WO2008024857A2

WO2008024857A2 - An apparatus and method for optimization of cardiac resynchronization therapy

Info

Publication number: WO2008024857A2
Application number: PCT/US2007/076543
Authority: WO
Inventors: Guanggen Cui; Luyi Sen
Original assignee: The Regents Of The University Of California
Priority date: 2006-08-23
Filing date: 2007-08-22
Publication date: 2008-02-28
Also published as: WO2008024857A3

Abstract

An apparatus ( 10) and method for biventricular pacing comprises means and steps for i) evidence-based, 11) optimized, in) simultaneously evidence-based and optimized endomyocardium and ιv) optimized epimyocardium pacing in cardiac resynchronization Monophasic action potential is mapped by evidence-based and individualized optimization of cardiac resynchronization, pacing and implantable cardioverter defibrillators in percutaneous procedures, thoracoscopic procedures or open chest surgeries The optimized electrode sites are identified without MAP mapping without use of an electrophysiologic system for optimι/ed cardiac resynchronization, pacing and an implantable cardioverter defibrillator in percutaneous procedures, thoracoscopic procedures or open chest surgeries The effectiveness of this therapy is optimized in a majority of patients with heart failure, IeIt ventricular (LV) or right ventricular (RV) dysfunction, cardiomyopathies, arrhythmias, congenital heart diseases, heart transplantations, and/or in patients immediately after open heart surgeries for fast recovery.

Description

AN APPARATUS AND METHOD FOR OPTIMIZATION OF CARDIAC RESYNCHRONIZATION THERAPY

[0001] The present application is related to U.S. Provisional Patent

Application, serial no. 60/844,600, filed on Sept. 13, 2006, and U.S. Provisional Patent Application, serial no. 60/839,957, filed on Aug. 23, 2006. both of which are incorporated herein by reference and to which priority is claimed pursuant to 35 USC 119.

Background of the Invention

Field of the Invention

[001] The invention relates to the field of endomyocardium and epicardium biventricular pacing.

Description of the Prior Art

[002] Congestive heart- failure is the first listed diagnosis in 875,000 hospitalizations and the most common diagnosis in hospital patients over age 65. Almost 5 million Americans have congestive heart failure, a further 550,000 are diagnosed with congestive heart failure annually, and congestive heart failure represented the primary diagnosis for approximately 1 million hospital discharges. Approximately 25% to 40% of congestive heart failure patients do not die of progressive congestive heart failure, but instead die suddenly, often without obvious prior symptoms.

[003] Sudden death, also known as sudden cardiac arrest, is 6 to 9 times more likely in persons diagnosed with congestive heart failure than in the general population. Sudden death is caused most commonly by ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with underlying impaired left ventricular (LV) function.

[004] Most people who experience sudden cardiac arrest do not survive.

Overall, 90% of patients do not survive their first cardiac arrest. Today, with new heart failure options like cardiac resynchronization therapy (CRT), the outlook for people with heart failure is more encouraging than ever before. [005] Cardiac resynchronization therapy is a way of treating heart failure with an implantable device similar to a pacemaker. Basically, it is a heart failure pacemaker that helps both ventricles of the heart beat together again in a more synchronized pattern. This improves the heart's ability to pump blood and oxygen to the body. The heart failure pacemaker is implanted under the skin of the chest and connected to three leads (soft insulated wires) that are inserted through the veins into the heart. The device is battery-powered and delivers small electrical pulses to both ventricles which makes them beat in a synchronized way. These small impulses are usually not felt. Cardiac resynchronization therapy, in combination with a complete program of therapy, has proven to improve the quality of life for many patients by reducing symptoms of heart failure, increasing exercise capacity and allowing them to resume many daily activities. [006] Currently, the two main implantable cardiac devices for the management of congestive heart failure include implantable cardioverter defibrillators (ICDs) and biventricular pacing, also known as cardiac resynchronization therapy (CRT). The implantable cardioverter defibrillator continuously monitors the cardiac rhythm and provides backup bradycardia pacing and anti-tachycardia pacing or shock therapy for life threatening ventricular arrhythmias. Cardiac resynchronization therapy, which was developed to provide hemodynamic improvement with restoration of atrioventricular, interventricular, and intraventricular synchrony, can be used in conjunction with defibrillator capabilities (CRT-D).

[007] Biventricular pacing could provide a more coordinated pattern of contraction than the dissynchronous ventricular activation which occurs in patients with interventricular conduction defects, which is common in patients with congestive heart failure. The MUSTIC trial, which was recently published, demonstrated that biventricular pacing might improve symptoms and quality of life in selected patients with congestive heart failure. Despite promising results, up to 30% of the patients are classified as "non-responders" to the current techniques of cardiac resynchronization with or without an implantable cardioverter defibrillator. Discordance between the site of maximal delay and the pacing site can be a potential explanation for the lack of benefit. More than 70% of "non-responders" cases were due inability to find the optimized "responding" pacing site. The site for maximally delayed conduction is different in each patient and may also different in various diseases underlying congestive heart failure. Current practices for cardiac resynchronization, pacing and implantable cardioverter defibrillator are standardized, not individualized and optimized . Most importantly, even though the majority of the patients have a "response", they do not reach the optimized effectiveness of this therapy due to discordance between the site of maximal delay and the pacing site.

