Editorial

High-sensitivity Cardiac Troponin: From Theory to Clinical PracticeTroponina cardiaca ultrasensible: de la teoría a la práctica clínica

INTRODUCTION

Since 2000, cardiac troponin (cTn) has been the recommended biomarker for the evaluation of patients with a possible diagnosis of acute myocardial infarction (AMI).¹ Most of the cTn immunoassays currently in use lack the analytical sensitivity to accurately measure the upper reference limit (URL), ie, the 99th percentile reference value, which is the guideline-mandated cutoff value for myocardial injury. Consequently, current methods fail to detect some cTn values slightly higher than the 99th

DEFINITION OF A HIGH-SENSITIVITY ASSAY

Several authors have endorsed the idea that hs-cTn assays should detect cTn in most healthy reference participants. Three levels of hs-cTn assays have been proposed, including categories that detect cTn in 50% to 75%, 75% to 95%, and more than 95% of the reference participants, respectively. In a subsequent analysis that evaluated the percentage of detectable cTn values measured with 19 cTn assays in the same population of reference participants, only 2 assays (1 of which was an investigational

WHO IS A NORMAL REFERENCE PARTICIPANT?

The diagnosis of AMI relies on the combination of clinical symptoms, electrocardiographic changes, and increased values of a biomarker. For cTn, the recommended cutoff for a diagnosis of myocardial infarction is the 99th percentile URL. Given its relevance for diagnosis, the 99th percentile should be obtained with maximal accuracy. The accuracy of this determination depends on the characteristics of the reference population. At present, there are no universal recommendations on how to select

ANALYTIC ISSUES

The minor analytic issues that occur with all immunoassays will be much more critical with these very high-sensitivity assays, in which minor changes could make marked differences. For example, cTnT is reduced by hemolysis⁸ and some cTnI assay values are increased. Given that most samples from critically-ill patients are obtained from lines, careful scrutiny of the important preanalytical processes used to obtain samples will be critical. In addition, the recent problem with the hs-cTnT

USING HIGH-SENSITIVITY CARDIAC TROPONIN TO DIAGNOSE ACUTE MYOCARDIAL INFARCTION

Because high-sensitivity assays detect values in apparently healthy participants with subclinical cardiac disease, a significant proportion of patients presenting with possible AMI will have hs-cTn values above the 99th percentile URL. Thus, all AMI guidelines recommend serial cTn sampling to observe a rise and/or fall in values in a clinical setting, giving rise to significant suspicion for an acute coronary syndrome. Unfortunately, a clear definition, based on data, of the optimal significant

THE TIMING OF DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION

Multiple studies have suggested that, when hs-cTn assays are used, most–if not all–patients will have elevations by 2 to 3 h. However, as with the delta, the inclusion of new events that can be detected only by hs-cTn assays will add to the time required for all patients to be ruled in. In a recent analysis, the time required was 5 h.²

However, novel rule-out strategies are possible. One strategy already suggested with hs-cTnT is that AMI is very unlikely when the cTnT value at presentation is

TYPES OF ACUTE MYOCARDIAL INFARCTION

The global definition of AMI recognizes multiple types of AMI.¹ The standard or wild-type AMI is thought to be due to plaque. It is thought that these AMIs provide larger cTn responses than those that are due to supply-demand abnormalities, with or without coronary artery disease, or those associated with vasospasm or endothelial dysfunction. Type 1 patients clearly benefit from aggressive anticoagulation therapy and an early invasive strategy. However, patients with tachycardia, hypertension,

THE CONTRIBUTION OF HIGH-SENSITIVITY CARDIAC TROPONIN ASSAYS TO THE MANAGEMENT OF CHRONIC CARDIOVASCULAR DISEASE

The management of chronic cardiovascular disease will be a major area of improvement in patient care. It is now clear that minor elevations of hs-cTn are common and are almost always associated with cardiovascular comorbidities.¹⁴ Some of these comorbidities are so subtle that they are not detectable clinically or even with imaging studies. However, in a variety of community-based studies, these comorbidities have been shown to be associated with an increased risk for adverse cardiac events

CONCLUSIONS

High-sensitivity assays are currently available. If we use these assays optimally, they will represent a major advance. If we fail to understand how to use them, they will become a source of confusion and a common cause of medical error. Hopefully, this article will help those who are ready and willing to move forward.

CONFLICTS OF INTEREST

Dr. Ordonez-Llanos acknowledges currently receiving or previous receipt of honoraria for speaking, consultation, and support for research from Abbott Diagnostics, Alere, BioRad, Roche Diagnostics, Siemens Medical Solutions, STAT Diagnostics and Thermo Fisher Scientific. Dr. Jaffe acknowledges that he has previously consulted for most of the major diagnostic companies and is currently doing so.