Methods
Temporal Variability of Global Longitudinal Strain in Stable Patients Undergoing Chemotherapy With Trastuzumab

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Global longitudinal strain (GLS) is used to evaluate left ventricular (LV) performance after chemotherapy. Differentiating between reduction in GLS due to clinical change and normal temporal variability in measurement remains a challenge. We quantified interobserver, test-retest variability of GLS by expert observers in relation to variability of GLS quantified for clinical assessment by sonographers in our laboratory. We examined the temporal variability of GLS in 30 patients with normal LV ejection fraction (LVEF >53%) undergoing chemotherapy in the absence of change in medications and clinical symptoms in up to 5 sequential echocardiograms. GLS was quantified using EchoPAC (GE Healthcare, Milwaukee, Wisconsin) and 2-dimensional biplane LVEF was measured from 4- and 2- chamber views. Interobserver test-retest variability of GLS measured in 10 random patients by 2 expert readers was calculated using a one-way analysis of variance. Square root of mean squared error provided the SEM for temporal variability. Baseline LVEF was 59.3 ± 5.1% and remained relatively unchanged over 12 months, p = 0.87. Temporal variability of GLS measured by sonographers was 1.28% and similar to interobserver test-retest variability of GLS measured by expert observers, 1.12% (p = 0.17). Maximum detectable difference in GLS measured by expert observers was similar to that derived from sequential measurements of GLS (3.2% vs 3.6%, respectively). Temporal variability of GLS among clinically stable patients is 1.28% and similar to interobserver test-retest variability of 1.12% measured by expert observers. In conclusion, a reduction in strain >3.2% during sequential echocardiograms under these conditions may be significant.

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Methods

This is a retrospective analysis of data from 30 consecutive female patients with a history of breast cancer who underwent chemotherapy with trastuzumab and echocardiography in our laboratory from June 2011 to December 2015. Patients were included if they satisfied the following criteria: (1) at least 3 sequential echocardiograms, including a baseline echocardiogram before treatment with each performed at 3-month intervals; (2) all echocardiography studies performed with Vivid 7 or E9 (GE

Results

Thirty women receiving trastuzumab were included with a mean age of 57.1 ± 11.3 years. Medications initiated before chemotherapy included β blockers (carvedilol or metoprolol) in 11 patients; angiotensin-converting enzyme inhibitors (lisinopril and ramipril) in 5 patients and statins in 4 patients (Table 1). None of the patients received insulin or antiplatelet medications including aspirin and clopidogrel (Bristol-Myers Squibb, Bridgewater, New Jersey). There were no changes of medications in

Discussion

Chemotherapy with HER2 antibodies for breast cancer has been documented to cause LV dysfunction. A reduction in GLS may represent one of the earliest signs of cardiotoxicity and may provide incremental value in identifying patients who would experience subsequent systolic dysfunction.6, 7, 8, 9, 10, 11 In a consensus document by the American Society of Echocardiography and European Association of Cardiovascular Imaging, subclinical LV dysfunction is defined as a relative reduction in GLS by

Disclosures

The authors have no conflicts of interest to disclose.

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Cited by (6)

Drs. Koneru and Collier equally contributed to this study.

Dr. Tamarappoo was supported by the American Heart Association Clinical Research Program: 11CRP5050015 and the NIH CTSA KL2 grant: 2KL2TR000440.

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