Patent Abstract:
Epicardial fat pad ablation is conducted using a catheter inserted through the chest wall, using ultrasound ablation, or using a catheter fitted with a directional ultrasound transducer and capable of being aligned with the epicardium. The epicardial fat pad locations are determined using noninvasive imaging methods, or using electrical maps. These locations are then displayed on maps or images of the heart, and thus targeted for minimally invasive or non invasive therapy. The methods of the present invention are less invasive than conventional methods of ablation, and permit flexible access to substantially any point on the epicardium.

Full Description:
BACKGROUND OF THE INVENTION  
       [0001]     1. Field of the Invention  
         [0002]     This invention relates to control of cardiac arrhythmias. More particularly, this invention relates to minimally invasive methods for modifying the effects of the autonomic nervous system on the heart by denervation of epicardial fat pads.  
         [0003]     2. Description of the Related Art  
         [0004]     Innervation of the heart by the parasympathetic nervous system has a marked influence on aspects of the heart rhythm, and inter alia on atrial fibrillation. Recent research has demonstrated that parasympathetic ganglia are located in discrete epicardial fat pads:  
         [0005]     The RPV fat pad, situated at the junction of the right atrium (RA) and right pulmonary veins (RPV), provides direct vagal inhibition of the sinoatrial (SA) node.  
         [0006]     The IVC-ILA fat pad, situated at the junction of the inferior vena cava (IVC) and the inferior left atrium (ILA), selectively innervate the atrioventricular (AV) nodal region and regulate AV conduction.  
         [0007]     The SVC-AO fat pad, situated between the medial superior vena cava (SVC) and aortic root superior to the right pulmonary artery, connects to vagal fibers projecting to both atria and to the IVC-ILA and PV fat pads.  
         [0008]     It is known that individuals having a high level of vagal tone are predisposed to supraventricular arrhythmias, particularly atrial fibrillation. Ablation of epicardial fat pads has been found to affect vagally mediated atrial fibrillation. For example, in the document  Catheter Ablation of Cardiac Autonomic Nerves for Prevention of Vagal Atrial Fibrillation , Jackman et al., Circulation 2000; 102:2774-2780, transvascular radiofrequency (RF) ablation of cardiac autonomic nerves for prevention of vagal atrial fibrillation in dogs is described, using an ablation catheter in the right pulmonary artery and or superior or inferior vena cava. A catheter that can be used for this purpose is described in commonly assigned U.S. Pat. No. 6,292,695 to Webster et al, which is herein incorporated by reference.  
         [0009]     Surgical denervation of the fat pads has also been described.  
         [0010]     The methods of parasympathetic denervation that are described in the literature generally involve surgical or transvascular approaches. There remains a need for improved, less invasive methods of denervating epicardial cardiac fat pads for prevention and treatment of supraventricular arrhythmias.  
       SUMMARY OF THE INVENTION  
       [0011]     The present invention is based on the realization that because the fat pads that contain many of the parasympathetic ganglia are located on the epicardium, they are amenable to minimally invasive ablative techniques.  
         [0012]     In embodiments of the invention, epicardial ablation is conducted using a catheter inserted through the chest wall. The catheter has transducers for directing laser energy, microwave energy or ultrasound energy toward target tissue.  
         [0013]     Epicardial fat pad locations are determined using noninvasive imaging methods, i.e., cardiac CT or MR imaging, cardiac neurotransmission imaging using SPECT and PET or can be found using epicardial electrical maps. These locations are then displayed on maps or images of the heart, and thus targeted for minimally invasive or noninvasive therapy. The methods of the present invention are less invasive than conventional methods of ablation, and permit flexible access to substantially any point on the epicardium.  
         [0014]     The invention provides a method for ablating epicardial tissue within a body of a subject, which is carried out by inserting a probe into the pericardial cavity, locating epicardial target tissue in the pericardial cavity for ablation thereof, disposing the probe in proximity to the target tissue, and directing sufficient energy from the probe preferentially toward the target tissue to ablate neural structures therein.  
         [0015]     One aspect of the method includes orienting the probe with respect to the target tissue so as to maximize energy transfer from the probe to the target tissue.  
         [0016]     According to yet another aspect of the method, orienting the probe includes sensing location and orientation information of the probe, and moving the probe responsively to the information.  
         [0017]     According to another aspect of the method, the energy includes ultrasound energy. The ultrasound energy may be focused onto the target tissue.  
         [0018]     According to a further aspect of the method, the energy is laser energy.  
         [0019]     According to yet another aspect of the method, the energy is microwave energy.  
