Abstract Recent experimental and clinical studies have shown that the epicardial autonomic ganglia play an important role in the initiation and maintenance of atrial fibrillation (AF). In this ...review, the authors present the current data on the role of the autonomic ganglia in the pathogenesis of AF and discuss potential therapeutic implications. Experimental studies have demonstrated that acute autonomic remodeling may play a crucial role in AF maintenance in the very early stages. The benefit of adding ablation of the autonomic ganglia to the standard pulmonary vein isolation procedure for patients with paroxysmal AF is supported by both experimental and clinical data. The interruption of axons from these hyperactive autonomic ganglia to the pulmonary vein myocardial sleeves may be an important factor in the success of pulmonary vein isolation procedures. The vagus nerve exerts inhibitory control over the autonomic ganglia, and attenuation or loss of this control may allow these ganglia to become hyperactive. Autonomic neuromodulation using low-level vagus nerve stimulation inhibits the activity of the autonomic ganglia and reverses acute electrical atrial remodeling during rapid atrial pacing and may provide an alternative nonablative approach for the treatment of AF, especially in the early stages. This notion is supported by a preliminary human study. Further studies are warranted to confirm these findings.
Low-level tragus stimulation (LLTS) is a non-invasive approach of transcutaneous vagus nerve stimulation. LLTS has applications in diseases of multiple systems, including epilepsy, depression, ...headache and potentially several cardiovascular diseases. LLTS has shown promising results in suppressing AF, alleviating post-MI ventricular arrhythmias and ischaemia-reperfusion injury along with improving diastolic parameters in heart failure with preserved left ventricular ejection fraction (HFpEF). Preliminary pilot clinical studies in patients with paroxysmal AF, HFpEF, heart failure with reduced ejection fraction and acute MI have demonstrated promising results. The beneficial effects are likely secondary to favourable alteration of the sympathovagal imbalance. On-going exploratory work focused on underlying mechanisms of LLTS in cardiovascular disease states and larger scale clinical trials will shed more light on the non-invasive modulation of the neuro-immune axis.
Intrinsic Cardiac Ganglia Activity Inhibited by Low‐Level Vagal Stimulation. Introduction: We hypothesized that low‐level vagosympathetic stimulation (LL‐VNS) can suppress atrial fibrillation (AF) by ...inhibiting the activity of the intrinsic cardiac autonomic nervous system (ICANS).
Methods and Results:
Wire electrodes inserted into both vagosympathetic trunks allowed LL‐VNS at 10% or 50% below the voltage required to slow the sinus rate or atrioventricular conduction. Multielectrode catheters were attached to atria, atrial appendages and all pulmonary veins. Electrical stimulation at the anterior right and superior left ganglionated plexi (ARGP, SLGP) was used to simulate a hyperactive state of the ICANS. Effective refractory period (ERP) and window of vulnerability (WOV) for AF were determined at baseline and during ARGP+SLGP stimulation in the presence or absence of LL‐VNS. Neural activity was recorded from the ARGP or SLGP. ARGP+SLGP stimulation induced shortening of ERP, increase of ERP dispersion and increase of AF inducibility (WOV), all of which were suppressed by LL‐VNS (10% or 50% below threshold) at all tested sites. Sham LL‐VNS failed to induce these changes. The effects of LL‐VNS were mediated by inhibition of the ICANS, as evidenced by (1) LL‐VNS suppression of the ability of the ARGP stimulation to slow the sinus rate, (2) the frequency and amplitude of the neural activity recorded from the ARGP or SLGP was markedly suppressed by LL‐VNS, and (3) the spatial gradient of the ERP and WOV from the PV‐atrial junction toward the atrial appendage was eliminated by LL‐VNS.
Conclusions:
LL‐VNS suppressed AF inducibility by inhibiting the neural activity of major GP within the ICANS. (J Cardiovasc Electrophysiol, Vol. 22, pp. 455‐463)
Rapid firing within pulmonary vein sleeves frequently initiates atrial fibrillation. The role of the autonomic nervous system in facilitating spontaneous firing is unknown.
