The Role And Mechanism Of Autonomic Nerve Remodeling In The Development Atrial Fibrillation In High Altitude Population

Background: Atrial fibrillation is one of the most common arrhythmias in clinical practice.It is associated with increased risk of ischemic stroke and systemic artery embolism.In patients with organic heart disease,atrial fibrillation is associated with increased cardiac injury.Meanwhile,atrial fibrillation is associated with cognitive impairment.Studies have found that the risk of arrhythmias in healthy people after entering a high altitude environment is increased,which is due to the compensatory changes in their body under acute or chronic hypoxia,and once the compensatory adaptation limit is broken,organic damage will be caused.There is insufficient research on the incidence of atrial fibrillation in people who have lived at high altitudes for generations.This study examined the incidence of atrial fibrillation in a large sample of people at different altitudes.Independent samples were collected for biological experiments to further explore the role and mechanism of autonomic nerve remodeling in atrial fibrillation with valvular heart disease in high altitude population.Methods:(1)Cross-sectional study: Data of patients undergoing cardiac surgery from January 2013 to December 2018 were collected from the medical record database of Sichuan Provincial People’s Hospital.The propensity score matching method was used to achieve 1:1 matching between low-altitude patients and high-altitude patients,and the incidence of atrial fibrillation,perioperative data,postoperative complications,postoperative mortality and other data were analyzed in the matched group.(2)Prospective study: A total of 25 patients who underwent cardiac surgery in Sichuan Provincial People’s Hospital from June 2020 to January 2021 were enrolled and divided into low-altitude sinus rhythm group(n=8),low-altitude atrial fibrillation group(n=7),high-altitude sinus rhythm group(n=6)and high-altitude atrial fibrillation group(n=4)according to altitude and ECG detection.The right atrial appendage and serum of the target patients were collected,and the concentration of HIF-1α in serum was determined by enzyme-linked immunosorbent assay.Immunohistochemistry,Western Blot and RT-q PCR were used to analyze the protein expression and m RNA expression levels of autonomic nerve markers to verify the differences in autonomic nerve remodeling.Results:(1)A total of 2185 complete patient data were collected,and 474 matched cohorts were obtained by propensity score matching.Statistical analysis showed that the incidence of atrial fibrillation was higher in the high-altitude group than in the lowaltitude group(27.8% VS 26.6%),but there was no statistically difference(P=0.418).Patients living at high altitudes had the similar incidence of atrial fibrillation as those living at low altitudes(OR=1.07;95%CI,0.71-1.60),lifetime exposure to high altitude does not increase the risk of atrial fibrillation.(2)In the prospective study,the expression of HIF-1α,Ch AT,TH,and GAP43 were not significantly different between the four groups of low-altitude sinus rhythm,lowaltitude atrial fibrillation,high-altitude sinus rhythm,and high-altitude atrial fibrillation,according to the analysis of 25 patients.Conclusions: Lifelong exposure to high altitude does not significantly increase the incidence of atrial fibrillation in patients with organic heart disease,and there is no significant difference in the level of autonomic remodeling.