Mapping sympathetic nerve distribution for renal ablation and catheters for same
09743845 · 2017-08-29
Assignee
Inventors
Cpc classification
A61B18/18
HUMAN NECESSITIES
A61B5/367
HUMAN NECESSITIES
A61B18/1492
HUMAN NECESSITIES
A61B5/0036
HUMAN NECESSITIES
A61B2018/00654
HUMAN NECESSITIES
International classification
A61B5/02
HUMAN NECESSITIES
Abstract
This invention provides methods for mapping and ablating renal nerves to treat disease caused by systemic renal nerve hyperactivity, e.g. hypertension, heart failure, renal failure and diabetes. Also provided are catheters for performing the mapping and ablating functions.
Claims
1. A method for identifying patients responsive to renal ablation for treatment of disease caused by systemic renal nerve hyperactivity, comprising the steps of: a. introducing a catheter into the lumen of a renal artery of a patient such that a tip of said catheter contacts a site on the inner renal artery wall; b. measuring one or more physiological parameters to obtain baseline measurements before introducing an electrical current to the site, said physiological parameters are selected from the group consisting of systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate; c. applying electrical stimulation by introducing said electrical current to the site via the catheter, wherein said electrical current is controlled to be sufficient to elicit an increase in said one or more physiological parameters when there is an underlying nerve at the site; d. measuring said one or more physiological parameters at a specific time interval after each electrical stimulation, wherein an increase of said physiological parameters over the baseline measurements after said electrical stimulation would indicate that said patient is responsive to renal ablation; and e. performing renal ablation on said patient.
2. The method of claim 1, wherein said specific time interval in step (d) is from about 5 seconds to about 2 minutes.
3. The method of claim 1, wherein said one or more physiological parameters includes systolic blood pressure, and said increase in systolic blood pressure is in the range of 4 to 29 mmHg.
4. The method of claim 1, wherein said one or more physiological parameters includes diastolic blood pressure, and said increase in diastolic blood pressure is in the range of 1.5 to 20 mmHg.
5. The method of claim 1, wherein said one or more physiological parameters includes mean arterial pressure, and said increase in mean arterial pressure is in the range of 3 to 17 mmHg.
6. The method of claim 1, wherein said one or more physiological parameters includes heart rate, and said increase in heart rate is in the range of 4 to 12 beats/min.
7. The method of claim 1, wherein the electrical current sufficient to elicit changes in the physiological parameters comprises one or more of the following parameters: a. voltage of between 2 and 30 volts; b. resistance of between 100 and 1000 ohms; c. current of between 5 and 40 miliamperes; or d. applied between 0.1 and 20 milliseconds.
Description
DETAILED DESCRIPTION OF THE FIGURES
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DETAILED DESCRIPTION OF THE INVENTION
(39) Please note that as referred to throughout this specification, the term “catheter” references the entire length of a catheter apparatus, from the distal portion intended for introduction into the desired target anatomy for ablation or other action, extending through to the juncture where the catheter meets the cable linking the catheter to an RF generator. As referenced to through this specification, the term “catheter tip” is used to reference the distal portion of the catheter which carries electrodes, and performs stimulative, ablative, and mapping functions within the body at a targeted site of action. The term “catheter tip” is used interchangeably with terms referencing the “distal portion” of any recited catheter.
(40) The present invention provides a method of mapping renal nerves for ablative procedures to treat disease caused by systemic renal nerve hyperactivity, comprising the steps of: (a) introducing catheters that perform stimulatory and ablative processes into renal arteries; (b) measuring indicia of disease before site-specific electrical stimulation to obtain baseline measurements; (c) introducing electrical current through the catheter in a site-specific manner to portions of the renal artery lumen in order to stimulate underlying renal nerves; (d) optionally moving the catheter tip of the catheters according to a specified protocol in order to make contact with desired portions of the renal artery lumen; (e) measuring indicia of disease after each site-specific electrical stimulation and recording changes over baseline; and (f) correlating changes in disease indicia with the portions of the renal artery lumen which were stimulated to produce said changes, thereby mapping specific locations of renal nerves underlying the renal artery lumen.
