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Department of Pathology; UT Southwestern Medical Center; Dallas, TX; frank.wians{at}utsouthwestern.edu
To the Editor:
Recently, Almog et al. (1) reported that increased plasma levels of NT-proBNP were associated with increased mortality in critically ill patients. We agree that NT-proBNP could have predictive power in a critical care setting; however, we are concerned about the following issues:
First, it is not clear why patients with a "single" increased cardiac troponin T (cTnT, or cTnI, see below) value were included in their cohort of study patients when they intended to exclude patients with an acute coronary syndrome (ACS). According to the American College of Cardiology/American Heart Association Guidelines for the management of a patient with unstable angina and non-ST segment elevation myocardial infarction, "serial" measurement of a cardiac troponin is their "Clinical Recommendation" (2).
Second, in their Methods section the authors describe the measurement of cTnT using "a commercial micro-particle enzyme immunoassay (AxSYM Troponin-T; Abbott Laboratories, Abott Park, IL)." To our knowledge, the AxSYM method for quantifying troponin is a troponin I assay, not a troponin T assay. In addition, the authors stated, "the assay characteristics were as follows: detection limits of 0.3 ng/mL, analytical range 050 ng/mL." However, the authors also indicated that "Thus, a cTnT serum level >0.03 ng/mL was considered abnormal." If the lower limit of detection (LLD) of the assay is 0.3 ng/mL, then only values >0.3 ng/mL can be considered abnormal. According to the manufacturer's product insert for the cTnI assay in the Abbott AxSYM instrument, the LLD of this assay is 0.3 ng/mL, which suggests that the authors did, in fact, use the cTnI, not cTnT, assay in the AxSYM instrument.
Third, in their Discussion section, Almog et al. (1) state that their study was "the largest of its kind evaluating a nonselected cohort of critically ill patients." We disagree that this cohort can be called "nonselected," because several patient groups were excluded including those with ACS, chronic hemodialysis, abnormal electrocardiogram, or cardiogenic pulmonary edema and major surgery during the month preceding admission.
Fourth, in their Discussion section, Almog et al. (1) stated, "NT-pro-BNP was measured within 6 h" (of admission). However, in their Methods section, the authors state, "After completion of patient recruitment, serum samples were thawed, and NT-pro-BNP levels were determined on the same day using a commercial assay (Roche, Dyn Diagnostics, Indianapolis, IN)." Therefore, the aforementioned sentence should read, "Blood samples for NT-pro-BNP testing were obtained within 6 h of admission."
Finally, we agree with the limitations of their study, cited by the authors in their Discussion section, especially their suggestion that "biologic variability of NT-proBNP may prove to be an important limitation in its future widespread application." In a study by Bruins et al. (3) the interindividual biological variability of NT-proBNP, CVI, ranged from 3.1% to 80% (day-to-day CVI) and 7.6%103% (week-to-week CVI). Moreover, in a critical care setting, this factor could play an especially large role in the validity of NT-proBNP as a marker with good prognostic value in critically ill patients. In addition, references cited in the study by Bruins et al. (3) indicate that many factors, including infusion of fluids, may increase the plasma NT-proBNP level by >200% in a delayed fashion after a few hours. Therefore, in the critically ill patients included in the authors' study, many of these patients were most likely receiving IV fluids on admission such that obtaining blood samples for NT-proBNP measurement within 6 h of admission might cause a rapid elevation in NT-proBNP and lead to placement of this patient into the wrong quartile. We also agree with the authors that more studies are necessary to validate the predictive power of NT-proBNP in a critical care setting.
REFERENCES
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Y. O. Almog NT-proBNP as a Prognostic Marker in Critically Ill Patients Anesth. Analg., April 1, 2007; 104(4): 999 - 1000. [Full Text] [PDF] |
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