Aortic stiffness increases upon receipt of anthracycline chemotherapy

Abstract

PURPOSE Cancer survivors exposed to anthracyclines experience an increased risk of cardiovascular (CV) events. We hypothesized that anthracycline use may increase aortic stiffness, a known predictor of CV events. PATIENTS AND METHODS We performed a prospective, case-control study involving 53 patients: 40 individuals who received an anthracycline for the treatment of breast cancer, lymphoma, or leukemia (cases), and 13 age- and sex-matched controls. Each participant underwent phase-contrast cardiovascular magnetic resonance measures of pulse wave velocity (PWV) and aortic distensibility (AoD) in the thoracic aorta at baseline, and 4 months after initiation of chemotherapy. Four one-way analyses of covariance models were fit in which factors known to influence thoracic aortic stiffness were included as covariates in the models. Results At the 4-month follow-up visit, aortic stiffness remained similar to baseline in the control participants. However, in the participants receiving anthracyclines, aortic stiffness increased markedly (relative to baseline), as evidenced by a decrease in AoD (P < .0001) and an increase in PWV (P < .0001). These changes in aortic stiffness persisted after accounting for age, sex, cardiac output, administered cardioactive medications, and underlying clinical conditions known to influence aortic stiffness, such as hypertension or diabetes (P < .0001). CONCLUSION A significant increase in aortic stiffness occurs within 4 months of exposure to an anthracycline which was not seen in an untreated control group. These results indicate that previously regarded cardiotoxic cancer therapy adversely increases thoracic aortic stiffness, a known independent predictor of adverse cardiovascular events.

Fig 1.

(A) Sagittal magnitude image of the thoracic aorta was used to select the axial plane at the level of pulmonary artery and perpendicular to aortic flow (solid white line). The distance between ascending and descending thoracic aorta was obtained by tracing the centerline of the aortic lumen (red line). The two velocity–time curves are shown across the thoracic aorta. The sagittal magnitude image demonstrates the velocity–time curves for the ascending and descending thoracic aorta. Transit time of the flow wave was computed on the basis of the upstroke time difference of the velocity–time curve at two different regions (blue line). The location of the best cross-correlation of two partial upstroke velocity curves was used to estimate the time delay. Pulse wave velocity (PWV) was calculated by dividing the distance between the ascending and descending thoracic aorta by the transit time of the flow wave. (B) After slice selection from the initial sagittal images, axial phase-contrast cardiovascular magnetic resonance of the ascending and proximal descending thoracic aorta was obtained. From these images, maximum and minimum aortic areas over the cardiac cycle were determined by manually tracing the region of interest (red boundaries). Distensibility was then calculated by dividing relative change in aortic area by pulse pressure multiplied by the resting area at end-diastole.

Fig 2.

Results of ascending aortic distensibility for the control participants (A) and the participants receiving cancer therapy (B). As shown, the aortic distensibility decreased in participants receiving cancer therapy.

Fig 3.

Pulse wave velocity (PWV) results for the control participants (A) and the participants receiving cancer therapy (B). PWV increased in participants receiving cancer therapy.