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Changes in LV Diastolic Function and Breast Cancer Therapy
Study Questions:
What is the incidence of diastolic dysfunction in patients with breast cancer undergoing chemotherapy?
Methods:
The authors used for this study the Cardiotoxicity of Cancer Therapy (CCT), a prospective cohort of 362 adult women (median age 49 years, 70% white, 2% metastatic) with breast cancer undergoing chemotherapy with doxorubicin (60%), trastuzumab (23%), or both (17%), who underwent baseline and follow-up echocardiography (median of five echocardiograms per individual). Longitudinal changes in indices of diastolic dysfunction were examined: E/e’ as a continuous variable, 2) E/e’ >14 as a categorical variable, and 3) incident diastolic function, as defined by the 2016 American Society of Echocardiography guidelines. The authors also assessed whether diastolic indices were associated with subsequent systolic dysfunction. Analyses were done separately for each treatment regimen.
Results:
A total of 94 (26%) participants had abnormal diastolic function grade at baseline (24% grade 1, 1.3% grade 2, 0.6% grade 3, and 21% indeterminate). Over a median follow-up of 2.1 years (interquartile range, 1.1-4.1 years), incident diastolic dysfunction developed in 184 of 258 participants with normal or indeterminate diastolic function grade at baseline. A total of 18 participants (5%) developed an abnormal E/e’ ratio >14 at follow-up. Baseline predictors of incident diastolic dysfunction varied depending on the outcome (grade or E/e’ ratio). Changes in diastolic indices were only significant in patients on doxorubicin-containing regimens. Baseline abnormal diastolic function alone (grade >0) was not associated with a significant change in systolic function at follow-up. However, a worsening in diastolic function grade from baseline was associated with a 1.4% decrease in left ventricular ejection fraction (LVEF) from baseline (p = 0.006) and increased the hazard of subsequent cardiotoxicity (LVEF decline of 10% to below 50%, hazard ratio, 2.2; 95% confidence interval, 1.1-4.3).
Conclusions:
Contemporary breast cancer therapy is associated with a modest worsening in diastolic dysfunction. Worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction.
Perspective:
The study of cancer therapy–related cardiotoxicity has long focused on changes in systolic function and longitudinal strain. This study is important in that it is the first to examine changes in diastolic indices associated with doxorubicin and trastuzumab in patients with breast cancer. The assessment of diastolic dysfunction is, however, challenging and requires combining history and physical exam with echocardiography to determine whether abnormal indices of diastolic function are clinically meaningful. The current study focuses solely on echocardiographic findings of diastolic function and highlights the following: 1) changes in diastolic indices do occur with cardiotoxic regimens, but 2) these indices vary widely with time, and 3) are associated with only a small increase in the risk of subsequent systolic dysfunction. Determining whether changes in these indices are clinically meaningful warrants a study with larger sample sizes and hard outcomes.
Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Echocardiography/Ultrasound
Keywords: Breast Neoplasms, Cardiotoxicity, Diagnostic Imaging, Diastole, Doxorubicin, Echocardiography, Heart Failure, Systole, Ventricular Dysfunction
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