Transcriptomic analysis of epicardial adipose tissue reveals the potential crosstalk genes and immune relationship between type 2 diabetes mellitus and atrial fibrillation.

BACKGROUND: The complex relationship between atrial fibrillation (AF) and type 2 diabetes mellitus (T2DM) suggests a potential role for epicardial adipose tissue (EAT) that requires further investigation. This study employs bioinformatics and experimental approaches to clarify EAT's role in linking T2DM and AF, aiming to unravel the biological mechanisms involved. METHOD: Bioinformatics analysis initially identified common differentially expressed genes (DEGs) in EAT from T2DM and AF datasets. Pathway enrichment and network analyses were then performed to determine the biological significance and network connections of these DEGs. Hub genes were identified through six CytoHubba algorithms and subsequently validated biologically, with further in-depth analyses confirming their roles and interactions. Experimentally, db/db mice were utilized to establish a T2DM model. AF induction was executed via programmed transesophageal electrical stimulation and burst pacing, focusing on comparing the incidence and duration of AF. Frozen sections and Hematoxylin and Eosin (H&E) staining illuminated the structures of the heart and EAT. Moreover, quantitative PCR (qPCR) measured the expression of hub genes. RESULTS: The study identified 106 DEGs in EAT from T2DM and AF datasets, underscoring significant pathways in energy metabolism and immune regulation. Three hub genes, CEBPZ, PAK1IP1, and BCCIP, emerged as pivotal in this context. In db/db mice, a marked predisposition towards AF induction and extended duration was observed, with HE staining verifying the presence of EAT. Additionally, qPCR validated significant changes in hub genes expression in db/db mice EAT. In-depth analysis identified 299 miRNAs and 33 TFs as potential regulators, notably GRHL1 and MYC. GeneMANIA analysis highlighted the hub genes' critical roles in stress responses and leukocyte differentiation, while immune profile correlations highlighted their impact on mast cells and neutrophils, emphasizing the genes' significant influence on immune regulation within the context of T2DM and AF. CONCLUSION: This investigation reveals the molecular links between T2DM and AF with a focus on EAT. Targeting these pathways, especially EAT-related ones, may enable personalized treatments and improved outcomes.

Effect of uninterrupted dabigatran or rivaroxaban on achieving ideal activated clotting time to heparin response during catheter ablation in patients with atrial fibrillation.

BACKGROUND: Uninterrupted use of oral anticoagulants before atrial fibrillation (AF) ablation can reduce the incidence of perioperative thromboembolic events. However, the effect of new oral anticoagulants on activated clotting time (ACT) in response to heparin during AF ablation in Chinese populations remains unknown. The aim of the present retrospective study was to investigate the value of ACTs in response to intraoperative heparin administration in patients using dabigatran or rivaroxaban. METHODS: From January 2018 to December 2021, a total of 173 patients undergoing AF ablation were included in the study, in which 101 patients were treated with dabigatran, 72 patients were treated with rivaroxaban. The intraoperative ACT values were examined in both groups. The incidence of periprocedural complications was evaluated. RESULTS: Initial heparin dosage (88 ± 19 U/kg vs. 78 ± 27 U/kg, P < 0.05), total heparin dosage (137 ± 41 U/kg vs. 106 ± 52 U/kg, P < 0.05) during the ablation procedure were higher in the dabigatran group than those in the rivaroxaban group. Mean ACT (280 ± 36 s vs. 265 ± 30 s, P < 0.05), and the percentage of ACTs within the therapeutic range (250-350 s) (74% ± 26% vs. 60% ± 29%, P < 0.05) were significantly lower in the dabigatran group than those in the rivaroxaban group, particularly in male patients. Furthermore, the average time of achieving the target ACT (250-350 s) was also found longer in the dabigatran group (P < 0.05) as compared with the rivaroxaban group. No significant difference was found in the incidence of periprocedural complications between the two groups. CONCLUSIONS: The anticoagulant effect of uninterrupted rivaroxaban therapy appears to be more stable and efficient than dabigatran administration during catheter ablation in patients with AF.

[Dynamic comparisons of epicardial electrograms between the left atrium and pulmonary veins in atrial fibrillation in goat model].