[008] Currently, the pacing sites for biventricular pacing with or without implantable cardioverter defibrillator are standardized in all patients, in percutaneous intervention, two electrode leads are placed in the endomyocardium of high right atrium and right ventricular apex. The third lead is placed in the lateral left ventricular free wall midway between the base and apex, through posterolateral cardiac vein. Therefore, it is closer to the epicardium. In open chest surgery, three leads are sewed onto epicardium of right atrium- ventricular groove, right ventricular apex and left ventricular lateral free wall. [009] Clinical, electrophysiological, or mechanical predictors of response were studied or are still under extensive investigation. The widest baseline QRS and QRS width reduction with cardiac resynchronization therapy seems to be associated with responders. Assessments of dyssynchrony by echocardiography, tissue Doppler imaging, nuclear medicine or nuclear magnetic resonance also identify which population is best suitable for clinical benefit from Cardiac resynchronization therapy. However, all of these techniques can only be used for assessing the out come of Cardiac resynchronization therapy, but can not be used for precisely determined the optimized pacing site in situ. Brief Summary of the Invention

[010] The illustrated embodiments of the invention establish the concept and applicable methodology for optimized endomyocardium and/or epicardium biventricular pacing. The illustrated embodiments include four components, namely the concept, device and technology for i) evidence-based, ii) optimized, iii) simultaneously evidence-based and/or optimized endomyocardium and/or iv) optimized epimyocardium pacing in cardiac resynchronization. [011] An object of the invention is to introduce a new strategy for personalized and evidence based optimization of cardiac resynchronization applied in percutaneous intervention, open chest or thoracoscopic surgeries. To perform optimized cardiac resynchronization, we disclose three illustrative embodiments.

[012] The first embodiment for evidence-based optimized endomyocardium pacing in cardiac resynchronization uses a lantern catheter with 64 or 128, or even more Ag-AgCI plated electrodes made by laser microfabrication and deposition technology. The lantern catheter allows simultaneous, three-dimensional mapping of the entire or substantially all of the endomyocardium MAP. The lantern catheter can be percutaneously inserted through peripheral veins and/or arteries using standardized cardiac intervention. We are able to three dimensionally, real-time map the endomyocardium monophasic action potential in each atrium and/or ventricle. The pattern and/or the magnitude or size of the alteration of the action potential, changes in the action potential duration and/or the site or sites of 90% of the action potential duration (APD₉₀), the slowest action potential repolarization and/or depolarization (dv/dt), and/or other parameters can be determined in each patient. With the standard electrophysiologic system all these parameters can be directly visualized and/or recorded. Most importantly, using this real-time three- dimensional mapping, the site and sites of the myocardium with maximum dispersion of these parameters among 128 or more recording sites can be identified that indicates the pathology of the myocardium, even in an early disease stage. By analyzing the changes of parameters using advanced software, the individualized optimized pacing site(s) can be determined precisely in combination with the analysis of hemodynamic parameters in as short a time as 10 minutes.

[013] The Constellation™ catheter produced by EP Technology of Boston

Scientific can only map electric grain, and not monophasic action potential, so that it cannot record the amplitude, duration, depolarization and repolarization rate of the action potential. Electrodes on the Constellation™ catheter do not make tight contact with endomyocardium as with the lantern catheter. All electrodes on the Constellation™ catheter float in the blood, which causes noise to be generated and often interferes with the measurement of conduction time, which is the only parameter that can be measured. Constellation™ catheter also can not be used as making reliable pacing device, since it dose not have a tight contact with myocardium. [014] The second embodiment for optimized endomyocardium pacing in cardiac resynchronization is as follows. In most community hospitals, there is no electrophysiologic recording systems available. Therefore, it is impossible to record the monophasic action potential or any other electric parameters. However, the lantern catheter can be used for determine the optimized pacing site or the combination of sites using a programmed pacing protocol. In this case, the electrodes on the lantern catheter may be platinum plated, and need not be Ag-AgCI plated. The site with the best hemodynamic responses in parameters such as peak amplitude and/or dp/dt of left ventricular (LV) and/or right ventricular (RV) systolic pressure, left ventricular (LV) and/or right ventricular (RV) diastolic pressure, pulse pressure and the like will be determined by pacing individual electrodes or pacing electrodes in sequential combinations. [015] The third embodiment for evidence-based optimized epimyocardium pacing in cardiac is as follows. In open chest or open heart surgery, an elastic mash with 128 or more Ag-AgCI plated electrode array can be used to cover the entire heart. With tight contact of the electrodes to the epicardium, we will be able to three dimensionally, real time map the epimyocardium monophasic action potential in the atriums and/or ventricles simultaneously. In less than 5 minutes, we will be able to directly observe and/or record the patterns and/or the site or sites of the alteration of maximal action potential during APD₉₀ and/or the slowest action potential repolarization and/or depolarization (dv/dt) in individual patients using a conventional electrophysiologic system. The individualized optimized pacing site(s) can be determined precisely in combination with the analysis of hemodynamic parameters. Especially in the case of coronary artery bypass surgery involving two, three or more vessels, more than three pacing sites may be applied. This mapping system can provide more evidence for the basis of the treatment, and can create a new strategy for the cardiac resynchronization. [016] The fourth embodiment for optimized epimyocardium pacing in cardiac resynchronization is as follows, in most community hospitals, there is no electrophysiologic recording system available. The standard open chest operating room also does not come equipped with an electrophysiologic system. In open chest surgery, an elastic mash with 128 or more platinum plated electrodes array can be used to cover the entire heart. The electrodes on the lantern catheter may be platinum plated, and need not be Ag-AgCI plated. The site with the best hemodynamic responses in parameters such as peak amplitude and/or dp/dt of left ventricular (LV) and/or right ventricular (RV) systolic pressure, left ventricular (LV) and/or right ventricular (RV) diastolic pressure, pulse pressure and the like will be determined by pacing individual electrodes or pacing electrodes in sequential combinations.

