Macrophage-specific protein perforin-2 is associated with poor neurological recovery and reduced survival after sudden cardiac arrest

Biomarkers 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. To examine the association between circulating perforin-2 protein measured within 6-h of sR-OHCA, mortality and neurological outcomes. We 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. At 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. This 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.