Project Grant K23HL175123

ASSESSMENT OF MYOCARDIAL DYSFUNCTION AND INFLAMMATION AFTER PEDIATRIC CARDIAC ARREST - PROJECT SUMMARY PEDIATRIC CARDIAC ARREST OCCURS IN OVER 20,000 CHILDREN ANNUALLY IN THE UNITED STATES, WITH MORTALITY RATES AS HIGH AS 50%. IN CHILDREN WHO SURVIVE THEIR ARREST, POST-CARDIAC ARREST SYNDROME (PCAS) MANIFESTS AS SECONDARY ORGAN INJURY WITH THE RETURN OF CIRCULATION, INCLUDING BRAIN INJURY, ISCHEMIA-REPERFUSION, AND MYOCARDIAL DYSFUNCTION. PEDIATRIC PCAS IS RELATIVELY UNDERSTUDIED, SPECIFICALLY IN THE DOMAINS OF POST-CARDIAC ARREST MYOCARDIAL DYSFUNCTION AND SYSTEMIC AND CARDIAC INFLAMMATION. PRELIMINARY DATA, THOUGH IN SMALL COHORTS AND RETROSPECTIVE IN NATURE, HAVE DEMONSTRATED ASSOCIATIONS BETWEEN MYOCARDIAL DYSFUNCTION AND ELEVATED MARKERS OF INFLAMMATION AND INJURY WITH POST-CARDIAC ARREST MORTALITY. THIS K23 PROPOSAL LEVERAGES THE ROBUST RESEARCH INFRASTRUCTURE WITHIN THE CHILDREN'S HOSPITAL OF PHILADELPHIA (CHOP) AND THE UNIVERSITY OF PENNSYLVANIA (UPENN) TO CONDUCT A LARGER, SINGLE-CENTER PROSPECTIVE OBSERVATIONAL STUDY IN A TOTAL OF 200 CRITICALLY ILL CHILDREN AFTER CARDIAC ARREST. ADVANCED ECHOCARDIOGRAPHIC IMAGING AFTER ARREST WILL INCLUDE GLOBAL LONGITUDINAL STRAIN (GLS), A MORE SENSITIVE MEASURE OF MYOCARDIAL DYSFUNCTION COMPARED TO STANDARD MEASURES OF EJECTION AND SHORTENING FRACTION. SYSTEMIC AND MYOCARDIAL INFLAMMATION WILL BE ASSESSED EARLY AFTER CARDIAC ARREST BY CIRCULATING BIOMARKERS IN A CUSTOMIZED PANEL OF PROTEINS ASSOCIATED WITH OUTCOMES IN OTHER DISEASE PROCESSES. THESE MEASURES WILL BE INDIVIDUALLY EXAMINED FOR THEIR ASSOCIATION WITH HOSPITAL MORTALITY, AND SURVIVAL TO HOSPITAL DISCHARGE WITH UNFAVORABLE NEUROLOGIC OUTCOME. TOGETHER, WITH CLINICAL DATA, THESE MEASURES WILL BE ASSESSED WITH LATENT CLUSTER ANALYSIS TO CREATE PEDIATRIC PCAS PHENOTYPES WHICH WILL BE DISTINCTLY ASSOCIATED WITH OUTCOMES. THIS PHENOTYPING WILL ALLOW FOR BETTER UNDERSTANDING OF PEDIATRIC PCAS TO ALLOW FOR TRIAL ENRICHMENT IN FUTURE INTERVENTIONAL STUDIES. THE PRINCIPAL INVESTIGATOR OF THIS STUDY, DR. MONIQUE GARDNER, IS UNIQUELY POSITIONED TO COMPLETE THIS STUDY WITH HER TRAINING IN PEDIATRICS, PEDIATRIC CARDIOLOGY, AND PEDIATRIC CRITICAL CARE, AS WELL AS HER EXPERIENCE TO DATE WITH RESEARCH IN CRITICALLY ILL CHILDREN WITH CARDIAC DISEASE. SUPPORTED BY HER MENTORSHIP TEAM AND RESEARCH ENVIRONMENT, SHE WILL LEVERAGE THE OPPORTUNITY TO STUDY ADVANCED BIOSTATISTICAL TECHNIQUES, ECHOCARDIOGRAPHY, AND BIOMARKER ASSESSMENT TO MATURE INTO AN INDEPENDENT PATIENT-ORIENTED CLINICIAN-SCIENTIST TO IMPROVE OUTCOMES FOR CRITICALLY ILL CHILDREN.