Low to Moderate Dose Anthracycline-Based Chemotherapy Is Associated With Early Noninvasive Imaging Evidence of Subclinical Cardiovascular Disease

Abstract

Objective To determine if low to moderate doses of anthracycline-based chemotherapy (Anth-bC) are associated with subclinical cardiovascular (CV) injury. Background Cancer survivors that receive Anth-bC experience premature CV events. It is unknown whether low to moderate doses of anthracyclines a) promote early subclinical CV disease manifested by deteriorations in left ventricular ejection fraction (LVEF) or increases in aortic stiffness, or b) are associated with change 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 (PWV), late gadolinium enhancement, serum B-type natriuretic peptide (BNP), troponin I (TnI), 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 19–80) years in age, 58% were women, 17% were black, and they each received a range of 50 to 375 mg/m2 of doxorubicin equivalent chemotherapy. Left ventricular end systolic volume (LVESV; 48±3 to 54±3 ml; p=0.02), left ventricular strain (−17.7±0.4 to −15.1±0.4; p=0.0003), PWV (6.7±0.5 to 10.1±1 m/sec; p=0.0006), and QOL deterioration (15.4±3.3 to 28.5±3.9; p=0.008) increased, while 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 Low to moderate doses of Anth-bC are 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.

Expert Consensus for Multimodality Imaging Evaluation of Adult Patients during and after Cancer Therapy: A Report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

“…In the study revealed a rate of sub-clinical LV dysfunction (LVEF , 50%) of Expert consensus for multimodality imaging evaluation of adult patients 26% at 6 months of follow-up after therapy. 233 As a result, this committee recommends follow-up at the completion of therapy for regimens including doses ,240 mg/m 2 . After exceeding the dose of 240 mg/m 2 , an evaluation before each additional cycle is considered prudent (Figures 13 and 15).…”

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

“…Najpowszechniej akceptowanym patofizjologicznym mechanizmem kardiotoksyczności wywoływanej przez antracykliny jest hipoteza stresu oksydacyjnego, zgodnie z którą wytwarzanie wolnych rodników tlenowych i peroksydacja lipidów błony komórkowej powodują uszkodzenie kardiomiocytów. Uważa się, że rolę mogą odgrywać również inne mechanizmy [26][27][28][29][30][31]. Mechanizmy komórkowe i molekularne szczegółowo omówiono w dwóch pracach przeglądowych na ten temat [32,33].…”

“…W przypadku schematów terapii obejmujących większe dawki antracyklin oraz u pacjentów z dużym początkowym ryzykiem proponuje się wcześniejszą ocenę czynności serca po podaniu łącznej dawki 240 mg/m 2 doksorubicyny (lub dawki równoważnej, patrz tab. 5) [10,31,85]. Początkowo można rozważyć oznaczenie co najmniej jednego biomarkera sercowego -troponiny (I lub T) oznaczanej metodą o dużej czułości lub peptydu natriuretycznego, a pomiar stężenia troponiny I metodą o dużej czułości proponuje się po każdym cyklu chemioterapii obejmującej antracykliny [86,87].…”

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.…”