Abstract
Ablation and anti-arrhythmic medications have shown promise but have been met with varying success and unwanted side effects such as myocardial injury, arrhythmias, and morbidity from invasive surgical intervention. The answer to improving efficacy of ablation may include modulation of the cardiac aspect of the autonomic nervous system. Our lab has developed a novel approach and device to navigate the oblique sinus and to use DC current and saline/alcohol irrigation to selectively stimulate and block the autonomic ganglia found on the epicardial side of the heart. This novel approach minimizes myocardial damage from thermal injury and provides a less invasive and targeted approach. For feasibility, proof-of-concept, and safety monitoring, we carried out canine studies to test this novel application. Our results suggest a safer and less invasive way of modulating arrhythmogenic substrate that may lead to improved treatment of AF in humans.
1
Introduction
Atrial fibrillation (AF) affects 2 million people in the United States, accounts for nearly six billion dollars in health care costs, and is predicted to continue to increase . AF is associated with serious morbidities such as stroke, increased hospitalizations, and mortality . Anti-arrhythmic drug therapies pose many side effects, as these agents are not tissue selective and can be pro-arrhythmic . Ablative strategies have been promising; however, they leave scarring of previously viable myocardial tissue from thermal injury . In conjunction with the aging population, there is an urgent need to develop improved modalities for effective treatment.
Manipulation of the autonomic nervous system has found increased use for ventricular arrhythmia management . These procedures require surgical techniques in order to ablate the neuronal ganglia . Interestingly, post-cardiac transplant patients have been shown to not have AF, suggesting that the denervated hearts are disconnected from a trigger for AF . These findings suggest that autonomic innervation plays a critical role in genesis or propagation of AF . Because of the location of the cardiac nerves and ganglia, an epicardial approach to ablation of these neurally active tissues may provide a means of modulating the AF trigger through a less-invasive approach. Furthermore, such an approach would not destroy myocardium from traditional endocardial ablation.
2
Methods and results
We conducted studies in canines for proof-of-concept and feasibility by carrying out autonomic modulation through an epicardial approach. We developed and employed novel leads and a percutaneous approach to stimulate, block, and ablate the epicardially situated autonomic nerves as a treatment for arrhythmia (Patent WO 2011/075328 A1) ( Fig. 1 ).
We employed a novel approach to navigate the pericardial space by using deflectable, asymmetrically shielded, linear electrodes which were placed under fluoroscopic guidance in order to record epicardial signals ( Fig. 2 ). The nitinol mesh-based electrode was constructed to fit into the oblique sinus ( Fig. 3 ). These electrodes have irrigation ports to which saline or alcohol can be injected. This allowed pointed irrigation toward the ganglia but also prevented delivery to the esophagus and surrounding cardiac structures. These approaches allowed for targeted therapy to the autonomic ganglia with sparing of the myocardium.
We collected data on 8 canine experiments. We first tested for signals to determine if we were in contact with the cardiac ganglia. Once the signal was recorded and verified, arrhythmias were induced by addition of acetylcholine. Once signal was recorded showing arrhythmia, we manipulated the arrhythmogenic substrate by using direct current (DC) and irrigation with saline or alcohol to temporarily block and/or ablate neural activity ( Fig. 4 ). In order to evaluate safety of the percutaneous epicardial approach we evaluated for and demonstrated viable tissue in two separate animal experiments ( Figs. 5 and 6 ).
