Background.
The intrinsic cardiac autonomic nervous system (ICANS), which forms a neural network, has been shown to be a critical element responsible for the initiation and maintenance of atrial ...fibrillation (AF). We developed a technique to localize and ablate the ganglionated plexi (GP), which serves as the “integration centers” of the ICANS.
Method.
The four major atrial GP are localized by delivering high frequency stimulation (HFS; 20 Hz, 10–150 V, 1–10 ms pulse width) to atrial tissue where GP are presumed to be located. Sites showing a parasympathetic response, which is arbitrarily defined as ≥50% increase in mean R‐R interval during AF, was assigned as a GP site. Radiofrequency current is then applied to that site to eliminate the parasympathetic response. All patients received ablation of the four major atrial GP, followed by pulmonary vein antrum ablation.
Results.
Our preliminary results showed that all the four major atrial GP can be identified in the vast majority of patients. The parasympathetic response can be eliminated by applying radiofrequency current. In the first 83 patients, the percent of patients free of symptomatic AF or atrial tachycardia after a single ablation procedure was 80% at 12 months and 86% at a mean follow‐up of 22 months.
Conclusion.
These results indicate additional benefits of GP ablation to PV antrum ablation and improvement with time, particularly ≥ 12 months after ablation. We postulate that this late benefit may result from destruction of the autonomic neurons in the GP that cannot regenerate.
Abnormal cardiac metabolism or cardiac metabolic remodeling is reported before the onset of heart failure with reduced ejection fraction (HFrEF) and is known to trigger and maintain the mechanical ...dysfunction and electrical, and structural abnormalities of the ventricle. A dysregulated cardiac autonomic tone characterized by sympathetic overdrive with blunted parasympathetic activation is another pathophysiological hallmark of HF. Emerging evidence suggests a link between autonomic nervous system activity and cardiac metabolism. Chronic β-adrenergic activation promotes maladaptive metabolic remodeling whereas cholinergic activation attenuates the metabolic aberrations through favorable modulation of key metabolic regulatory molecules. Restoration of sympathovagal balance by neuromodulation strategies is emerging as a novel nonpharmacological treatment strategy in HF. The current review attempts to evaluate the ‘neuro-metabolic axis’ in HFrEF and whether neuromodulation can mitigate the adverse metabolic remodeling in HFrEF.
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The aim of this study was to investigate whether the combination of conventional pulmonary vein isolation (PVI) by circumferential antral ablation with ganglionated plexi (GP) modification in a ...single ablation procedure, yields higher success rates than PVI or GP ablation alone, in patients with paroxysmal atrial fibrillation (PAF).
Conventional PVI transects the major left atrial GP, and it is possible that autonomic denervation by inadvertent GP ablation plays a central role in the efficacy of PVI.
A total of 242 patients with symptomatic PAF were recruited and randomized as follows: 1) circumferential PVI (n = 78); 2) anatomic ablation of the main left atrial GP (n = 82); or 3) circumferential PVI followed by anatomic ablation of the main left atrial GP (n = 82). The primary endpoint was freedom from atrial fibrillation (AF) or other sustained atrial tachycardia (AT), verified by monthly visits, ambulatory electrocardiographic monitoring, and implantable loop recorders, during a 2-year follow-up period.
Freedom from AF or AT was achieved in 44 (56%), 39 (48%), and 61 (74%) patients in the PVI, GP, and PVI+GP groups, respectively (p = 0.004 by log-rank test). PVI+GP ablation strategy compared with PVI alone yielded a hazard ratio of 0.53 (95% confidence interval: 0.31 to 0.91; p = 0.022) for recurrence of AF or AT. Fluoroscopy duration was 16 ± 3 min, 20 ± 5 min, and 23 ± 5 min for PVI, GP, and PVI+GP groups, respectively (p < 0.001). Post-ablation atrial flutter did not differ between groups: 5.1% in PVI, 4.9% in GP, and 6.1% in PVI+GP. No serious adverse procedure-related events were encountered.
Addition of GP ablation to PVI confers a significantly higher success rate compared with either PVI or GP alone in patients with PAF.
The aim of this study was to investigate whether low-level tragus stimulation (LL-TS) treatment could reduce myocardial ischemia-reperfusion injury in patients with ST-segment elevation myocardial ...infarction (STEMI).
The authors' previous studies suggested that LL-TS could reduce the size of myocardial injury induced by ischemia.
Patients who presented with STEMI within 12 h of symptom onset, treated with primary percutaneous coronary intervention, were randomized to the LL-TS group (n = 47) or the control group (with sham stimulation n = 48). LL-TS, 50% lower than the electric current that slowed the sinus rate, was delivered to the right tragus once the patients arrived in the catheterization room and lasted for 2 h after balloon dilatation (reperfusion). All patients were followed for 7 days. The occurrence of reperfusion-related arrhythmia, blood levels of creatine kinase-MB, myoglobin, N-terminal pro-B-type natriuretic peptide and inflammatory markers, and echocardiographic characteristics were evaluated.
The incidence of reperfusion-related ventricular arrhythmia during the first 24 h was significantly attenuated by LL-TS. In addition, the area under the curve for creatine kinase-MB and myoglobin over 72 h was smaller in the LL-TS group than the control group. Furthermore, blood levels of inflammatory markers were decreased by LL-TS. Cardiac function, as demonstrated by the level of N-terminal pro-B-type natriuretic peptide, the left ventricular ejection fraction, and the wall motion index, was markedly improved by LL-TS.
