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

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 MEASURESThe 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,; 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 RELEVANCEIn 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.

Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis

“…In patients exposed to anthracyclines, the duration of cardiac monitoring should be at least one year, as almost all patients that will develop LV dysfunction display an important decline in cardiac function within the first year 45 . Additional to standard LVEF measurements, deformation imaging by means of global longitudinal strain has shown promising results to detect early changes in myocardial contractility in this setting 52 . Other screening methods include biomarkers, of which the most promising is troponin with a negative predictive value of 93% 53 .…”

Healthcare utilization and hospital variation in cardiac surveillance during breast cancer treatment: a nationwide prospective study in 5000 Dutch breast cancer patients

“…Changes in global longitudinal strain (GLS) can be detected prior to LVEF reduction. A relative reduction of 11% compared to baseline or a value of < 19% is an indication of cardiotoxicity [17,19]. Additionally, novel CMR multi-parametric techniques, such as T1 and T2 mapping, allow accurate characterization of myocardial tissue.…”

Cardiac Imaging in Oncology Patients in Europe: a Model for Advancement of CV Safety and Development of Comprehensive CV Care

“…However, this definition is not universally accepted to guide clinical and research strategies and does not give us information regarding preclinical myocardial dysfunction. To guide the diagnosis and management of early reversible stages of myocardial damage, echo-based myocardial strain and cardiac magnetic resonance (CMR) myocardial tissue characterization are the preferred techniques [9,15,16].Regarding non-myocardial toxicities (arrhythmic, metabolic, vascular, and thromboembolic events), cardiac imaging testing may help to stratify baseline risk and to optimize CV treatment [9]; however, during cancer treatment, monitoring is generally based on biomarkers, ECG, and clinical findings [2,3].…”