Aortic Stiffness Increases Upon Receipt of Anthracycline Chemotherapy

Abstract

A B S T R A C T PurposeCancer 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 MethodsWe 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 ageand 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. ResultsAt 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 Ͻ .0001) and an increase in PWV (P Ͻ .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 Ͻ .0001). ConclusionA 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.

Ventricular-Arterial Coupling in Breast Cancer Patients After Treatment With Anthracycline-Containing Adjuvant Chemotherapy

“…Increased aortic stiffness [3,4], endothelial dysfunction [5], and arterial remodeling [6] have been reported up to 1 year following Anth-C administration. However, in the present study and contrary to our hypothesis, Ea was not different at rest or during any stage of exercise.…”

“…To date, investigators have focused almost exclusively on the cardiac-specific effects of Anth-C (primarily through evaluation of resting assessment of left ventricular ejection fraction [LVEF]), with minimal attention to vascular damage. Increased aortic stiffness [3,4], endothelial dysfunction [5], and arterial remodeling [6] have been demonstrated during or up to 1 year following Anth-C. However, whether these impairments in vascular structure (e.g., arterial stiffness and carotid intimamedia thickness [CIMT]) and function (e.g., endothelialdependent flow-mediated dilation [FMD]) persist in the years following Anth-C and whether they contribute to the impaired cardiac function observed in breast cancer survivors is currently unknown.…”

Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

“…A significant increase in aortic stiffness was observed after 4 months of exposure to anthracyclines [93]. In addition, in childhood cancer survivors treated with chemotherapy, AS was increased compared with patients without cancer [94].…”

Chemotherapy-Induced Ovarian Failure as a Prototype for Acute Vascular Toxicity

“…Furthermore, brachial artery flow-mediated dilation in patients undergoing doxorubicin-based chemotherapy was markedly attenuated after a single dose of doxorubicin [25]. Recently, it was shown, using phase-contrast cardiovascular magnetic resonance measurements of pulse wave velocity and aortic distensibility, that anthracyclines induce a significant thoracic aorta stiffening in patients receiving anthracyclines, compared with age-and sex-matched controls [26]. Our study links the paradigm of ovarian vascular toxicity as a possible contributor to the etiology of chemotherapy-induced ovarian dysfunction, manifested by amenorrhea.…”