| Subject | beta adrenergic receptor blocking agent; brain natriuretic peptide; C reactive protein; cyclophosphamide; dipeptidyl carboxypeptidase inhibitor; doxorubicin; epidermal growth factor receptor 2; fluorouracil; trastuzumab; troponin T; adult; breast cancer; cancer adjuvant therapy; cardiomyopathy; cardiotoxicity; cardiovascular magnetic resonance; clinical article; diagnostic imaging; drug efficacy; drug safety; drug withdrawal; female; heart failure; heart left ventricle ejection fraction; heart left ventricle endsystolic volume; heart left ventricle failure; sensitivity and specificity; transthoracic echocardiography; treatment duration; treatment response; adult; antibodies, monoclonal; biological markers; breast neoplasms; C-reactive protein; echocardiography, doppler; heart; magnetic resonance imaging, cine; middle aged; natriuretic peptide, brain; peptide fragments; receptor, erbB-2; risk assessment; sensitivity and specificity; troponin T; ventricular dysfunction, left |
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| Abstract | Objectives: The aim of this study was to evaluate whether cardiac biomarkers, tissue velocity (TVI) and strain imaging, and cardiac magnetic resonance imaging can predict early left ventricular (LV) dysfunction in human epidermal growth factor receptor IIpositive breast cancer patients treated with trastuzumab in the adjuvant setting. Background: Early indexes of LV systolic dysfunction with noninvasive cardiac imaging would be useful for addressing the cardiac safety profile of trastuzumab, potentially avoiding the detrimental effects of heart failure. Methods: We used cardiac biomarkers, TVI and strain imaging, and cardiac magnetic resonance imaging to detect pre-clinical changes in LV systolic function, before conventional changes in left ventricular ejection fraction (LVEF) in human epidermal growth factor receptor IIpositive breast cancer patients treated with trastuzumab in the adjuvant setting. Results: Of 42 patients (mean age 47 ± 9 years) prospectively followed between 2007 and 2009, 10 (25%) developed trastuzumab-mediated cardiomyopathy (CM). Troponin T, C-reactive protein, and brain natriuretic peptide did not change over time. Within 3 months of adjuvant therapy with trastuzumab, there was a significant difference in the lateral S′ between the normal cohort and the CM group (9.1 ± 1.6 cm/s and 6.4 ± 0.6 cm/s, respectively, p < 0.05). Similarly, the peak global longitudinal and radial strain decreased as early as 3 months in the trastuzumab-mediated cardiotoxicity group. As compared with both global longitudinal and radial strain, only S′ was able to identify all 10 patients who developed trastuzumab-mediated CM. The LVEF subsequently decreased at 6 months of follow-up in all 10 patients, necessitating discontinuation of the drug. All 10 patients demonstrated delayed enhancement of the lateral wall of the LV within the mid-myocardial portion, consistent with trastuzumab-induced CM. Conclusions: Both TVI and strain imaging were able to detect pre-clinical changes in LV systolic function, before conventional changes in LVEF, in patients receiving trastuzumab in the adjuvant setting. © 2011 American College of Cardiology Foundation. |
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