         [0020]     According to still another aspect of the method, the target tissue is an epicardial fat pad.  
         [0021]     According to an additional aspect of the method, the target tissue includes an epicardial ganglion that is external to an epicardial fat pad.  
         [0022]     In still another aspect of the method, the probe includes a resonant circuit, and the method is further carried out by generating radiofrequency energy at a site remote from the resonant circuit at the circuit&#39;s resonant frequency, causing the resonant circuit to re-radiate energy toward the target tissue.  
         [0023]     The invention provides a system for minimally invasive ablation of epicardial tissue of a heart of a living body, including a probe, which has a distal end configured for insertion into the pericardial cavity of the body. The probe has an exposed front surface and a back surface, and includes in proximity to the distal end at least one position sensing device and a transducer disposed so as to transmit energy directionally from the front surface to epicardial target tissue.  
         [0024]     According to an additional aspect of the system, the probe includes a resonant circuit, the system further including a plurality of radiofrequency transmitters operative for generating radiofrequency energy at a site remote from the resonant circuit at the circuit&#39;s resonant frequency, causing the resonant circuit to re-radiate energy toward the target tissue.  
         [0025]     The invention provides a system for minimally invasive ablation of epicardial tissue of a heart of a living body, including a first probe, having a first distal end configured for insertion into a pericardial cavity of the body, the first probe including in proximity to the first distal end at least one position sensing device. The system includes a second probe, which has a second distal end and having a transducer for delivery of energy to target tissue on the epicardial surface of the heart. The second probe is exchangeable with the first probe. The system further includes a source of the energy, which is coupled to the transducer, a processor, alternatively coupled to the first probe for determining position coordinates of the first distal end relative to the epicardial surface, using the position sensing device, and to the second probe. The processor is further adapted to control the source of the energy. The system includes a display, controlled by the processor, for displaying locations of the first probe and the second probe relative to the epicardial surface of the heart.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0026]     For a better understanding of the present invention, reference is made to the detailed description of the invention, by way of example, which is to be read in conjunction with the following drawings, wherein like elements are given like reference numerals, and wherein:  
         [0027]      FIG. 1  is a schematic illustration of an ablation system, which is constructed and operative in accordance with a disclosed embodiment of the invention;  
         [0028]      FIG. 2  is a perspective view of the distal end of a catheter for use in the system shown in  FIG. 1 ;  
         [0029]      FIG. 3  is an illustration of an ablation system, which is constructed and operative in accordance with an alternate embodiment of the invention; and  
         [0030]      FIG. 4  is a flow chart of a method of ablation of epicardial neural structures in accordance with a disclosed embodiment of the invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0031]     In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent to one skilled in the art, however, that the present invention may be practiced without these specific details. In other instances, well-known circuits, control logic, and the details of computer program instructions for conventional algorithms and processes have not been shown in detail in order not to obscure the present invention unnecessarily.  
       EMBODIMENT 1  
       [0032]     Turning now to the drawings, reference is initially made to  FIG. 1 , which is an illustration of a system  20 , which is constructed and operative in accordance with a disclosed embodiment of the invention. The system  20  is used in determining the position of a probe, for the acquisition of anatomic and electrical data, and for tissue ablation using a catheter  22 , which is percutaneously inserted into the pericardial cavity that includes a heart  24  of a subject  26 . The distal tip of the catheter  22  comprises one or more electrodes, and in some embodiments includes one or more ablation transducers, e.g., ultrasound transducers. The electrodes and transducers are connected by wires through the insertion tube of the catheter  22  to a control unit  28 . The control unit  28  determines position coordinates of the catheter  22  relative to the epicardial surface of the heart  24 . The control unit drives a display  40 , which shows the catheter position inside the body. The control unit  28  also drives the ablation transducers, which are located generally at the tip of the catheter  22 . The catheter  22  is used in generating anatomic images or even an electrical map, wherein the electrodes on the catheter are used alternately for position sensing and for ablation.  
         [0033]     The system  20  can be the Carto® Navigation System, available from Biosense Webster, Inc., 3333 Diamond Canyon Road, Diamond Bar, Calif. 91765, configured for use with suitable epicardial location and/or ablation catheters. Using this system, the entire procedure can be carried out in a single session without disconnecting the subject  26  from the system.  
