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a CTL, healthy control subjects. (From ref. 11.)

a CTL, healthy control subjects. (From ref. 11.)

Control

Fig. 3. The concentration of cTnT correlates with the severity of CHF. (From ref. 16.)

Control

Fig. 3. The concentration of cTnT correlates with the severity of CHF. (From ref. 16.)

able levels (20 ± 5 vs 26 ± 7%; p = 0.023) with a trend toward higher intracardiac pressures. Notably, there was no histological evidence of myocarditis in those patients with elevated cTnl, and the cause of CHF was evenly distributed among ischemic and nonischemic etiologies.

The important observation that cardiac troponin is associated with outcome as well as severity of disease in patients with CHF has been corroborated by several studies. In a study of 56 consecutive patients with chronic heart failure from a variety of etiologies, Setsuta et al. (16) showed that levels of cTnT correlated with the severity of heart failure as determined by NYHA functional class (Fig. 3). In addition, a concentration of cTnT >0.02 ng/ mL was associated with a significantly higher risk of death or readmission for worsening heart failure (Fig. 4). Similarly, in a prospective study of 84 patients with acute cardiogenic pulmonary edema without myocardial infarction, Perna et al. (17) found that cTnT >0.1 ng/mL measured in samples obtained 6 and 12 h after admission was strongly associated with lower 3-yr survival (29 vs 76% in patients with elevated vs normal cTnT results,

Fig. 2. (Opposite page) Box and whisker plots of serum concentrations of cTnl, CK-MB, and myoglobin in patients with CHF (n = 35), healthy control subjects (n = 55), hospitalized control subjects without cardiovascular disease (n = 25), and both control groups (n = 80). The line within the box is the mean value, the upper and lower box values represent ±1 times the SE, the whiskers in the plot are defined as the mean ± 1.96 times the SE, and the closed circles are individual data points exceeding this specified value. (A) *p < 0.01 vs all groups; (B) *p < 0.01 vs hospitalized control subjects and combined control subjects; (C) *p < 0.01 vs all groups. (From ref. 11.)

Fig. 4. Survival free of cardiac events (death or rehospitalization) for heart failure among patients with CHF stratified by cTnT at hospitalization. (From ref. 16.)

log-rank test;p < 0.001). In the largest ofthese studies, Horwich et al. (14) evaluated 238 patients with advanced heart failure referred for cardiac transplantation who had cTnl measured at the time of initial presentation. A significant correlation was also found between the baseline concentration of cTnl and the progressive decline in LVEF over time. Moreover, by virtue of the larger sample size, this study revealed that cTnl was associated with increased mortality independently of the patient's age, cause of CHF, and LV function (adjusted relative risk [RR]: 1.85; 95% CI: 1.04-3.26). Other important findings of the study were that the optimal cutpoint identified by receiver operator curve analysis was at the lower reference limit for the assay used, and that higher levels of cTnl were not associated with additional risk. In other words, any detectable elevation in cTnl conferred a similar level of increased risk. The fact that any positive cTnl result rather than the absolute value of the result carried an increased risk has important clinical implications and makes the finding ofthe study applicable to laboratories using different immunoassays to measure troponin.

More important, the prognostic relationship between cardiac troponin and outcome is apparent in stable ambulatory patients with heart failure and is independent of the most commonly used NYHA functional classification. Hudson et al. (18) collected prospective data from NYHA functional class II-IV heart failure patients with a LVEF of <35%. The end points of the study were death or hospitalization for heart failure. Of136 patients, 33 (24%) had a level of cTnT >0.02 ng/mL. An elevated level of cTnT was associated with increased risk of death or hospitalization for heart failure (RR: 2.7; 95% CI: 1.7-4.3; p = 0.001) and death alone (RR: 4.2; 95% CI: 1.8-9.5; p = 0.001) during follow-up. Troponin T and NYHA functional class were both independent predictors of death or heart failure hospitalization in this study. The investigators concluded that approximately one-fourth of ambulatory patients with chronic heart failure had ongoing myocardial necrosis, as shown by abnormal troponin values, which were associated with increased mortality and morbidity.

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