P2514Pupillary area predicts all-cause mortality in patients with cardiovascular disease
Authors: Nozaki K , Kamiya K , Hamazaki N , Matsuzawa R , Ichikawa T , Nakamura T , Yamashita M , Maekawa E , Matsunaga A , Tojo M , Ako J 
Published: October 2019

Abstract

Background
Autonomic dysfunction is among the most important pathophysiological factors involved in the high mortality rate associated with cardiovascular disease (CVD). Autonomic function is generally evaluated by heart rate variability, which is obtained by Holter electrocardiography. However, the measurement of heart rate variability requires continuous electrocardiographic monitoring for 24 h, which is time consuming and not always feasible. The pupillary area is controlled by the autonomic nervous system; however, limited data are available regarding the utility of the pupillary area for predicting prognosis in patients with CVD.

Purpose
We aimed to investigate whether pupillary area can be used as a novel prognostic marker in patients with CVD.

Methods
We retrospectively reviewed 1342 consecutive Japanese patients hospitalized for CVD. The study was performed in accordance with the tenets of the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of our University Hospital. The pupillary area measurement was performed on both eyes at least 7 days after hospitalization for CVD using a portable videopupillography system (Iriscorder Dual C10641; Hamamatsu Photonics, Hamamatsu, Japan) consisting of a goggle-shaped measurement portion with a charge-coupled device camera and a control portion with a video monitor and microcomputer with software for data analysis. After securing the goggles on the patient's face and fully covering the patient's eyes, a 5-minute period was allowed for dark adaptation. All patients were tested once between 09:00 and 12:00 h. The primary outcome of this study was all-cause mortality, and the endpoint time was calculated as the number of days from the date of pupillary area measurement up to three years. We performed the Kaplan–Meier and log-rank tests and multivariable Cox regression analysis to evaluate the prognostic predictive capability of the pupillary area.

Results
The study population had a mean age of 65±13 years, and 69.4% of the patients were male. The median of the pupillary area was 18.5 mm2 (interquartile range: 13.3–23.4 mm2). Over a median follow-up period of 1.9 years (interquartile range: 1.0–3.0 years), a total of 114 deaths occurred in the patient population. The Kaplan–Meier and log-rank tests revealed that all-cause mortality was significantly higher in the small pupillary area group than in the large pupillary area group (P<0.0001, Figure). Furthermore, Cox regression analysis indicated that the pupillary area was an independent predictor of mortality (Hazard ratio: 0.96; 95% confidence interval: 0.93–0.98; P=0.006) even after adjusting for several preexisting prognostic factors.
Kaplan-Meire Curve

Conclusion
The pupillary area can be an independent predictor of prognosis in patients with CVD, and our observations suggest that the assessment of the pupillary area can be useful as a new noninvasive prognostic predictor in patients with CVD.