The Utility of Cardiac Biomarkers, Tissue Velocity and Strain Imaging, and Cardiac Magnetic Resonance Imaging in Predicting Early Left Ventricular Dysfunction in Patients With Human Epidermal Growth Factor Receptor II–Positive Breast Cancer Treated With Adjuvant Trastuzumab Therapy

Study Questions:

What is the predictive value of cardiac biomarkers, tissue velocity (TVI) and strain imaging, and cardiac magnetic resonance imaging to identify early left ventricular (LV) dysfunction in human epidermal growth factor receptor II–positive breast cancer patients treated with trastuzumab in the adjuvant setting?

Methods:

The investigators used cardiac biomarkers, TVI and strain imaging, and cardiac magnetic resonance imaging to detect preclinical changes in LV systolic function, before conventional changes in LV ejection fraction (LVEF) in human epidermal growth factor receptor II–positive breast cancer patients treated with trastuzumab in the adjuvant setting. Receiver-operator characteristic curve analysis was applied to determine cutoff values, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for S’, longitudinal strain, and radial strain measurements.

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:

The authors concluded that both TVI and strain imaging were able to detect preclinical changes in LV systolic function, before conventional changes in LVEF, in patients receiving trastuzumab in the adjuvant setting.

Perspective:

The current study suggests that cardiac biomarkers did not predict the development of cardiac dysfunction, but both TVI and strain imaging were able to detect preclinical changes in LV systolic function, before conventional changes in LVEF. Early detection of trastuzumab-mediated cardiotoxicity may allow one to adjust treatment and/or the prophylactic administration of cardioprotective agents, before the development of irreversible cardiac dysfunction. Given the small sample size of the current study, a larger population with longer follow-up is indicated to substantiate these findings.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Novel Agents, Heart Failure and Cardiac Biomarkers, Magnetic Resonance Imaging

Keywords: Antibodies, Monoclonal, Humanized, Follow-Up Studies, Biological Markers, Cardiomyopathies, Breast Neoplasms, Ventricular Dysfunction, Left, Magnetic Resonance Imaging, Systole, Cardiotonic Agents, Receptor, Epidermal Growth Factor


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