[017] The illustrated embodiments can be used to the advantage of any patients with an indication for cardiac resynchronization, pacing and/or defibrillation: such as heart failure induced by ischemic cardiomyopathic, myocardities, idiopathic dilated cardiomyopathy, restricted cardiomyopathy, drug induced heart failure, heart ^'transplant rejection, surgically related cardiac dysfunction and/or heart failure, congenital heart diseases, or various arrhythmias, such as various right and/or left ventricular bundle branch blocks, intraventricular conduction block, AV block, VT, SVT, AF, Af, various AV block etc. with or without heart failure. In these cases an electrophysiologic system is required.

[018] The illustrated embodiments can be further used to the advantage of any patients with an indication for cardiac resynchronization, pacing and/or defibrillation, such as: heart failure induced by ischemic cardiomyopathy, myocardities, idiopathic dilated cardiomyopathy, restricted cardiomyopathy, drug induced heart failure, heart ^"transplant rejection, operation related cardiac dysfunction and/or heart failure, congenital heart diseases, and/or various arrhythmias, such as: various right and/or left ventricular bundle branch blocks, intraventricular conduction block, AV block, VT, SVT, AF, Af, various AV block etc. with or without heart failure. In these cases an electrophysiologic system is not required.

[019] The illustrated embodiments can be further used to the advantage of patients undergoing open chest surgery for coronary artery bypass grafting, heart transplantation, valve repair and/or replacement, aneurysms, various surgeries for congenital heart diseases, assistance device implantation, pacemaker implantation, defibrillation device implantation, and the like. Optimized single or multiple site(s) pacing can improve the cardiac function, shorten the cardiac recovery time with or without a bypass pump, improve the cardiac remodeling, reduce the incidence of arrhythmias, and decrease the incidence of sudden death. In these cases an electrophysiologic system is required.

[020] The illustrated embodiments can be further used to the advantage of patients undergoing open chest surgery for coronary artery bypass grafting, heart transplantation, valve repair and/or replacement, aneurysms, various surgeries for congenital heart diseases, assistance device implantation, pacemaker implantation, defibrillation device implantation, and the like. Optimized single or multiple site(s) pacing can improve the cardiac function, shorter the cardiac recovery time with or without bypass pump, improve the cardiac remodeling, reduce the incidence of arrhythmias, decrease the incidence of sudden death. In these cases an electrophysiologic system is not required. [021] The elastic mash with 128 or more Ag-AgCI plated electrodes array can also be inserted into the chest through thoracoscopy without open chest surgery. Thus, epicardium pacing can be applied. The indication of this procedure is the same as described in open chest surgery above. In this case an electrophysiologic system is required.

[022] In a hospital without electrophysiologic recording system, the optimization of the epimyocardium pacing can still be performed using an elastic mesh with 128 or more platinum plated electrode array inserted into the chest through thoracoscopy without open chest surgery. The indication of this procedure is the same as described in open chest surgery above. In this case an electrophysiologic system is not required. [023] The illustrated embodiments of the invention introduce a novel monophasic action potential mapping techniques for evidence-based and/or individualized optimization of cardiac resynchronization, pacing and/or implantable cardioverter defibrillators in percutaneous procedures, thoracoscopic procedures or open chest surgeries. The apparatus and/or methods of the invention to identify the optimized electrode sites without MAP mapping can be practiced in hospitals or operating rooms without an electrophysiologic system for optimized cardiac resynchronization, pacing and/or an implantable cardioverter defibrillator in percutaneous procedures, thoracoscopic procedures or open chest surgeries.

[024] The illustrated embodiments of the invention will turn the "non- responders" to responders, and moderate response to optimized response. We can optimize the effectiveness of this therapy in a majority of patients with heart failure, left ventricular (LV) or right ventricular (RV) dysfunction, cardiomyopathies, arrhythmias, congenital heart diseases, heart transplantations, and also help all patients immediately after open heart surgeries for fast recovery.

[025] The illustrated embodiments of the invention are safer, e.g. 5 - 10 times faster and less demanding on physician skill as compared with current interventionist procedures which manually move the electrodes to find the better pacing site or the best combination of sites. [026] The illustrated embodiments of the invention will let us avoid unnecessary use of high energy for cardiac pacing to improve the response. This will avoid scar formation and/or improve the cardiac remodeling. [027] The illustrated embodiments of the invention introduces a novel concept and technique that can help us to understand the unrevealed mechanism of cardiac resynchronization, arrhythmia and/or antiarrhythmia, cardiac remodeling, and similar cardiac functions at a cellular level in patients. [028] The illustrated embodiments of the invention will also help us to improve our understanding of electrophysiology of various cardiac diseases in human and develop new therapeutic strategies, such as low energy multi-site pacing for cardiac resynchronization, pacing and implantable cardioverter defibrillating, high energy-microwave pacing for cardiac resynchronization, and the like.

[029] While the apparatus and method has or will be described for the sake of grammatical fluidity with functional explanations, it is to be expressly understood that the claims, unless expressly formulated under 35 USC 112, are not to be construed as necessarily limited in any way by the construction of "means" or "steps" limitations, but are to be accorded the full scope of the meaning and equivalents of the definition provided by the claims under the judicial doctrine of equivalents,^' and in the case where the claims are expressly formulated under 35 USC 112 are to be accorded full statutory equivalents under 35 USC 112. The invention can be better visualized by turning now to the following drawings wherein like elements are referenced by like numerals. Brief Description of the Drawings

[030] Fig. 1 is a diagrammatic side view of the lantern catheter used in the illustrated embodiments.

[031] Fig. 2 is a diagrammatic end view of the lantern catheter used in the illustrated embodiments.

[032] Fig. 3a is a side cut-away view of the human heart showing the endovascular placement of the collapsed lantern catheter of Figs. 1 and 2 according to the invention.

