Abstract

The autonomic nervous system plays a central role in the initiation and maintenance of atrial fibrillation (AFib). Primary autonomic failure is characterized by impaired cardiovascular autonomic reflexes due to α-synuclein deposition in central or peripheral autonomic nerves causing absence of norepinephrine secretion during orthostatic stress in neurodegenerative conditions such as Parkinson disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB) and pure autonomic failure. We hypothesized that primary autonomic failure would lead to decrease risk of AFib This was a retrospective analysis that included patients diagnosed with primary autonomic failure based on autonomic reflex testing at Vanderbilt Autonomic Dysfunction Center between 2015-2022. An age and sex-matched cohort of patients without a diagnosis of primary autonomic failure were used as a control population. Logistic regression analysis was used to identify factors associated with AFib. A total of 114 patients with primary autonomic failure were included (age 72.7±8.3, 64% males); of whom 52 (45.6%) had PD, 37 (32.5%) had MSA, 2 (1.8%) had DLB and 23 (20.2%) had pure autonomic failure. Patients with primary autonomic failure had elevated supine BP 155±26/86±14 mmHg and orthostatic hypotension (standing BP decreased to 104±28/65±16 mmHg). Impaired sympathetic reflexes were evident by a reduced sinus arrythmia ratio 1.09±0.09, profound BP decreased during phase II of the Valsalva maneuver 89±28/59±18 mmHg and no BP recovery during phase IV of Valsalva 131±28/59±16 mmHg. Compared to age (72.7±8.1 years) and sex-matched (65.1% males) controls, patients with primary autonomic failure had lower prevalence of diabetes, hypertension, heart failure, coronary artery diseases, and chronic kidney disease. The prevalence of AFib was significantly lower in patients with primary autonomic failure compared to the control population (4.4% vs 32.1%; p <0.001). In a multivariate regression model adjusting for hypertension, chronic kidney disease and heart failure, the only independent predictors of AFib were older age (OR 1.07, 95% CI 1.01-1.13; p 0.01) and presence of primary autonomic failure (OR 0.05, 95% CI 0.01-0.22; p <0.001), which was protective. AFib is significantly less prevalent in patients with primary autonomic failure compared to age and sex-matched controls. The etiology is possibly related to the autonomic failure. Further prospective studies are warranted.

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