Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

OBJECTIVE: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms. METHODS: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA). RESULTS: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation. CONCLUSION Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; 23(4): 398-414.
Animals ; Male ; Rats, Sprague-Dawley ; STAT3 Transcription Factor/metabolism* ; alpha7 Nicotinic Acetylcholine Receptor/metabolism* ; Janus Kinase 2/metabolism* ; Atrial Fibrillation/metabolism* ; Vagus Nerve/physiopathology* ; Rats ; Acupuncture Therapy ; Signal Transduction ; Macrophages/metabolism* ; Inflammation/therapy*

Atrial fibrillation (AF) is one of the most common arrhythmias, which does great harm to patients. Effective methods were urgently required to prevent the recurrence of AF. Four methods were used to analyze RR sequence in this paper, and differences between Pre-AF (preceding an episode of AF) and Normal period (far away from episodes of AF) were analyzed to find discriminative criterion. These methods are: power spectral analysis, approximate entropy (ApEn) and sample entropy (SpEn) analysis, recurrence analysis and time series symbolization. The RR sequence data used in this research were downloaded from the Paroxysmal Atrial Fibrillation Prediction Database. Supporting vector machine (SVM) classification was used to evaluate the methods by calculating sensitivity, specificity and accuracy rate. The results showed that the comprehensive utilization of recurrence analysis parameters reached the highest accuracy rate (95%); power spectrum analysis took second place (90%); while the results of entropy analyses and time sequence symbolization were not satisfactory, whose accuracy were both only 70%. In conclusion, the recurrence analysis and power spectrum could be adopted to evaluate the atrial chaotic state effectively, thus having certain reference value for prediction of AF recurrence.
Atrial Fibrillation ; diagnosis ; Entropy ; Heart Atria ; physiopathology ; Humans ; Recurrence ; Sensitivity and Specificity ; Support Vector Machine

Inter atrial block (IAB) is a prevailing cardiac conduction abnormality that is under-recognized in clinical practice. IAB has strong association with atrial arrhythmia, left atrial enlargement, and electromechanical discordance, increasing the risk of atrial fibrillation (AF) and myocardial ischemia. IAB was generally believed to be caused by impaired conduction along the Bachmann bundle (BB). However, there are three other conduction pathways, including the fibers posteriorly in the vicinity of the right pulmonary veins (VRPV), transseptal fibers in the fossa ovalis (FO), and muscular bundles on the inferior atrial surface near the coronary sinus (CS). We hypothesized that the importance of BB on IAB might have been overestimated. To test this hypothesis, various combinations of conduction pathway blocks were simulated based on a realistic human atrial model to investigate their effects on the index of clinical diagnosis standard of IAB using a simulated 12-lead electrocardiogram (ECG). Firstly, the results showed that the BB block alone could not generate typical P wave morphology of IAB, and that the combination of BB and VRPV pathway block played important roles in the occurrence of IAB. Secondly, although single FO and CS pathways play subordinate roles in inter atrial conduction, their combination with BB and VRPV block could also produce severe IAB. In summary, this simulation study has demonstrated that the combinations of different inter atrial conduction pathways, rather than BB alone, resulted in ECG morphology of IAB. Attention needs to be paid to this in future pathophysiological and clinical studies of IAB.
Adult ; Arrhythmias, Cardiac/physiopathology* ; Atrial Fibrillation/physiopathology* ; Computer Simulation ; Coronary Sinus/physiopathology* ; Electrocardiography ; Heart ; Heart Atria ; Humans ; Male ; Models, Anatomic ; Models, Cardiovascular ; Pulmonary Veins/physiopathology*

To evaluate the volume and function of left atrium and left atrial appendage in patients with atrial fibrillation by three-dimensional transesophageal echocardiography and transthoracic echocardiography.
 Methods: A total of 112 patients with atrial fibrillation were divided into two groups: a paroxysmal atrial fibrillation (ParAF) group (n=80) and a persistent atrial fibrillation (PerAF) group (n=32). Control group was people without atrial fibrillation (n=40). Clinical data of the participants were collected. Left atrial dimension (LAD), left atrial volume (LAV), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were measured by transthoracic echocardiography, while left atrial appendage peak emptying flow velocity (LAAeV), left atrial appendage peak filling flow velocity (LAAfV), left atrial appendage maximum volume (LAAVmax) and left atrial appendage minimum volume (LAAVmin) were measured by three-dimensional transesophageal echocardiography. Left atrial volume index (LAVI), left ventricular ejection fraction (LVEF) and left atrial appendage ejection fraction (LAAEF) were calculated. 
 Results: Compared with the control group, LAAEF, LAAeV and LAAfV in the ParAF group were decreased obviously, while LAD, LAV, LAVI, LAAVmax and LAAVmin in the ParAF group were increased obviously (P<0.05). Compared with the ParAF group, LAAEF, LAAeV and LAAfV in the PerAF group were also decreased obviously, and LAD, LAV, LAVI, LAAVmax and LAAVmin in the ParAF group were also increased obviously (P<0.05). There was no statistically significant difference in LVEDV, LVESV, LVEF between the ParAF group and the PerAF group (P<0.05).
 Conclusion: Left atrium and left atrial appendage were enlarged and the function of left atrial appendage was declined in patients with AF, and the changes were more obvious in patients with PerAF compared with patients with ParAF by three-dimensional transesophageal echocardiography and transthoracic echocardiography.
Atrial Appendage ; physiopathology ; Atrial Fibrillation ; physiopathology ; Echocardiography, Transesophageal ; Heart Atria ; physiopathology ; Humans