(41) The renal nerve architecture is of paramount consideration before successful ablation can take place; therefore, individual renal nerve architecture must be carefully considered or mapped before catheterization for denervation can be successfully accomplished. The presence of aberrant or unusual renal architecture, as well as normal variation in renal nerve architecture among individuals require mapping of the renal nerves before ablation. In other words, mapping of the renal nerves is required before catheter denervation because the best spots for ablation are “random” in the sense that the best spots for ablation vary from one person to another, and from one artery to another. Optimal ablation thus requires identification or mapping of renal nerves prior to catheter ablation.
(42) The catheters used in the above method perform both stimulatory and ablative processes. In one embodiment, the catheters used are the catheters described herein below. In another embodiment, the catheters can be ablative catheters currently in use to treat cardiac arrhythmias.
(43) In one embodiment, the indicia of disease measured in the above method comprise indicia of hypertension, indicia of diabetes, or indicia of congestive heart failure generally known in the art. For example, the indicia of hypertension may include systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, muscular sympathetic activity, and urine output.
(44) In one embodiment, the optional protocol for moving the catheter tip in the above method comprises moving the stimulatory or ablative section of the catheter tip from the half of the renal artery closer to the interior of the kidney to the half of the renal artery closer to the aorta and applying one or more electrical stimulation to each of the two halves.
(45) In another embodiment, the optional protocol for moving the catheter tip comprises turning the stimulatory or ablative section of the catheter tip within the renal artery in the following sequence: (a) turning from the anterior wall to the posterior wall of the artery; (b) turning from the posterior wall to the superior wall of the artery; and (c) turning from the superior wall to the inferior wall of the artery, wherein each turn is 90° or less. In one embodiment, one or more electrical stimulations are applied after each turning of the catheter tip within the renal artery.
(46) In one embodiment, the electrical stimulation applied falls within the following parameters: (a) voltage of between 2 to 30 volts; (b) resistance of between 100 to 1000 ohms; (c) current of between 5 to 40 milliamperes; (d) applied between 0.1 to 20 milliseconds.
(47) The present invention also provides a method of ablating renal nerves to treat disease caused by systemic renal nerve hyperactivity, comprising the steps of: (a) applying the mapping method described herein to map renal nerves; and (b) applying radiofrequency energy through the catheter to site-specific portions of the renal artery lumen to ablate the mapped renal nerves. In further embodiments, based on the mapping of the renal nerves, other ablative techniques generally known in the art can be utilized on renal artery walls to ablate the sympathetic renal nerves, e.g. ablative techniques using other ablative energy such as laser energy, high intensive focused ultrasound or cryoablative techniques.
(48) The present invention also provides a method for mapping and ablating renal nerves to treat disease caused by systemic renal nerve hyperactivity, comprising the steps of: (a) introducing a catheter into the renal architecture at a desired location where it remains stationary; (b) keeping the catheter stationary while electrical current is introduced through individual electrodes of the catheter and while indicia of disease are measured to perform renal nerve mapping according to the method described herein; and (c) keeping the catheter stationary while radiofrequency energy is introduced through individual electrodes of the catheter to ablate the mapped renal nerves. As discussed above, besides radiofrequency energy, other generally known ablative techniques using other ablative energy can also be used.
(49) The present invention also provides a catheter for performing the mapping method described herein, wherein the catheter comprises catheter tip possessing electrodes that lie proximal to the arterial lumen, and wherein the electrodes can deliver both a direct and alternating current as well as radiofrequency energy. In one embodiment, the electrodes perform both stimulatory and ablative functions. The electrodes may be activated independently of one another or in any combination. In one embodiment, the entire catheter is between 1.0 to 2.0 m in length, wherein the catheter tip is between 2.0 and 6.0 cm in length, wherein the catheter tip has a diameter of from 2.0 mm to 10.0 mm.
(50) In another embodiment, the shape of the catheter tip is either a single helix or a double helix, wherein the coil of the helix is either round or flat in shape and the electrodes are spaced along the length of the coil, wherein said electrodes may be round in shape if the coil is round or flat in shape if the coil is flat in shape. In one embodiment, the electrodes are evenly spaced along the length of the helix or helices 60° 90° or 120° or 180° from each other.
