Analysis of the Pediatric Heart Network Echocardiogram Database to Establish Left Ventricular Strain Z-scores

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PROJECT SUMMARY In children, calculating ejection (EF) and shortening fraction (SF) using echocardiography (echo) is the standard of care for evaluating left ventricular (LV) function. Despite their ubiquitous use, EF and SF are poorly reproducible, calculated from multiple measurements each with their own error that is propagated, and measure endocardial volume change without directly measuring contractility. Deformation strain is fundamentally different from EF and SF. Instead of measuring volumes, echo software technology provides speckle-tracking of myocardial movement to measure regional and global myocardial deformation to obtain LV strain. Since this process is automated, it removes a large degree of observer-dependence. In addition, since strain is a single measurement rather than a derived parameter calculated from multiple measurements, the error for machine-derived strain should be substantially reduced. LV strain has been widely studied in adults where normal reference ranges are validated and it is used to predict clinical outcomes and refine therapies. In contrast, LV strain reference values based on a large, diverse population of children are not available and strain remains largely a research tool in the pediatric population. To address this, we will establish Z-scores using the PHN Echo Database. This database includes all images needed for LV strain measurements from 3526 echoes obtained in a well-characterized population of healthy children ranging in age from birth to 18 years. Z-scores account for the effects of maturation and growth by considering body size, age, gender, and/or race when evaluating whether measurements are normal or, if abnormal, how many standard deviations they deviate from the mean. Establishing Z-scores is the most powerful and flexible approach to normalizing cardiovascular parameters for the effects of age and body size and has become the standard approach in pediatric cardiology. We will determine if independent parameters such as age, height, weight, body surface area, or heart rate can predict changes in LV strain with maturation and/or growth. To guide clinical use, we will determine the feasibility and reproducibility of LV strain measurements for images collected as part of routine clinical care rather than as part of a rigorous research protocol. We will evaluate the effect of sampling frequency on Z-scores for clinically indicated studies by comparing those with ≥30 vs. <30 frames/heartbeat in each age category. This project is highly significant and will impact nearly every pediatric subspecialty. LV strain Z-scores will enable longitudinal studies to determine if LV strain is more predictive of outcomes than EF or SF in children. If so, strain would move into clinical use and lead to a paradigm shift in the evaluation and management of diseases where the child is at risk for LV dysfunction and subsequent heart failure. The PHN database of normal echo images obtained as routine clinical care from a large, well-characterized population of healthy children provides a unique, cost-effective opportunity to establish normal LV strain Z-scores and rapidly deploy them for use in the real world setting of a busy pediatric echo lab.