Significance of Circulating Troponins in Heart Failure

Abstract

Biomarkers serve 2 potential roles: They provide insight into the pathophysiology of disease, and they aid clinical decision making by clarifying diagnosis, prognosis, or response to therapy. Fulfillment of one role does not ensure fulfillment of the other. For instance, some biomarkers associated with disease progression turn out to provide little incremental clinical value. Thus, studies like the one by Latini and colleagues1 in this issue of Circulation are valuable because they couple investigation of a biologically interesting association, in this case the link between circulating troponins and heart failure (HF), with a rigorous assessment of clinical utility. The following commentary focuses on 2 questions raised by the study by Latini et al. First, what is the pathophysiological significance of circulating troponins in HF? Second, should we be measuring cardiac troponins in chronic HF patients? Article p 1242 The troponins comprise 3 proteins (troponin T, I, and C) that regulate actin and myosin interactions during muscle contraction. Troponins T and I have distinct isoforms that exist in skeletal and cardiac muscle; newer-generation assays permit the detection of the isoforms unique to cardiac tissue. The release of these proteins into the bloodstream from cardiomyocyte necrosis accounts for their utility as biomarkers of acute coronary syndromes. In the past decade, it has been recognized that elevated concentrations of cardiac troponins also are detectable in patients with HF in the absence of unstable coronary syndromes. In 1997, Missov and colleagues2 used a highly sensitive research assay to demonstrate elevated concentrations of troponin I in 35 patients with advanced HF. Subsequent reports extended these observations to troponin T.3–5 For instance, in a Japanese study, troponin T was detectable by a second-generation assay (detection limit, 0.02 ng/mL) in 30 of 58 patients (52%) with chronic HF compared with 4% of healthy control …