1. Field of the Invention
The present invention relates to the treatment of medical conditions associated with the heart, and more particularly to treatment of cardiac arrhythmia by modification of neuronal signaling through one or more of the fat pads of the heart, and more particularly to treatment of post-operative atrial fibrillation by temporary modification of neuronal signaling through the atrioventricular and sinoatraial nodal fat pads of the heart.
2. Description of the Related Art
The autonomic nervous system (ANS) is divided into sympathetic and parasympathetic systems. Neural control of the heart is dependent on the levels of activity of the sympathetic and parasympathetic neurons and the interactions that occur between them. As disclosed in McGuirt, A. S., Autonomic interactions for control of atrial rate are maintained after SA nodal parasympathectomy, Am. J. Physiol. 272 (Heart Circ. Physiol. 41), 1997, H2525-H2533, for control of regional cardiac function, both pre- and post-junctional interactions occur between the separate autonomic projections to the heart, particularly at the end-organ target sites such as the SA node, the AV node, and contractile elements of the atria and ventricles. The sympathetic system increases the heart rate and ventricular contraction, dilates the blood vessels in skeletal muscles, constricts blood vessels in the skin and guts, increases blood sugar level, stimulates sweating, dilates the pupils, inhibits activities of the guts and gastric secretion. The parasympathetic system is more active at rest, having in general anabolic effects. For example, it slows down the heart rate, constricts the pupils, increases gastric secretion and intestinal motility.
The autonomic nervous system is formed from nerve cells or neurons, which receive, process, initiate and transmit messages through various signaling mechanisms. A neuron may terminate at one of three structures: a muscle, a gland, or another neuron. When a neuron terminates on a muscle or a gland, the neuron is said to “innervate” the structure. However, when two neurons join together, as they do within, for example, ganglionated plexsus of the nervous system, the junction between them is known as a “synapse.” Typically, a synapse involves a junction between an axon terminal of one neuron, which is referred to as the presynaptic neuron, and the dendrites or cell body of a second neuron, which is referred to as postsynaptic neuron. The dendrites and to a lesser extent the cell body of most neurons receive thousands of synaptic inputs, which are axon terminals from many other neurons. The grand postsynaptic potential depends on the sum of the activities of all presynaptic inputs.
The heart is formed from muscle cells that display pacemaker activity, which is to say that the heart initiates its own action potentials without any external influence. Cardiac cells are interconnected by gap junctions that enhance the spread of action potentials through the heart. In the normal physiologic process, heart conduction moves from cell to cell, from the sinoatrial (“SA”) node to the atrioventricular (“AV”) node, and from the atrium to the ventricles. Although the heart like many other organs is innervated by the autonomic nervous system, the role of the autonomic nervous system is essentially to modify the rate and strength of contraction.
Cardiac arrhythmias are abnormal conditions associated with the various chambers and other structures of the heart. Atrial fibrillation (“AF”) is the most frequently occurring sustained cardiac arrhythmia, particularly among the elderly and among patients with organic heart disease, as well as among patients recovering from coronary artery bypass graft (“CABG”) surgery; see Steinberg, Jonathan S., Postoperative Atrial Fibrillation: A Billion-Dollar Problem, Journal of the American College of Cardiology, Vol. 43, No. 6, 2004. AF occurs in, for example, as many as 50% of patients undergoing cardiac operations. Patients with chronic AF have symptomatic tachycardia or low cardiac output and have a 5-10% risk of thromboembolic complications and events.
Many treatments for AF are performed directly on the heart itself. A common treatment for AF is cardioversion, alone or in combination with anti-arrhythmic therapy, to restore sinus rhythm. Recurrence rates after such therapy as high as 75% have been reported. Pharmacologic therapy is associated with adverse effects in a significant proportion of patients with AF. Other more current conventional methods of treating AF center around ablation (destruction) of the aberrant conduction pathways, either through a surgical approach or by use of various forms of energy to ablate conduction to electrically isolate discrete atrial regions. However, ablation causes structural damage to the heart. Unfortunately, these techniques involve actions performed directly on the heart itself, and further have significant adverse consequences.
Ablation can involve removal of ganglia of the autonomic nervous system. The pulmonary veins and atria have rich autonomic innervation, largely via autonomic ganglia that exist in fat pads in various well defined pericardial locations, some adjacent to the pulmonary veins. It has long been recognized that autonomic manipulation and intervention can dramatically alter the threshold for AF induction and persistence, and this knowledge has in the past been used experimentally to create appropriate models of AF. Emerging data from clinical trials based on strategies for PV isolation indicate that clinical success may be possible without achieving complete isolation. These observations indicate that what is being achieved is not only isolation of the triggers for AF, but also modification of the substrate by ablation of autonomic innervation. See, for example, Lazzara et al., Selective In Situ Parasympathetic Control of the Canine Sinoatrial and Atrioventricular Nodes, Circulation Research, Vol. 32, March 1973, p. 393-401; Scherlag et al., Stimulation of the Sino-Atrial Fat Pad Converts Focal Pulmonary Vein Firing Into Atrial Fibrillation in the Dog Heart, Circulation, Vol. 108, No. 17, Oct. 28, 2003, p. 396. Various researchers have reported that experimental interference with the autonomic ganglia in the fat pads can achieve modification of tendency to AF, and early clinical studies ablating around the mouths of pulmonary veins by targeting sites at which stimulation produces measurable changes in autonomic tone, indicating sites of autonomic innervation downstream from the autonomic ganglia, have shown success in abolishing AF. See, for example, Pappone et al., Pulmonary Vein Denervation Enhances Long-Term benefit After Circumferential Ablation for Paroxysmal Atrial Fibrillation, Circulation, Vol. 109, 2004, r7-r14.
Unfortunately, conventional surgical excision and conventional energy ablation have many problems. Responses to ablation energy delivery modalities include hyperthermia along with collagen shrinkage and other substantial scarring responses. Moreover, many ablation techniques suffer from control of energy delivery and extent of impact therefrom in tissues at or beyond the targeted location. For example, many RF energy ablation devices and techniques cause charring, which is associated with the high temperature gradient. Undesired energy dissipation into surrounding tissues is often observed using many conventional energy ablation techniques.