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.

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Background: Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined and the relevance of these findings to human disease is unclear.Methods and Results: Wild type mice were sacrificed one week after intraperitoneal administration of doxorubicin (1-25 mg/kg), revealing a dose-dependent decrease in cardiac mass (R 2 = 0.64, p < 0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336 ± 29 vs. 188 ± 14 μm 2 , p < 0.0001). Myocardial tissue analysis identified a dose-dependent #

Background Cardiovascular magnetic resonance (CMR) T1 mapping characteristics are elevated in adult cancer survivors; however, it remains unknown whether these elevations are related to age or presence of coincident cardiovascular comorbidities. Methods and Results We performed blinded CMR analyses of left ventricular (LV) T1 and extracellular volume fraction (ECV) in 327 individuals (65% women, aged 64±12 years). Thirty-seven (37) individuals had breast cancer or a hematologic malignancy but had not yet initiated their treatment, and 54 cancer survivors that received either anthracycline-based (n=37) or non-anthracycline-based (n=17) chemotherapy 2.8±1.3 years earlier were compared to 236 cancer-free participants. Multivariable analyses were performed to determine the association between T1/ECV measures and variables associated with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058±7 ms) and post- (1040±7 ms) receipt of anthracycline chemotherapy versus comparators (965±3 ms, p<0.0001 for both). Age-adjusted ECV, a marker of myocardial fibrosis, was elevated in anthracycline-treated cancer participants (30.4±0.7%) compared with either pre-treatment cancer (27.8±0.7%, p<0.01) or cancer-free comparators (26.9±0.2%, p<0.0001). T1 and ECV of non-anthracycline survivors was no different than pre-treatment survivors (p=0.17 and p=0.16, respectively). Native T1 and ECV remained elevated in cancer survivors after accounting for demographics (including age), myocardial fibrosis risk factors, and LV ejection fraction or myocardial mass index (p<0.0001 for all). Conclusions Three years after anthracycline-based chemotherapy, elevations in myocardial T1 and ECV occur independent of underlying cancer or cardiovascular comorbidities suggesting that imaging biomarkers of interstitial fibrosis in cancer survivors are related to prior receipt of a potentially cardiotoxic cancer treatment regimen.

Patients with or receiving potentially cardiotoxic treatment for cancer are susceptible to developing decrements in left ventricular mass, diastolic function, or systolic function. They may also experience valvular heart disease, pericardial disease, or intracardiac masses. Cardiovascular magnetic resonance may be used to assess cardiac anatomy, structure, and function and to characterize myocardial tissue. This combination of features facilitates the diagnosis and management of disease processes in patients with or those who have survived cancer. This report outlines and describes prior research involving cardiovascular magnetic resonance for assessing cardiovascular disease in patients with or previously having received treatment for cancer.