• Sharma Kattel, Hardik Bhatt, Shirley Xu, Sharda Gurung, Saraswati Pokharel, and Umesh C Sharma.
• Department of Medicine, Division of Cardiology, Jacob's School of Medicine and Biomedical Sciences, Buffalo, NY, United States; Department of Medicine, Division of Cardiology, Yale School of Medicine, New Haven, CT, United States.
• Resuscitation. 2020 Oct 1; 155: 180188180-188.

BackgroundBiomarkers involved in inflammation and stress response were implicated in patients who were successfully resuscitated from out of hospital cardiac arrest (sR-OHCA). Here we report that macrophage-expressed gene, perforin-2, an evolutionarily conserved protein with membrane attack domain, is associated with poor neurological outcomes and mortality after sR-OHCA.ObjectivesTo examine the association between circulating perforin-2 protein measured within 6-h of sR-OHCA, mortality and neurological outcomes.MethodsWe prospectively enrolled 144 sR-OHCA patients from 4 different tertiary care centers. We measured perforin-2 and other conventional clinical biomarkers and compared between survivors vs. non-survivors. The neurological outcomes were dichotomized as poor or good according to the cereberal performance score.ResultsAt the end of the hospital stay, 45% of the patients had died and 46% had poor neurological outcomes. Serum perforin-2 levels were significantly higher in patients with poor neurological recovery, compared to the ones with good neurological recovery (ng/mL, 13.7 ± 45.9 vs. 1.2 ± 7.0, p = 0.01). There were no differences in other routinely measured biomarkers and left ventricular ejection fraction. On multivariate logistic regression, elevated perforin-2 (OR: 12.78, 95% CI: 1.0-17.8, p = 0.02), comatose on presentation (OR: 27.82, 95% CI: 0.2-19.5, p = 0.02) and non-shockable rhythm (OR: 17.04, 95% CI: 0.7-15.7, p = 0.01) were the significant predictors of poor neurological outcome.ConclusionsThis study reports a novel macrophage-expressed circulating biomarker perforin-2 to be strongly associated with reduced survival and poor neurological outcomes in sR-OHCA. These data can guide clinicians to prognosticate survival and neurological outcomes in sR-OHCA, and also form the basis for future therapeutic approaches.Copyright © 2020 Elsevier B.V. All rights reserved.

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