Brain natriuretic peptide level as marker of cardiac function in imatinib—Treated chronic myeloid leukemia patients: No evidence of cardiotoxicity of imatinib therapy

Abstract

Brain natriuretic peptide level as marker of cardiac function in imatinib-treated chronic myeloid leukemia patients: no evidence of cardiotoxicity of imatinib therapy To the Editor: In the last year, the issue of cardiotoxicity of imatinib mesylate (IM) was on focus. After the original work from Kerkelä et al. [1], various papers reported a low incidence of severe cardiac adverse events in large groups of patients treated with imatinib for chronic myeloid leukemia (CML) [2][3][4][5] and gastrointestinal stromal tumor (GIST) [6]. Safety issues are particularly important, as imatinib is the frontline treatment of CML [7], and patients are expected to receive treatment for indefinite time.B-type natriuretic peptide (BNP) is released by the heart in response to myocardial tension [8] and is considered an accurate test for the diagnosis of heart failure. The measurement of BNP in the serum is a rapid and easy tool for evaluation of left ventricular ejective function (LFEV), also in asymptomatic patients [9].We have measured BNP level in 49 consecutive patients with chronic phase CML during imatinib therapy and in five newly diagnosed CML patients that were tested before IM start and after 1, 2, and 3 months of therapy. BNP level was measured using a direct chemiluminescent sandwich immunoassay: the analytical range extends from 0 to 5,000 pg/ml, with a sensitivity <2 pg/ml. Normal range is as follows: <100 pg/dl.Characteristics of the 49 patients studied while in treatment with IM are provided in Table I. All patients were asymptomatic and without signs of cardiac impairment at time of BNP evaluation. The mean level of BNP was 22.4 pg/ml (SD ± 26.6); only two patients had values >100 pg/ml. As expected [10], there was a linear correlation between age and BNP levels (t-value ¼ 3.850). Fifteen out of 24 (62.5%) patients aged !60 had BNP >22 pg/ml (mean 37.2 ± 31.4), compared to only 1/25 (4%) in the cohort <60-years-old (mean 8.2 ± 5.7) (P < 0.0001). BNP level was not affected by IM daily dose or by therapy duration. Patients with hypertension had higher levels of BNP (33.4 ± 35.6 vs 16.5 ± 18.3, P ¼ 0.03), despite an equivalent IM dose and treatment duration. This data could be explained by a higher incidence of hypertension in the older patients. No patient experienced major cardiac adverse event during IM therapy. An echocardiogram was performed in the two patients with higher BNP values: both of them were older than 60 and suffered from hypertension, but echocardiogram revealed a normal cardiac function (LVEF >65%). In the five consecutive patients (Table II) tested for BNP before start of IM and monthly during treatment there was no significant change in BNP levels during imatinib therapy (Fig. 1). Mean BNP value before start of IM was 20.9 ± 10.6, after three months of therapy was 14.8 ± 13.8.With the limits of a relatively small study population, our data indicates that imatinib therapy does not cause an increase in BNP, a rapid and reliable marker for the assessment of ventricular function. The role of BNP in ...

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