title: Ventricular-Arterial Coupling in Breast Cancer Patients After Treatment With Anthracycline-Containing Adjuvant Chemotherapy.
abstract: BACKGROUND
  Anthracycline-containing chemotherapy (Anth-C) is associated with long-term cardiovascular mortality. Although cardiovascular risk assessment has traditionally focused on the heart, evidence has demonstrated that vascular dysfunction also occurs during and up to 1 year following Anth-C. Whether vascular dysfunction persists long-term or negatively influences cardiac function remains unknown. Hence, the present study evaluated ventricular-arterial coupling, in concert with measures of vascular structure and function, in the years following Anth-C.
  
  
  METHODS
  Arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were measured during rest and exercise using echocardiography. Resting vascular function (flow-mediated dilation) and structure (carotid intima-media thickness, arterial stiffness) were also measured.
  
  
  RESULTS
  Thirty breast cancer survivors (6.5 ± 3.6 years after Anth-C) with normal left ventricular ejection fraction (LVEF) (60% ± 6%) and 30 matched controls were studied. At rest, no differences were found in Ea, Ees, Ea/Ees, or LVEF between groups. The normal exercise-induced increase in Ees was attenuated in survivors at 50% and 75% of maximal workload (p < .01). Ea/Ees was also higher at all workloads in the survivors compared with the controls (p < .01). No differences in vascular structure and function were observed between the two groups (p > .05).
  
  
  CONCLUSIONS
  In the years after Anth-C, ventricular-arterial coupling was significantly attenuated during exercise, primarily owing to decreased LV contractility (indicated by a reduced Ees). This subclinical dysfunction appears to be isolated to the heart, as no differences in Ea were observed. The previously reported adverse effects of Anth-C on the vasculature appear to not persist in the years after treatment, as vascular structure and function were comparable to controls.
  
  
  CONCLUSIONS
  Anthracycline-induced cardiotoxicity results in significantly impaired ventricular-arterial coupling in the years following chemotherapy, owing specifically to decreased left ventricular contractility. This subclinical dysfunction was identified only under exercise stress. A comprehensive evaluation of vascular structure and function yielded no differences between those treated with anthracyclines and controls. Combined with a stress stimulus, ventricular-arterial coupling might hold significant value beyond characterization of integrative cardiovascular function, in particular as a part of a risk-stratification strategy after anthracycline-containing chemotherapy. Although vascular function and structure were not different in this cohort, this does not undermine the importance of identifying vascular (dys)function in this population, because increases in net arterial load during exercise might amplify the effect of reductions in contractility on cardiovascular function after anthracycline-containing chemotherapy.
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Kelowna, British Columbia, Canada.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Koelwyn
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Kelowna, British Columbia, Canada.
authors.forename: Nia C
authors.initials: NC
authors.lastname: Lewis
authors.affiliation: British Columbia Cancer Agency-Southern Interior, Kelowna, British Columbia, Canada.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ellard
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Kelowna, British Columbia, Canada.
authors.forename: Jinelle C
authors.initials: JC
authors.lastname: Gelinas
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada Interior Health, Kelowna General Hospital, Kelowna, British Columbia, Canada.
authors.forename: J Douglass
authors.initials: JD
authors.lastname: Rolf
authors.affiliation: Interior Health, Kelowna General Hospital, Kelowna, British Columbia, Canada.
authors.forename: Bernie
authors.initials: B
authors.lastname: Melzer
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Thomas
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Douglas
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Michel G
authors.initials: MG
authors.lastname: Khouri
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia, Kelowna, British Columbia, Canada neil.eves@ubc.ca.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Eves
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D066126:Cardiotoxicity / Q000473:pathology / Q000628:therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality / Q000473:pathology; D059168:Carotid Intima-Media Thickness / Q000401:mortality; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D004452:Echocardiography; D015444:Exercise; D005260:Female; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018943:Anthracyclines
keywords: Cardiotoxicity; Contractility; Echocardiography; Exercise; Vascular