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However, these studies differ in the GLS cutoff values used and the populations studied. 10 Several studies have linked threshold changes in GLS or an absolute GLS value during cancer treatment with the subsequent development of CTRCD. 6, 7, 8 In the absence of robust risk prediction models, there is an interest in the use of sensitive markers to detect early myocardial dysfunction, 9 with the hope of instituting interventions to prevent CTRCD.ДЄmong measures of myocardial function, echocardiography-measured peak systolic global longitudinal strain (GLS) is the most extensively studied marker and provides an easy, inexpensive, and quantitative assessment of global long-axis systolic function. 3, 4, 5 The development of LV dysfunction (cancer therapyвЂ“related cardiac dysfunction ) is associated with poor prognosis and contributes to long-term cardiovascular morbidity and mortality. While the incidence of overt heart failure is less than 5% typically, subclinical left ventricular (LV) dysfunction, defined by a threshold change in LV ejection fraction (LVEF), may be seen in up to 42% of patients with cancer in selected treatment groups. 2 One of the most worrisome adverse effects is ventricular dysfunction and heart failure.

1 Unfortunately, several chemotherapeutic agents (eg, anthracyclines, trastuzumab) commonly used in the treatment of these malignancies are known to have cardiotoxic effects. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.ДЄdvances in cancer treatment over the last decades have remarkably improved the survival rates of patients diagnosed as having solid and hematologic malignancies. Both indices showed significant publication bias. For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82 95% CI, 5.84-42.85 area under the HSROC, 0.86 95% CI, 0.83-0.89). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from в€’21.0% to в€’13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27 95% CI, 7.73-19.47 area under the HSROC, 0.86 95% CI, 0.83-0.89). The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study collection, management, analysis, and interpretation of the data preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.ДЄnalysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab.

This research was funded in part through the Support Grant P30 CA008748 from the National Institutes of Health/National Cancer Institute Cancer Center. Study supervision: Kokkinidis, Kampaktsis, Gupta, Thavendiranathan.Д¬onflict of Interest Disclosures: None reported.ДЇunding/Support: Dr Thavendiranathan is supported by New Investigator Award 147814 from the Canadian Institutes of Health Research. Statistical analysis: Oikonomou, Kokkinidis, Marwick.ДЄdministrative, technical, or material support: Oikonomou, Kampaktsis. Study concept and design: Oikonomou, Kokkinidis, Marwick, Gupta, Thavendiranathan.ДЄcquisition, analysis, or interpretation of data: Oikonomou, Kokkinidis, Kampaktsis, Amir, Thavendiranathan.Дrafting of the manuscript: Oikonomou, Kokkinidis, Kampaktsis, Thavendiranathan.Д¬ritical revision of the manuscript for important intellectual content: Oikonomou, Kokkinidis, Amir, Marwick, Gupta, Thavendiranathan.

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doi:10.1001/jamacardio.2019.2952ДЄuthor Contributions: Dr Oikonomou had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Corresponding Author: Paaladinesh Thavendiranathan, MD, MSc, Peter Munk Cardiac Center, Ted Rogers Program in Cardiotoxicity Prevention, University Health Network, Toronto General Hospital, University of Toronto, 4N-490, 585 University Ave, Toronto, ON M5G 2N2, Canada ( Online: August 21, 2019.

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