[033] Fig. 3b is a side cut-away view of the human heart showing the expanded deployment of the lantern catheter of Figs. 1 and 2 according to the invention.

[034] Fig. 3c is an image of a MAP-mapping produced by the parameter analysis generated by the computer connected to the cardiac amplifier in Fig. 3b. [035] Fig. 4a is a side perspective view of a segment of the insulated basket wire with electrodes of the lantern catheter.

[036] Fig. 4b is a layout of the microfabricated supporting wires for electrical coupling to the electrodes on the basket wire of Fig. 4a. [037] Fig. 4c is a cross section view of the basket wire of Fig. 4a as seen through section lines 4c - 4c of Fig. 4a.

[038] Fig. 5a is a diagram showing deployment of another embodiment of the lantern catheter having both an atrial and ventricular basket. [039] Fig. 5b is a side view of the embodiment used in Fig. 5a. [040] Fig. 6 is a diagram showing deployment of another embodiment of the MAP-mapping and pacing device where it is deployed exteriorly to the heart during open-chest operation.

[041] Fig. 7a is a side plan view of another embodiment that is the electrode-array mesh for epimyocardium MAP-mapping and pacing which is used to contact the exterior surface of the heart.

[042] Fig. 7b is an enlargement of a plan view of a portion of the electrode-array mesh of Fig. 7a shown in an open configuration.

[043] Fig. 7c is a side perspective view of the wires of the electrode-array mesh of Figs. 7a and 7b.

[044] Fig. 7d is a cross sectional view taken of an electrode ring taken through section lines 7d - 7d of Fig. 7c.

[045] Fig. 8 is a diagram of the use of the electrode-array mesh of Figs.

7a - 7d used to optimize epimyocardium pacing with or without MAP-mapping, but an epicardium electrode array mesh is placed using endoscopic or robotic surgery approaches.

[046] The invention and its various embodiments can now be better understood by turning to the following detailed description of the preferred embodiments which are presented as illustrated examples of the invention defined in the claims. It is expressly understood that the invention as defined by the claims may be broader than the illustrated embodiments described below. Detailed Description of the Preferred Embodiments

[047] The first embodiment for evidence-based optimized endomyocardium pacing in cardiac resynchronization uses a lantern catheter with 64 or 128, or even more Ag-AgCI plated electrodes made by laser microfabrication and deposition technology. The lantern catheter is described in detail in U.S. Patent 6,738,655, which is incorporated herein by reference. The "lantern" catheter, generally denoted by reference numeral 10 in Fig, 1 , allows simultaneous, three-dimensional mapping of the entire endomyocardium MAP. Catheter 10 as shown in the diagrammatic side view of FIG. 1 is retained within a protection sheath (not shown) which retains basket 12 in a collapsed condition. Basket 12 is connected to a catheter lead through which insulated copper wires 16 are disposed. Wires 16 are connected to electrodes 24 in basket 12 at their distal ends and to a multichannel amplifier or multiplexer and other appropriate electronics 42 at its proximal end. Central trunk 31 of the catheter supports all of the wires 16 as diagrammatically shown in Fig. 1. Wires 26 are insulated or nonconducting so that they function as mechanical supports for electrodes 24. A plurality of very fine wires 16 are electrically coupled to corresponding electrodes 24, which are therefore selectively and individually accessible for detection and recording through the electronics. Distal tip 22 of basket 12 may be provided with a radioopaque platinum or gold marker 30 to aid in its fluoroscopic detection and visualization, since stainless steel wires 26 and electrodes 24 can be very fine or small and difficult to unambiguously show in a fluoroscopic image. The "lantern" 10 shall collectively denote basket 12 of wires 26 and electrodes 24. Each electrode 24 is preferably made of or plated with Ag/AgCI. Wires 26 are preferably made from stainless steel, which provides the needed degree of resiliency and flexibility. Other alloy choices, gauges and material choices could be made for wires 26 consistent with the teachings of the invention. [048] A central guide wire 46 extends through basket catheter 10 from distal tip 22 to the proximal grounded end 48. A central wire spring or lock 50 bears against a washer 52 to act as a stop for compliant spring 54 which is coaxially positioned around wire 46 and its plastic central wire sheath 58. Sheathed wire 46 is in turn coaxially disposed in a flexible shaft 62 which extends from washer 60 to a stainless steel ring 64 adjacent to the proximal end of basket 12. Central wire sheath 58 is sized and has a surface treatment or material quality, such as a Teflon^® composition, which allows the free telescopic movement of guidewire 46 within it. Washer 60 bears against the distal end of compliant spring 54. Wires 16 are disposed in the concentric coaxial space between shaft 62 and heat shrink tubing 68. Collectively sheath 58, shaft 62, wires 16 and tubing 68 comprise an electrode array tube 66 through which guidewire 46 freely telescopes. Wires 16 extend into ring 64 to be lead along various ones of the basket wires 26 to corresponding electrodes 24, which are mounted wires 26 and connected to a selected one of the wires 16. Basket wires 26 are mounted to ring 64. Wires 26 are covered by a laser-cut microfabricated insulating covering or tube 27. A hole is cut or formed into tube 27 at each location where an electrode 24 is exposed and extends above the level of tube 27 for contact with the myocardium.