(51) In another embodiment, the catheter tip comprises a balloon around which is wrapped a helical coil or an umbrella component, wherein spaced along the length of the helical coil or the umbrella component are electrodes. In one embodiment, the umbrella component is either open-ended or close-ended.
(52) The invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative, and are not meant to limit the invention as described herein, which is defined by the claims which follow thereafter.
(53) Throughout this application, various references or publications are cited. Disclosures of these references or publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
(54) It is to be noted that the transitional term “comprising”, which is synonymous with “including”, “containing” or “characterized by”, is inclusive or open-ended and does not exclude additional, un-recited elements or method steps.
Example 1
Renal Nerves Mapping
(55) Acute pig experiments were designed and performed in order to achieve the following:
(56) 1. To test currently existing cardiac ablation catheters (7F,B-Type, spacing 2-5-2 mm, CELSIUS® RMT Diagnostic/Ablation Steerable Catheter, Biosense Webster, Diamond Bar, Calif. 91765, USA) and a radiofrequency generator (STOCKERT 70 RF Generator, Model Stockert GmbH EP-SHUTTLE ST-3205, STOCKERT GmbH, Freiburg, Germany) for the purposes of renal nerve mapping and ablation.
(57) 2. To test renal nerve mapping via examination of changes in blood pressure and heart rate during emission of electrical stimulation at different sites within the lumen of the left and right renal arteries.
(58) 3. To determine the safe range of high radiofrequency energy to be emitted to renal arteries for renal nerve ablation via examination of visual changes of renal arterial walls and histology.
(59) 4. To use changes in blood pressure and heart rate as indices of efficient ablation of renal nerves during renal ablation.
(60) Acute pig experiments were performed for renal nerve mapping. Three pigs (body weight from 50-52 kg) were anesthetized with sodium pentobarbital (15 mg/kg, iv). Systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were monitored. The experimental design and protocol are illustrated below in
(61) For baseline measurements, systolic, diastolic and mean arterial blood pressure and heart rate were measured before electrical stimulation was applied to the renal artery. Electrical stimulation was then applied to several sites within the renal artery; afterwards, mean arterial blood pressure and heart rate were then measured 5 seconds to 2 minutes after the electrical stimulation to measure the effects of the stimulation. It was found that once electrical stimulation was applied to some segments (these segments varied from animal to animal) of the renal artery, blood pressure and heart rate were significantly increased; however, if the same electrical stimulation was applied to other segments of the renal artery, blood pressure and heart rate were only minimally changed.
(62) Separate stimulations took place either on the abdominal aortic side of the renal artery (“AO Side”) or on the segment of the renal artery close to the kidney (the “kidney side”). In order to demonstrate that electrical stimulation applied to different locations of renal arteries may result in different effects on blood pressure and heart rate, and to further demonstrate that the location of renal nerves can be detected via electrical stimulations at different locations in the renal artery, several stimulation strategies were used. Detailed parameters of the electrical stimulations and changes in blood pressure and heart rate from Pig #1 are shown in Table 2.
