Ganglionated plexi as neuromodulation targets for atrial fibrillation

The autonomic nervous system plays an important role in the genesis of atrial fibrillation and is one of the candidate targets for atrial fibrillation therapy. This review focuses on the role of the autonomic nervous system in atrial fibrillation development and discusses the results of the ganglionated plexi catheter and surgical ablation in preclinical and clinical studies. The heart is innervated by the extrinsic and intrinsic autonomic nervous systems. The intrinsic autonomic nervous system consists of multiple ganglionated plexi and axons, which innervate the neighboring atrial myocardium and control their electrophysiological properties. Abnormal autonomic innervation has been observed in an animal model of atrial fibrillation and in humans. Direct recordings of autonomic nerve activity in canine models showed that atrial tachyarrhythmia episodes were invariably preceded by intrinsic cardiac autonomic nerve activity, thus supporting the importance of intrinsic cardiac autonomic nerve activity as the triggers for atrial tachyarrhythmia. Targeting ganglionated plexi with catheter ablation improves the outcomes of paroxysmal atrial fibrillation ablation in addition to pulmonary vein antrum isolation. Ablation of ganglionated plexi alone without pulmonary vein isolation is also useful in controlling paroxysmal atrial fibrillation in some patients. However, surgical ganglionated plexi ablation in patients with a large left atrium, persistent atrial fibrillation, and/or a history of prior catheter ablation does not result in additional benefits. These different outcomes suggest that ganglionated plexi ablation is effective in managing patients with paroxysmal atrial fibrillation, but its effects in patients with persistent atrial fibrillation and advanced atrial diseases might be limited

Effects of carvedilol on cardiac autonomic nerve activities during sinus rhythm and atrial fibrillation in ambulatory dogs

AIMS: We hypothesized that carvedilol can effectively suppress autonomic nerve activity (ANA) in ambulatory dogs during sinus rhythm and atrial fibrillation (AF), and that carvedilol withdrawal can lead to rebound elevation of ANA. Carvedilol is known to block pre-junctional β2-adrenoceptor responsible for norepinephrine release. METHODS AND RESULTS: We implanted radiotransmitters to record stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and superior left ganglionated plexi nerve activity (SLGPNA) in 12 ambulatory dogs. Carvedilol (12.5 mg orally twice a day) was given for 7 days during sinus rhythm (n = 8). Four of the eight dogs and an additional four dogs were paced into persistent AF. Carvedilol reduced heart rate [from 103 b.p.m. (95% confidence interval (CI), 100-105) to 100 b.p.m. (95% CI, 98-102), P = 0.044], suppressed integrated nerve activities (Int-NAs, SGNA by 17%, VNA by 19%, and SLGPNA by 12%; all P < 0.05 vs. the baseline), and significantly reduced the incidence (from 8 ± 6 to 3 ± 3 episodes/day, P < 0.05) and total duration (from 68 ± 64 to 16 ± 21 s/day, P < 0.05) of paroxysmal atrial tachycardia (PAT). Following the development of persistent AF, carvedilol loading was associated with AF termination in three dogs. In the remaining five dogs, Int-NAs were not significantly suppressed by carvedilol, but SGNA significantly increased by 16% after carvedilol withdrawal (P < 0.001). CONCLUSION: Carvedilol suppresses ANA and PAT in ambulatory dogs during sinus rhythm

Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index:a nationwide population-based study

We evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: 2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI 2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight

Efficacy and Safety of Oral Anticoagulants for Atrial Fibrillation Patients With Chronic Kidney Disease:A Systematic Review and Meta-Analysis

