Echocardiography in Breast Cancer Patients and HF Symptoms
What are the changes in echocardiographic parameters of left ventricular (LV) structure, function, and ventricular-arterial (VA) coupling among patients treated for breast cancer, and are there associations between these parameters and LV ejection fraction (LVEF) or heart failure (HF) symptoms?
In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin, trastuzumab, or both, 1,249 echocardiograms were obtained over a median follow-up interval of 2.0 years (interquartile range, 1.0-3.0 years). Measures of LV structure (LV end-diastolic volume and end-systolic volume, mass, and relative wall thickness); LV contractile function (LVEF, end-systolic elastance [Eessb]; longitudinal, circumferential, and radial strain); LV diastolic function (E/e’); and VA coupling (effective arterial elastance [Ea]) were quantified in a core laboratory blinded to participant characteristics. Changes in echocardiographic parameters were evaluated over time, and repeated-measures regression models were used to define their association with LVEF decline and recovery. Linear regression models were used to define the association between early changes in these parameters and subsequent changes in LVEF and HF symptoms.
Overall, 177 patients (64%) received doxorubicin; 51 (18%) received trastuzumab; and 49 (18%) received doxorubicin + trastuzumab. With doxorubicin, there was a sustained, modest decrease in LVEF over the follow-up duration (1-year change in LVEF, -3.6%; 95% confidence interval [CI], -4.4% to -2.8%; 3-year change, -3.8%; 95% CI, -5.1% to -2.5%). With trastuzumab, a similar LVEF decline was observed at 1 year (-4.5%; 95% CI, -6.0% to -2.9%) and 3 years (-2.8%; 95% CI, -5.3 to -0.4%). Participants receiving doxorubicin + trastuzumab demonstrated the greatest declines at 1 year (-6.6%; 95% CI, -8.2 to -5.0%), with partial recovery at 3 years (-2.8%; 95% CI, -4.8 to -0.8%). LVEF declines and recovery were associated primarily with changes in systolic volumes; longitudinal and circumferential strain; and VA coupling indices effective arterial elastance (Ea) and the coupling ratio Ea/Eessb, without evidence for effect modification across therapies. Early changes in volumes, strain, and Ea/Eessb at 4-6 months were associated with 1- and 2-year LVEF changes. Similarly, early changes in strain and Ea were associated with worsening HF symptoms at 1 year.
Doxorubicin and trastuzumab resulted in modest, persistent declines in LVEF at 3 years. Changes in volumes, strain, and VA coupling were consistently associated with concurrent and subsequent LVEF declines and recovery across therapies.
The development of and assessment for cardiovascular disease among patients receiving chemotherapy for breast cancer can be a challenge. In this study of patients receiving doxorubicin and/or trastuzumab, echocardiographic measures of LV volumes, strain, and VA coupling were consistently associated with concurrent changes in LVEF. Of interest will be whether it is possible to predict (and therefore potentially alter therapy to avoid) future change in LVEF, future development of HF symptoms, or future permanent LV dysfunction.
Keywords: Breast Neoplasms, Cardiotoxicity, Diagnostic Imaging, Diastole, Doxorubicin, Echocardiography, Heart Failure, Stroke Volume, Systole, Ventricular Function, Left
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