Author + information
- Received November 10, 2017
- Revision received January 2, 2018
- Accepted January 4, 2018
- Published online August 6, 2018.
- Kathleen W. Zhang, MDa,
- Brian S. Finkelman, MD, PhDb,
- Gaurav Gulati, MDc,
- Hari K. Narayan, MDd,
- Jenica Upshaw, MDc,
- Vivek Narayan, MDe,
- Ted Plappert, CVTf,
- Virginia Englefield, CVTf,
- Amanda M. Smith, BA, MSf,
- Carina Zhang, BAf,
- W. Gregory Hundley, MDg and
- Bonnie Ky, MD, MSCEf,h,∗ ()
- aDivision of Cardiology, Barnes-Jewish Hospital, St. Louis, Missouri
- bDepartment of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- cDivision of Cardiology, Tufts Medical Center, Boston, Massachusetts
- dDepartment of Pediatrics, Division of Cardiology, Rady Children’s Hospital San Diego, The University of California-San Diego, San Diego, California
- eDivision of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- fPenn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- gDivision of Cardiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
- hCenter for Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
- ↵∗Address for correspondence:
Dr. Bonnie Ky, University of Pennsylvania School of Medicine, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104.
Objectives The objective of this study was to evaluate the changes in three-dimensional (3D) speckle-tracking echocardiography–derived measures of mechanics and their associations with systolic and diastolic dysfunction after anthracyclines.
Background An improved understanding of the changes in 3D cardiac mechanics with anthracyclines may provide important mechanistic insight and identify new metrics to detect cardiac dysfunction.
Methods A total of 142 women with breast cancer receiving doxorubicin (240 mg/m2) with or without trastuzumab underwent 3D speckle-tracking echocardiography at standardized intervals prior to, during, and annually after chemotherapy. Left ventricular ejection fraction (LVEF), global circumferential strain (GCS), global longitudinal strain (GLS), principal strain, twist, and torsion were quantified. Linear regression analyses defined the associations between clinical factors and 3D parameters. Linear regression models with cluster robust variance estimators determined the associations between 3D measures and 2-dimensional (2D) LVEF and Doppler-derived E/eʹ over time.
Results There were significant abnormalities in 3D LVEF, GCS, GLS, and principal strain post-doxorubicin compared with control subjects (p < 0.001). The 3D parameters worsened post-anthracyclines, and only partially recovered to baseline over a median of 2.1 years (interquartile range: 1 to 4 years). Higher blood pressure and body mass index were associated with worse post-anthracycline 3D GCS and GLS, respectively. All 3D measures were associated with 2D LVEF at the same visit; only 3D LVEF, GCS, GLS, and principal strain were associated with 2D LVEF at subsequent visits (p < 0.05). In exploratory analyses, 3D LVEF and GCS were associated with subsequent systolic function independent of their corresponding 2D measures. The 3D LVEF, GCS, principal strain, and twist were significantly associated with concurrent, but not subsequent, E/eʹ.
Conclusions Anthracyclines result in early and persistent abnormalities in 3D mechanics. The 3D LVEF and strain measures are associated with concurrent and subsequent systolic dysfunction, and concurrent diastolic dysfunction. Future research is needed to define the mechanisms and clinical relevance of abnormal 3D mechanics.
This work was supported by the National Heart, Lung, and Blood Institute grants R01-HL118018 and K23-HL095661, the McCabe Fellow Award, and the American Cancer Society Institutional Research Grant 78-002-30 (to Dr. Ky). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Zhang, Finkelman, and Gulati contributed equally to this work, and are joint first authors.
- Received November 10, 2017.
- Revision received January 2, 2018.
- Accepted January 4, 2018.
- 2018 American College of Cardiology Foundation
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