Jennifer H Jordan1, Sharon M Castellino2, Giselle C Meléndez1,3, Heidi D Klepin4, Leslie R Ellis4, Zanetta Lamar4, Sujethra Vasu1, Dalane W Kitzman1, William O Ntim1, Peter H Brubaker5, Nathaniel Reichek6, Ralph B D'Agostino7, W Gregory Hundley8,9. 1. Sections on Cardiovascular Medicine (J.H.J., G.C.M., S.V., D.W.K., W.O.N., W.G.H.). 2. Pediatrics (S.M.C.). 3. Department of Internal Medicine, Section on Comparative Medicine, Department of Pathology (G.C.M.). 4. Hematology and Oncology (H.D.K., L.R.E., Z.L.). 5. Wake Forest School of Medicine, and Department of Health and Exercise Sciences (P.H.B). 6. Wake Forest University, Winston-Salem, NC. Research and Education, The Heart Center, St Francis Hospital, Roslyn, NY (N.R.). 7. Department of Biostatistical Sciences, Division of Public Health Sciences (R.B.D'A.). 8. Sections on Cardiovascular Medicine (J.H.J., G.C.M., S.V., D.W.K., W.O.N., W.G.H.) ghundley@wakehealth.edu. 9. Department of Radiological Sciences (W.G.H.).
Abstract
BACKGROUND: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. METHODS AND RESULTS: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non-Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11-0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=-0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. CONCLUSIONS: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.
BACKGROUND:Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. METHODS AND RESULTS: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non-Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11-0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=-0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. CONCLUSIONS: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.
Authors: Dalane W Kitzman; William C Little; Peter H Brubaker; Roger T Anderson; W Gregory Hundley; Christian T Marburger; Bridget Brosnihan; Timothy M Morgan; Kathryn P Stewart Journal: JAMA Date: 2002-11-06 Impact factor: 56.272
Authors: Steven E Lipshultz; Stuart R Lipsitz; Stephen E Sallan; Virginia M Dalton; Suzanne M Mone; Richard D Gelber; Steven D Colan Journal: J Clin Oncol Date: 2005-04-20 Impact factor: 44.544
Authors: D Iarussi; M Galderisi; G Ratti; M A Tedesco; P Indolfi; F Casale; M T Di Tullio; O de Divitiis; A Iacono Journal: Clin Cardiol Date: 2001-10 Impact factor: 2.882
Authors: W G Hundley; D W Kitzman; T M Morgan; C A Hamilton; S N Darty; K P Stewart; D M Herrington; K M Link; W C Little Journal: J Am Coll Cardiol Date: 2001-09 Impact factor: 24.094
Authors: Bharathi Upadhya; Michael V Rocco; Nicholas M Pajewski; Tim Morgan; Joseph Blackshear; William Greg Hundley; Suzanne Oparil; Elsayed Z Soliman; Debbie L Cohen; Craig A Hamilton; Monique E Cho; William J Kostis; Vasilios Papademetriou; Carlos J Rodriguez; Dominic S Raj; Ray Townsend; Sujethra Vasu; Sara Zamanian; Dalane W Kitzman Journal: Hypertension Date: 2019-07-01 Impact factor: 10.190
Authors: Naomi Dempsey; Amanda Rosenthal; Nitika Dabas; Yana Kropotova; Marc Lippman; Nanette H Bishopric Journal: Breast Cancer Res Treat Date: 2021-06-11 Impact factor: 4.872
Authors: David I Chu; Abdulla M Ehlayel; Jill P Ginsberg; Kevin E Meyers; Maryjane Benton; Melissa Thomas; Claire Carlson; Thomas F Kolon; Gregory E Tasian; Jason H Greenberg; Susan L Furth; Michelle R Denburg Journal: J Pediatr Date: 2020-12-05 Impact factor: 4.406
Authors: Dulguun Amgalan; Thomas P Garner; Ryan Pekson; Xiaotong F Jia; Mounica Yanamandala; Victor Paulino; Felix G Liang; J Jose Corbalan; Jaehoon Lee; Yun Chen; George S Karagiannis; Luis Rivera Sanchez; Huizhi Liang; Swathi-Rao Narayanagari; Kelly Mitchell; Andrea Lopez; Victoria Margulets; Marco Scarlata; Gaetano Santulli; Aarti Asnani; Randall T Peterson; Rachel B Hazan; John S Condeelis; Maja H Oktay; Ulrich Steidl; Lorrie A Kirshenbaum; Evripidis Gavathiotis; Richard N Kitsis Journal: Nat Cancer Date: 2020-03-02