(63) TABLE-US-00001 TABLE 2 Renal Nerve Stimulation for Mapping Animal #1: Systolic Diastolic Mean blood Blood Arterial Heart Stimulation pressure Pressure Pressure Rate Parameters (mmHg) (mmHg) (mmHg) (b/min) Left Renal Stimulation (Kidney Side, Anterior Wall) Baseline 15 V/0.4 ms/ 141 109 123 140 Response (2 min 400 Ohm/17 mA 151 114 127 130 after) Left Renal Stimulation (Kidney Side, Posterior Wall) Baseline 15 V/0.4 ms/ 140 116 123 150 Response (2 min 400 Ohm/28 mA 142 117 128 151 after) Left Renal Stimulation (Abdominal Aorta Side, Anterior Wall) Baseline 15 V/0.2 ms/ 136 107 120 145 Response (2 min 400 Ohm/28 mA 141 110 125 141 after) Left Renal Stimulation (Abdominal Aorta Side, Posterior Wall) Baseline 15 V/0.2 ms/ 132 99 113 141 Response (2 min 540 Ohm/28 mA 151 108 125 138 after) Right Renal Stimulation (Kidney Side) Baseline 15 V/0.2 ms/ 152 112 131 144 Response (2 min 600 Ohm/25 mA 156 113 130 135 after) Right Renal Stimulation (Abdominal Aorta Side) Baseline 15 V/0.2 ms/ 155 113 130 141 Response (2 min 520 Ohm/25 mA 158 113 130 146 after)
(64) With respect to pig one (Table 2), four separate stimulations took place in the left renal artery and two separate stimulations were performed in the right renal artery, respectively. As preliminary approaches, on the abdominal side of the left renal artery, two separate electrical stimulations were applied: one to the anterior wall and one to the posterior wall of the artery. On the kidney side of the left renal artery, two separate electrical stimulations were applied: one to the anterior wall and one to the posterior wall of the artery. Different effects of these stimulations on blood pressure and heart rate were observed. In the right renal artery, one electrical stimulation was applied to the renal artery on the abdominal side and the kidney side, respectively. The same stimulation strategy (one on the abdominal side and one on the kidney site) was used for Pig #2 and Pig #3. Detailed stimulation parameters and changes in blood pressure and heart rate in response to these stimulations are summarized in Table 3 and Table 4, respectively.
(65) TABLE-US-00002 TABLE 3 Renal Nerve Stimulation for Mapping Animal #2: Systolic Diastolic Mean blood Blood Arterial Heart Stimulation pressure Pressure Pressure Rate Parameters (mmHg) (mmHg) (mmHg) (b/min) Left Renal Stimulation (Kidney Side) Baseline 15 V/0.2 ms/ 155 112 130 132 Response (2 min 580 Ohm/26 mA 159 115 133 120 after) Left Renal Stimulation (Abdominal Aorta Side) Baseline 15 V/0.2 ms/ 155 114 131 126 Response (2 min 480 Ohm/28 mA 159 116 132 132 after) Right Renal Stimulation (Kidney Side) Baseline 15 V/0.2 ms/ 153 113 130 135 Response (2 min 520 Ohm/28 mA 166 119 141 147 after) Right Renal Stimulation (Abdominal Aorta Side) Baseline 15 V/0.2 ms/ 157 114 132 120 Response (2 min 500 Ohm/28 mA 162 117 135 117 after)
(66) TABLE-US-00003 TABLE 4 Renal Nerve Stimulation for Mapping Animal #3: Systolic Diastolic Mean blood Blood Arterial Heart Stimulation pressure Pressure Pressure Rate Parameters (mmHg) (mmHg) (mmHg) (b/min) Left Renal Stimulation (Kidney Side) Baseline 15 V/9.9 ms/ 173 119 141 138 Response (2 min 800 Ohm/28 mA 202 139 158 142 after) Left Renal Stimulation (Abdominal Aorta Side) Baseline 15 V/9.9 ms/ 169 110 136 159 Response (2 min 800 Ohm/28 mA 170 115 138 150 after) Right Renal Stimulation (Kidney Side) Baseline 15 V/9.9 ms/ 154 110 127 129 Response (2 min 800 Ohm/28 mA 167 113 136 135 after) Right Renal Stimulation (Abdominal Aorta Side) Baseline 15 V/9.9 ms/ 157 112 130 126 Response (2 min 800 Ohm/28 mA 162 110 131 123 after)
(67) These results shown above clearly showed that electrical stimulation applied to different locations in the renal artery caused different effects on systolic, diastolic and mean blood pressures, as well as heart rates with respect to each test pig. For instance, in the left kidney, the maximal change in systolic blood pressure in response to electrical stimulation was 19.5 mmHg and 29 mmHg in Animal #1 and Animal #3, respectively; the minimal change of systolic blood pressure was 2 mmHg and 1 mmHg in Animal #1 and Animal #3, respectively. However, in animal #2, changes in systolic blood pressure were consistent when the electrical stimulations were applied to either the abdominal aorta side or the kidney side. Furthermore, the stimulation location which caused the maximal effect or minimal effect varies from animal to animal, indicating that the distribution of renal sympathetic nerves is not consistent between animals. These results are summarized in Table 5A.