[049] The resiliency of wires 26 tend to keep basket 12 in a collapsed condition. As described in U.S. Patent 6,738,655 hollow cylindrical shaft 62 is telescopically movable on guidewire 46 to open and close basket 12. A lock 50 disposed on guidewire 46 is provided to fix basket 12 in its open position while in the heart chamber and while being used to make the MAP mapping or recording. Lock 50 is disposed within shaft 62 when basket 12 is in its collapsed configuration. A catheter (not shown) is advanced over guidewire 46, moving shaft 62 to the left in the illustration of Fig. 1 , thereby causing basket 12 to expand as shown. As shaft 62 is advanced lock 50 in its collapsed state be forced out of the end of shaft 62 and through spring 54 which abuts shaft 62. Lock 50 is then freed and snaps open by reason of its inherent resiliency to then provide a mechanical stop for the proximal end of spring 54. Lock 50 can be released by insertion into the catheter (not shown) by advancing the catheter over lock 50 and reinserting lock 50 through the inner space of coil spring 54 and/or shaft 62. This will then allow basket 12 to collapse and be withdrawn from the heart chamber. Spring 54 abuts the proximal end of shaft 62 to give basket 12 some flexibility during heart contractions and relaxations during each beat, i.e. basket 12 can be partially compressed and re-expanded by the surrounding beating heart walls while electrodes 24 maintain continuous and firm contact with the heart tissue. Electrodes 24 are spherical or rounded and sized to extend from wires 16 and thereby to provide positive and firm contact with the surrounding heart tissue. This feature in combination with the resilient nature of the basket/spring combination insure continuous and firm or intimate contact between electrodes 24 and the heart tissue, which contact is important to obtain valid readings.

[050] Wire 26 is shown in greater detail in Figs. 4a - 4c. The side perspective view of Fig. 4a shows a segment of wire 26 in which a plurality of Ag/AgCi plated conductive electrode rings 70, each carrying an electrode 24, are inset or mounted in longitudinal sequence into or onto insulation tube 27 through which wire 26 is coaxially disposed. A laser-cut microfabricated flexible sheet of wires 16 as shown in Fig. 4b is wrapped around insulation tube 27 to provide electrical connection between 'individual wires 16 and each electrode 24. A sectional view through section lines 4c - 4c of Fig. 4a shows in Fig. 4c a plan view of ring 70. In the illustrated embodiment wire 26 has a diameter of about 0.012 inch (0.30mm) and is disposed in a central lumen 72 defined in insulation tube 27 which has a diameter of about 0.014 inch (0.36mm). The outer diameter of insulation tube 27 is approximately 0.020 inch (0.51mm) or less, which matches the inner diameter 74 of ring 70. The height 76 from the base of ring 70 to the top of electrode 24 is approximately 0.035 (0.89mm) ± .002 inch (0.05mm). The upper surface of electrode 24 has a radius of curvature of approximately 0.005 inch (0.1mm). The thickness 78 of ring 70 is approximately 0.002 inch (0.05mm) +.004 inch (0.1mm) or -.002 inch (0.05mm).

[051] Turn now and consider the method for evidence-based optimized endomyocardium pacing according to the invention as illustrated in Figs. 3a and 3b. The first step in the method is the step of placing two lantern catheters 10 with the basket 12 in the closed position in into the atriums 32a, 32b or ventricles 34a, 34b as shown in Fig. 3a. For the right portion of the heart, a lantern catheter 10a can be percutaneously or directly placed into venous system, then into the right atrium 32a or further advanced into right ventricle 34a through superior vena cava 36 or inferior vena cava 38. For the left portion of the heart, a lantern catheter 10b can be percutaneously or directly inserted into the venous system, then from the right atrium 32a into left atrium 32b using a transseptal approach. The catheter can also be further advanced into left ventricle 34b. To reach the left ventricle 34b, another approach is to percutaneously or directly insert the catheter 10b into arterial system, then advance the catheter 10b into the left ventricle 34b retroactively through aorta 40. [052] The second step is to perform real-time three-dimensional endomyocardium monophasic action potential (MAP)-mapping. The basket 12 on the lantern catheter 10a, 10b will be unfolded and expended to let all electrodes 24 tightly contact the endomyocardium of the atriums 32a, 32b and ventricles 34a, 34b. All 64 or 128, or even, more electrodes 24 are connected to an electrophysiologic amplifier 42. Endomyocardium monophasic action potentials are recorded from all electrodes 24 simultaneously. A computer 44 with software for real-time three-dimensional endomyocardium monophasic action potential- mapping parameter analysis is connected to the amplifier 42. [053] A three-dimensional MAP-map is recorded from both atrium 32a,

32b and/or ventricles 34a, 34b simultaneously or serially. MAP parameters, including action potential amplitude, depolarization dv/dt, repolarization dv/dt, ADP₉₀, and the like are recorded. Real-time three-dimensional MAP mapping also allows us to analyzed the dispersion of all MAP parameters among a atrium 32a or 32b and/or a ventricle34a or 34b, two atriums 32a and 32b or two ventricles 34a and 34b, one atrium 32a or 32b and one ventricle34a or 34b, any three chambers, or all four chambers. A color image of the mapping parameters, especially the dispersions of each parameter help the physician to visually localize the maximum and minimum of a parameter at a cardiac site that implicates the pathology of the myocardium and help to identify the optimized pacing spot and the combination of spots.

[054] The third step is to perform a comparative programmed test pacing to determine the optimized pacing spots in the heart. Each of the electrodes 24 are programmed to be paced one-by-one or in different combinations using a programmed pacing stimulator. At the same time, observing the improvement on the real-time three-dimensional MAP-mapping parameters and color imaging, and the hemodynamic parameters are used for verifying the optimal pacing spot or combination of spots.

[053] The fourth step is to pace the temporally or permanently placed pacing leads after the optimized pacing spot or spots are identified, and then withdraw the MAP-mapping catheters 10a and 10b.

