PROJECT SUMMARY Sudden cardiac arrest (SCA), a sudden catastrophic loss of the pulse, continues to be a major public health issue. A proportion of SCA events occur in persons engaging in drug use and given that drug overdose deaths are at unprecedented levels in the United States, the epidemiology of drug related SCA is changing rapidly. Recognition and characterization of drug related SCA events is critical for accurate estimates of mortality associated with drug use, and to inform public health measures, especially in the context of the ongoing opioid epidemic. This proposed study will address several of the major knowledge gaps. This K01 Career Development Award leverages the existing infrastructure and clinical data archive of two ongoing prospective community-based studies of SCA. Dr. Norby will use this data to examine the epidemiology of SCA associated with drug use, with the overall goal of improving community-based approaches to SCA prevention. This proposal aims to 1) identify opportunities that will improve survival from SCA in the setting of drug use, and 2) identify substrate-trigger factors that initiate SCA in the presence of drug use. Taken together, these aims will interface community-based surveillance and comprehensive investigative reports to fill in the epidemiology and research gaps in SCA events related to substance use. To address these research aims, Dr. Norby will assemble records and reports in these two communities for SCA cases that have previously been excluded due to evidence of drug use. The overall goal of this K01 is to inform a sequence of R series grants to further investigate the prediction and prevention of SCA, and to improve survival after an SCA event related to drug use. With the support of this K01 award, Dr. Norby will be able to pursue this goal and transition to independent investigator status through essential training and mentorship. She will gain advanced training in 1) combining multimodal health records across systems and extracting pertinent information; 2) pharmacoepi drug use research and analysis of drug-drug combination; and 3) SCA mechanisms, SCA response and care, and additionally gain familiarity with toxicology and autopsy reports. Cedars-Sinai Smidt Heart Institute provides the ideal infrastructure to complete the research and training activities. Through the proposed research, training, and career development Dr. Norby will gain the scientific and professional skills necessary to become a successful independent investigator and lead a research program that advances the field of SCA associated with drug use.