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Pupil area predicts all-cause mortality and readmission due to HF in HF patients
Literature - Nozaki K, Hamazaki N, Yamamoto S et al. - ESC Heart Fail. 2020 Aug 10. doi: 10.1002/ehf2.12933.

Introduction and methods

The autonomic nervous system plays a crucial role in cardiovascular physiology and dysregulation contributes to the pathophysiology of many CV disorders [1]. Autonomic dysregulation (AD) in patients with heart failure (HF), i.e. the upregulation of the sympathetic nervous system and downregulation of the parasympathetic nervous system, and abnormal CV function is associated with poor outcomes [2].

AD is generally assessed by heart rate variability, which is determined by electrocardiography [3]. However, HF patients have a 20-50% prevalence rate for atrial fibrillation (AF) and non-sinus rhythm [4-7], which makes it impossible to assess the autonomic regulation on the basis of heart rate variability in this particular subgroup of HF patients.

The radius of the pupil is under the control of the sympathetic and parasympathetic autonomic nervous system in response to light and was therefore postulated to be a useful prognostic tool to predict the prognosis in HF patients [8].

Aim of this study was to determine whether pupil area measurements can be used for risk stratification in HF patients. 870 patients (≥18 years) were included who were admitted to Kitasato University Hospital (Sagamihara, Japan) with acute HF between January 2012 and December 2017. Patients with a history of ocular surgery or ocular disease that would affect pupil reflexes were excluded. Pupil area was measured for both eyes at least 7 days after hospitalization using a portable infrared videopupillography system. Patients were divided into a small (median pupil area 11.9 mm2, IQR: 8.9-14.2, n=434) and large (median pupil area 21.8 mm2, IQR: 19.2-26.0, n=436) pupil area group according to the median pupil area of 16.6 mm2 (IQR: 12.0-21.8, n=870) in this cohort. Primary endpoint was all-cause mortality, secondary endpoint was readmission due to HF. Median follow-up was 1.9 years (IQR: 1.0-3.7).

Main results

  • Compared with the large pupil area group, patients in the small pupil area group were significantly older, had a lower body weight and BMI, lower hemoglobin, lower LDL-c, lower eGFR, greater severity of HF (based upon Seattle Heart Failure Score (SHFS) and New York Heart Association (NYHA) functional classification) and more often rehospitalized due to HF.
  • All-cause mortality was significantly lower in the large pupil area group compared to the small pupil area group (44 (10.1%) patients vs. 87 (20%), P<0.001, respectively). In a multivariate Cox regression model, large pupil area was associated with reduced all-cause mortality (HR 0.72, 95%CI: 0.59-0.88, P=0.001).
  • Readmission due to HF was lower in the large pupil group compared to small pupil area group (28.2% vs. 47.2%, respectively, P<0.001). In a multivariate Cox regression model, large pupil area was associated with lower readmission due to HF (HR 0.82, 95% CI: 0.73-0.93, P=0.003).
  • Subgroup analyses demonstrated consistent improved outcomes with large pupil area across various subgroups (LVEF, SHFS, BMI, BNP, eGFR, prior HF, heart rhythm).
  • Area under the curve improved with addition of pupil area to SHFS compared to SHFS only (0.72, 95%CI: 0.66-0.78 vs. 0.69, 95%CI: 0.65-0.74, P=0.034).
  • Patients with a small pupil area had a significantly higher CV mortality rate compared to patients in the large pupil area group (61 patients (14.1%) vs. 29 patients (6.7%), P<0.001, respectively).


This study demonstrates that pupil area measurements have prognostic value for all-cause mortality and readmission due to HF in patients previously hospitalized for acute HF.


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8. Nozaki K, Kamiya K, Matsue Y et al. Pupillary light reflex as a new prognostic marker in patients with heart failure. J Card Fail. 2019;25:156-63

Find this article online at ESC Heart Fail

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