Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease

Abstract

Objectives: The goal of this study was to determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury.

Background: Cancer survivors who receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or if these doses are associated with changes in quality of life (QOL).

Methods: In 53 men and women with breast cancer, leukemia, or lymphoma, we assessed left ventricular volumes, LVEF, circumferential strain, aortic pulse wave velocity, late gadolinium enhancement, serum B-type natriuretic peptide, troponin I, and the impact of treatment on QOL before and 1, 3, and 6 months after receipt of Anth-bC.

Results: Participants averaged 50 ± 2 (range 19 to 80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m(2) of doxorubicin-equivalent chemotherapy. Left ventricular end-systolic volume (48 ± 3 ml to 54 ± 3 ml; p = 0.02), left ventricular strain (-17.7 ± 0.4 to -15.1 ± 0.4; p = 0.0003), pulse wave velocity (6.7 ± 0.5 m/s to 10.1 ± 1 m/s; p = 0.0006), and QOL deterioration (15.4 ± 3.3 to 28.5 ± 3.9; p = 0.008) increased, whereas LVEF (58 ± 1% to 53 ± 1%; p = 0.0002) decreased within 6 months after low to moderate doses of Anth-bC. All findings persisted after accounting for age, gender, race (white/black), doxorubicin-equivalent dose, doxorubicin administration technique, comorbidities associated with CV events, and cancer diagnosis (p = 0.02 to 0.0001 for all). There were no new late gadolinium enhancement findings after 6 months.

Conclusions: In these study patients, low to moderate doses of Anth-bC were associated with the early development of subclinical abnormalities of cardiac and vascular function that in other populations are associated with the future occurrence of CV events.

Keywords: Anth-bC; B-type natriuretic peptide; BNP; CMR; CV; LVEDV; LVEF; LVESV; MLHFQ; Minnesota Living with Heart Failure Questionnaire; PWV; QOL; TE; TR; TnI; anthracycline-based chemotherapy; cardiac magnetic resonance; cardio-oncology; cardiotoxicity; cardiovascular; chemotherapy; echo time; left ventricular ejection fraction; left ventricular end-diastolic volume; left ventricular end-systolic volume; pulse wave velocity; quality of life; repetition time; troponin I.

Figure 1

Time dependent changes in left ventricular end diastolic volume (LVEDV) (left y-axis; panel A) and left ventricular end systolic volume (LVESV) (right y-axis; panel A); in left ventricular ejection fraction (LVEF) (left y-axis; panel B) and mean mid wall circumferential strain (right y-axis; panel B). The mean ± the standard error are shown. There was a significant increase in LVESV and mean mid-wall circumferential strain while at the same time a decrease in LVEF from baseline to 6 months after administration of low to moderate doses of anthracycline-based chemotherapy.

Figure 1

Time dependent changes in left ventricular end diastolic volume (LVEDV) (left y-axis; panel A) and left ventricular end systolic volume (LVESV) (right y-axis; panel A); in left ventricular ejection fraction (LVEF) (left y-axis; panel B) and mean mid wall circumferential strain (right y-axis; panel B). The mean ± the standard error are shown. There was a significant increase in LVESV and mean mid-wall circumferential strain while at the same time a decrease in LVEF from baseline to 6 months after administration of low to moderate doses of anthracycline-based chemotherapy.

Figure 2

Time dependent changes in pulse wave velocity (y-axis). The mean ± the standard error are shown. There was a significant increase in pulse wave velocity from baseline to 6 months after administration of low to moderate doses of anthracycline-based chemotherapy.

Figure 3

Time dependent changes in quality of life (QOL) assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The total point mean ± the standard error are shown. There was a significant increase in the total score, indicating a negative impact on QOL, from baseline to 1 month after administration of low to moderate doses of anthracycline-based chemotherapy that was maintained through 6 months.

Figure 4

Changes in left ventricular ejection fraction (LVEF; y-axis; panel A) and pulse wave velocity (PWV; y-axis; panel B) versus the cumulative doses of doxorubicin equivalent (x-axes; panels A and B). Each symbol represents data from a participant, and the regression line and equations are shown for each panel. No association between changes in LVEF or PWV and the doses of doxorubicin equivalent chemotherapy were observed.

Figure 4

Changes in left ventricular ejection fraction (LVEF; y-axis; panel A) and pulse wave velocity (PWV; y-axis; panel B) versus the cumulative doses of doxorubicin equivalent (x-axes; panels A and B). Each symbol represents data from a participant, and the regression line and equations are shown for each panel. No association between changes in LVEF or PWV and the doses of doxorubicin equivalent chemotherapy were observed.