Decreased 24-hour Parasympathetic Activity following Intracerebral Hemorrhage: A Key Factor Correlated with Adverse Perihematomal Edema and Poor Functional Outcomes

Abstract

Aims: This study aimed to investigate the association between autonomic activity, assessed by 24-hour heart rate variability (HRV), and the development of perihematomal edema (PHE) as well as 3-month functional outcomes following intracerebral hemorrhage (ICH).

Methods: We retrospectively included patients with ICH who underwent 24-hour electrocardiographic (ECG) monitoring within 14 days of onset from a prospective cohort. HRV parameters were calculated from ECG data. A poor functional outcome at 3 months was defined as a modified Rankin Scale (mRS) score ≥ 3. PHE volume was measured on 7-day computed tomography scans using 3D Slicer software, and adverse PHE was defined as relative PHE (edema volume/hematoma volume) ≥ 2. Univariate and multivariate logistic regression analyses were performed to identify predictors of adverse PHE and poor outcomes. Partial correlation analysis was conducted to examine the association between HRV parameters and adverse PHE. Five machine-learning algorithms were applied to develop predictive models for 3-month poor outcomes.

Results: A total of 312 patients were included, of whom 45.2% (141/312) had poor outcomes at 3 months and 48.6% (122/251) had adverse PHE. Parasympathetic hypoactivity, indicated by low high-frequency power, was independently associated with poor 3-month outcomes. In addition, parasympathetic hypoactivity (measured by the root mean square of successive differences between adjacent NN intervals) and relative sympathetic hyperactivity (measured by the ratio of low-frequency to high-frequency power) independently predicted adverse PHE. Among the machine-learning models, the eXtreme Gradient Boosting (XGBoost) algorithm achieved the highest predictive performance for poor 3-month outcomes, with an AUC of 0.883.

Conclusions: Twenty-four-hour parasympathetic hypoactivity is associated with adverse PHE and poor functional outcomes following ICH.

Keywords: autonomic activity; intracerebral hemorrhage; perihematomal edema.