Are the cardiovascular side effects of bevacizumab caused by autonomic nervous system toxicity?

Abstract

429 Background: Bevacizumab, a monoclonal antibody that inhibits the activity of vascular endothelial growth factor, has demonstrated activity against several malignancies. Reported adverse effects include hypertension, endothelial dysfunction, and heart failure. Animal models have suggested ANS toxicity as the mechanism. This pilot study investigates the effects of bevacizumab on short and long-term ANS function using a pre-post intervention design protocol. We report on the acute effects herein. Methods: Patients were recruited among those starting bevacizumab for colon cancer. A 10-minute ECG was recorded prior to, during, and following a first dose and analysed for heart rate variability (HRV), a marker of ANS dysfunction. The HRV values were compared using paired t-tests and repeated measures ANOVA. Plasma hormones were drawn before and after infusion and compared using paired t-tests. Results: Nine patients without a cardiac history were tested. Mean age was 63 years and 5 were male. All were in sinus rhythm with normal systolic function by echo. The Table reports changes in HRV indices and plasma hormones. Conclusions: Acute administration of bevacizumab produced a statistically significant decrease in plasma aldosterone and was associated with a trend towards decreases in plasma norepinephrine and the low/high frequency domain ratio of HRV. These changes may be signs of an early ANS imbalance. Both a larger patient series and longer follow-up are planned to characterize the effects of bevacizumab on the ANS. [Table: see text]