Prognostic Value of Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity

The findings of a new study published in JAMA Cardiology suggest that  measuring global longitudinal strain (GLS), which detects early subclinical ventricular dysfunction, after the initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent cancer therapy–related cardiac dysfunction (CTRCD).

This study was a systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018. Researchers assessed the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD and included 21 studies comprising 1,782 patients with cancer – including breast cancer, hematologic cancers, or sarcomas, who were treated with anthracyclines with or without trastuzumab.

The researchers utilized random-effects meta-analysis as well as hierarchical summary receiver operating characteristic curves (HSROCs) to abridge the prognostic and discriminatory performance of GLS indices. Moreover, they implemented the Egger test to appraise any publication bias and performed meta-regression to evaluate sources of heterogeneity. The study’s primary endpoint was stipulated as CTRCD, which was defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms.

Prognostic Efficacy

According to the results of this study, 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, results showed that 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 to 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 to 42.85; area under the HSROC, 0.86; 95% CI, 0.83 to 0.89). Both indices showed notable publication bias. Furthermore, meta-regression discerned differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.

Despite these positive findings, the study authors note that the “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.”