The purpose of this study ...was to determine if autonomic nerve stimulation within canine atrium and pulmonary vein sleeves initiates arrhythmia formation.
Extracellular bipolar and intracellular microelectrode recordings were obtained from isolated superfused canine pulmonary veins (N = 28) and right atrium (N = 5) during local autonomic nerve stimulation.
Autonomic nerve stimulation decreased pulmonary vein sleeve action potential duration (APD90 = 160 +/- 17 to 92 +/- 24 ms; P < .01) and initiated rapid (782 +/- 158 bpm) firing from early afterdepolarizations in 22 of 28 pulmonary vein preparations. The initial spontaneous beat had a coupling interval of 97 +/- 26 ms. Failure to induce arrhythmia was associated with a failure to shorten APD90 (151 +/- 18 to 142 +/- 8 ms; P = .39). Muscarinic receptor blockade (atropine: 3.2 x 10(-8) M) prevented APD90 shortening in 8 of 8 preparations and suppressed firing in 6 of 8 preparations, whereas beta1-adrenergic receptor blockade (atenolol: 3.2 x 10(-8) M) suppressed firing in 8 of 8 preparations. Suppression of the Ca transient with ryanodine (10(-5) M) completely suppressed firing in 6 of 6 preparations. Inhibition of forward Na/Ca exchange by a transient increase in Ca+2o completely suppressed firing in 4 of 6 preparations. The same stimulus trains produce atropine-suppressed APD90 shortening in superfused right atrial free wall but fail to produce triggered arrhythmia.
The data demonstrate triggered firing within canine pulmonary veins with combined parasympathetic and sympathetic nerve stimulation. Both an enhanced Ca transient and increased Na/Ca exchange may be required for arrhythmia formation.
Animal models suggest that the neurotransmitter inhibitor, botulinum toxin, when injected into the epicardial fat pads can suppress atrial fibrillation inducibility. The aim of this prospective ...randomized double-blind study was to compare the efficacy and safety of botulinum toxin injection into epicardial fat pads for preventing atrial tachyarrhythmias.
Patients with history of paroxysmal atrial fibrillation and indication for coronary artery bypass graft surgery were randomized to botulinum toxin (Xeomin, Merz, Germany; 50 U/1 mL at each fat pad; n=30) or placebo (0.9% normal saline, 1 mL at each fat pad; n=30) injection into epicardial fat pads during surgery. Patients were followed for 1 year to assess maintenance of sinus rhythm using an implantable loop recorder. All patients in both groups had successful epicardial fat pad injections without complications. The incidence of early postoperative atrial fibrillation within 30 days after coronary artery bypass graft was 2 of 30 patients (7%) in the botulinum toxin group and 9 of 30 patients (30%) in the placebo group (P=0.024). Between 30 days and up to the 12-month follow-up examination, 7 of the 30 patients in the placebo group (27%) and none of the 30 patients in the botulinum toxin group (0%) had recurrent atrial fibrillation (P=0.002). There were no complications observed during the 1-year follow-up.
Botulinum toxin injection into epicardial fat pads during coronary artery bypass graft provided substantial atrial tachyarrhythmia suppression both early as well as during 1-year follow-up, without any serious adverse events.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01842529.
Pseudo-vagal Responses Elicited by Cryoballoon Ablation Sohinki, Daniel; Mehta, Vinay; Ardell, Jeffrey ...
