Pupils a novel prognostic marker of HF?

The pupil of the eye may independently predict all‐cause mortality and readmission due to heart failure (HF), suggesting its prognostic predictive capability in patients with HF, a retrospective analysis has shown.

“The high mortality rate associated with HF is influenced by a number of pathophysiological factors, among which, neuro-endocrine dysregulation is one of the most important … [This] is observed mainly as an imbalance of autonomic control,” said the researchers. Autonomic function is typically assessed based on heart rate variability; however, this requires continuous monitoring, which is time-consuming and not feasible for all patients. [J Am Coll Cardiol 2008;51:1725-1733]

While pupillary light reflex (PLR) may predict prognosis in this patient setting, this may be taxing especially for older individuals as the eyes need to be kept open for 5 seconds during measurement. [J Card Fail 2019;25:156-163]

“[P]upil area is useful as an index of autonomic function and can be measured more easily than PLR, because the result can be obtained instantaneously and does not require [keeping the] eyes open for several seconds … [Our] results suggest that [the] pupil area … can be used for risk stratification in HF patients,” said the researchers.

Pupils of 870 consecutive patients (mean age 67 years, 37 percent female) were measured via pupillometry at least 7 days post-hospitalization for acute HF. [ESC Heart Fail 2020;doi:10.1002/ehf2.12933]

After adjusting for potential confounders including SHFS*, the pupil area was independently associated with all‐cause mortality (hazard ratio [HR], 0.72; p=0.001) and readmission due to HF (HR, 0.82; p=0.003).

“We used the SHFS as an adjusting variable because this is one of the best risk scores for HF with the use of easily obtained clinical characteristics, which provides an accurate estimate of survival,” explained the researchers.

Small, but terrible?

The incidence of CV death was markedly higher among participants with small vs large pupil areas (61 vs 29; p<0.001). The poor prognosis with small vs large pupil areas is magnified by the significantly lower survival and higher readmission rates (p<0.001 for both), as well as the more severe HF and autonomic dysfunction tied to the former vs the latter, noted the researchers.

However, the association between small pupils and the more severe autonomic dysfunction appears to contradict the typical autonomic nervous dysregulation pattern in HF, which involves dilation of pupils, the researchers noted. “[While] the mechanism underlying this association has yet to be determined … it may be similar to [that] of chronotropic incompetence** [which could be attributed to autonomic dysfunction].” [Clin Cardiol 1996;19:503-508]

Although pupils typically dilate in the dark owing to appropriate autonomic nervous activity, in patients with HF, autonomic dysfunction may have caused pupil dysregulation, noted the researchers. “[This] would prevent the pupil from dilating appropriately in the dark.”

A window to the heart

“[Taken together,] pupil area measurement is a simple, noninvasive method that provides insight into the balance of both branches of the autonomic nervous system,” said the researchers. However, the small sample and limited follow‐up may have introduced bias. The findings may also not be extrapolated to individuals with severe retinopathy and other ophthalmological diseases that may affect pupil mobility and lead to false conclusions, the researchers noted.

“[Nonetheless, pupil area] measurement … has good reproducibility and can be obtained rapidly, easily, and noninvasively in routine clinical practice … [This method] may subsequently be a suitable alternative for evaluating autonomic function in patients with HF,” they added.