Background: Atrial fibrillation (AF) may be linked to cognitive impairment in heart failure (HF) patients. Regular exercise training has numerous benefits, including improving adults' overall health and cognitive function. However, the effects of exercise training on cognitive function in heart failure patients with reduced ejection fraction and permanent atrial fibrillation (HFAF) are not well understood. Objective: To test the hypothesis that exercise training improves cognitive function and neurovascular control in patients with HFAF. Methods: This randomized clinical trial included patients with HFAF, LVEF ≤40%, and resting HR ≤80 bpm. Montreal Cognitive Assessment score (MoCA), muscle sympathetic nerve activity (MSNA), and forearm blood flow (FBF) assessment were performed before and after the 12-week protocol period. Results: Twenty-six patients were randomized to exercise training (HFAF-trained, n=13) or no training (HFAF-untrained, n=13). At baseline, no differences between groups were found. Exercise significantly improved the MoCA score from 14.85 to 22.62 (P<0.0001), as well as those measuring processing visuospatial, memory, and attention function from 2.23 to 3.31 (P=0.02); from 1.92 to 2.69 (P=0.01); and from 2.62 to 3.85 (P=0.002), respectively. HFAF-training significantly decreased MSNA from 49.6±9.5 to 32.0±7.2 burst/min (P<0.0001) and forearm vascular resistance from 48.8±13.1 to 28.1±7 units (P<0.0001). Concomitantly, FBF increased from 1.9±0.5 to 3.0±0.7 mL/min/100mL (P<0.0001). The untrained group increased MSNA from 50.9±10.6 to 57.6±9.2 burst/min (P=0.004). No significant changes were found in the other variables in untrained patients. Conclusion: Exercise training improves cognitive function and neurovascular control in patients with heart failure with reduced ejection fraction and permanent atrial fibrillation.

The authors have declared no competing interest.

NCT03550872

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP # 2013/17031-6) Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq # 301957/2017-7)

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of the Heart Institute - Clinical Hospital, Medical School University of Sao Paulo

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The data presented in this study are available on request from the 415 corresponding author.