Comparing the Effects of Cognitive Training and Physical Exercise on Cognition, Cerebral Autoregulation and Cerebral Vasoreactivity in Men and Women with Heart Failure

The objective of this project is to assess the effects of combined physical exercise and cognitive training interventions on cognitive and brain health in patients with heart failure (HF). Also, the role of sex on the effects of the interventions will be assessed.

Cognitive impairment (CI) affects up to 50% of patients with heart failure (HF), and is associated with high mortality rates, poor quality of life, reduced functional capacities, and an overwhelming economic burden in Western countries. Non-pharmacological strategies could help enhance cognition in HF patients with CI. Combined physical exercise and cognitive training interventions have recently shown promising enhancement effects on cognition in patients with cardiovascular risk factors and mild cognitive impairment. The effects of combined interventions have never been tested in HF.

The main objective is to assess the effects of combined physical exercise and cognitive training interventions on cognition in patients with HF. Secondary objectives include: to characterize baseline and intervention-related changes in cerebral autoregulation and vasoreactivity and to assess the role of sex on the effects of the interventions.

Two-hundred and sixteen participants (36 men and 36 women/group) with stable HF regardless of aetiology and LVEF will take part in this study. All participants will have signed a written consent form before taking part in the study.

Patients will be stratified according to sex and LVEF (FEVG \< 40% et FEVG \> 40%), and will be randomly assigned to one of the 3 following study arms: 1) Combined physical exercise and cognitive training; 2) Physical exercise alone; and 3) Usual medical care.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 60 years old
* Stable chronic HF on maximally tolerated background treatment for at least 2 months (stable therapy with ACE-I, ARBs and MRA for at least 2 months), regardless of LVEF
* with no limitation of physical activity in ordinary physical activity (i.e. NYHA class I), moderate symptoms (i.e. NYHA class II) or marked limitation in activity (i.e. NYHA class III)
* Able to perform cognitive and physical training.

Exclusion Criteria:

* Acute cardiovascular event 1 month prior to randomization, including emergency visit or hospitalization for decompensated HF, acute myocardial infarction, stroke, and transient ischemic attack
* Planned cardiovascular intervention within 6 months (implantation of any cardiac device, cardiac revascularization, heart transplantation)
* Severe exercise intolerance
* Contraindications for exercise testing (e.g., uncorrected severe aortic or carotid stenosis, severe pulmonary hypertension, severe non-revascularizable coronary disease including left main coronary stenosis, significant myocardial ischemia or arrhythmia during low-intensity exercise, acute HF)
* Severe respiratory disease
* Non-cardiopulmonary limitation to exercise (e.g., arthritis, claudication or any peripheral neurological disease including other neurodegenerative diseases such as disabling Parkinson)
* Uncontrolled diabetes or untreated thyroid dysfunction
* Current or recent malignancy with life expectancy \< 1 year
* Chronic hemodialysis or peritoneal dialysis
* Unable to read the informed consent form or unable to understand the oral explanations provided by the assessor.