(68) Similar phenomenon in diastolic blood pressure, mean arterial blood pressure and heart rate during electrical stimulation in the left renal artery were observed and further summarized in Table 5B, 5C and 5D, respectively.
(69) TABLE-US-00004 TABLE 5A Changes in Systolic Blood Pressure (SBP) During Electrical Stimulation in Left Renal Artery Left Renal Stimulation SBP Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 131.5 151 19.5 AO Side 140 142 2 Renal Side Pig 2 155 159 4 Renal Side 155 159 4 AO Side Pig 3 173 202 29 Renal Side 169 170 1 AO Side Average 153.2 170.7 17.5 154.7 157.0 2.3 SD 20.8 27.4 12.6 14.5 14.1 1.5
(70) TABLE-US-00005 TABLE 5B Changes in Diastolic Blood Pressure (DBP) During Electrical Stimulation in Left Renal Artery Left Renal Stimulation DBP Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 99 108 9 AO Side 116 117 1 Renal Side Pig 2 112 115 3 Renal Side 114 116 2 AO Side Pig 3 119 139 20 Renal Side 110 115 5 AO Side Average 110.0 120.7 10.7 113.3 116.0 2.7 SD 10.1 16.3 8.6 3.1 1.0 2.1
(71) TABLE-US-00006 TABLE 5C Changes in Mean Arterial Pressure (MAP) During Electrical Stimulation in Left Renal Artery Left Renal Stimulation MAP Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 112.5 125 12.5 AO Side 123 128 5 Renal Side Pig 2 130 133 3 Renal Side 131 132 1 AO Side Pig 3 141 158 17 Renal Side 136 138 2 AO Side Average 127.8 138.7 10.8 130.0 132.7 2.7 SD 14.4 17.2 7.1 6.6 5.0 2.1
(72) TABLE-US-00007 TABLE 5D Changes in Heart Rate (HR) During Electrical Stimulation in Left Renal Artery Left Renal Stimulation HR Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 150 151 1 Renal Side 140 130 −10 Renal Side Pig 2 126 132 6 AO Side 132 120 −12 Renal Side Pig 3 138 142 4 Renal Side 159 150 −9 AO Side Average 138.0 141.7 3.7 143.7 133.3 −10.3 SD 12.0 9.5 2.5 13.9 15.3 1.5
(73) Similar phenomenon in systolic, diastolic and mean arterial pressure and heart rate during electrical stimulation in the right renal artery were also observed and further summarized in Table 6A, 6B, 6C and 6D, respectively.
(74) TABLE-US-00008 TABLE 6A Changes in Systolic Blood Pressure (SBP) During Electrical Stimulation in Right Renal Artery Right Renal Stimulation SEP Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 151.5 156 4.5 Renal Side 155 158 3 AO Side Pig 2 153 166 13 Renal Side 157 162 5 AO Side Pig 3 154 167 13 Renal Side 157 162 5 AO Side Average 152.8 163.0 10.2 156.3 160.7 4.3 SD 1.3 6.1 4.9 1.2 2.3 1.2
(75) TABLE-US-00009 TABLE 6B Changes in Diastolic Blood Pressure (DBP) During Electrical Stimulation in Right Renal Artery Right Renal Stimulation DPB Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 111.5 113 1.5 Renal Side 113 113 0 AO Side Pig 2 113 119 6 Renal Side 114 117 3 AO Side Pig 3 110 113 3 Renal Side 112 110 −2 AO Side Average 111.5 115.0 3.5 113.0 113.3 0.3 SD 1.5 3.5 2.3 1.0 3.5 2.5
(76) TABLE-US-00010 TABLE 6C Changes in Mean Arterial Pressure (MAP) During Electrical Stimulation in Right Renal Artery Right Renal Stimulation MAP Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 130 130 0 AO Side 131 130 −1 Renal Side Pig 2 130 141 11 Renal Side 132 135 1 AO Side Pig 3 127 130 3 Renal Side 130 131 1 AO Side Average 129.0 133.7 4.7 131.0 132.0 1.0 SD 1.7 6.4 5.7 1.0 2.6 2.0
(77) TABLE-US-00011 TABLE 6D Changes in Heart Rate (HR) During Electrical Stimulation in Right Renal Artery Right Renal Stimulation HR Maximal Responses (mmHg) Minimal Responses (mmHg) Animal Stimulation Stimulation No. Baseline Maximal Δ Location Baseline Minimal Δ Location Pig 1 141 146 5 AO Side 144 135 −9 Renal Side Pig 2 135 147 12 Renal Side 120 117 −3 AO Side Pig 3 129 135 6 Renal Side 126 123 −3 AO Side Average 135.0 142.7 7.7 130.0 125.0 −5.0 SD 6.0 6.7 3.8 12.5 9.2 3.5
