Modeling Brain–Heart Crosstalk Information in Patients with Traumatic Brain Injury
Authors: Dimitri Giovanna Maria , Beqiri Erta , Placek Michal M. , Czosnyka Marek , Stocchetti Nino , Ercole Ari , Smielewski Peter , Lió Pietro ,   the CENTER-TBI Collaborators, Anke Audny , Beer Ronny , Bellander Bo-Michael , Beqiri Erta , Buki Andras , Cabeleira Manuel , Carbonara Marco , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Czeiter Endre , Czosnyka Marek , Depreitere Bart , Ercole Ari , Frisvold Shirin , Helbok Raimund , Jankowski Stefan , Kondziella Daniel , Koskinen Lars-Owe , Kowark Ana , Menon David K. , Meyfroidt Geert , Moeller Kirsten , Nelson David , Piippo-Karjalainen Anna , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rhodes Jonathan , Rocka Saulius , Rossaint Rolf , Sahuquillo Juan , Sakowitz Oliver , Smielewski Peter , Stocchetti Nino , Sundström Nina , Takala Riikka , Tamosuitis Tomas , Tenovuo Olli , Unterberg Andreas , Vajkoczy Peter , Vargiolu Alessia , Vilcinis Rimantas , Wolf Stefan , Younsi Alexander , Zeiler Frederick A. 
Published: October 2021

Abstract
Background
Traumatic brain injury (TBI) is an extremely heterogeneous and complex pathology that requires the integration of different physiological measurements for the optimal understanding and clinical management of patients. Information derived from intracranial pressure (ICP) monitoring can be coupled with information obtained from heart rate (HR) monitoring to assess the interplay between brain and heart. The goal of our study is to investigate events of simultaneous increases in HR and ICP and their relationship with patient mortality..

Methods
In our previous work, we introduced a novel measure of brain–heart interaction termed brain–heart crosstalks (ctnp), as well as two additional brain–heart crosstalks indicators [mutual information ($$mi_{ct}$$

m

i

ct

) and average edge overlap (ωct)] obtained through a complex network modeling of the brain–heart system. These measures are based on identification of simultaneous increase of HR and ICP. In this article, we investigated the relationship of these novel indicators with respect to mortality in a multicenter TBI cohort, as part of the Collaborative European Neurotrauma Effectiveness Research in TBI high-resolution work package.

Results
A total of 226 patients with TBI were included in this cohort. The data set included monitored parameters (ICP and HR), as well as laboratory, demographics, and clinical information. The number of detected brain–heart crosstalks varied (mean 58, standard deviation 57). The Kruskal–Wallis test comparing brain–heart crosstalks measures of survivors and nonsurvivors showed statistically significant differences between the two distributions (p values: 0.02 for $$mi_{ct}$$

m

i

ct

, 0.005 for ctnp and 0.006 for ωct). An inverse correlation was found, computed using the point biserial correlation technique, between the three new measures and mortality: − 0.13 for ctnp (p value 0.04), − 0.19 for ωct (p value 0.002969) and − 0.09 for $$mi_{ct}$$

m

i

ct

(p value 0.1396). The measures were then introduced into the logistic regression framework, along with a set of input predictors made of clinical, demographic, computed tomography (CT), and lab variables. The prediction models were obtained by dividing the original cohort into four age groups (16–29, 30–49, 50–65, and 65–85 years of age) to properly treat with the age confounding factor. The best performing models were for age groups 16–29, 50–65, and 65–85, with the deviance of ratio explaining more than 80% in all the three cases. The presence of an inverse relationship between brain–heart crosstalks and mortality was also confirmed.

Conclusions
The presence of a negative relationship between mortality and brain–heart crosstalks indicators suggests that a healthy brain–cardiovascular interaction plays a role in TBI.