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

Abstract

Background: 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.Objectives: To examine the association between circulating perforin-2 protein measured within 6-hours of sR-OHCA, mortality and neurological outcomes. Methods: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.Results: At the end of the hospital stay, 47% of the patients had poor neurological status, of whom 95% had in-hospital mortality. Serum perforin-2 levels were significantly higher in patients with poor neurological status, 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 were the significant predictors of poor neurological outcome.

Inflammatory response after out‐of‐hospital cardiac arrest—Impact on outcome and organ failure development

“…GDF‐15 at admission was also independently associated with increased six‐month mortality 75 . Perforin‐2 at admission was independently associated with both neurological outcome at hospital discharge and 90‐day mortality 76 . There was a significant but unadjusted increase in sTREM‐1 levels between admission and day one in OHCA patients who died of shock but not in survivors 36 .…”

“…75 Perforin-2 at admission was independently associated with both neurological outcome at hospital discharge and 90-day mortality. 76 There was a significant but unadjusted increase in sTREM-1 levels between admission and day one in OHCA patients who died of shock but not in survivors. 36 Semaphorin 3F on day three was significantly higher in patients who did not survive to hospital discharge but no adjusted model was applied.…”