Normalization of Electrocardiogram-Derived Cardiac Risk Indices: A Scoping Review of the Open-Access Literature

Featured Application: This scoping review provides an overall assessment of the application of normalization on electrocardiogram-derived cardiac risk indices, aiming to clarify the rationale behind its application and the consistency and comparability of these normalized indices in the literature. Changes in cardiac function and morphology are reflected in variations in the electrocardiogram (ECG) and, in turn, in the cardiac risk indices derived from it. These variations have led to the introduction of normalization as a step to compensate for possible biasing factors responsible for inter- and intra-subject differences, which can affect the accuracy of ECG-derived risk indices in assessing cardiac risk. The aim of this work is to perform a scoping review to provide a comprehensive collection of open-access published research that examines normalized ECG-derived parameters used as markers of cardiac anomalies or instabilities. The literature search was conducted from February to July 2024 in the major global electronic bibliographic repositories. Overall, 39 studies were selected. Results suggest extensive use of normalization on heart rate variability-related indices (49% of included studies), QT-related indices (18% of included studies), and T-wave alternans (5% of included studies), underscoring their recognized importance and suggesting that normalization may enhance their role as clinically useful risk markers. However, the primary objective of the included studies was not to evaluate the effect of normalization itself; thus, further research is needed to definitively assess the impact and advantages of normalization across various ECG-derived parameters.