Vagus Nerve Stimulation Suppresses Atrial Fibrillation
Vagus Nerve Stimulation Suppresses Atrial Fibrillation
Background Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines.
Objectives This study examined the antiarrhythmic and anti-inflammatory effects of LLTS in humans.
Methods Patients with paroxysmal AF who presented for AF ablation were randomized to either 1 h of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 h of LLTS or sham treatment. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor alpha and C-reactive protein, using a multiplex immunoassay.
Results There were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared with baseline in the LLTS group, but not in the control subjects (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in control subjects (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus tumor necrosis factor (TNF)-alpha and C-reactive protein levels decreased significantly only in the LLTS group.
Conclusions LLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF.
The most common cardiac arrhythmia, atrial fibrillation (AF), is associated with significant cardiovascular morbidity and mortality. The current therapy to maintain sinus rhythm in patients with drug-refractory AF is surgical or catheter ablation. Despite being more efficacious than antiarrhythmic drugs, the long-term outcome of ablation for even the earliest stage of AF (paroxysmal AF) is disappointing (event-free survival <50% at 5 years). As the population ages, the AF population in the United States is expected to reach 15 million by 2050, leading to a quest for alternative nonpharmacological, nonablative therapies for managing patients with drug-refractory AF.
Neuromodulation is a novel therapy that has been used successfully in various diseases, including epilepsy and heart failure (HF). We and other investigators have shown that low-level cervical vagus nerve stimulation (LLVNS), at voltages substantially below that associated with slowing the sinus rate or atrioventricular (AV) nodal conduction, significantly suppresses AF inducibility and shortens AF duration. More recently, we demonstrated in canines that AF inducibility was suppressed by LLVNS using a completely noninvasive approach by transcutaneous low-level stimulation of the tragus (LLTS), the anterior protuberance of the ear, where the auricular branch of the vagus nerve is accessible. In the present study, we evaluated the antiarrhythmic effects of 1-h LLTS in patients referred for catheter ablation of paroxysmal AF. In addition, we examined the anti-inflammatory effects of LLTS in these patients.
Abstract and Introduction
Abstract
Background Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines.
Objectives This study examined the antiarrhythmic and anti-inflammatory effects of LLTS in humans.
Methods Patients with paroxysmal AF who presented for AF ablation were randomized to either 1 h of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 h of LLTS or sham treatment. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor alpha and C-reactive protein, using a multiplex immunoassay.
Results There were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared with baseline in the LLTS group, but not in the control subjects (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in control subjects (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus tumor necrosis factor (TNF)-alpha and C-reactive protein levels decreased significantly only in the LLTS group.
Conclusions LLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF.
Introduction
The most common cardiac arrhythmia, atrial fibrillation (AF), is associated with significant cardiovascular morbidity and mortality. The current therapy to maintain sinus rhythm in patients with drug-refractory AF is surgical or catheter ablation. Despite being more efficacious than antiarrhythmic drugs, the long-term outcome of ablation for even the earliest stage of AF (paroxysmal AF) is disappointing (event-free survival <50% at 5 years). As the population ages, the AF population in the United States is expected to reach 15 million by 2050, leading to a quest for alternative nonpharmacological, nonablative therapies for managing patients with drug-refractory AF.
Neuromodulation is a novel therapy that has been used successfully in various diseases, including epilepsy and heart failure (HF). We and other investigators have shown that low-level cervical vagus nerve stimulation (LLVNS), at voltages substantially below that associated with slowing the sinus rate or atrioventricular (AV) nodal conduction, significantly suppresses AF inducibility and shortens AF duration. More recently, we demonstrated in canines that AF inducibility was suppressed by LLVNS using a completely noninvasive approach by transcutaneous low-level stimulation of the tragus (LLTS), the anterior protuberance of the ear, where the auricular branch of the vagus nerve is accessible. In the present study, we evaluated the antiarrhythmic effects of 1-h LLTS in patients referred for catheter ablation of paroxysmal AF. In addition, we examined the anti-inflammatory effects of LLTS in these patients.
Source...