A novel technology for measuring cumulative cardiac biomarker exposure over time: what happened when we weren't looking?

Abstract

Cardiac troponin testing is front and center for the diagnosis of acute myocardial infarction (MI) in patients with signs and symptoms suggestive of an acute coronary syndrome, and in the absence of an ST-segment elevation on their electrocardiogram. For at least 15 years, the troponin concentration on presentation or the peak value during hospitalization has been recognized to carry both shortand long-term prognostic information. More recently, longitudinal follow-up of biomarkers after an MI has led to the recognition that patients with persistent increases in cardiac troponin or natriuretic peptide concentrations also have a poor prognosis compared with post-MI patients who have a decrease in concentrations (1, 2 ). With the recent evolution to “high-sensitivity” cardiac troponin assays, which can achieve a 10-fold increase in low-end sensitivity compared with their contemporary counterparts, detectable troponin concentrations can now be measured in 25%– 67% of the general population, depending on the patient’s age (3, 4 ). Even these low-level increases are not benign in these seemingly asymptomatic individuals, because such increases are associated with an increased risk of adverse cardiovascular events, including MI. Although cardiac imaging can provide some insight into the cardiac pathology underlying a persistent biomarker increase after an MI or in the general population, imaging still provides limited insight into a longitudinal process, given the cross-sectional nature of an imaging study. For example, in a patient with a high coronary calcium score according to computed tomography and an increased left ventricular mass by echocardiography, it is difficult to determine whether a detectable cardiac troponin concentration is due to a clinically unrecognized MI or to a persistent increase caused by myocardial pathology. Examples of 2 possible post-MI patterns for patients identified with a chronic troponin increase are shown in Fig. 1. Over an extended period of time, the patient with a second, now clinically silent MI would release more cardiac troponin in total than the patient with low-level chronic increases due to a nonacute coronary syndrome etiology, despite their having similar concentrations on retesting at a later time. Given that 22%– 40% of MIs in the general population are clinically unrecognized (5 ), a percentage that is likely higher after a recent MI, a technology that could differentiate these high-risk patients from others with persistent small troponin increases could provide the opportunity to initiate disease-modifying therapy. Differentiating a clinically silent or an atypical MI from nonacute coronary syndrome etiologies of increased troponin concentrations is only one of several scenarios in which interpretation by occasional spot checks of cardiac biomarker concentrations is problematic for clinicians. Another scenario that is occurring with increased frequency because of the evolution of chemotherapy is chemotherapy-related cardiac toxicity. The appropriate timing and frequency of cardiac biomarker measurements necessary to make this diagnosis is a source of debate. Lastly, there is increasing interest in the use of cardiac biomarkers, specifically the natriuretic peptides, to guide heart failure therapy in order to reduce hospitalizations and ultimately mortality. One of the limitations to the use of natriuretic peptides to guide therapy has been not only determining the optimal target for therapy but also deciding the frequency of testing, because the measurement-tomeasurement variation can be substantial. One approach has been to increase the frequency of measurement, such as by including a home-testing approach. Even with such a system, which would be similar to the finger-stick glucose meter checks of diabetics, discerning the long-term efficacy of heart failure management may remain difficult. Currently, there is no serum marker analogous to glycohemoglobin that would reflect the cumulative long-term release of markers of cardiac injury or their hemodynamics. A new technology may overcome this limitation, however, and make measurement of the total release of a biomarker over time a clinical reality. To address the conundrum posed by the clinical scenarios outlined above, Ling et al. have carried out an intriguing proof-of-concept study of a novel technology for Division of Cardiology, University of Maryland School of Medicine, Baltimore, MD. * Address correspondence to the author at: Division of Cardiology, University of Maryland School of Medicine, G3K63, 22 South Greene St., Baltimore, MD 21201. E-mail cdefilip@medicine.umaryland.edu. Received October 18, 2011; accepted October 24, 2011. Previously published online at DOI: 10.1373/clinchem.2011.175158 Clinical Chemistry 58:1 25–27 (2012) Perspectives

DOI: 10.1373/clinchem.2011.175158

1 Figure or Table

Cite this paper

@article{deFilippi2012ANT, title={A novel technology for measuring cumulative cardiac biomarker exposure over time: what happened when we weren't looking?}, author={Christopher deFilippi}, journal={Clinical chemistry}, year={2012}, volume={58 1}, pages={25-7} }