Objective: To compare epicardial electrograms between the left atrium (LA) and pulmonary veins (PVs) dynamically at development of persistent atrial fibrillation(AF) in goats PVs. Methods: Ten female goats were instrumented with electrodes at the LA and left side PV. Sustained AF (＞24 h) was induced in the goat by rapid intermittent left atrial pacing for(9.5±2.3)days at a pacing interval of 20 ms for 1 s with a maximum output of 6.0 V, followed by a 2-s period without pacing. Characteristics of PVs and LA epicardial electrograms were analyzed in the development of AF. Results: With prolonged stimulation, the duration of AF was prolonged, complex fractionated atrial electrograms(CFAEs) in LA and was increased gradually, PVs had more CFAEs than LA all the time. When induced AF lasted for more than 24 h, CFAEs in PVs became sustained approximately (2.7%±3.6% vs 92.6%±6.4%, at onset of AF vs AF lasted for more than 24 h, P＜0.05), and the ratio of CFAEs in PVs was more than that in LA (92.6%±6.4% vs 72.8%±5.3%, P＜0.05). Conclusion: The epicardial CFAEs are in specific area, which increase along with electrical remodeling. The epicardial CFAEs may play an important role in the maintenance of AF in this model.

Amplitude reduction of autonomic nerve function is correlated with ablation lesion quality in patients with paroxysmal atrial fibrillation.

OBJECTIVE: Circumferential pulmonary vein isolation (CPVI) is a common procedure that is performed on patients with atrial fibrillation (AF). However, AF may recur in some patients after treatment. This study assesses the association between autonomic modulation and late recurrence after CPVI and between autonomic modulation and ablation lesion quality. METHODS: We prospectively enrolled 72 patients with paroxysmal AF who underwent CPVI from January 2017 to January 2018. Pre- and post-ablation 24 h electrocardiograms were performed to document heart rate variability (HRV), which represents cardiac autonomic function. The intraablation force-time integral (FTI) was used to indicate the extent of ablation injury. Patients were followed up for 12 months after the procedure and cases of AF recurrence were recorded. RESULTS: Changes in HRV decreased after the procedure, which was correlated with FTI (ΔSDNN: r = -0.26, P = 0.03; ΔrMMSD: r = -0.28, P = 0.02; ΔlnHF: r = -0.22, P = 0.04; ΔLnLF: r = -0.29, P = 0.01). Patients without AF recurrence had more pronounced ΔLF (-21.84 ± 33.21% vs. -8.68 ± 34.59%, P = 0.01) and ΔHF (-17.26 ± 16.61% vs. -1.28 ± 9.81%, P = 0.01) than patients with recurrence. Multivariate regression analysis showed that both ΔLF (HR: 1.07, P = 0.04) and ΔHF (HR: 1.11, P = 0.01) were associated with AF recurrence. After adjusting for FTI, ΔLF was no longer associated with AF recurrence (HR: 1.05, P = 0.10). ΔHF remained associated with AF recurrence (HR: 1.08, P = 0.03), but the correlation coefficient was decreased (HR: 1.08, P = 0.03). CONCLUSION: Decreased autonomic nerve function is a valid predictor of AF recurrence and is indicated by the extent of ablation injury, which is independently associated with AF recurrence after CPVI.

Effects of Statin on Arrhythmia and Heart Rate Variability in Healthy Persons With 48-Hour Sleep Deprivation.

BACKGROUND: It has been reported that sleep deprivation is associated with cardiac autonomic disorder, inflammation, and oxidative stress. Statins have significant cardiovascular protective effects in patients with cardiovascular disease. This study aimed to investigate the protective effect of statins on arrhythmia and heart rate variability in young healthy persons after 48-hour sleep deprivation. METHODS AND RESULTS: This study enrolled 72 young healthy participants aged 26.5±3.5 years. All participants received 48-hour continuous ambulatory electrocardiogram monitoring. Arrhythmia, time, and frequency domain parameters were analyzed for all participants. The primary end point, low/high frequency ratio, was significantly lower in the statin group than in the control group (2.48±1.12 versus 3.02±1.23, P<0.001). After 48-hour sleep deprivation, low frequency-the frequency of premature atrial complexes and premature ventricular complexes-was significantly decreased in the statin group compared with the control group (P<0.05). There was also a significant increase in high frequency in the statin group compared with the control group (P<0.05). There was a significant decrease in serum high-sensitivity C-reactive protein and malondialdehyde levels after 48-hour sleep deprivation in the statin group compared with the control group (P<0.05). CONCLUSIONS: Statin use might be associated with improvement in arrhythmia and heart rate variability in healthy persons with 48-hour sleep deprivation. This finding should be confirmed by larger scale trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02496962.

Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: The Beijing PLA Hospital Atrial Fibrillation Project.

