Prognostic implications of Global Longitudinal Strain versus Ejection Fraction in End-stage Renal Disease: a systematic review protocol

BackgroundIn hemodialysis (HD) patients, the presence of Heart failure (HF) at the start of dialysis is a strong and independent predictor of short and long-term mortality, and its prevalence increases with declining kidney function and HD time. Left ventricular (LV) ejection fraction (EF) is widely used as a measure of systolic function. Reduced EF (<50%) is an important prognostic marker, however, less than 15% of End-stage Renal Disease (ESRD) patients have detectable systolic dysfunction and the EF is susceptible to loading conditions, which change dramatically during interdialytic intervals. Global Longitudinal Strain (GLS) derived by 2D Speckle-Tracking Echocardiography (STE) is an emerging technique for measuring more subtle disturbances in LV systolic function. Although ESRD patients have subclinical evidence of impaired strain but preserved EF, there is evidence that GLS is better in ESRD group receiving maintenance HD compared with moderate-advanced CKD patients. This systematic review will evaluate the evidence related to the incremental prognostic value of LV GLS by 2D-STE concerning mortality and cardiovascular (CV) events in ESRD patients. MethodsThis protocol is reported according to the PRISMA-P guideline. The databases PubMed, EMBASE, LILACS, Web of Science, and Google Scholar system will be searched and double screening for longitudinal studies that assessed the prospective association of STE-derived parameters with at least one of the pre-specified outcomes in ESRD patients. Discrepancies will be resolved through consensus. A modified version of the Newcastle-Ottawa Quality Assessment Scale of cohort studies will be used. We intend to use the random-effects model, considering at least moderate heterogeneity between studies. If data allow, we will perform meta-regression to explore potential sources of between-study heterogeneity. An adaptation of the GRADE framework for prognostic studies will be employed to judge the quality of evidence for each outcome reported in this systematic review. DiscussionThis systematic review will summarize current evidence about STE-derived measures in the ESRD patients and clarify the incremental prognostic value of this diagnostic tool versus LVEF in these patients. Evidence about other measures (circumferential and radial strain) or 3D STE-derived indices will also be investigated. Systematic review registrationThis systematic review protocol was submitted to the PROSPERO international registry of systematic reviews (Registration number: CRD42020222505). O_TEXTBOXStrengths and limitations of this study [-&gt;]The PROSPERO registry helps to promote and maintain transparency in the process and to assist in minimizing the risk of bias. Four databases and one additional grey literature source helps ensure more complete coverage of the topic. A modified version of the Newcastle-Ottawa Quality Assessment Scale of cohort studies will be used and an adaptation of the GRADE framework for prognostic studies to assess the quality of evidence for each outcome reported will be applied. All the review phases will be peer-reviewed and will be validated by methodological and clinical experts. [-&gt;]Left ventricular (LV) ejection fraction (EF) is widely used as a measure of systolic function. Reduced EF (50%) is an important prognostic marker, however, less than 15% of End-Stage Renal Disease (ESRD) patients have detectable systolic dysfunction. Global Longitudinal Strain (GLS) derived by 2D Speckle-Tracking Echocardiography (STE) is an emerging technique for measuring more subtle disturbances in LV systolic function, however, its incremental prognostic value to ESRD is controversial. [-&gt;]This study has limitations. Because heterogeneity is quite common in these systematic reviews, there may be limited scope for meta-analysis. Possibly, the spectrum of patients in different research sites is the main factor, in most cases, but heterogeneity in associations between studies may be difficult to explain. [-&gt;]This systematic review will evaluate the evidence related to the GLS incremental prognostic value in End-Stage Renal Disease patients, which may lower morbidity and mortality and influence its use as a prognostic marker for ESRD patients. C_TEXTBOX