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

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: Following three months of treatment, participants showed a statistically significant improvement in left ventricular ejection fraction (LVEF) (<i>p</i> = 0.043), depression severity (<i>p</i> = 0.025) and a non-significant trend toward improvement in abstract reasoning scores (<i>p</i> = 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 (<i>p</i> = 0.057). Improvements in LVEF were not significantly associated with the changes in mood (<i>p</i> = 0.93), cognitive function (<i>p</i> = 0.34) or verbal fluency (<i>p</i> = 0.46). <b>Conclusions</b>: 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.