BACKGROUND: Data on different direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with renal impairment are insufficient. We aimed to perform pairwise and network meta-analysis comparing oral anticoagulants (OACs) in AF patients with renal impairment, including advanced chronic kidney disease (CKD) with creatinine clearance <30 mL/min. METHODS: PubMed, Embase, Cochrane Database, and references of related articles were searched up to April 2021. We included randomized trials and non-randomized studies using propensity-score or multivariable-model adjustments that compared clinical outcomes among OACs. Hazard ratios (HRs) for stroke or thromboembolism, major bleeding, and all-cause death were pooled using random-effects model. RESULTS: From 19 studies, 124,628 patients were included. In patients with AF and CKD, DOACs presented significantly lower risks of stroke or thromboembolism [HR(pooled) = 0.78, 95% confidence interval (CI) = 0.73–0.85, I(2) = 16.6%] and major bleeding [HR(pooled) = 0.76 (0.64–0.89), I(2) = 85.7%] when compared with warfarin, regardless of the severity of renal impairment. Results were consistent in advanced CKD patients for stroke or thromboembolism [HR(pooled) = 0.60 (0.43–0.85), I(2) = 0.0%] and major bleeding [HR(pooled) = 0.74 (0.59–0.93), I(2) = 30.4%]. In the network meta-analysis, edoxaban and apixaban presented the highest rank probability to reduce the risk of stroke or thromboembolism (edoxaban, P-score = 94.5%) and major bleeding (apixaban, P-score = 95.8%), respectively. Apixaban remained the safest OAC with the highest rank probability for major bleeding (P-score = 96.9%) in patients with advanced CKD. CONCLUSION: DOACs, particularly apixaban and edoxaban, presented superior efficacy and safety than warfarin in AF patients with CKD. Apixaban was associated with the lowest risk of major bleeding among OACs for patients with advanced CKD. SYSTEMATIC REVIEW REGISTRATION: [PROSPERO], identifier [CRD42021241718]

Clinical outcomes in patients with persistent atrial fibrillation after technologic advances including contact force-guided and ablation index-guided ablation

We aimed to evaluate the influence of technological advances on ablation outcomes in patients with persistent atrial fibrillation (AF) (PeAF). Radiofrequency ablation for patients with AF has advanced, including contact force (CF)-sensing catheters and the ablation index (AI). Between 2009 and 2018, we analyzed 173 patients with PeAF who underwent catheter ablation. We categorized them into three groups: AF ablation without CF and AI information (no-CF group, n = 63), with CF without AI (CF-only group, n = 49), and with optimal AI-guided ablation (AI group, n = 61). Early (within 3months, ER) and late (from 3months to 1year, LR) AF recurrence after ablation was assessed. Procedure-related complications were also evaluated. The baseline characteristics were similar among the 3 groups, excluding the baseline antiarrhythmic drug history. Additional substrate modification after pulmonary vein isolation was significantly low in frequency in the AI group (71.4%, no-CF; 69.4%, CF-only; 41.0%, AI, p = 0.001). The AI group had a shorter mean procedure-related time than the other groups. Both ER and LR of PeAF showed a trend of reduction with technological advances. With a short experience (less than 1year), the CF-only group showed more ER and LR than that shown by the AI group. However, with a long experience (more than 1year), ER and LR occurred similarly in the two groups. Procedure-related complications improved with technological advances. As ablation technology advanced, favorable clinical outcomes with short procedural times were observed. However, prospective, large multicenter studies are needed to verify these results.This work was supported by the Korea Medical Device Development Fund grant funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14) and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (Grant 2020R1F1A106740)

Impedance drop determines ablation lesion volume at the same level of ablation index

New parameters such as ablation index (AI) have been developed to create reliable ablation lesions. This study was performed to evaluate whether RF energy delivery with the same ablation index creates the similar ablation lesion volume. Ablation lesions were created in 5 pig hearts at ex-vivo state. Ablation was performed using an external-irrigation contact-force sensing catheter on the epicardial side of the left ventricle with 90-degree of angle. RF ablation time was adjusted for targeting AI 600 at 8 different conditions. Lesion volume created with 0–5g of contact force at 20 W was significantly lower than that of 11–20g at 40W despite of the same AI (125 ± 76.2 vs. 272 ± 49.5 mm3, P < 0.05). Quality of ablation lesion was variable in the condition of poor contact at low power for the ablation of ex-vivo swine left ventricle, and high-quality lesions could be expected when the impedance drop is satisfactory even though the same level of AI is applied during ablation