Catheter apparatuses for renal neuromodulation

0001Cross-reference of related applications This application is filed on April 26, 2010, US Provisional Patent Application No. 61 / 328,105, and October 21, 2010, No. 61 / 405,472, and May 28, 2010. Claims the interests of US Patent Application No. 12 / 790,639 and No. 12 / 871,457 filed on August 30, 2010, each of which is incorporated herein by reference in its entirety. ..

0002The techniques disclosed in this application generally relate to catheter devices, systems, and methods for intravascular nerve regulation. More specifically, the techniques disclosed herein relate to catheter devices, systems, and methods for achieving intravascular renal nerve regulation through the application of thermal and / or electrical energy.

0003Hypertension, heart failure, chronic kidney disease, insulin resistance, diabetes, and metabolic syndrome represent significant and increasing global health problems. Current treatments for these conditions include non-pharmacological, pharmacological, and instrument-based approaches. Despite this variety of treatment options, the rate of control of blood pressure, as well as the therapeutic effect of preventing the progression of these conditions and their sequelae, remains unsatisfactory. Reasons for this situation are diverse, including the problem of non-compliance with prescribed therapies, heterogeneity of response in terms of both efficacy and adverse event profile, and others, but current therapies for these conditions. It is clear that alternative options are needed to supplement the therapeutic regime.

0004Reduction of renal sympathetic activity (eg, via denervation) can reverse these processes. Palo Alto, CA's Ardian, Inc. states that the energy field includes and comprising an electric field, irreversible electroporation, electrofusion, apoptosis, necrosis, excision, thermal alteration, altered gene expression, or another. We have found that renal nerve regulation can be evoked through denervation caused by the preferred mode of.

<p num="0005"> Catheter-based interventions are widely used in medical care where access to locations throughout the body is obtained, for example, through the blood vessels of the cardiovascular system. Ardian, Inc. shows that energy fields can be applied to the renal sympathetic nerves from within the renal arteries. The renal arteries have unique characteristics from other blood vessels or parts of the body, and therefore applying an energy field from within the renal arteries to the renal sympathetic nerves is not trivial. Therefore, there is a need for catheters that can effectively deliver energy from within the renal arteries to the renal sympathetic nerves, where the catheters reduce the risk of i) applying traumatic forces to the arterial wall. Proceeding through the renal arteries, ii) placing the energy delivery element exactly where it wants on the vessel wall, and iii) during the pulsatile and respiratory movements of the renal artery, on the energy delivery element and vessel wall. Better configured to maintain stable contact with the site.</p>

<p num="0006"> The following summary is provided solely for the benefit of the reader and is not intended to limit this disclosure in any way. The present application provides catheter devices, systems, and methods for achieving electrical and / or heat-induced renal nerve regulation by intravascular access.</p><p num="0007"> One aspect of the application provides a device, system, and method for incorporating a catheter treatment device with an elongated shaft. The elongated shaft is sized and configured to deliver at least one energy delivery element to the renal arteries via intravascular pathways including the femoral, iliac, and aorta. Different compartments of elongated shafts perform different mechanical functions in use. The divisions are (i) percutaneous introduction into the femoral or humerus artery through a small diameter access site, (ii) through a tortuous intravascular route through the iliac artery, into the aorta, and to the left of each. For non-traumatic passage into the right renal artery, (iii) to significant deflection at the junction of the left / right renal artery and the aorta to obtain entry into each left or right renal artery. Respond, (iv) Respond to controlled translation, deflection, and / or rotation within each renal artery to achieve access to the lining of each renal artery and desired alignment with them. , (V) Allowing placement of at least one energy delivery element in contact with tissue on the inner wall in an orientation that optimizes the active surface area of the energy delivery element, and (vi) Respiratory and / or blood pulsation. Their size, composition, and mechanical, including allowing a substantially stable contact force between at least one energy delivery element and the inner wall during the movement of the renal arteries involving the aorta due to sex. Distinguished in terms of characteristics.</p>