[054] Another embodiment of lantern catheter 10a is diagrammatically shown in Figs. 5a and 5b. Catheter 10a has a smaller atrium basket 12a and a larger ventricular basket 12b coupled to the same guidewire 46. The details of construction of catheter 10b are illustrated in Fig. 5b and are similar to that described in connection with Fig. 1. Thus, the design and construction of atrium basket 12a and ventricular basket 12b is similar except for sizing and except the addition of an atrial double spring 80 and atrial shaft 82. Catheter 10a of Fig. 5b is similar in overall construction and operation to catheter 10 of Fig. 1 with respect to the same referenced elements. Wire 46 is telescopically disposed through ventricular shaft 62 and atrial shaft 82 and is led back to an additional atrial basket lock 50a. Lock 50a operates in a manner similar to lock 50 with respect to an introducing catheter (not shown) to temporarily lock atrial basket 12a in the expanded configuration. Atrial shaft 82 is telescopically disposed inside of ventricular shaft 62 and can be independently advanced on wire 46 to independently expand atrial basket 12a from the expansion of ventricular basket 12b by advancement of ventricular shaft 62. Spring 80 allows for relative movement of baskets 12a and 12b to accommodate a beating heart. [055] After insertion into the atrium 32a and ventricle 34a as shown in

Fig. 5a, lantern catheter 10a is expanded to make every electrode 24, 24a and 24b tightly contact the endomyocardium. Fig. 5a shows a ventricular lantern catheter 10 being inserted into the left ventricle 34b while catheter 10a is inserted into the right atrium 32a and ventricle 34a. Each electrode 24, 24a, 24b is programmed to be serially paced or in a selected combination. The improvement of hemodynamic parameters will be used for identify the optimized pacing spot or spot combinations. Then the temporally or permanent pacing lead(s) are paced and the lantern catheter 10a is withdrawn. [056] epimyocardium MAP-Mapping electrode-array mesh catheter 10b is placed outside of the heart.

[057] In the second step, a real-time three dimensional MAP-mapping analysis is performed to identify the optimal pacing spot or spot combinations. All electrodes 24 on the mesh of catheter 10b are in tight contact with the epicardium. About 128 to 256, or even more electrodes 24 are connected to an electrophysiologic amplifier 42. Epimyocardium monophasic action potentials at each electrode 24 are recorded simultaneously. A computer 44 with software for generating a real-time three-dimensional epimyocardium monophasic action potential-mapping parameter analysis is connected to the amplifier 42. MAP parameters, including action potential amplitude, depolarization dv/dt, repolarization dv/dt, ADP₉₀, etc. are mapped onto a three dimensional heart surface. Real-time three dimensional MAP mapping also allows us to analyze the dispersion of all MAP parameters on whole heart. A color image of the mapping parameters is generated similar to that shown in Fig. 3c, which graphically maps the dispersions of each parameter, which allows us to visually localize the maximum and minimum sites of a parameter. [058] The third step of the method is to perform the comparative programmed test pacing to determine the optimized pacing spots on the heart. Each electrode 24 is programmed to be paced one-by-one or in different combinations using a program stimulator. At the same time, observing the improvement in the color image of the real-time three dimensional MAP-mapping parameters and the hemodynamic parameters are used to identifying the optimal pacing spot or spots combination.

[059] The fourth step of the method is to pace the temporally or permanent pacing leads after the optimized pacing spot or spots are identified, and to withdraw the MAP-mapping catheter 10b.

[060] The structure of catheter 10b is shown in Figs. 7a - 7d. Fig. 7a is a diagram of the mesh basket 12 of catheter 10b shown in a collapsed condition. The mesh basket 12 is comprised of 16 wires 26 forming a cylindrical sock around which is spirally disposed a plurality of electrodes 24 and a spiral elastic fiber 84 which provides a resilient force which tends to keep basket 12 collapsed or at least in a tight contact with the heart tissue. A closing string 86 is provided around the distal end of basket 12 to allow the surgeon to close the distal end to maintain basket 12 tightly wrapped around the heart. Wires 26 are connected to a connecting ring 88 and thence by a multiple wire cable 90 to amplifier 42. The arrangement of the above elements are seen more clearly in the flat layout of the diagram of Fig. 7b showing basket 12 in an open configuration. Wires 26 are structured as shown in Fig. 7c in a manner which similar to that described in connection with Figs. 4a and 4b. As shown in Fig. 7d ring 70 is provided outside a laser-cut wire circuit 92 on which electrode wires 16 are formed, which is wrapped around PTFE insulation 27 through which basket wire 26 is coaxially disposed.

[061] Fig. 8 is a diagram which illustrates an embodiment of the method in which optimized endomyocardium pacing is performed with out MAP-mapping. As shown in Fig. 8, epimyocardium electrode array catheter 10b is not only deployed and used during open heart surgery, but it can also be deployed in vivo using endoscopic and robotic surgery approach using an endoscopic entry tube 94. In the first step of the method, an epicardium electrode array mesh catheter 10b is deployed using an endoscope. Each electrode 24 is again tightly contacted with the epicardium. In the second step of the method, each electrode 24 is programmed to be paced serially, or in a selected combination. The improvement of hemodynamic parameters is used to identify the optimized pacing spot or spot combinations with the optional use of an instrument endoscopic entry tube 96. Then the temporally or permanent pacing lead(s) are paced and the lantern catheter 10b is withdrawn.

[062] Many alterations and modifications may be made by those having ordinary skill in the art without departing from the spirit and scope of the invention. Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following invention and its various embodiments.