LL-TS reduces myocardial ischemia-reperfusion injury in patients with STEMI. This proof-of-concept study raises the possibility that this noninvasive strategy may be used to treat patients with STEMI undergoing primary percutaneous coronary intervention.
Objectives We hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS). Background Previously, we showed that VNS can be ...antiarrhythmogenic. Methods Thirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9). Results Group 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms both p < 0.001; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms both p < 0.001). Conclusions LL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results.
Objectives This study was conducted to simulate sleep apnea-induced atrial fibrillation (AF) in an experimental model and to determine whether neural ablation will prevent AF. Background An ...increasing number of clinical reports have associated sleep apnea and AF, and many possible mechanisms responsible for this relationship have been proposed. Methods Thirty dogs anesthetized with Na-pentobarbital were ventilated by a positive pressure respirator. Protocol 1 (n = 14): After a right thoracotomy, atrial and pulmonary vein programmed pacing at 2× and 4× threshold determined the shortest atrial refractory period. Obstructive apnea was induced by turning off the respirator during end expiration for 2 min. During apnea, programmed pacing was performed with S1-S2 = 5 to 10 ms earlier than the atrial refractory period. Neural activity was monitored from the ganglionated plexi (GP) adjacent to the right pulmonary veins. Protocol 2 (n = 16): Electrical stimulation identified the GP at the right pulmonary artery (RPA). Programmed pacing was again instituted, below atrial refractory period, during 2 min of apnea. After radiofrequency ablation of the RPA GP, continuous programmed pacing was again repeated during 2 min of apnea. In 5 dogs, blood gases were determined at baseline and at 2 min of apnea. Results Protocol 1: During apnea, S1-S2 induced AF within 85 ± 38 s (9 of 10). In 1 case, AF occurred spontaneously at 1 min 36 s of apnea. Recorded GP neural activity progressively increased before AF onset. Systolic but not diastolic blood pressure rose significantly before AF (149 ± 26 mm Hg to 193 ± 38 mm Hg, p < 0.05). In 4 dogs, autonomic blockade prevented apnea-induced AF. Protocol 2: AF induced by pacing occurred in 8 of 11 dogs within the 2-min period of apnea, before neural ablation. After ablation, 0 of 6 showed AF during 2 min of apnea (p = 0.009). Conclusions This experimental model of apnea shows a reproducible incidence of AF. After neural ablation of the RPA GP or autonomic blockade, AF inducibility was significantly inhibited.
Epicardial adipose tissue (EAT) remodelling is closely related to the pathogenesis of atrial fibrillation (AF). We investigated whether metformin (MET) prevents AF‐dependent EAT remodelling and AF ...vulnerability in dogs. A canine AF model was developed by 6‐week rapid atrial pacing (RAP), and electrophysiological parameters were measured. Effective refractory periods (ERP) were decreased in the left and right atrial appendages as well as in the left atrium (LA) and right atrium (RA). MET attenuated the RAP‐induced increase in ERP dispersion, cumulative window of vulnerability, AF inducibility and AF duration. RAP increased reactive oxygen species (ROS) production and nuclear factor kappa‐B (NF‐κB) phosphorylation; up‐regulated interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α) and transforming growth factor‐β1 (TGF‐β1) levels in LA and EAT; decreased peroxisome proliferator‐activated receptor gamma (PPARγ) and adiponectin (APN) expression in EAT and was accompanied by atrial fibrosis and adipose infiltration. MET reversed these alterations. In vitro, lipopolysaccharide (LPS) exposure increased IL‐6, TNF‐α and TGF‐β1 expression and decreased PPARγ/APN expression in 3T3‐L1 adipocytes, which were all reversed after MET administration. Indirect coculture of HL‐1 cells with LPS‐stimulated 3T3‐L1 conditioned medium (CM) significantly increased IL‐6, TNF‐α and TGF‐β1 expression and decreased SERCA2a and p‐PLN expression, while LPS + MET CM and APN treatment alleviated the inflammatory response and sarcoplasmic reticulum Ca2+ handling dysfunction. MET attenuated the RAP‐induced increase in AF vulnerability, remodelling of atria and EAT adipokines production profiles. APN may play a key role in the prevention of AF‐dependent EAT remodelling and AF vulnerability by MET.
The autonomic nervous system is known to play a significant role in the genesis and maintenance of arrhythmias. Neuromodulation, mostly designed to increase the parasympathetic tone and suppress the ...sympathetic tone, has become an emerging therapeutic strategy for the treatment of arrhythmias. Emerging therapeutic approaches include cervical vagal stimulation, transcutaneous auricular vagal stimulation, baroreceptor activation therapy spinal cord stimulation, ganglionated plexi ablation, renal sympathetic denervation, and left cardiac sympathetic denervation.
The ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and left cardinal vein, and contains fat and fibrous tissues, blood vessels, muscle bundles, nerve fibers, and ganglia. The ...complexity of LOM's structure makes it as a source of triggers and drivers as well as substrates of re‐entry for atrial arrhythmias, especially for atrial fibrillation (AF). LOM also serves as a portion of left atrial macro‐re‐entrant circuit, especially peri‐mitral isthmus re‐entrant circuit. Experimental studies demonstrate that the LOM acts as a sympathetic conduit between the left stellate ganglion and the ventricles, and participates in the initiation and maintenance of ventricular arrhythmias. Endocardial or epicardial catheter ablation or ethanol infusion into the vein of Marshall may serve as an important adjunct therapy to pulmonary vein isolation in patients with advanced stage of AF, and may help alleviate ventricular arrhythmias as well.
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