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Original Investigation
August 21, 2019

Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Internal Medicine, Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut
  • 2Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, New York, New York
  • 3Department of Cardiology, New York Presbyterian Hospital, Weill Cornell Medical College, New York
  • 4Division of Medical Oncology, Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada
  • 5Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  • 6Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 7Peter Munk Cardiac Centre, Ted Rogers Program in Cardiotoxicity Prevention, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
JAMA Cardiol. 2019;4(10):1007-1018. doi:10.1001/jamacardio.2019.2952
Key Points

Question  What is the value of left ventricular global longitudinal strain (GLS) for the prediction of cancer therapy–related cardiac dysfunction (CTRCD)?

Findings  In this systematic review and meta-analysis of 21 prognostic studies, worse absolute GLS during chemotherapy and a greater relative deterioration compared with baseline were associated with a higher risk of CTRCD. Additionally, there was significant publication bias and interstudy heterogeneity.

Meaning  Global longitudinal strain measured after treatment initiation has strong prognostic value for subsequent CTRCD, but available evidence is limited to specific regimens and cancer types and has publication bias and clinical heterogeneity, highlighting the need for larger prospective multicenter studies.

Abstract

Importance  Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy–related cardiac dysfunction (CTRCD) has not been performed, to our knowledge.

Objective  To explore the prognostic value of GLS for the prediction of CTRCD.

Data Sources  Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018.

Study Selection  Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD.

Data Extraction and Synthesis  Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.

Main Outcomes and Measures  The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms.

Results  Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. 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%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from −21.0% to −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). 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). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.

Conclusions and Relevance  In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.

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