title: Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy.
abstract: Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise "stress" is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to -17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (-16.1 ± 0.9 vs. -20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 l min(-1) m(-2) mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0.001). Resting 3DE, GLS, and exercise stress 2DE detect subclinical cardiac dysfunction not apparent with resting 2DE in post-DOX breast cancer patients.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Box 3085, Durham, NC, 27710, USA.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Khouri
authors.forename: Whitney E
authors.initials: WE
authors.lastname: Hornsby
authors.forename: Niels
authors.initials: N
authors.lastname: Risum
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
authors.forename: Samantha
authors.initials: S
authors.lastname: Thomas
authors.forename: Amy
authors.initials: A
authors.lastname: Lane
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Scott
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Koelwyn
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Douglas
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D025401:Echocardiography, Stress / Q000379:methods; D005080:Exercise Test / Q000379:methods; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged
chemical_list: D004317:Doxorubicin