(78) These data provide proof of concept of renal mapping—specifically, that a substantial physiologic response, in this case, the maximal increase in measured blood pressure, was induced by electrical stimulation via a catheter placed at a defined location where renal nerve branches are abundantly distributed, so that an optimum location for ablation to be performed at a site was identified. Averaged data (mean±SD) calculated from Table 5 and Table 6 are graphically represented in
(79) Subsequent to the stimulation studies for renal mapping, ablations of the renal nerves were also performed in the same pigs. Four ablations were each delivered to the left and to the right renal arteries starting from the kidney side and moving to the abdominal aorta side in the order of movement from the anterior, to the posterior, to the superior and then to the inferior wall; each ablation was <5 mm apart from the location of the previous ablation and the electrode head (catheter tip) of the ablation catheter was turned 90 degrees after each ablation. Based on the literature (Krum 2009, 2010), low energy level (5-8 watts) should be used for renal ablation; therefore, 5 watts and 8 watts were used for renal ablation. For left renal artery ablation, the energy level applied was 5 watts and the time length of ablation was 120 seconds; for the right renal artery, the ablation energy level applied was 8 watts and the time length was 120 seconds. The temperature at the ablation site was measured to be from 40° C. to 50° C. Arterial systolic pressure, diastolic pressure, mean arterial pressure and heart rate were examined during ablations. The data clearly showed that ablation at different locations within the renal artery resulted in differing changes in blood pressure and heart rate, further demonstrating that renal nerves are not equally distributed along the renal arteries and that changes in hemodynamic parameters such as blood pressure and heart rate can be used as indicators of an effective renal ablation measured concurrently at the time of ablation.
(80) Changes in arterial systolic and diastolic pressure, mean arterial pressure and heart rate during four separate renal ablations in the renal arteries of the left kidney were summarized in
(81) Changes in arterial systolic and diastolic pressure, mean arterial pressure and heart rate during four separate renal ablations in the renal arteries of the right kidney were summarized in
(82) At the end of the experiments, both left and right renal arteries were cut open. There was no visual damage to the arterial endothelium and arterial wall; histological data confirmed these visual observations, demonstrating that the energy levels of 5 watts and 8 watts, and treatment of 120 seconds used for ablation were safe.
Example 2
Renal Mapping Catheter Designs
(83) New catheters designed with functions of stimulation, mapping, ablation and angiography are hereby disclosed.
(84) The catheter apparatus comprises an elongated catheter having a catheter tip on the distal end which, once inserted, is intended to remain in a static position within the renal vascular architecture; a proximal end; and a plurality of ablation electrodes. In one embodiment, the ablation electrodes are evenly-spaced down the length of the elongated catheter tip. The plurality of these ablation electrodes are spaced from the proximal end and from the distal end of the elongated catheter tip by electrically nonconductive segments. In one embodiment, the first electrode on the tip side of the catheter or on the end side of the catheter can be used as a stimulation reference for any other electrodes to deliver electrical stimulation; alternatively, any one of these electrodes can be used as a reference for other electrodes.
(85) In one embodiment, the elongated catheter tip is of a helical shape.
