# The Effect of Sacubitril/Valsartan on Mood and Cognitive Function in Patients with Heart Failure with Reduced Ejection Fraction

## TL;DR

This study explores whether sacubitril/valsartan improves mood and cognitive function in heart failure patients, finding some short-term benefits unrelated to heart improvement.

## Contribution

Preliminary evidence suggests sacubitril/valsartan may improve mood and reasoning in heart failure patients, independent of cardiac improvements.

## Key findings

- Participants showed significant improvement in depression severity after three months of treatment.
- There was a non-significant trend toward improvement in abstract reasoning scores.
- Improvements in heart function were not linked to changes in mood or cognitive function.

## Abstract

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is associated with significant neuropsychological burden, including cognitive impairment and mood disturbances. While sacubitril/valsartan has demonstrated cardiovascular benefits, its effects on cognitive and emotional functioning remain underexplored, particularly in Middle Eastern populations. We aimed to evaluate the impact of sacubitril/valsartan on intellectual capacity, cognitive function and mood in patients with HFrEF using an idiographic study design. Methods: This study was conducted in adult patients with HFrEF selected to take sacubitril/valsartan to improve their clinical status. Participants were assessed at baseline and 3 months after treatment initiation using Al Khoudh Cognitive Test, PHQ-9 and Raven’s Progressive Colored Matrices. Results: Following three months of treatment, participants showed a statistically significant improvement in left ventricular ejection fraction (LVEF) (p = 0.043), depression severity (p = 0.025) and a non-significant trend toward improvement in abstract reasoning scores (p = 0.051). On the other hand, participants did not demonstrate significant improvements in the cognitive subdomains assessed by the Al Khoudh Test. Among these subdomains, the largest improvement was observed with verbal fluency (p = 0.057). Improvements in LVEF were not significantly associated with the changes in mood (p = 0.93), cognitive function (p = 0.34) or verbal fluency (p = 0.46). Conclusions: This study provides preliminary, hypothesis-generating evidence of potential short-term improvement in mood and reasoning scores in HFrEF patients treated with sacubitril/valsartan. Notably, these changes were not attributed to the observed improvements in cardiac function. These findings underscore the need for further investigation into the neurocognitive benefits of sacubitril/valsartan in larger and more diverse populations.