The Journal of innovations in cardiac rhythm management (Print),
12/2023, Letnik:
14, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Pulmonary vein isolation via cryoballoon (CB) ablation is the cornerstone ablation strategy for the treatment of atrial fibrillation (AF). Acute intraprocedural hypotensive and/or bradycardic ...responses have been reported in patients undergoing CB ablation for AF. However, it remains unclear as to whether these are due to a true vagal response (VR), which can be used to predict long-term outcomes of CB ablation. We analyzed 139 freezes across 17 patients who received CB ablation for paroxysmal AF, measuring vital signs and freeze characteristics. Only one freeze was associated with both hypotension and bradycardia, constituting a true VR. Several freezes were associated with hypotension only that did not respond to atropine administration, suggesting that these responses are not associated with a VR. Hypotensive responses were significantly associated with ice bubble bursts during CB deflation. Unlike the true VR reported in patients undergoing conscious sedation, the presence of acute hypotension shortly after CB deflation cannot be used as a predictor for long-term ablation outcomes.
Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) ...would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.
Abstract
Aims
Mitral isthmus (MI) ablation is challenging. We hoped to close those conduction breakthrough sites (CBS) across the MI by elaborate mapping.
Methods and results
After the initial linear ...ablation, elaborately mapping large areas above and below the MI line and inside the coronary sinus (CS) was sequentially performed to identify the CBS. The shortest distance from the CBS to the MI line was measured. The distant CBS (D-CBS) was identified as those CBS >5.0 mm away from the MI line. We prospectively enrolled 177 consecutive patients. Bidirectional conduction blockage across MI was obtained in 50 (28.2%) patients after the initial linear ablation and was achieved in additional 115 (65.0%) patients following elaborate mapping and reinforcement ablation. After initial linear ablation, 272 CBS (2.14 ± 0.99 CBS/person) were identified, and 226 (83.1%) of them were characterized as D-CBS, including 98 sites (36.0%) >10.0 mm and 39 sites (14.3%) >15.0 mm away. Endocardial and epicardial (CS) reinforcement ablation eliminated 119/272 (43.8%) and 58/272 (21.3%) CBS, respectively. Among the 177 eliminated CBS, 138 D-CBS (78.0%, 11.2 ± 5.6 mm) were confirmed in 95 (74.8%) patients. Moreover, CBS along the course of ligament of Marshall was closed by endocardial ablation more frequently than that along the course of great cardiac vein (52.6%% vs. 35.1%, P = 0.004). Eventually, CS ablation was required only in 64 (38.8%) patients.
Conclusion
Distant CBS, accounted for the majorities of the residual conduction across the MI after initial ablation, could be effectively identified and accurately eliminated by elaborate mapping and ablation around the MI ablation line.
Renal Sympathetic Nerves and Ventricular Arrhythmias
Introduction
Renal sympathetic nerve (RSN) activity plays a key role in systemic sympathetic hyperactivity. Previous studies have shown that ...cardiac sympathetic hyperactivity, especially the left stellate ganglion (LSG), contributes to the pathogenesis of ventricular arrhythmias (VAs) after acute myocardial infarction (AMI).
Methods and Results
Twenty‐eight dogs received 3 hours of continuous left‐sided electrical stimulation of RSN (LRS; Group‐1, n = 9), sham RSN stimulation (Group‐2, n = 9), or LSG ablation plus 3 hours of LRS (Group‐3, n = 10) were included. AMI was induced by ligating the proximal left anterior descending coronary artery. LRS was performed using electrical stimulation on the adventitia of left renal artery at the voltage increasing the systolic blood pressure (BP) by 10%. BP, heart rate variability (HRV), serum norepinephrine (NE) level, and LSG function were measured at baseline and the end of each hour of LRS. C‐fos and nerve growth factor (NGF) protein expressed in the LSG were examined in Group‐1 and Group‐2. Compared with baseline, 3 hours of LRS induced a significant increase in BP, sympathetic indices of HRV, serum NE level, and LSG function. The incidence of VAs in Group‐1 was significantly higher than other groups. The expression of c‐fos and NGF protein in the LSG was significantly higher in Group‐1 than Group‐2.
Conclusion
Three hours of LRS induces both systemic and cardiac sympathetic hyperactivity and increases the incidence of ischemia‐induced VAs.
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