Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

Abstract

Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF). It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007). Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab) (Genetech, Inc. 2008). This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG) and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical) atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.

Keywords: bevacizumab; cardiomyopathy; chemotherapy; metastatic cancer; takotsubo; vascular endothelial growth factor.

Figure 1

The ECG for case one demonstrated prominent ST elevations in the anterior and inferior leads.

Figure 2

In case one, noncritical, distal lesions of the right coronary artery (RCA) (a) and noncritical atherosclerotic lesions of the left main coronary artery (b) did not correspond with the wall motion abnormality observed on ventriculography. In case two, there was no evidence of coronary arterial stenosis of either the RCA (c) or the left anterior descending artery (d).

Figure 3

In the second case, the ECG was notable for new Q-waves in inferior and precordial leads as well as ST elevation suggestive of acute ischemia or injury in the anterior-septal leads.

Figure 4

(a) This image is a left ventriculogram obtained during systole in the first patient. Hypercontractility of the basal segment and akinesis of the apical segment create the apical ballooning effect. (b) The ventriculogram obtained in the second case also demonstrates apical ballooning.