The risks of major bleeding and intracranial hemorrhage (ICH) are higher in Asian patients with atrial fibrillation (AF) compared to non-Asians. We aimed to investigate risk factors for bleeding, and validate the predictive value of available bleeding risk scores (mOBRI, HEMORR2HAGES, Shireman, HAS-BLED, ATRIA and ORBIT) in a large cohort of Chinese inpatients with AF. Using hospital electronic medical databases, we identified 4824 AF patients (mean age 67 years; 34.9% female) from January 1, 1995 to May 30, 2015, with median (interquartile) in-hospital days of 10 (7-16) days. On multivariate analysis, prior bleeds, vascular disease, anemia, prior stroke, and liver dysfunction were independent risk factors of major bleeding (all p < 0.05). C-statistics (95%CI) of the HAS-BLED score were 0.72 (0.65-0.79) for major bleeding events and 0.83 (0.75-0.91) for ICH (all p < 0.001). Compared to other risk scores, the HAS-BLED score was significantly better in predicting major bleeding events (Delong test, all P < 0.05, apart from mOBRI, HEMORR2HAGES) and ICH (all p < 0.05), and additionally, resulted in a net reclassification improvement (NRI) of 17.1-65.5% in predicting major bleeding events and 29.5-67.3% in predicting ICH (all p < 0.05). We conclude that the HAS-BLED score had the best predictive and discriminatory ability for major bleeding and ICH in an Asian/Chinese AF population.

Is dabigatran efficacy enough to prevent stroke in atrial fibrillation patient with high CHADS2 score during peri-procedural catheter radiofrequency ablation? A case report with literature review.

Atrial fibrillation (AF) is a major cause of thromboembolic (TE) events including stroke and transient ischemic attacks, catheter radiofrequency ablation (CA) has been demonstrated to effectively eliminate AF in majority of patients. During the peri-procedural CA of AF, dabigatran, a reversible direct thrombin inhibitor, has been proved as safe and efficacy as warfarin in the prevention of thromboembolic complication. However, for patients with CHADS2 score ≥3, sometimes dabigatran may not be an ideal substitute of warfarin. The current study presents delayed stroke occurred in a middle-aged AF patient with high CHADS2 score who had undergone successful CA of AF being on dabigatran, trans esophageal echocardiogram (TEE) detected a clot in the left atrium appendage (LAA) and magnetic resonance image (MRI) indicated stroke of left basal ganglia, therefore anticoagulant was switched to warfarin with well controlled international normalization ratio (INR) ranging from 2.0-3.0 and the patient eventually recovered without any TE events during the subsequent follow-up.

Renal denervation suppresses atrial fibrillation in a model of renal impairment.

BACKGROUND: A close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity. OBJECTIVE: The main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI. METHODS: Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured. RESULTS: Embolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN. CONCLUSIONS: RDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue.

Electrophysiological characteristics of paroxysmal atrial fibrillation originating from superior vena cava: a clinical analysis of 30 cases.

To analyze characteristics of electrocardiogram (ECG), electrophysiological intracardiac mapping and radiofrequency ablation (RF) of paroxysmal atrial fibrillation (PAF) originating from superior vena cava (SVC), aiming to investigate electrophysiological characteristics of PAF with SVC origin. Clinical data of 30 subjects (18 men and 12 women, aged, 58.6 ± 15.5 years) with PAF of SVC origin were retrospectively analyzed; All patients underwent RF during 2006.9-2012.7. ECG of AF and atrial premature contractions (APCs), procedure and fluoroscopic time, numbers of ablation sites within SVC, complications and success rate were studied. Compared with P wave of sinus rhythm (SR), APCs of SVC origin exhibited higher amplitude in lead II (0.23 ± 0.11 vs. 0.15 ± 0.06 mv), III (0.19 ± 0.09 vs. 0.13 ± 0.08 mv), AVF (0.21 ± 0.13 vs. 0.14 ± 0.10 mv), V2 (0.24 ± 0.07 vs. 0.15 ± 0.09 mv) and V3 (0.21 ± 0.09 vs. 0.12 ± 0.05 mv) (P < 0.05), as well as more biphasic polarity in lead V1 (80.0% vs. 26.6%, P < 0.05) and isoelectric in AVL (60.0% vs. 6.7%, P < 0.05). In terms of left pulmonary vein (LPV) and right pulmonary vein (RPV) electrical isolation, procedure time (14.3 ± 11.5 vs. 33.7 ± 14.2, 28.1 ± 6.8 min, P < 0.05), fluoroscopic time (9.6 ± 3.8 vs. 21.1 ± 9.3, 19.4 ± 9.7 min, P < 0.05), ablation sites (11.2 ± 3.1 vs. 37.1 ± 13.7, 31.4 ± 10.4 points, P < 0.05) of SVC isolation (SVCI) remarkably decreased compared with that of mean LPV and RPV. After the procedure, 9 patients still presented paroxymal rapid firing within the SVC in the setting of SR restoration, 2 patients developed paroxysmal atrial flutter within 1 month after completion of ablation and were controlled by antiarrhythmic drugs. The APCs and AF of SVC origin manifested distinctive ECG features, which could be helpful to distinguish SVC from other foci before ablation, the completion of SVCI required shorter procedure and fluoroscopic time, as well as less ablation points, and meanwhile, the success rate was high with less complication.