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA₂DS₂-VASc score 2.4±1.5 vs. 3.1±1.7, p < 0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.
Administration, Oral ; Aged ; Antithrombins/administration & dosage/therapeutic use ; Atrial Fibrillation/drug therapy/*physiopathology ; Female ; Heart Rate/*physiology ; Humans ; Kaplan-Meier Estimate ; Male ; Proportional Hazards Models ; Prospective Studies ; Stroke/drug therapy/*etiology/*physiopathology ; Treatment Outcome

BACKGROUNDIn the early stages of atrial remodeling, aortic stiffness might be an indication of an atrial myopathy, in particular, atrial fibrosis. This study aimed to investigate the association between left atrial (LA) mechanical function, assessed by two-dimensional speckle tracking echocardiography, and aortic stiffness in middle-aged patients with the first episode of nonvalvular atrial fibrillation (AF).

METHODSThis prospective study included 34 consecutive patients with the first episode of AF, who were admitted to Kartal Koşuyolu Research and Training Hospital between May 2013 and October 2015, and 31 age- and gender-matched healthy controls. During the 1 st month (mostly in the first 2 weeks) following their first admission, 34 patients underwent the first pulse wave measurements. Then, 21 patients were recalled for their second pulse wave measurement at 11.8 ± 6.0 months following their initial admission. Echocardiographic and pulse wave findings were compared between these 34 patients and 31 healthy controls. We also compared the pulse wave and echocardiographic findings between the first and second measurements in 21 patients.

RESULTSPulse wave analysis showed no significant differences between the AF patients and healthy controls with respect to PWV (10.2 ± 2.5 m/s vs. 9.7 ± 2.1 m/s; P = 0.370), augmentation pressure (9.6 ± 7.4 mmHg vs. 9.1 ± 5.7 mmHg; P = 0.740), and aortic pulse pressure (AoPP; 40.4 ± 14.0 mmHg vs. 42.1 ± 7.6 mmHg, P = 0.550). The first LA positive peak of strain was inversely related to the augmentation pressure (r = -0.30; P = 0.02) and aortic systolic pressure (r = -0.26, P = 0.04). Comparison between the two consecutive pulse wave measurements in 21 patients showed similar results, except for AoPP. In 21 patients, the AoPP at the second measurement (45.1 ± 14.1 mmHg) showed a significant increase compared with AoPP at the first measurement (39.0 ± 10.6 mmHg, P = 0.028), which was also higher than that of healthy controls (42.1 ± 7.6 mmHg, P = 0.000).

CONCLUSIONThe association between aortic stiffness with reduced atrial strain and the key role of AoPP in the development of AF should be considered when treating nonvalvular AF patients with normal LA sizes.

Adult ; Atrial Fibrillation ; physiopathology ; Atrial Function, Left ; physiology ; Atrial Remodeling ; physiology ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Vascular Stiffness ; physiology

OBJECTIVETo investigate the effect of atrial fibrillation on the accuracy of parameters monitored by transpulmonary thermodilution method.

METHODSTotally 12 patients from emergency intensive care unit with paroxysmal atrial fibrillation were enrolled. The hemodynamic parameters such as heart rate, mean arterial pressure, cardiac index, systemic vascular resistance index, intrathoracic blood volume index, and extravascular lung water index were monitored by transpulmonary thermodilution method before paroxysmal atrial fibrillation and during atrial fibrillation, the number of B-lines was detected by lung ultrasonography before and during paroxysmal atrial fibrillation. The changes of all the parameters were analyzed.

RESULTSWhen the paroxysmal atrial fibrillation happened, the heart rate increased significantly [(123.3±20.0) beat/min vs. (98.9±12.3) beat/min, P=0.006]; the mean arterial pressure [(86.9±10.2) mmHg vs. (93.0±12.5) mmHg, P=0.058], cardiac index [(2.82±0.62) L/(min·m(2)) vs. (3.31±1.02) L/(min·m(2)), P=0.058] and systemic vascular resistance index [(2254±947) dyn·s·cm(-5)·m(2) vs. (2302±828) dyn·s·cm(-5)·m(2), P=0.351] had no obvious change; however, the intrathoracic blood volume index significantly increased [(1333±90) ml/m(2) vs. (937±111) ml/m(2), P<0.001]; extravascular lung water index also increased significantly [(16.1±1.1) ml/kg vs. (6.5±1.9) ml/kg, P<0.001]. No significant difference was found in the number of B-lines detected by lung ultrasonography before and during atrial fibrillation (10.0±4.2 vs. 9.4±4.4, P=0.180).

