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Prospective Evaluation of Anthracycline-Related Early Cardiac Damage: How Do We Monitor It?

Ospedale A. Manzoni, Azienda Ospedaliera Lecco, Lecco, Italy
Ospedali Riuniti di Treviglio, Aziena Ospedaliera de Treviglio Bergamo, Bergamo, Italy

To the Editor:In their study on cardiac function in patients with invasive breast cancer 1 year after adjuvant epirubicin (cumulative doses of 360 or 450 mg/m²), Meinardi et al¹ found an overall significant reduction of mean left ventricular ejection fraction (LVEF) from 0.61 to 0.54 (P = .001) and an increase of natriuretic peptides (NPs). However, their absolute values remained within the normal range in all but two patients, and in six out of 40 patients with an LVEF decreased to below 0.50, the NP values did not show any pathologic increase. The authors concluded that epirubicin impairs the cardiac function early, and this side effect seems best detected by radionuclide ventriculography (RV). They gave no significance to the NP plasma determination because no patient developed symptoms of heart failure.

Here we report our experience in 30 female patients (median age, 57 ± 9 years) who received adjuvant epirubicin (cumulative dose, 360 mg/m²) and who underwent a similar cardiac evaluation. The follow-up ranged from 19 to 33 months. Before chemotherapy and at 12, 18, and 24 months, we monitored cardiac function by measuring LVEF by RV and, at the same time, determining the brain natriuretic peptide (BNP) plasma levels. BNP is the most sensitive NP related to the function of the left ventricle.^2,3 BNP plasma levels were determined by the immunoradiometric method assay method (Shionogi, Japan), with a cutoff of more than 25 pg/mL because a sensitive test should really rule out a systolic dysfunction rather than confirm it.⁴ All patients had a basal LVEF above 0.50 (mean, 0.62 ± 0.05), and BNP determinations were within the normal range (mean, 14.2 ± 5.5 pg/mL). After epirubicin, the mean LVEF decreased significantly to 0.54 (P < .05), thereby confirming the early cardiac impairment was epirubicin-related. The BNP plasma determinations overall were increased (19.3 ± 4.6 pg/mL), even if the difference was not significant. However, nine patients showed an LVEF reduction below 0.50, and in five of them, the data were persistent throughout the follow-up (from 0.56 ± 0.04 to 0.44 ± 0.06; P < .005). These nine patients have had a significant increase of mean BNP values compared with the remaining 21 (21.3 ± 6.8 pg/mL v 11.2 ± 4.5 pg/mL; P < .05). Even more, out of these nine patients, six have had BNP plasma levels greater than 25 pg/mL. On the contrary, out of 21 patients whose LVEF did not drop below 0.50 throughout the follow-up, only three unexpectedly have had BNP values greater than 25 pg/mL. On the basis of these results, we suggest that BNP should be further and more carefully investigated as an indicator of anthracycline-related cardiac dysfunction because, when tested in the general population, it is able to stratify the cardiac mortality risk beside and beyond the LVEF evaluation.⁵ With respect to RV, it has the advantage of being easier to perform, and last by not least, it saves costs, allowing a better allocation of resources and freeing up the already overworked laboratories of cardiology and nuclear medicine departments.

REFERENCES

1. Meinardi MT, van Veldhuisen DJ, Gietema JA, et al: Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients. J Clin Oncol 19: 2746-2753, 2001[Abstract/Free Full Text]

2. Clerico A, Del Ry S, Giannessi D: Measurement of cardiac natriuretic hormones (atrial natriuretic peptide, brain natriuretic peptide, and related peptides) in clinical practice: The need for a new generation of immunoassay methods. Clin Chem 46: 1529-1534, 2000[Abstract/Free Full Text]

3. McDonagh TA, Robb SD, Murdoch DR, et al: Biochemical detection of left-ventricular systolic dysfunction. Lancet 351: 9-13, 1998[Medline]

4. Waku S, Iida N, Ishihara T, et al: Significance of brain natriuretic peptide measurement as a diagnostic indicator of cardiac function. Methods Inf Med 39: 249-253, 2000[Medline]

5. McDonagh TA, Cunningham AD, Morrison CE, et al: Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population. Heart 86: 21-26, 2001[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ciotti, R. Articles by Baccheta, G. Search for Related Content PubMed PubMed Citation Articles by Ciotti, R. Articles by Baccheta, G. Social Bookmarking                            What's this?