Establishment of a model of renal impairment with mild renal insufficiency associated with atrial fibrillation in canines.

BACKGROUND: Chronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF. METHODS: Unilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed. RESULTS: Embolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group. CONCLUSIONS: We successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model.

Protective effect of metoprolol on arrhythmia and heart rate variability in healthy people with 24 hours of sleep deprivation.

PURPOSE: Sleep deprivation, which is a strong stressor, can greatly affect the cardiovascular system of rescue workers. This study aimed to investigate the effect of 24-h sleep deprivation on heart rate variability (HRV) in young healthy people and the protective effect of metoprolol on arrhythmia. METHODS: Sixty young, healthy subjects (6 women and 54 men), aged 25 ± 4.5 years, were enrolled in this study. All participants received 24-h continuous ambulatory electrocardiogram monitoring. Arrhythmia, time, and frequency domain parameters were analyzed in subjects at the following three stages: normal sleep stage, sleep deprivation stage, and metoprolol treatment before sleep deprivation stage. RESULTS: After 24-h sleep deprivation, the high frequency (HF) of HRV was significantly decreased (p < 0.05), low frequency (LF) was remarkably increased (p < 0.05), and LF/HF was significantly increased compared with those in normal sleep (p < 0.05). Some subjects presented with mild palpitation due to premature atrial complexes and premature ventricular complexes. At the metoprolol treatment stage, compared with the sleep deprivation stage, LF and LF/HF were significantly reduced, HF of HRV was elevated (p < 0.05), and the total amount of premature atrial and ventricular complexes was decreased. CONCLUSION: The underlying mechanism of arrhythmia and HRV alteration after 24-h sleep deprivation could be attributable to lower vagal activity and elevated sympathetic activity. Metoprolol improves the change in autonomic nervous system activity after 24-h sleep deprivation, which may be responsible for its protective role on arrhythmia in healthy subjects undergoing sleep deprivation.

[Ultrastructural study of the pulmonary veins in pigs].

OBJECTIVE: To explore the possible relationship between the ultrastructural characteristics of pulmonary veins and the pathogenesis of atrial fibrillation originating from pulmonary veins. METHODS: The pulmonary veins from domestic pigs were serially sectioned (2 mm) transversely along the vessels. The odd number sections were fixed in 10% phosphate buffered formalin solution and the even number sections were fixed in 3% Glutaral for further electron microscopy observations. RESULTS: Two cell types were found in the pulmonary veins of pigs. One cell type was the P-like cells that had an empty-appearing cytoplasm containing only sparse myofibrils and small mitochondria, both of which were randomly distributed. Another cell type was slender transitional cells with plenty of longitudinally displayed myofibrils. CONCLUSION: P-like cells in the pig pulmonary veins were found using electron microscopy in this study and ectopic beats from P-like cells in the myocardial sleeves in the pulmonary veins might be responsible for atrial fibrillation originating from pulmonary veins.

[Effects of atrial excitable period on the stability of atrial fibrillation in goats].

OBJECTIVE: To investigate the effects of atrial excitable period (EP) on the stability of atrial fibrillation (AF) in goats. METHODS: Ten female goats were instrumented with epicardial electrodes patches on the left atrium (LA) free wall. AF was induced and maintained by a home-made stimulator with frequency of 50 Hz at a 1-second duration and a 2-seconds interval. The stimulator was disconnected regularly. AF-induced duration, average AF cycle length (AFCL), and atrial effective refractory period during AF (ERP(AF)) were measured; EP was calculated by AFCL-ERP(AF). RESULTS: Eight goats were studied. Persistent AF (> 24 h) could be induced in all the 8 goats within 6-16 days. When the induced AF lasted for 3-10 min or 24 h, the AFCL was 98.3 ms +/- 11.0 ms and 84.9 ms +/- 5.2 ms (P < 0.05), respectively, ERP(AF) was 90.5 ms +/- 13.2 ms and 63.0 ms +/- 4.8 ms (P < 0.05), respectively, and EP was 7.8 ms +/- 2.4 ms and 21.9 ms +/- 3.5 ms (P < 0.05), respectively. CONCLUSION: The decrease in ERP(AF) is more significant than the shortening in AFCL, resulting in the gradually widening of EP which may contribute to the perpetuation of AF.