Cardiomyopathy
Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients

https://doi.org/10.1016/j.amjcard.2011.01.006Get rights and content

As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro–B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro–B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality.

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Methods

Patients >18 years of age diagnosed with HER-2-overexpressing breast cancer and either scheduled to receive treatment including anthracyclines and trastuzumab or scheduled to receive trastuzumab after previous anthracycline treatment were eligible. Patients with LVEFs <50% were excluded.

Patients were enrolled at 4 institutions. All patients signed informed consent forms, which were approved by the institutional review board of the participating institutions.

Patients were studied before

Results

Forty-five eligible consecutive women were prospectively enrolled in the study. One woman withdrew from the study and 1 was withdrawn because of negative HER-2 status on a second analysis. Therefore, a total of 43 women participated in the study. Ten women received anthracyclines before entering the study. The median delay time between the anthracycline treatment and the initial study time point was 3.5 months (range 2 to 144). There was no difference in the baseline or changes in the clinical

Discussion

In the present study, we report that in patients treated with a combination of anthracyclines and trastuzumab, an early decrease in myocardial strain or elevation in plasma troponin as detected with a high-sensitivity assay predicts the later occurrence of cardiotoxicity. Subsequent cardiotoxicity is not clearly predicted by early changes in the LVEF or NT-proBNP level.

Patients enrolled in our study experienced decreases in the LVEF of similar magnitude as those reported previously in patients

Acknowledgment

We would like to thank Laurie Farrell, RN, from the Cardiology Division for her help in the blood sampling and processing; Alisha Polewarczyk from the Gillette Center for Breast Cancer of Massachusetts General Hospital for her contribution in recruiting patients; Stephanie Fuoco, RN, from the Sir Mortimer B. Davis-Jewish General Hospital and McGill University and Jose Banchs, MD, Liza Sanchez, BS, and Mona Massey, RN, from the M.D. Anderson Cancer Center for coordinating patient enrollment; and

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Dr. Scherrer-Crosbie was supported by an investigator-initiated grant from the Susan G. Komen for the Cure Foundation, Dallas, Texas, a Claflin Distinguished Scholar Award, and a Clinical Innovation Award, Boston, Massachusetts. Dr. Ky was supported by the Kynett Focus Junior Faculty Investigator Award, Philadelphia, Pennsylvania.

Dr. Januzzi has received grant support from Roche Diagnostics GmbH, Mannheim, Germany, Siemens Medical Systems, Erlangen, Germany, and Critical Diagnostics, San Diego, California. Dr. Plana is on the speaker's bureau of GE Healthcare, Milwaukee, Wisconsin.

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