CONCLUSIONBoth intrathoracic blood volume and extravascular lung water monitored by transpulmonary thermodilution method were overvalued during paroxysmal atrial fibrillation, which may mislead the clinical judgment and decision-making.

Atrial Fibrillation ; physiopathology ; Blood Pressure ; Blood Volume ; Cardiac Output ; Extravascular Lung Water ; Heart Rate ; Hemodynamics ; Humans ; Intensive Care Units ; Thermodilution ; Vascular Resistance

BACKGROUNDWarfarin is the most common oral anticoagulant to decrease the stroke risk associated with atrial fibrillation (AF). There are very few prospective studies that have explored whether warfarin has an association with damage on renal function in Chinese patients with nonvalvular AF (NVAF). The aim of this study was to evaluate the effects of warfarin on renal function and study the factors associated with kidney dysfunction in Chinese adult NVAF patients without dialysis therapy.

METHODSFrom January 2011 to December 2013, a total of 951 NVAF patients from 18 hospitals were enrolled. The estimated glomerular filtration rate (eGFR) was calculated from baseline and follow-up serum creatinine levels. Kaplan-Meier survival curves compared the survival of a ≥25% decline in eGFR (hereafter, endpoint), while Cox models estimated hazard ratios (HR s) and 95% confidence intervals for this event after adjustment for age, gender, and selected potential risk factors for renal dysfunction. Cox regression analysis of the various clinical potential variables was performed to identify the predictors of a ≥25% decline in eGFR.

RESULTSAfter a 58-month follow-up, 951 NVAF patients were divided by observation into warfarin (n = 655) and no anticoagulation groups (n = 296) and 120 (12.6%) patients experienced renal endpoint. Kaplan-Meier survival curves showed that the survival period was not different in the two groups (χ2 = 0.178, log-rank P= 0.67), but patients with systolic blood pressure (SBP) <140 mmHg have significant difference with patients with SBP ≥140 mmHg (χ2 = 4.903, log-rank P= 0.03). Multivariate Cox regression analysis revealed baseline eGFR and SBP as independent predictors of the endpoint, with HR s of 1.00, and 1.02, respectively.

CONCLUSIONIn patients with NVAF, eGFR and SBP are associated with the deterioration of kidney function while Warfarin is not the risk factor of the ≥25% decline in eGFR.

TRIAL REGISTRATIONChinese Clinical Trial Registry (No. ChiCTR-OCH-13003729); http://www.chictr.org.cn/showproj.aspx?proj = 5831.

Aged ; Anticoagulants ; adverse effects ; therapeutic use ; Atrial Fibrillation ; drug therapy ; physiopathology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Kaplan-Meier Estimate ; Kidney ; drug effects ; Male ; Middle Aged ; Prospective Studies ; Warfarin ; adverse effects ; therapeutic use

Catheter ablation has been recommended as a treatment option for paroxysmal atrial fibrillation (PAF) patients complicated with type 2 diabetes mellitus (T2DM). PAF patients with T2DM have a higher recurrence rate after catheter ablation. Prolongation of corrected QT (QTc) interval has been linked to poor outcomes in T2DM patients. Whether the abnormal QTc interval is associated with the ablation outcome in the PAF patients with T2DM remains unknown. In this study, 134 PAF patients with T2DM undergoing primary catheter ablation were retrospectively enrolled. Pre-procedural QTc interval was corrected by using the Bazett's formula. Cox proportional hazards models were constructed to assess the relationship between QTc interval and the recurrence of AF. After a 29.1-month follow-up period, 61 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had a longer QTc interval than non-recurrent patients (425.2±21.5 ms vs. 414.1±13.4 ms, P=0.002). Multivariate Cox regression analysis revealed that QTc interval [hazard ratio (HR)=1.026, 95% confidence interval (CI) 1.012-1.040, P=0.005] and left atrial diameter (LAD) (HR=1.125, 95% CI 1.062-1.192, P=0.003) were independent predictors of recurrent atrial tachyarrhythmia. Receiver operating characteristic analysis demonstrated that the cut-off value of QTc (418 ms) predicted arrhythmia recurrence with a sensitivity of 55.7% and a specificity of 69.9%. A combination of LAD and QTc was more effective than LAD alone (P<0.001) in predicting arrhythmia recurrence after the procedure. QTc interval could be used as an independent predictor of arrhythmia recurrence in T2DM patients undergoing AF ablation, thus providing a simple method to identify those patients who likely have a better outcome following the procedure.
Aged ; Atrial Fibrillation ; complications ; physiopathology ; surgery ; Catheter Ablation ; adverse effects ; Diabetes Mellitus, Type 2 ; complications ; physiopathology ; surgery ; Electrocardiography ; Female ; Heart Atria ; physiopathology ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Risk Factors ; Tachycardia ; physiopathology ; Treatment Outcome