[063] Therefore, it must be understood that the illustrated embodiment has been set forth only for the purposes of example and that it should not be taken as limiting the invention as defined by the following claims. For example, notwithstanding the fact that the elements of a claim are set forth below in a certain combination, it must be^* expressly understood that the invention includes other combinations of fewer, more or different elements, which are disclosed in above even when not initially claimed in such combinations. A teaching that two elements are combined in a claimed combination is further to be understood as also allowing for a claimed combination in which the two elements are not combined with each other, but may be used alone or combined in other combinations. The excision of any disclosed element of the invention is explicitly contemplated as within the scope of the invention.

[064] The words used in this specification to describe the invention and its various embodiments are to be understood not only in the sense of their commonly defined meanings,^" but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus if an element can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself.

[065] The definitions of the words or elements of the following claims are, therefore, defined in this specification to include not only the combination of elements which are literally set forth, but all equivalent structure, material or acts for performing substantially the same function in substantially the same way to obtain substantially the same result. In this sense it is therefore contemplated that an equivalent substitution of two or more elements may be made for any one of the elements in the claims below or that a single element may be substituted for two or more elements in a claim. Although elements may be described above as acting in certain combinations and even initially claimed as such, it is to be expressly understood that one or more elements from a claimed combination can in some cases be excised from the combination and that the claimed combination may be directed to a subcombination or variation of a subcombination.

[066] Insubstantial changes from the claimed subject matter as viewed by a person with ordinary skill in the art, now known or later devised, are expressly contemplated as being equivaiently within the scope of the claims. Therefore, obvious substitutions now or later known to one with ordinary skill in the art are defined to be within the scope of the defined elements.

[067] The claims are thus to be understood to include what is specifically illustrated and described above, what is conceptionally equivalent, what can be obviously substituted and also what essentially incorporates the essential idea of the invention.

Claims

We claim:

1. A method for evidence-based optimized endomyocardium pacing in cardiac resynchronization of a heart, the endomyocardium being characterized by a three-dimensional distribution of a monophasic action potential (MAP), comprising: simultaneously, three-dimensionally, real-time mapping substantially ali of the endomyocardium monophasic action potential; determining a pattern of cardiac parameters; and identifying at least one site of the endomyocardium with maximum dispersion of the cardiac parameters to indicate a pathology of the endomyocardium.

2. The method of claim 1 where determining a pattern of a cardiac parameter further comprises determining a magnitude of the cardiac parameter with its pattern.

3. The method of claim 1 where determining a pattern of a cardiac parameter comprises determining a pattern of alteration of the monophasic action potential, changes in the action potential duration, and at least one site of 90% of an action potential duration (APD9₀), or a slowest action potential repolarization and depolarization (dv/dt).

4. The method of claim 1 where identifying at least one site of the endomyocardium with maximum dispersion of the cardiac parameters to indicate a pathology of the endomyocardium comprises analyzing changes of the cardiac parameters using software to determine at lest one individualized optimized pacing site in combination with the analysis of at least one hemodynamic parameter.

5. The method of claim 1 where simultaneously, three-dimensionally, realtime mapping substantially all of the endomyocardium monophasic action potential comprises performing the mapping endovascularly using a lantern catheter with multiple electrodes.

6. The method of claim 1 where simultaneously, three-dimensionally, realtime mapping substantially all of the epimyocardium monophasic action potential comprises mapping substantially all of the epicardium during open heart surgery using an elastic mash with a multiple electrode array to cover substantially all of the heart.

7. The method of claim 6 further comprising pacing the heart at more than one pacing sites during coronary artery bypass surgery.

8. A method for evidence-based optimized endomyocardium pacing in cardiac resynchronization using a programmed pacing protocol, the endomyocardium being characterized by a three-dimensional distribution of a monophasic action potential (MAP), comprising: sequentially, real-time, three-dimensionally, mapping selected sites of the endomyocardium monophasic action potential; determining a pattern of cardiac parameters among the selected sites; and identifying at least one site of the endomyocardium with maximum dispersion of the cardiac parameters to indicate a pathology of the endomyocardium.

9. The method of claim 8 where identifying at least one site of the endomyocardium with maximum dispersion of the cardiac parameters to indicate a pathology of the endomyocardium comprises identifying at least one site among the selected sites with the best hemodynamic responses to the cardiac parameters.

10. The method of claim 9 where identifying at least one site among the selected sites with the best hemodynamic responses in the cardiac parameters comprises identifying at least one site with hemodynamic responses to the cardiac parameters, namely the cardiac parameter, peak amplitude and dp/dt of left ventricular (LV) with respect to the hemodynamic response, right ventricular (RV) systolic pressure, left ventricular (LV) and right ventricular (RV) diastolic pressure, or pulse pressure.

11. The method of claim 8 where sequentially, three-dimensionally, mapping selected sites of the endomyocardium monophasic action potential comprises mapping selected sites during open heart surgery using an elastic mash with a multiple electrode array to cover substantially all of the heart.

12. The method of claim 11 where identifying at least one site of the endomyocardium with maximum dispersion of the cardiac parameters to indicate a pathology of the endomyocardium comprises identifying at least one site among the selected sites with the best hemodynamic responses to the cardiac parameters.

13. The method of claim 12 where identifying at least one site among the selected sites with the best hemodynamic responses in the cardiac parameters comprises identifying at least one site with hemodynamic responses to the cardiac parameters, namely the cardiac parameter, peak amplitude and dp/dt of left ventricular (LV) with respect to the hemodynamic response, right ventricular (RV) systolic pressure, left ventricular (LV) and right ventricular (RV) diastolic pressure, or pulse pressure.

14. The method of claim 1 further comprising performing cardiac resynchronization, pacing or defibrillation in patients with the indicated pathology of the endomycardium including heart- failure induced by ischemic cardiomyopathic, myocardities, idiopathic dilated cardiomyopathy, restricted cardiomyopathy, drug induced heart failure, heart transplant rejection, surgically related cardiac dysfunction and heart failure, congenital heart diseases, or various arrhythmias including various right and left ventricular bundle branch blocks, intraventricular conduction block, AV block, VT, SVT, AF, Af, or various AV blocks with or without heart failure.

