A 34-year-old African American woman with no significant past medical history was diagnosed with Stage 1A ER-positive, HER2/neu-positive infiltrating ductal carcinoma of the right breast. She underwent six cycles of taxotere/carboplatin/trastuzumab/pertuzumab, had a double mastectomy, and was subsequently placed on trastuzumab. She began having regular echocardiograms to monitor for potential cardiotoxic effects of chemotherapy at the start of her cancer treatment. Her left ventricular (LV) function, as measured by LV ejection fraction (LVEF), and strain parameters [global longitudinal strain (GLS) and global circumferential strain] all remained normal until 3 months after starting trastuzumab. At that time, her LVEF decreased to 47%, and the GLS increased to -12%. She was asymptomatic during this time and had no evidence of heart failure (HF) or volume overload on physical exam. She was initiated on low-dose beta-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy. Trastuzumab was withheld for two doses. Initial repeat echocardiograms showed improvement in LVEF and strain parameters. She remained on beta-blocker and ACEI therapy throughout the remainder of her cancer therapy; all subsequent echocardiograms also demonstrated normal LVEF and strain parameters (Table 1).
LVEF (Biplane Simpson's Method %)
Global Circumferential Strain (%)
After initiation of HF therapy and interruption of trastuzumab for 2 doses
Resumption of trastuzumab with continuation of HF therapies
Imaging performed on Philips Ultrasound Machine (Koninklijke Philips N.V., Amsterdam, Netherlands)
During chemotherapy, what percent change in GLS is considered abnormal and suggestive of subclinical LV dysfunction?
The correct answer is: D. 16%
Deformation indices like strain and strain rate have been shown to predict subclinical LV dysfunction in anthracycline- and trastuzumab-based chemotherapy. GLS, in particular, is considered the ideal parameter to follow over time to demonstrate if a change has taken place subsequent to cancer therapy. Most commonly, a reduction in deformation indices precedes a decrease in LVEF and can even be seen hours after chemotherapy administration. Current guidelines suggest that changes in GLS of <8% are unlikely to be significant; a reduction in GLS of >15% is more likely to be clinically relevant. It is important to note that measurements should be made on the same echocardiography machine to ensure that changes in GLS are not simply due to a change in the imaging platform. Of note, it is not yet clear what the long-term consequences of changes in strain and strain rate mean for patients clinically. In this case, the patient's strain parameters and LVEF returned to normal, which is seen commonly in patients diagnosed with chemotherapy-related cardiac dysfunction from trastuzumab who are placed on anti-remodeling therapy. These patients often return to their baseline cardiac status and then remain clinically stable despite re-challenge with trastuzumab in the future.
Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2014;27:911-39.
Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH. Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol 2014;63:2751-68.