Clinical Research
Imaging and Biomarkers
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

https://doi.org/10.1016/j.jacc.2010.11.063Get rights and content
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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 II–positive 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 II–positive 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.

Key Words

biomarkers
breast cancer
cardiac MRI
cardiomyopathy
doxorubicin
strain
tissue velocity imaging
trastuzumab

Abbreviations and Acronyms

a′
late diastolic annular velocity of the lateral wall
AC
adriamycin and cyclophosphamide
BNP
brain natriuretic peptide
CHF
congestive heart failure
CM
cardiomyopathy
CRP
C-reactive protein
CV
coefficient of variation
e′
early diastolic annular velocity of the lateral left ventricular wall
FEC
fluorouracil, epirubicin, and cyclophosphamide
LGE
late gadolinium enhancement
LV
left ventricle/ventricular
LVEF
left ventricular ejection fraction
MRI
magnetic resonance imaging
NPV
negative predictive value
PPV
positive predictive value
S′
systolic annular velocity of the lateral left ventricular wall
TnT
troponin T
TTE
transthoracic echocardiography
TVI
tissue velocity imaging

Cited by (0)

The present study was supported by the Manitoba Medical Services Foundation, St. Boniface General Hospital and Research Foundation, and the Health Sciences Centre Research Foundation. Mr. Walker is a recipient of the Manitoba Health and Research Council studentship award. Dr. Singal is the holder of the Naranjan S. Dhalla chair in Cardiovascular Research supported by the St. Boniface Hospital and Research Foundation. Dr. Jassal is the recipient of the Heart and Stroke Foundation New Investigator award. All other authors have reported that they have no relationships to disclose.