Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer

Abstract

ImportanceThere is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy–related cardiac dysfunction (CTRCD).ObjectiveTo describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD.Design, Setting, and ParticipantsThis was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)–positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto–affiliated hospitals. Data were analyzed from July 2021 to June 2022.ExposuresSequential therapy with anthracyclines, trastuzumab, and radiation.Main Outcomes and MeasuresCMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses.ResultsOf 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD.Conclusions and RelevanceIn women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

CT Images in Follicular Lymphoma: Changes after Treatment Are Predictive of Cardiac Toxicity in Patients Treated with Anthracycline-Based or R-B Regimens

“…Our study stems from the hypothesis that early identification and application of radiological patterns can detect anthracycline-induced cardiological damage early and identify patients with occult cardiological disease onset who would benefit from anthracycline-free treatment. Studies which have investigated this topic and have used MRI or CT for the extrapolation of early markers of anthracycline-induced cardiac damage such as ECV and EAT are few in the literature and mainly concern oncology in the context of breast cancer [16,18,[38][39][40][41][42].…”

Advances in multimodality imaging and the application of new cardiac imaging technologies for radiation‐induced heart disease

“…Studies have demonstrated that CMR and speckle-tracking echocardiography (STE) are effective diagnostic tools for acute myocarditis [37]. CMR can assess LV volume, LVEF, myocardial strain, early gadolinium enhancement (EGE) to assess hyperemia (inflammation marker), and late gadolinium enhancement (LGE) to assess replacement fibrosis, and it can be used to perform native/post-contrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis and T2 mapping to assess edema [38]. LVEF may not be a sensitive indicator for identifying the early risk of cardiomyopathy after radiotherapy, but we know that the disease tends to have a long latency period and requires infinite vigilance.…”

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy

“…Some small-scale studies employing CMR have also demonstrated early myocardial edema following anthracycline therapy using T2w sequences [65]. The presence of edema has been associated with persistent RV function reduction in follow-up examinations [6].…”