15. The method of claim 8 further comprising performing cardiac resynchronization, pacing or defibrillation in patients with the indicated pathology of the endomycardium including heart failure induced by ischemic cardiomyopathy, myocardities, idiopathic dilated cardiomyopathy, restricted cardiomyopathy, drug induced heart failure, heart transplant rejection, operation related cardiac dysfunction and heart failure, congenital heart diseases, and various arrhythmias, including various right and left ventricular bundle branch blocks, intraventricular conduction block, AV block, VT, SVT, AF, Af, or various AV block with or without heart failure.

16. The method of claim 1 where mapping, determining a pattern and identifying at least one site is performed in patients undergoing open chest surgery for coronary artery bypass grafting, heart transplantation, valve repair and replacement, aneurysms, various surgeries for congenital heart diseases, assistance device implantation, pacemaker implantation, or defibrillation device implantation.

17. The method of claim 8 where mapping, determining a pattern and identifying at least one site is performed in patients undergoing open chest surgery for coronary artery bypass grafting, heart transplantation, valve repair and replacement, aneurysms, various surgeries for congenital heart diseases, assistance device implantation, pacemaker implantation, or defibrillation device implantation.

18. The method of claim 1 where simultaneously, three-dimensionally, realtime mapping substantially all of the epimyocardium monophasic action potential comprises inserting an elastic mash with a multiple electrode array into the chest through thoracoscopy without open chest surgery.

19. The method of claim 18 further comprising cardiac resynchronizing, pacing or cardioverter defibrillating in a percutaneous procedure or thoracoscopic procedure at the least one identified site.

20. The method of claim 8 where sequentially, three-dimensionally, mapping selected sites of the epimyocardium monophasic action potential comprises inserting an elastic mash with a multiple electrode array into the chest through thoracoscopy without open chest surgery.

21. The method of claim 20 further comprising cardiac resynchronizing, pacing or cardioverter defibrillating in a percutaneous procedure or thoracoscopic procedure at the least one identified site.

22. An apparatus for atrial-ventricular, biventricular or three chamber pacing of a heart comprising: a stationary lantern catheter to identify at least one optimal pacing site: and means electrically communicated to the lantern catheter for performing i) evidence-based, ii) optimized, iii) simultaneously evidence-based and optimized endomyocardium or iv) optimized epimyocardium pacing in cardiac resynchronization.

23. The apparatus of claim 22 where the means for performing pacing in cardiac resynchronization comprises means for monophasic action potential mapping by evidence-based or individualized optimization of cardiac resynchronization, pacing or implantable cardioverter defibrillation in a percutaneous procedure or a thoracoscopic procedure.

24. The apparatus of claim 22 where the means for performing pacing in cardiac resynchronization comprises means for identifying at least one optimized electrode site without MAP mapping without use of an electrophysiologic system for optimized cardiac resynchronization, pacing and implantable cardioverter defibrillation in a percutaneous procedure or a thoracoscopic procedure.

25. The apparatus of claim 22 where the means for performing pacing in cardiac resynchronization comprises means for optimizing pacing effectiveness in a patient with heart failure, left ventricular (LV) or right ventricular (RV) dysfunction, cardiomyopathy, arrhythmia, congenital heart disease, heart transplantation or in a patient immediately after open heart surgeries for fast recovery.

26. The apparatus of claim 22 where the lantern catheter comprises multiple Ag-AgCI plated electrodes made by laser microfabrication and deposition.

27. The apparatus of claim 22 where the heart is characterized by an endomyocardium monophasic action potential in each atrium and ventricle and where the means for performing pacing in cardiac resynchronization comprises means for three dimensionally, real-time mapping the endomyocardium monophasic action potential in each atrium and ventricle and for determining a pattern and at least one site of at least two cardiac parameters, namely an alteration of maximal action potential during action potential duration at 90% repolarization (APD90) and a slowest action potential repolarization and depolarization (dv/dt) in each patient and to directly visualize and record these two cardiac parameters in combination with the analysis of hemodynamic parameters in 10 minutes or less.

28. An apparatus for optimized endomyocardium and epicardium atrial- ventricular, biventricular or three chamber pacing of a heart comprising: an elastic mash with multiple platinum or Ag-AgCI plated electrodes array arranged and configured to cover the entire heart in open heart surgery to determine at least one pacing site with optimal hemodynamic responses, namely left ventricular (LV) and right ventricular (RV) systolic pressure, left ventricular (LV) or right ventricular (RV) diastolic pressure, or pulse pressure, to a cardiac parameter, namely peak amplitude or dp/dt at the at least one pacing site; and means electrically communicated to the mesh for providing pacing pulses to individual electrodes of the mesh or to electrodes of the mesh in sequential combinations.

29. An apparatus for optimized endomyocardium and epicardium atrial- ventricular, biventricular or three chamber pacing of a heart comprising: an elastic mash with multiple Ag-AgCI plated electrodes array to cover the entire heart with tight contact of the electrodes to the epicardium of the heart in open heart surgery to simultaneously obtain a three dimensionally, real-time map of the endomyocardium monophasic action potential in the atriums and ventricles of the heart in 5 minutes or less to directly observe and record the patterns and at least one site of alteration of maximal action potential during APD90 or slowest action potential repolarization and depolarization (dv/dt) in an individual patient and to identify at least one individualized optimized pacing site as indicated by analysis of hemodynamic parameters in response to pacing at the at least one individualized optimized pacing site.