Brain Heart InterActioNs in Cardiac Arrest. Ancillary Study of the HEAVENwARd Trial
Despite advances in post-resuscitation care of patients with cardiac arrest (CA), the majority of survivors who are treated after restoration of spontaneous circulation (ROSC) will have sequelae of hypoxic-ischemic brain injury ranging from mild cognitive impairment to a vegetative state. Current recommendations suggest using a multimodal approach to predict poor prognosis, meaning combining markers together. Yet, a substantial proportion of patients do not have a clear prognostic evaluation even when applying the latest ESICM recommendations algorithm published in 2021. It is therefore important to identify new prognostic markers to predict both unfavorable and favorable outcomes. Data regarding the pathophysiological mechanisms of post-anoxic encephalopathy suggest a diffuse anoxo-ischemic injury. However, post-mortem neuropathology data suggest that these lesions do not uniformly affect neuroanatomical structures, with some regions (especially hippocampal and insular) appearing more sensitive to anoxia. Conversely, the brainstem appears less affected by anoxic lesions. Under physiological conditions, there are interactions between the heart and the brain, and between the brain and the heart mainly related to the autonomic nervous system, through interactions between central cortical control structures (especially insular) and brainstem structures (at the level of the bulb) and peripheral structures of the heart. Exploring the pathophysiological mechanisms of heart-brain interactions post-CA could thus help better understand the pathophysiology of anoxo-ischemic encephalopathy, before considering potential therapeutic targets. Furthermore, this heart-brain dysfunction could have prognostic value. Indeed, recent studies in healthy subjects and patients with consciousness disorders suggest that autonomic nervous system activity measured by brain-heart interactions could be a reliable marker of consciousness and cognitive processing. These coupled heart-brain interactions can be evaluated through synchronous electroencephalogram (EEG) and electrocardiogram (ECG) recordings, as there are coupled interactions between the signals of these two organs. The existence of abnormal brain-heart coupling could be associated, on the one hand, with the severity of post-anoxic encephalopathy, and on the other hand, with neurological prognosis in patients with persistent coma post-CA.
This ancillary study of a multicentre prospective cohort "HEAVENwARd study" (NCT06044922) will assess the prevalence and prognostic value of bilateral brain-heart interactions in comatose patients after CA.
Heart Rate Variability in Early Prediction of a Noxic Brain Injury After Cardiac Arrest
Despite advances in post-resuscitation care of patients with cardiac arrest (CA), the majority of survivors who are treated after restoration of spontaneous circulation (ROSC) will have sequelae of hypoxic-ischemic brain injury ranging from mild cognitive impairment to a vegetative state.
Early prognostication in comatose patients after ROSC remains challenging. Recent recommendations suggest carrying out clinical and paraclinical tests during the first 72 h after ROSC, to predict a poor neurological outcome with a specificity greater than 95% (no pupillary and corneal reflexes, bilaterally absent N20 somatosensory evoked potential wave, status myoclonus, highly malignant electroencephalography including suppressed background ± periodic discharges or burst-suppression, neuron-specific enolase (NSE) > 60 µg/L, a diffuse and extensive anoxic injury on brain CT/MRI), but with a low sensitivity due to frequent confounding factors.
The heart rate variability (HRV) is a simple and non-invasive technique for assessing the autonomic nervous system function. In patients with a recent myocardial infarction, reduced HRV is associated with an increased risk for malignant arrhythmias or death. In neurology, reduced HRV is associated with a poor outcome in severe brain injury patients and allows to predict early neurological deterioration and recurrent ischemic stroke after acute ischemic stroke.
A reduced HRV could be a sensitive, specific and early indicator of diffuse anoxic brain injury after CA.
This multicenter prospective cohort study assesses the added value of early HRV (within 24h of ICU admission) for neuroprognostication after cardiac arrest.
Long-read Human Genome Sequencing in 72 Hours: "Ultra Rapid GEnome Sequencing"
Next-generation sequencing (NGS) has revolutionized the field of genomics, allowing the detection of genetic abnormalities for diagnostic or therapeutic purposes. Turnaround times for exome or genome sequencing results have decreased to an average of 3 to 6 months.
An increasing number of diagnostic and therapeutic fields are benefiting from the advancements in ultra-rapid sequencing. In some situations, a shorter turnaround time may be useful for making therapeutic and/or interventional management decisions.
This study aims to explore the feasibility of very rapid whole-genome sequencing, ultra-rapid genome sequencing (URGES) in 72 hours, that could benefit patients with cancer or rare diseases.
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