Author + information
- Received October 23, 2017
- Revision received May 5, 2018
- Accepted May 11, 2018
- Published online August 6, 2018.
- Thiago Ferreira de Souza, MDa,
- Thiago Quinaglia A.C. Silva, MD, PhDa,
- Felipe Osorio Costa, MDa,
- Ravi Shah, MDb,
- Tomas G. Neilan, MD, MPHb,
- Lício Velloso, MD, PhDa,
- Wilson Nadruz, MD, PhDa,
- Fabricio Brenelli, MDa,
- Andrei Carvalho Sposito, MD, PhDa,
- Jose Roberto Matos-Souza, MD, PhDa,
- Fernando Cendes, MD, PhDa,
- Otávio Rizzi Coelho, MD, PhDa,
- Michael Jerosch-Herold, PhDc and
- Otavio Rizzi Coelho-Filho, MD, PhD, MPHa,∗ (, )@Otavio_Coelho_F
- aFaculdade de Ciências Médicas, Universidade Estadual de Campinas, São Paulo, Brazil
- bMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- cNoninvasive Cardiovascular Imaging Program and Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Otávio Rizzi Coelho-Filho, Division of Cardiology, Department of Medicine, State University of Campinas (UNICAMP), Rua Tessália Viera de Camargo, 126, Campinas – SP – Brazil, CEP 13083-887.
Objectives The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy.
Background Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations.
Methods A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement.
Results At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 − ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy.
Conclusions A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036)
- cardiac troponin T
- left ventricular remodeling
- magnetic resonance imaging
- T1 mapping techniques
Dr. Coelho-Filho is supported by a National Council for Scientific and Technological Development Productivity in Research award grant (303366/2015-0) and travel award grant (453960/2016-2); and is supported by a Young Investigators Grant from the São Paulo Research Foundation (2015/15402-2). Dr. Neilan is supported by the Kohlberg Foundation, an American Heart Association Fellow to Faculty Award (12FTF12060588), the National Heart, Lung, and Blood Institute (grants 1R01HL130539-01A1 and 1R01HL137562-01A1), and the National Institutes of Health/Harvard Center for AIDS Research (P30 AI060354). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 23, 2017.
- Revision received May 5, 2018.
- Accepted May 11, 2018.
- 2018 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.