A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer
Maryam Esmaeilzadeh, Camila M Urzua Fresno, Emily Somerset, Tamar Shalmon, Eitan Amir, Chun-Po Steve Fan, Christine Brezden-Masley, Babitha Thampinathan, Yobiga Thevakumaran, Kibar Yared, C Anne Koch, Husam Abdel-Qadir, Anna Woo, Paul Yip, Thomas H Marwick, Rosanna Chan, Bernd J Wintersperger, Paaladinesh Thavendiranathan, Maryam Esmaeilzadeh, Camila M Urzua Fresno, Emily Somerset, Tamar Shalmon, Eitan Amir, Chun-Po Steve Fan, Christine Brezden-Masley, Babitha Thampinathan, Yobiga Thevakumaran, Kibar Yared, C Anne Koch, Husam Abdel-Qadir, Anna Woo, Paul Yip, Thomas H Marwick, Rosanna Chan, Bernd J Wintersperger, Paaladinesh Thavendiranathan
Abstract
Importance: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited.
Objective: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard.
Design, setting, and participants: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study.
Exposures: Sequential therapy with anthracyclines and trastuzumab.
Main outcomes and measures: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models.
Results: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD.
Conclusions and relevance: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually.
Trial registration: ClinicalTrials.gov Identifier: NCT02306538.
Conflict of interest statement
Conflict of Interest Disclosures: Drs Esmaeilzadeh and Urzua Fresno, Ms Somerset, Drs Shalmon, Amir, and Fan, Ms Thampinathan, Ms Thevakumaran, Drs Koch, Abdel-Qadir, Woo, and Yip, Ms Chan, and Drs Wintersperger and Thavendiranathan are affiliated with University Health Network, which has a master research agreement with Siemens Healthineers. Dr Amir has received fees for expert testimony from Genentech/Roche and personal fees for consulting from Sandoz and Exact Sciences outside the submitted work. Dr Brezden-Masley has received grants from Canadian Institutes of Health Research and Hoffmann La Roche during the conduct of the study as well as research funds, honoraria, and consultancy fees from Hoffman La Roche, Amgen, Viatris (Mylan), Astra Zeneca, Novartis, Eli Lilly, Agendia, Gilead Sciences, Bristol Myers Squibb, Pfizer, Taiho, Myriad, and ApoBioligix outside the submitted work. Dr Yared has received speaking honoraria from Servier, Amgen, Bristol Myers Squibb, Pfizer, and Amgen. Dr Abdel-Qadir has received honoraria from Amgen. Dr Abdel-Qadir reported personal fees from Amgen Canada during the conduct of the study and payment from the Canadian Vigour Centre to serve on an end point adjudication committee for the THEMIS trial that was funded by Astra Zeneca. Dr Yip reported grants and personal fees from Abbott Diagnostics and personal fees from Roche Diagnostics and Nova Biomedical outside the submitted work. Dr Marwick reported grants from General Electric Healthcare Systems for the SUCCOUR trial outside the submitted work. Dr Wintersperger reported personal fees from Siemens Healthineers, research support from Siemens Healthineers, and personal fees from Bayer AG outside the submitted work. Dr Thavendiranathan has received speaker’s honoraria from Amgen, Boehringer Ingelheim, and Takeda. No other disclosures were reported.
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Source: PubMed