Predictive Value of NT-proBNP in Patients with Acute Myocardial Infarction

To the Editor: We read with interest the recent article by Suzuki et al. concerning the measurement of trimethylamine N-oxide (TMAO)1 and risk stratification after acute myocardial infarction (AMI) (1). In their study of 1079 AMI patients, these authors analyzed the associations of TMAO with all-cause mortality or reinfarction in comparison with other biomarkers [including N-terminal pro–B-type natriuretic peptides (NT-proBNP)]. They found that TMAO concentrations were strongly associated with adverse outcome at 2 years, showing a predictive power superior to all other biomarkers. A particularly surprising finding of this study was the lack of an association between NT-proBNP concentrations and prognosis in any models tested by Cox proportional hazards survival analyses. Many other studies (2–4), including the very recent Clopidogrel as Adjunctive Reperfusion Therapy—Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) study (5), have demonstrated BNP or NT-proBNP measurements to be a strong predictor of adverse outcome in patients with AMI. Some pathophysiological and methodological issues need to be considered to explain these conflicting results regarding the predictive value of NT-proBNP. Plasma BNP/NT-proBNP concentrations increase immediately after AMI, the extent of the increase being related to infarct size (2, 3). Patients with smaller infarcts tend to have a monophasic increase in BNP/NT-proBNP, peaking within 24 h after the onset of symptoms. Heeschen et al. (4) reported that in patients with high baseline NT-proBNP, the absence of a rapid decline in NT-proBNP (≤250 ng/L) after myocardial injury was linked to an adverse short-term prognosis. Furthermore, in patients with low NT-proBNP at baseline, a rise in NT-proBNP ≥250 ng/L at 72 h after myocardial injury was also linked to 30-day adverse prognosis (4). In addition, a strong relation has been documented between plasma concentrations of BNP and NT-proBNP usually measured at hospital admission, and long-term, all-cause mortality, as well as rate of readmissions for heart failure after MI (2, 3). Finally, studies of serial measurements of NT-proBNP following admission for non–ST-elevation acute coronary syndromes have shown that persistently increased peptide concentrations are associated with the presence of refractory ischemia and high risk of short-term recurrent ischemic events (5). According to these data, the timing of plasma sampling for NT-proBNP assay needs to be reported explicitly in clinical studies for accurate risk stratification in AMI patients. Unfortunately, in the article by Suzuki et al. (1) only the time of sampling for TMAO assay [i.e., mean 3.5 (SD 1.1) days after admission] was reported, whereas the time of NT-proBNP sampling was not specified. Another important limitation of this study regards the characteristics of the cohort of AMI patients, which included a high proportion of patients with ST-elevation MI (STEMI) and low revascularization rate, making the results of this study difficult to compare with those of studies that have included patients with ACS-NSTEMI (acute coronary syndrome non–STEMI) (4). Analytical aspects may also play a role in explaining the conflicting results regarding prognostic accuracy of NT-proBNP concentrations. An inhouse method for NT-proBNP assay was used in the study of Suzuki et al., whereas the ECLIA (electrochemiluminescence immunoassay) using Elecsys and Cobas automated platforms (Roche Diagnostics), has been the most commonly used method in clinical laboratories. Another potential cause of the conflicting results may be the possible degradation of the peptide in plasma samples stored at −80 °C for several years (1). In conclusion, we believe that results reported by Suzuki et al. (1) regarding the prognostic value of NT-proBNP in patients with AMI are difficult to evaluate in comparison with other studies reported in the literature owing to the methodological limitations we have outlined here. trimethylamine N-oxide acute myocardial infarction N-terminal pro–B-type natriuretic peptide ST-elevation MI.