Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Dec 27;16(1):38.
doi: 10.3390/brainsci16010038.

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

Fahad Al Kindi  1   2 , Raya Al Maskari  1   3 , Fatma Al Mahruqi  4 , Adil Al Riyami  2 , Zuhra Al Yarabi  5 , Rasha Kaddoura  6 , Mujahid Al Busaidi  2 , Samir Al Adawi  5
Affiliations

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

Fahad Al Kindi et al. Brain Sci. .

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.

Keywords: HFrEF; cognitive function; heart failure; mood; sacubitril/valsartan.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart of study participants.
Figure 2
Figure 2
Within-individual comparisons of LVEF percentages at baseline and 3 months after treatment. Each line represents a participant. Boxplots display the median, interquartile range (IQR) and whiskers extending 1.5 times the IQR, summarizing the distribution of LVEF percentages at each time point.
Figure 3
Figure 3
Within-individual comparisons of PHQ-9 scores at baseline and 3 months after treatment. Each line represents a participant. Boxplots display the median, interquartile range (IQR) and whiskers extending 1.5 times the IQR, summarizing the distribution of scores at each time point.
Figure 4
Figure 4
Within-individual comparisons of Raven’s Colored Progressive Matrices scores at baseline and 3 months after treatment. Each line represents a participant. Boxplots display the median, interquartile range (IQR) and whiskers extending 1.5 times the IQR, summarizing the distribution of scores at each time point.
Figure 5
Figure 5
Within-individual comparisons of Al Khoudh subdomain scores at baseline and 3 months after treatment. Each line represents a participant. Boxplots display the median, interquartile range (IQR) and whiskers extending 1.5 times the IQR, summarizing the distribution of scores at each time point.
See this image and copyright information in PMC

References

    1. Kemp C.D., Conte J.V. The Pathophysiology of Heart Failure. Cardiovasc. Pathol. 2012;21:365–371. doi: 10.1016/j.carpath.2011.11.007. - DOI - PubMed
    1. Patel R.B., Greene S.J., Xu H., Alhanti B., Peterson P., Yancy C.W., Piccini J., Fonarow G.C., Vaduganathan M. Intersection of Atrial Fibrillation and Heart Failure with Mildly Reduced and Preserved Ejection Fraction in >400 000 Participants in the Get With The Guidelines-Heart Failure Registry. Eur. J. Heart Fail. 2023;25:63–73. doi: 10.1002/ejhf.2729. - DOI - PMC - PubMed
    1. Celutkiene J., Vaitkevicius A., Jakstiene S., Jatuzis D. Cognitive Decline in Heart Failure: More Attention Is Needed. Card. Fail. Rev. 2016;2:106–109. doi: 10.15420/cfr.2016:19:2. - DOI - PMC - PubMed
    1. Leto L., Feola M. Cognitive Impairment in Heart Failure Patients. J. Geriatr. Cardiol. 2014;11:316–328. doi: 10.11909/j.issn.1671-5411.2014.04.007. - DOI - PMC - PubMed
    1. Tromp J., Ouwerkerk W., van Veldhuisen D.J., Hillege H.L., Richards A.M., van der Meer P., Anand I.S., Lam C.S.P., Voors A.A. A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction. JACC Heart Fail. 2022;10:73–84. doi: 10.1016/j.jchf.2021.09.004. - DOI - PubMed

LinkOut - more resources