Background <p>Chronic heart failure patients are at high risk of cognitive deficits, which adds to the cardinal symptoms and can make the clinical picture even more challenging. Although various interventions, including pharmacological and lifestyle-based approaches, can help mitigate these deficits, many patients do not receive adequate treatment due to under-referral, limited access to care, or insufficient resources. This highlights the need for complementary and accessible strategies to support cognitive functioning in the heart failure population. Cognitive training is a safe and flexible way to help maintain and improve cognitive functioning in adults.&#xa0;However, the effects of individualized cognitive training in individuals with heart failure remain underexplored.</p> Methods <p>The SYNAPSE trial is a multicenter, single-blinded controlled trial with a cross-over design that aims to assess the effects of an individualized home-based cognitive training program on cognitive function in adults with heart failure. Fifty-four chronic heart failure participants aged 50 and over will be randomized to one of two arms, both including cognitive training and standard of care. The trial consists of 6 weeks of cognitive training (1 h 30/week), 6 weeks of standard of care, and three 2-week assessment times, for a total duration of 18&#xa0;weeks. The primary outcome concerns executive functions, with global cognition and three neuropsychological composite <i>z</i>-scores as secondary outcomes.</p> Discussion <p>This trial will provide evidence on the effects of individualized cognitive training on cognitive functioning in patients with chronic heart failure. Moreover, its findings will inform on how to manage cognitive deficits in this population.</p> <p>Trial registration</p> <p>ClinicalTrial.gov NCT05223426. Registered on March 2, 2022.</p>