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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-h 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, 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. CONCLUSIONS: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.

journal_name

Resuscitation

journal_title

Resuscitation

authors

Kattel S,Bhatt H,Xu S,Gurung S,Pokharel S,Sharma UC

doi

10.1016/j.resuscitation.2020.08.005

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

180-188

eissn

0300-9572

issn

1873-1570

pii

S0300-9572(20)30313-0

journal_volume

155

pub_type

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