Serial Natriuretic Peptide Testing Can Predict Anthracycline Cardiotoxicity Risk

September 27, 2007

September 27, 2007 (Washington, DC) - Measurement of brain-type natriuretic peptide (BNP) levels in cancer patients receiving anthracyclines can predict the treatment's risk of cardiotoxicity more reliably than troponin levels or echocardiographic assessment of LV function, according to a small prospective study [1].

For example, a BNP reading >100 pg/mL on two occasions signaled an 18-fold increase in risk of heart failure, arrhythmias, or other cardiovascular complications. The risk was much steeper if levels exceeded >200 pg/mL only once.

Even though oncologists well know to watch for the cardiotoxic effects of doxorubicin and other anthracyclines, "there's a range of how vigilant they might be," Dr Daniel J Lenihan (MD Anderson Cancer Center, Houston, TX), a cardiologist, told heart wire . "Some might look for them aggressively and others may not. The good thing about this is that it's a point-of-care test, so even in a small oncology practice, they can easily check a blood sample in their office while they're waiting to get the IV in. You can get the results in 15 minutes."

Serial BNP testing probably isn't enough on its own to indicate withdrawal of the drugs but can help identify patients who should be watched more carefully for cardiac side effects, according to Lenihan, who presented the study here at the Heart Failure Society of America 2007 Scientific Meeting.

A lot of its 109 patients, under treatment for various malignancies, also had cardiovascular risk factors, which may help promote anthracycline cardiotoxicity, Lenihan and his colleagues speculate. A tenth of the patients had documented CAD, a third had hyperlipidemia, 50% had hypertension, 35% were obese, and 12% had diabetes. Patients with unstable angina, a recent history of MI or acute heart failure, or an LVEF <40% were excluded.

Biomarkers were normal at baseline in virtually everyone; echocardiography was performed at baseline and at 18 and 24 weeks.

The patients received up to six courses of chemotherapy, each three weeks apart and preceded and followed by measurements of BNP and troponin I; 71 patients completed all six courses.

Eleven patients experienced cardiac events over a median of six months; the events included symptomatic heart failure in five, symptomatic arrhythmias in four, and ACS in two patients. All 11 had BNP levels >150 pg/mL on at least one occasion.

Unadjusted odds ratio (OR) for a cardiac event (95% CI) by BNP and LVEF finding

Risk factor OR (95% CI) p
1 BNP test >200 pg/mL 88 (10–761) <0.0001
2 BNP tests >150 pg/mL 23 (5–97) <0.0001
2 BNP tests >100 pg/mL 18 (4–88) 0.0005
LVEF indicative of cardiotoxicity 2.2 (0.1–9) 0.29

Troponin levels remained normal in all but two patients, both of whom were among those experiencing cardiac events.

In multivariate analysis, significant predictors of cardiac events included BNP levels >100 pg/mL, >150 pg/mL, and >200 pg/mL (p <0.0001 for each) prior to any such event. History of MI also emerged as a significant predictor (p=0.05), but it's hard to make anything of it, since it was present in only four patients, Lenihan said.

Most studies in oncology assess cardiotoxicity according to echocardiographic changes in LV function, he said; but a decline in LVEF considered indicative of cardiotoxicity was nota significant predictor of events in this study (p=0.376).

Whether elevated BNP levels by themselves are enough to justify stopping anthracycline chemotherapy remains an open question, according to Lenihan. They can help, he said, but it would depend on the patient's entire clinical picture. "I think it's a marker of risk. It doesn't necessarily mean you have to stop therapy, but it definitely identifies a group you should be more worried about."

Lenihan reports being a consultant for St Jude Medical and receiving honoraria from Novartis.

  1. Lenihan DJ, Massey MR, Baysinger KB, et al. Superior detection of cardiotoxicity during chemotherapy using biomarkers. J Cardiac Failure 2007; 13(Supple 2):S151. Heart Failure Society of America 2006 Scientific Meeting; September 17, 2007; Washington, DC. Abstract 265.

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