Abstract

Cardiotoxicity is a dose-limiting side-effect of cancer chemotherapeutics such as anthracyclines. The drug-induced cardiac toxicity is currently monitored with repeated assessments of the left ventricular ejection fraction (LVEF) using multigated equilibrium radionuclide ventriculography (MUGA) or echocardiography. However, the plasma cardiac biomarker B-type natriuretic peptide (BNP) has been suggested for early identification of cardiac dysfunction. The aim of the study was to compare LVEF obtained by MUGA and plasma BNP as predictors of developing congestive heart failure (CHF) or death in a population of anthracycline-treated cancer patients.MethodsWe prospectively followed 333 cancer patients referred to our department for routine monitoring of LVEF with MUGA and measurement of BNP, January-December 2004. Study end points were hospitalization for CHF and death during follow-up 2004-2010. Data were obtained from the Danish National Patient Registry.ResultsDuring follow-up (mean 1,360 days), 21 of the patients were admitted to hospital with a diagnosis of CHF and 194 of the patients died. BNP levels were significantly higher and LVEF lower in the group of patients that developed CHF. Using cut-off points of BNP>100 pg/ml (HR 5.5; CI 1.8–17.2; p = 0.003) and LVEF <50% (HR 7.9; CI 3.0–21.4; p<0.001) both significantly predicted CHF. Using the same cut-off points only BNP (HR 1.9; CI 1.3-2.9; p = 0.002) and not LVEF (HR 1.1; CI 0.7–1.8; p = 0.58) was predictive of overall death. In multivariate Cox analysis both BNP and LVEF were independent predictors of CHF while age remained the only independent predictor of overall death.ConclusionIn cancer patients treated with cardiotoxic chemotherapy both BNP and LVEF can significantly predict subsequent hospitalization with CHF. In addition, BNP and not LVEF has a prognostic value in detecting overall death. This prospective study based on the hitherto largest study population supports BNP as a clinical relevant method for monitoring chemotherapy-related cardiac failure and death.

Highlights

  • Cardiotoxicity associated with intensive chemotherapy affects life quality and overall survival of cancer patients

  • In cancer patients treated with cardiotoxic chemotherapy both B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) can significantly predict subsequent hospitalization with congestive heart failure (CHF)

  • BNP levels were significantly increased and LVEF were significantly lower in the group of patients that were subsequently admitted to hospital for CHF

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Summary

Introduction

Cardiotoxicity associated with intensive chemotherapy affects life quality and overall survival of cancer patients. The most common way to prevent the immediate chemotherapy-induced cardiotoxicity from leading to irreversible congestive heart failure (CHF) is to monitor cardiac function during and following treatment by estimating left ventricular ejection fraction (LVEF) using radionuclide ventriculography or echocardiography and if cardiac impairment is detected, treatment dose are lowered or cardioprotectants are added. Assessment of LVEF is limited by an inability to detect early changes that can predict late declines in cardiac function and there has been a growing interest in identifying circulating biomarkers as reproducible, sensitive and cost effective ways to identify patients in the risk of developing chemotherapyrelated cardiomyopathy [2,3,4].

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