Figure 1 represents the pathophysiological concept that CHF is characterized by a chronic low level of myocardial injury leading to degradation of structurally bound proteins, including cardiac troponin (9). The concept of measuring cardiac troponin in patients with CHF was introduced in 1995. In a pilot study, Missov et al. measured cTnI in 11 endstage heart failure patients and in 11 control subjects (10). They found that 2 of11 patients with CHF had levels of cTnI above the upper reference limit of the assay (0.1 ng/mL), whereas an increased concentration of troponin was not detectable in any of the control subjects. In a follow-up study, the same investigators used a more sensitive immunoassay to measure cTnI (11). This assay had a lower limit of detection, 3 pg/mL, and no cross-reactivity with the skeletal muscle isoform of troponin I. The results showed that the mean concentration of cTnI was 72.1 ± 15.8 pg/mL in stable ambulatory patients with New York Heart Association (NYHA) class III or IV heart failure, compared with 36.5 ± 5.5 pg/mL in hospitalized patients without cardiac disease, and 20.4 ± 3.2 pg/mL in
Congestive Heart Failure
Congestive Heart Failure
healthy blood donors (p < 0.01 for each vs heart failure patients) (Fig. 2A). Although lacking the high specificity of cardiac troponin for myocardial damage, measurements of cardiac-specific isofocus of creatine kinase (CK-MB) and myoglobin, two additional biomarkers of necrosis, produced similar results (Fig. 2B,C). These data provided the first evidence for ongoing myocyte injury and an increased concentration of cardiac troponin in the peripheral blood of patients with advanced heart failure and showed the potential usefulness of cardiac troponin as a specific and sensitive biomarker in severe CHF.
These findings have subsequently been validated in multiple clinical studies. In a study of a similar population of patients with heart failure and matched control subjects (12), heart failure patients had significantly elevated levels of cTnT (Table 1), with the concentration of cTnT correlating inversely with LV ejection fraction (LVEF). These data confirmed that sensitive biomarkers of necrosis are increased in patients with CHF and parallel the severity of the disease. Logeart et al. (13) also documented ongoing cardiac cell injury using cTnl in 71 patients with nonischemic cardiomyopathy and NYHA Class II-IV heart failure. In their study, heart failure patients with elevated cTnl were more likely to have echocardiographic findings of a concentric remodeling pattern and evidence of diastolic dysfunction. Others have shown that patients with advanced CHF and detectable levels of cTnI have significantly more impaired hemodynamic profiles, including higher pulmonary capillary wedge pressure and lower cardiac index (14).
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