Detailed Echocardiographic Phenotyping in Breast Cancer Patients: Associations with Ejection Fraction Decline, Recovery, and Heart Failure Symptoms over 3 Years of Followup
Background—Cardiovascular disease in breast cancer patients is of growing concern. The longitudinal effects of commonly used therapies, including doxorubicin and trastuzumab, on cardiac remodeling and function remain unknown in this population. We sought to define the changes in echocardiographic parameters of structure, function, and ventricular-arterial (VA) coupling, and their associations with left ventricular ejection fraction (LVEF) and heart failure (HF) symptoms.
Methods—In a longitudinal prospective cohort study of 277 breast cancer participants receiving doxorubicin (Dox), trastuzumab (Tras), or both (Dox+Tras), we obtained 1,249 echocardiograms over a median followup of 2.0 (interquartile range 1.0,3.0) years. LV structure; diastolic and contractile function; and VA coupling measures were quantified in a core laboratory blinded to participant characteristics. We evaluated changes in echocardiographic parameters over time, and used repeated-measures regression models to define their association with LVEF decline and recovery. Linear regression models defined the association between early changes in these parameters and subsequent changes in LVEF and HF symptoms.
Results—Overall, 177 (64%) received Dox; 51 (18%) Tras; and 49 (18%) Dox+Tras. With Dox, there was a sustained, modest decrease in LVEF over the followup duration (1-year change in LVEF -3.6%, 95% Confidence Interval [CI] -4.4%,-2.8%; 3-year change -3.8%, 95%CI -5.1%, -2.5%). With Tras, a similar LVEF decline was observed at 1 year (-4.5%, 95%CI -6.0%,-2.9%) and 3 years (-2.8%, 95%CI -5.3,-0.4%). Participants receiving Dox+Tras demonstrated the greatest declines at 1 year (-6.6%, 95%CI -8.2,-5.0%), with partial recovery at 3 years (-2.8%, 95%CI -4.8,-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 to 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.
Conclusions—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.
- Received May 12, 2016.
- Revision received January 4, 2017.
- Accepted January 13, 2017.