Lipidomics Detection of Brain Cardiolipins in Plasma Is Associated With Outcome After Cardiac Arrest.

OBJECTIVES: Brain mitochondrial dysfunction limits neurologic recovery after cardiac arrest. Brain polyunsaturated cardiolipins, mitochondria-unique and functionally essential phospholipids, have unprecedented diversification. Since brain cardiolipins are not present in plasma normally, we hypothesized their appearance would correlate with brain injury severity early after cardiac arrest and return of spontaneous circulation. DESIGN: Observational case-control study. SETTING: Two medical centers within one city. PARTICIPANTS (SUBJECTS): We enrolled 41 adult cardiac arrest patients in whom blood could be obtained within 6 hours of resuscitation. Two subjects were excluded following outlier analysis. Ten healthy subjects were controls. Sprague-Dawley rats were used in asphyxial cardiac arrest studies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed a high-resolution liquid chromatography/mass spectrometry method and determined cardiolipins speciation in human brain, heart, and plasma within 6 hours of (return of spontaneous circulation) from 39 patients with cardiac arrest, 5 with myocardial infarction, and 10 healthy controls. Cerebral score was derived from brain-specific cardiolipins identified in plasma of patients with varying neurologic injury and outcome. Using a rat model of cardiac arrest, cardiolipins were quantified in plasma, brain, and heart. Human brain exhibited a highly diverse cardiolipinome compared with heart that allowed the identification of brain-specific cardiolipins. Nine of 26 brain-specific cardiolipins were detected in plasma and correlated with brain injury. The cerebral score correlated with early neurologic injury and predicted discharge neurologic/functional outcome. Cardiolipin (70:5) emerged as a potential point-of-care marker predicting injury severity and outcome. In rat cardiac arrest, a significant reduction in hippocampal cardiolipins corresponded to their release from the brain into systemic circulation. Cerebral score was significantly increased in 10 minutes versus 5 minutes no-flow cardiac arrest and naïve controls. CONCLUSIONS: Brain-specific cardiolipins accumulate in plasma early after return of spontaneous circulation and proportional to neurologic injury representing a promising novel biomarker.

Early coronary angiography and percutaneous coronary intervention are associated with improved outcomes after out of hospital cardiac arrest.

AIM: Early coronary angiography (CAG) and percutaneous coronary intervention (PCI) are associated with better outcomes in subjects resuscitated from out-of-hospital cardiac arrest (OHCA). We sought to determine the relative contributions of early CAG and PCI to outcomes and adverse events after OHCA. METHODS: We analyzed 599 OHCA subjects from a prospective two-center registry. Hospital survival, functional outcomes and adverse events were compared between subjects undergoing early CAG (within 24h) with or without PCI and subjects not undergoing early CAG. We adjusted for propensity to perform early CAG and PCI and for post-resuscitation illness severity and care. RESULTS: Early CAG subjects had improved rates of hospital survival (56.2% versus 31.0%, OR 2.85 [95% CI 2.04-4.00]; p<0.0001) and better functional outcomes compared to no early CAG. Early PCI was associated with improved survival compared to early CAG without PCI (65.6% versus 45.5%, OR 2.29 [95% CI 1.41-3.69]; p<0.001). After multivariate adjustment and propensity matching, early PCI remained significantly associated with improved survival compared with early CAG without PCI and no early CAG, but early CAG without PCI was no longer significantly associated with improved outcome compared with no early CAG. Early CAG and early PCI were not associated with an increase in transfusions or acute kidney injury. CONCLUSIONS: Early CAG and PCI are associated with improved survival and functional outcomes after OHCA, but only early PCI was associated with a significant benefit after statistical adjustment. Our analysis supports the performance of immediate CAG to determine the need for PCI in selected patients following resuscitation from OHCA.