Natriuretic Peptides in Anthracycline-Induced Cardiotoxicity

With interest, we read the article of Daugaard and colleagues in this issue, in which the results of their study addressing the value of measuring natriuretic peptides for monitoring anthracycline-related cardiac dysfunction are presented 1. In 107 consecutive patients with disseminated cancer, left ventricular ejection fraction values and natriuretic peptide plasma levels were determined simultaneously during anthracycline-based chemotherapy. From their findings, the authors conclude that natriuretic peptide measurement cannot be used to replace serial left ventricular ejection fraction (LVEF) measurements during treatment in patients receiving anthracycline-based chemotherapy. When reading the article, some concerns were raised with regard to the interpretation of study results. Firstly, the authors describe that for most patients, the first and sole LVEF and natriuretic peptide measurement was performed when half of the chemotherapy regimen was completed. At this time, LVEF and natriuretic peptide values may have already been affected, which may have lead to an underestimation of the number of patients with cardiotoxicity during treatment. Secondly, anthracyclines can induce diastolic dysfunction 2, which is not detected by LVEF measurement. Natriuretic peptides can however be elevated in diastolic dysfunction. The authors demonstrate nicely that natriuretic peptide measurement cannot safely substitute LVEF measurement for the monitoring of anthracycline cardiotoxicity, since NT-ANP and BNP plasma levels were not predictive of a change in LVEF during treatment. However, no follow-up was performed to assess whether an increase in natriuretic peptide levels could predict the development of anthracycline-related cardiac dysfunction after chemotherapy. A decline in LVEF represents functional loss, and an increase in natriuretic peptide plasma levels can precede a decrease in LVEF. In a prospective evaluation, we previously observed that plasma N-terminal atrial natriuretic peptide (NT-ANP) and b-type natriuretic peptide (BNP) were raised during the first year after moderate-dose adjuvant epirubicin-based chemotherapy, in 40 women treated for high-risk breast cancer 3. In another study, an increase in plasma BNP was observed in 27 patients who received anthracycline chemotherapy 4. In both studies, natriuretic peptide levels did not predict symptomatic cardiac dysfunction. Long-term follow-up may therefore be needed to assess if increased natriuretic peptide levels are associated with the development of late cardiac dysfunction after anthracycline chemotherapy. Although natriuretic peptide measurement appears to be not useful to replace LVEF during anthracycline treatment, increased natriuretic peptide plasma levels may be of value for identifying patients at risk for late cardiac dysfunction, who require more intensive cardiac follow-up, to enable earlier intervention for limiting cardiac symptoms.