failure. Several groups have also studied the predictive value of small cTn elevations for adverse long-term cardiovascular outcomes [16], [17], [18], [19], [20], [21]. Using a sensitive cTnI assay, Eggers et al. [17] found that increased cTnI concentrations > 0.01 μg/l after an episode of non-ST-elevation ACS predicted mortality during long-term follow-up. However, how these findings will affect the interpretation of low-positive cTnI results and the utility of cardiac troponin assays with increased sensitivity for the diagnosis of ACS is not clear.

To clarify the impact of implementation of a more sensitive assay, we collected and analyzed data from 2 comparable, 5-month periods preceding and following implementation of the TnI-Ultra assay at the Brigham and Women's Hospital.