(86) In another embodiment, one or more conducting wires are coupled with and supplying direct or alternating electrical current to the plurality of electrodes via one or more conducting wires. A controller is configured to control the electrical current to the plurality of electrodes in either an independent manner, or a simultaneous manner while the catheter tip remains in a static position in the renal artery.
(87) In another embodiment, one or more conducting wires are coupled with and supplying radiofrequency (RF) energy to the plurality of electrodes, the RF energy being either unipolar RF energy or bipolar RF energy. A radiofrequency generator supplies energy via the one or more conducting wires to the plurality of electrodes. A controller is configured to control the energy source to supply energy to the plurality of electrodes in either an independent manner, a sequential manner, or a simultaneous manner while the catheter tip remains in a static position in the renal artery.
(88) The RF energy sent to the electrodes may be controlled so that only low-level electrical energy impulses are generated by the electrodes in order to merely stimulate underlying nerve tissue, and in particular, renal nerve tissue. Alternately, the RF energy sent to the electrodes may be controlled so that greater electrical energy impulses are generated by the electrodes in order to ablate underlying nerve tissue, and in particular, renal nerve tissue. The catheter tip, and in particular, the electrodes, are designed to remain in contact with the renal artery lumen, in the same place, throughout stimulation and ablation.
(89) In another embodiment, the catheter is capable of being used with radiofrequency generators currently utilized in the practice of cardiac tissue ablation. These radiofrequency generators may include, but are not necessarily limited to those currently produced by Medtronic, Cordis/Johnson & Johnson, St. Jude Medical, and Biotronic.
(90) Exemplary embodiments of the invention, as described in greater detail below, provide apparatuses for renal nerve denervation.
(91)
(92) In one embodiment, the catheter has an elongated tip of a helical shape. A plurality of electrodes is evenly spaced starting from their placement at the proximal end of the catheter tip through the distal end of the catheter tip by electrically nonconductive segments.
(93) In certain embodiments, the catheter tip of the ablation catheter comprises a single helix; in others, it is composed of double helix. The coil or coils of the helix or helices of the catheter tip may be either round or flat. Electrodes may be placed evenly down the length of the coils; for example, they can be space either 60°, 90° or 120° apart, but may be placed in other conformations or separated by different degrees.
(94) The electrodes may be either flat and rectangular or square in shape, if the coil of a helix is itself flattened. Alternately, the electrodes may be round and/or built into the helix if the coil is itself round. In one embodiment, the catheter tip has a length of from 2.0 cm to 6.0 cm and a diameter of 0.5 mm to 10.0 mm; the catheter's total length is from 1 m to 2.0 m.
(95) In another embodiment, the catheter tip of the ablation catheter comprises a balloon catheter system. In one embodiment, electrodes are evenly spaced at intervals along a helical coil which is either round or flat in shape and wrapped around the balloon; in other embodiments, electrodes are spaced along an umbrella frame apparatus which is either round or flat in shape and wrapped down the length of the balloon. In certain embodiments, the umbrella frame apparatus has an open end and in others, a closed end. The electrodes will come into contact with the renal architecture upon inflation of the balloon apparatus. In one embodiment, the catheter tip has a length of 2.0 cm to 6.0 cm and a diameter of from 0.5 mm to 10.0 mm when uninflated; the catheter's total length is from 1 m to 2.0 m. In one embodiment, the diameter of the catheter tip when the balloon is inflated may range from 0.5 mm to 10 mm.
(96) In one embodiment of this invention, there is provided a renal nerve modulation and ablation processes (on either the left side kidney, right side kidney, or both) comprising insertion of one of the catheters described above into either the left renal artery (LRA) or the right renal artery (RRA) followed by renal nerve mapping as substantially described above, followed by targeted ablation by individual electrodes.
(97) In one embodiment, nerve stimulation takes place by application of the following parameters: 0.1 ms-20 ms, 2V-30V, 5 mA-40 mA, and 100 Ohm-1000 Ohm. In one embodiment, nerve ablation takes place by application of the following parameters: below 8 watts and 30 seconds-180 seconds.
REFERENCES
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