Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients

Jennifer M. Kwan , Amit Arbune , Mariana L. Henry,Rose Hu, Wei Wei, Vinh Nguyen, Seohyuk Lee, Juan Lopez-Mattei, Avirup Guha, Steffen Huber, Anna S. Bader, Judith Meadows, Albert Sinusas, Hamid Mojibian, Dana Peters, Maryam Lustberg, Sarah Hull, Lauren A. Baldassarre


Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.


Monitoring for adverse cardiovascular outcomes associated with oncologic therapies is crucial in improving long term outcomes of breast cancer patients. Cardiac imaging plays a critical role during and after cancer treatment in identifying CTRCD. Recent European Society of Cardiology (ESC) guidelines recommend baseline echo using 3D analysis of left ventricular ejection fraction (LVEF) for those undergoing anthracycline therapy, regardless of cardiovascular risk, and use of CMR imaging as second line if echo is of suboptimal quality [13–15]. Ischemia, microvascular dysfunction and chemotherapy induced cardiotoxicity are potential diagnoses when a breast cancer patient presents with cardiac symptoms or cardiomyopathy after receiving chemotherapy [16]

Materials and methods

The sample consisted of 116 patients with a history of breast cancer. Of these 116 patients, 62 were in the AT group, while 54 were in the NAT group. Patients were excluded if they had poor quality/nondiagnostic CMRs (n = 3). Fig 1 depicts how the sample of patients was selected. A small subset (n = 13) had stress CMR performed during chemotherapy treatment. Information on patient comorbidities, demographics, cancer treatments, cardiac medications, and cardiovascular outcomes were obtained by chart review from the electronic health record system at Yale New Haven Hospital. The institutional review board of Yale University School of Medicine reviewed and approved this research.


Amongst the entire cohort of 116 breast cancer patients, the relationship between cardiovascular risk factors and cardiovascular outcomes was evaluated. Hypertension and preexisting systolic heart failure (Fig 4A) were univariately associated with an increased risk of CAD/ myocardial infarction (HR: 10.73, CI: 1.41–81.873, p = 0.022 and HR:8.56, CI: 1.04–70.30, p = 0.046, respectively) (Fig 4). Competing risk regression showed that HTN was significantly associated with a 9.8-fold increase in developing CAD/myocardial infarction (Fig 4B)


Our findings are generally consistent with the previous literature on cardiovascular disease in breast cancer patients and we also elucidate some novel findings that may impact management of breast cancer patients, such as evaluating CMR GCS, consistent with the 2022 ESC guideline recommendation of monitoring for cardiotoxicity with GCS by CMR [15]. Although echo is first line based on the guidelines due to ease of access, CMR can be complementary when echo quality is suboptimal, for evaluation or verification of an accurate ejection fraction, and when tissue characterization for assessment of inflammation or fibrosis is warranted [51].


CMR and CMR strain evaluation are important imaging tools to assess breast cancer patients for chemotherapy induced cardiotoxicity. Although patients may have preserved LVEF, many have abnormal strain, suggesting subclinical cardiotoxicity. Statin use may be associated with a reduction in future arrhythmias in this patient cohort.

Citation: Kwan JM, Arbune A, Henry ML, Hu R, Wei W, Nguyen V, et al. (2023) Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients. PLoS ONE 18(5): e0286364.

Editor: Raffaele Bugiardini, University of Bologna, ITALY

Received: November 5, 2022; Accepted: May 15, 2023; Published: May 30, 2023

Copyright: © 2023 Kwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: LAB was supported by AHA 18CDA34110361 and NCATS award UL1TR0001983. JMK was supported by YCCI NIH KL2 TR001862. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Enter: The authors have declared that no competing interests exist.

Abbreviations: ATC, anthracycline; AT, Anthracycline/trastuzumab; ASCVD, Atherosclerotic Cardiovascular Disease; BB, Beta Blocker; BSA, Body Surface Area; CAD, Coronary Artery Disease; CKD, Chronic Kidney Disease; CMR, Cardiac Magnetic Resonance Imaging; CO, Cardiac Output; DVT, Deep Vein Thrombosis; ECV, Extracellular Volume; ESRD, End Stage Renal Disease; GCS, Global Circumferential Strain; GLS, Global Longitudinal Strain; GRS, Global Radial Strain; ATC/ Her2i, Anthracycline/ Trastuzumab +/- Pertuzumab; Her2i, Her2 inhibitor; HLD, Hyperlipidemia; HTN, Hypertension; IHD, Ischemic Heart Disease; LAVAI, Left atrial volume area index; LGE, Late Gadolinium Enhancement; LVEDD, Left ventricular end diastolic diameter; LVEDVI, Left ventricular end diastolic volume index; LVEDV, Left ventricular end diastolic Volume; LVEF, Left Ventricle Ejection Fraction; LVESD, Left Ventricle; LVSV, Left Ventricular Stroke Volume; LVESVI, Left Ventricular Stroke Volume Index; MI, Myocardial Infarction; MRI, Magnetic Resonance Imaging; NAT, Non Anthracycline/trastuzumab; NSTEMI, Non-ST segment elevated myocardial infarction; PAD, Peripheral Artery Disease; PE, Pulmonary Embolism; pHTN, Pulmonary Hypertension; RVEDV, Right Ventricular End Diastolic Volume; RVEF, Right Ventricular Ejection Fraction; RVSV, Right Ventricular Stroke Volume; RVSVI, Right Ventricular Stroke Volume Index; SSFP, Steady state free precession; ss-GRE, Stress-only perfusion; ss-MPIR, Steady state magnetization preparation inversion recovery; TTE, Transthoracic Echocardiogram

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