         [0034]     Reference is now made to  FIG. 2 , which is a perspective view of a tip  50  of a catheter, which is suitable for use as the catheter  22  ( FIG. 1 ). The catheter is described in commonly assigned application Ser. No. 10/621,988 filed Jul. 17, 2003, which is herein incorporated by reference. However, a brief description will facilitate understanding of the present invention. An exposed section  52  at the tip  50  ranges from about 2 mm to about 4 mm in length, and includes an ultrasound transducer  54 . The exposed section  52  has a curved outer back surface  56  and a flat front surface  64 , which includes a cut out region  58 , on which the transducer  54  is mounted. A wire  60  connects the transducer  54  with an ultrasonic actuator (not shown). The energy output of the transducer  54  is directional, being transmitted away from and generally perpendicular to the exposed surface of the transducer  54 , as indicated by arrows  62 . In operation, the tip  50  is positioned so that when a surface  64  carrying the transducer  54  lies flat against the epicardium, ultrasonic energy is preferentially transmitted from the transducer  54  in the direction of the apposed epicardium. The catheter is provided with position sensors  66  for sensing the location and orientation of the tip  50  with respect to the epicardial surface, and a temperature sensor  68 , which is useful in assessing the progress of an ablation operation. The control unit  28  ( FIG. 1 ) is capable of sensing and displaying the orientation of the tip  50  as well as its location responsively to signals from the position sensors  66 .  
         [0035]     A deflection wire  70  is provided within the catheter for deflecting its distal portion. The deflection wire  70  is fixedly anchored near the tip  50 , and is attached to a control handle  72 . The deflection wire  70  is used to manipulate the catheter so as to align the exposed section  52  relative to a desired direction of energy emission.  
       EMBODIMENT 2  
       [0036]     In alternative embodiments of the system  20 , location information is first prepared as a map or an image. The location information and the ablation are performed at different times, using exchangeable catheters typically during a single session with the subject  26 . In such embodiments a first catheter contains position sensors and a second catheter contains at least one transducer that is used for tissue ablation, as well as components of a location and mapping system enabling its position to be identified.  
         [0037]     The system  20  may be adapted, mutatis mutandis, to employ the catheters disclosed in commonly assigned U.S. Pat. No. 6,716,166 or U.S. Pat. No. 6,773,402 for mapping the surface of the heart, which are herein incorporated by reference, as the catheter  22 .  
         [0038]     Referring again to  FIG. 1 , following identification of the epicardial fat pads, the catheter disclosed in copending application Ser. No. 10/245,613, which is herein incorporated by reference, can be used for ablation as the catheter  22 . This catheter employs laser energy, and a laser source (not shown) is controlled by the control unit  28 .  
       EMBODIMENT 3  
       [0039]     Embodiment 3 is similar to embodiment 2, except that a non-directional ultrasound catheter is employed as the catheter  22  ( FIG. 1 ). This can be the catheter disclosed in copending application Ser. No. 10/304,500, which is herein incorporated by reference. Microwave ablation catheters are also effective.  
       EMBODIMENT 4  
       [0040]     In this embodiment, a probe employing microwave energy as the ablation source is used as the catheter  22  ( FIG. 1 ). A suitable probe and microwave generator, the FLEX 4™ system, are available from Guidant Corporation, 111 Monument Circle, #2900, Indianapolis, Ind. 46204-5129,  
       EMBODIMENT 5  
       [0041]     In this embodiment, a probe employing high intensity focused ultrasound energy (HIFU) is used as the catheter  22  ( FIG. 1 ), as described in U.S. Patent Application Publication Nos. 2004/0162507 and 2004/0162550, of common assignee herewith, and herein incorporated by reference. A suitable probe and control is commercially available as the Epicor™ Cardiac Ablation System, available from St. Jude Medical, One Lillehei Plaza St Paul Minn. 55117-9913. Using this system, a simplified Cox maze procedure can be performed to eradicate target tissue as described above. Notably, it is not necessary to arrest the heart, nor to resort to cardiopulmonary bypass.  
       EMBODIMENT 6  
       [0042]     This embodiment is similar to Embodiment 5. The catheter  22  ( FIG. 1 ) is positioned within the heart using known methods, and ganglionated plexi constituting the target tissue are localized endocardially using high frequency stimulation and observing an immediate vagal response.  
       EMBODIMENT 7  
       [0043]     This embodiment is similar to Embodiment 6, except that the catheter  22  ( FIG. 1 ) is a therapeutic transesophageal probe, positioned within the esophageal lumen. HIFU energy is then directed from the esophagus toward the target tissue under continuous ultrasound imaging guidance.  
       EMBODIMENT 8  
       [0044]     Reference is now made to  FIG. 3 , which is an illustration of a system  45 , which is constructed and operative in accordance with a disclosed embodiment of the invention. The system  45  is similar to the system  20  ( FIG. 1 ), except that RF transmitters  47  are positioned external to the subject  26 , RF energy being directed toward a probe  49 . In this embodiment, the probe  49 , in which is incorporated a resonant circuit (not shown), is used as the catheter  22  ( FIG. 1 ). When an external RF field is generated at the circuit&#39;s resonant frequency, RF energy is re-radiated by the probe  49  toward the target tissue. The probe  49  and the transmitters  47  are more fully described in commonly assigned U.S. Patent Application Publication No. 2005/0101946, which is herein incorporated by reference. Operation.  
         [0045]     Continuing to refer to  FIG. 1 , reference is now made to  FIG. 4 , which is a flow chart of a method of ablation of epicardial neural structures, typically within epicardial fat pads, in accordance with a disclosed embodiment of the invention. It will be understood that the method disclosed herein can alternatively be practiced with any of the other embodiments described above. At initial step  80  the catheter  22  is introduced into the subject  26  and its distal end positioned in the pericardial cavity, using known introduction techniques. The catheter  22  can be placed, for example, using the PerDUCER® Access Device, available from Comedicus Inc., 3989 Central Avenue N.E., Suite 610, Columbia Heights, Minn. 55421.  
         [0046]     Next, at step  82 , the locations of the epicardial fat pads are accurately determined. Typically, the operator navigates the catheter to one of the known regions where the fat pads are usually located, and then accurately localizes it by using high frequency stimulation. A fat pad location is confirmed by the observation of an immediate vagal response, defined as an increase of at least 50% in R—R interval during atrial fibrillation. This localization technique was described by Nakagawa et al., in Heart Rhythm 2005; 2(5) AB 6-1. Alternatively, if the patient has undergone a previous imaging study, e.g., cardiac CT or MR, preacquired 3-dimensional image data can be imported to the CARTO mapping system. Using the CartoMerge™ module, available from Biosense-Webster, the data is then segmented to represent all four cardiac chambers individually, and the great vessels. During mapping, registration to the 3-dimensional models is accomplished by one or all of the following strategies: manual alignment; landmark pair matching; and surface registration. Once registered, the operator navigates the catheter directly to the predefined fat pads targets or, based on the exact anatomy, to the expected locations of the fat pads. Alternatively, the locations of the fat pads can be determined one-by-one, following ablation of each fat pad.  
         [0047]     Next, at step  84  the catheter tip is positioned at an epicardial fat pad to be targeted. If the energy output from the catheter tip is directional, then the orientation of the catheter tip is adjusted so as to direct the energy output at the fat pads. Maximizing the energy delivery to the fat pad reduces unintended damage to tissues other than the fat pad. It may be desirable to introduce coolant via accessory ports (not shown) in the catheter  22  in order to prevent charring of tissue.  
         [0048]     Next, at step  86  energy delivery to the fat pad is conducted. As noted above, many different types of ablative energy can be employed in step  86 . For example, using the directional ultrasound catheter described above in Embodiment 1, with the catheter tip positioned about 1-3 mm away from the tissue, a burn having a depth of about 8 mm can be obtained using 40 W of power for 120 sec., and irrigation of 10 ml/min. In general, satisfactory results are obtainable with this catheter at 10-45 W, and 0-30 ml/min irrigation.  
         [0049]     Control now proceeds to decision step  88 , where it is determined whether more epicardial fat pads remain to be ablated. If the determination at decision step  88  is affirmative, then control returns to step  84 .  
         [0050]     If the determination at decision step  88  is negative, then control proceeds to final step  90 . The catheter  22  is withdrawn, and the subject disconnected from the system  20 . The procedure terminates.  
       Additional Applications  
       [0051]     There has been substantial research in recent years showing the importance of innervation of the heart by the autonomic nervous system (sympathetic and parasympathetic) in causation and treatment of arrhythmias of various sorts. The methods of the present invention may similarly be applied to perform minimally invasive and noninvasive ablation procedures targeted at other ganglia on the epicardium.  
         [0052]     Patients can be classified as sympathetic dominant or parasympathetic dominant. For example, parasympathetic dominant individuals may be identified by neurophysiological testing, such as provocation of syncope during tilt testing. Parasympathetic-dominant individuals may be especially prone to arrhythmias resulting from parasympathetic nerve effects. Fat pad ablation may be prescribed specifically for these individuals in order to treat atrial fibrillation or reduce its occurrence following coronary artery bypass graft (CABG).  
         [0053]     It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and sub-combinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Technology Classification (CPC): 0