0008<figref num="1">It is a conceptual illustration of the sympathetic nervous system (SNS) and how the brain communicates with the body via SNS.</figref><figref num="2">It is an enlarged anatomical view of a nerve that innervates the left kidney so as to form a renal plexus surrounding the left renal artery.</figref><figref num="3">A and B provide anatomical and conceptual diagrams of the human body, showing neural efferent and afferent traffic between the brain and kidneys, respectively.</figref><figref num="4">A and B are anatomical views of human arterial and venous duct structures, respectively.</figref><figref num="5">FIG. 3 is a perspective view of a system for achieving heat-induced renal nerve regulation within a blood vessel, including a therapeutic device and a generator.</figref><figref num="6">A to D are anatomical views of intravascular delivery, deflection, and placement through the femoral artery and into the renal arteries of various embodiments of the therapeutic device shown in FIG.</figref><figref num="7">A to D are a series of elongated shafts of the therapeutic device shown in FIG. 5, showing different mechanical and functional areas incorporated by the elongated shaft.</figref><figref num="7E">An anatomical view of the arrangement of the treatment equipment shown in FIG. 5 within the dimensions of the renal artery is shown.</figref><figref num="8">A to C show the placement of thermal heating elements at the distal end of the elongated shaft of the therapeutic device shown in FIG. 5 that are directed to contact tissue along the renal arteries.</figref><figref num="9">A and B show the arrangement of the thermal heating elements shown in FIGS. 8A-8C in contact with tissue along the renal arteries and the delivery of heat treatment to the renal plexus.</figref><figref num="10">A and B show typical embodiments of the force transfer section of the elongated shaft of the therapeutic device shown in FIG.</figref><figref num="11">A to C show typical embodiments of the proximal flexion area of the elongated shaft of the therapeutic device shown in FIG.</figref><figref num="12">A to D show typical embodiments of the intermediate flexion zone of the elongated shaft of the treatment device shown in FIG.</figref><figref num="13">A to C show alternative embodiments of the intermediate flexion zone of the elongated shaft of the treatment device shown in FIG.</figref><figref num="14">A to C show alternative embodiments of the intermediate flexion zone of the elongated shaft of the treatment device shown in FIG.</figref><figref num="15">A to C show typical embodiments of the distal flexion area of the elongated shaft of the therapeutic device shown in FIG. D to F show a multi-plan view of the flexion capacity of the distal flexion area corresponding to the elongated shaft of the treatment device shown in FIG. G and H represent alternative embodiments of the distal flexion zone, corresponding to the elongated shaft of the therapeutic device shown in FIG.</figref><figref num="16">A and B show typical embodiments of the rotation control mechanism coupled to the handle assembly of the therapeutic device shown in FIG.</figref><figref num="17">A and B are representative alternatives to elongated shafts for therapeutic devices such as those shown in FIG. 5, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. An embodiment is shown.</figref><figref num="18">A to C are more alternative representatives of elongated shafts for therapeutic devices such as those shown in FIG. 5, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. The embodiment is shown.</figref><figref num="19">A to C are more alternative representatives of elongated shafts for therapeutic devices such as those shown in FIG. 5, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. The embodiment is shown.</figref><figref num="20">A and B are more alternative representatives of elongated shafts for therapeutic devices such as those shown in FIG. 5, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. The embodiment is shown.</figref><figref num="21">A to C show typical embodiments of the third flexion zone of the elongated shaft of the treatment device shown in FIG.</figref><figref num="21D">An anatomical view of the arrangement of the treatment equipment shown in FIG. 5 within the dimensions of the renal artery is shown.</figref><figref num="21">E to G show anatomical views of the arrangement of therapeutic devices shown in FIGS. 21A to 21C within the dimensions of the renal arteries.</figref><figref num="21">H to L show an example of the configuration of the force direction changing element.</figref><figref num="21">M and N represent alternative embodiments of the force damping section corresponding to the elongated shaft of the therapeutic device shown in FIG. 21A.</figref><figref num="22">A to G represent a further alternative representative embodiment of an elongated shaft for a therapeutic device, indicating a second flexion zone with preformed flexion.</figref><figref num="22">H to K represent a further alternative exemplary embodiment of an elongated shaft for therapeutic equipment, indicating a second flexion zone located longitudinally offset from the preformed bend.</figref><figref num="23">A to G represent more alternative exemplary embodiments of elongated shafts for therapeutic devices, showing examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated.</figref><figref num="24">A to D represent more alternative exemplary embodiments of elongated shafts for therapeutic devices, showing examples of different structural, mechanical, and functional areas in which the elongated shafts can be incorporated.</figref><figref num="25">A to C represent alternative representative embodiments of the second flexion zone of the elongated shaft of the therapeutic device shown in FIG. 5, which is configured for multi-directional deflection. D to M are more alternative representatives of elongated shafts for therapeutic devices such as those shown in FIG. 25A, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. Embodiment, wherein the second flexure area comprises a center-positioned spine. N to W are more alternative representatives of elongated shafts for therapeutic devices such as those shown in FIG. 25A, which show examples of different structural, mechanical, and functional areas in which the elongated shaft can be incorporated. The embodiment is shown.</figref><figref num="26">A to L show a further alternative representative embodiment of an elongated shaft for a therapeutic device, which shows an example of a shaft that deforms into a spiral.</figref><figref num="27">A to F show a further alternative representative embodiment of an elongated shaft for a therapeutic device, showing an example of a shaft that deforms into a complex flexion.</figref><figref num="28">A and B represent a further alternative representative embodiment of an elongated shaft for a therapeutic device having an electrically activated deflectable compartment.</figref><figref num="29">A and E represent more alternative exemplary embodiments of elongated shafts for therapeutic devices with hinged joints.</figref><figref num="30A">A perspective view of a further embodiment of the system of FIG. 5 configured for forced cooling of the therapeutic device.</figref><figref num="30B">An open circuit system for forcibly cooling the thermal heating element and / or the tissue to be contacted and its surroundings is shown.</figref><figref num="30C">Side and cross-sections of a closed circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings, respectively.</figref><figref num="30D">Side and cross-sections of a closed circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings, respectively.</figref><figref num="31A">Sectional view of the renal artery at the treatment site showing the effect of forced cooling.</figref><figref num="31B">A graph plotting temperature against tissue depth in the presence and absence of forced cooling, while keeping other parameters constant.</figref><figref num="32A">Sectional view of the renal artery at the treatment site showing the alternative effect of forced cooling.</figref><figref num="32B">Graph of temperature relative to tissue depth in the presence and absence of forced cooling, combined with increased energy delivery during forced cooling.</figref><figref num="33">A and B, respectively, in the presence and absence of forced cooling, which result in a reduced duration of treatment during forced cooling, i) show a faster rate of increase in temperature, and ii) higher temperatures. Temperature vs. time graph at target tissue depth.</figref><figref num="34">A to L represent a further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings.</figref><figref num="35">A graph plotting power and temperature over time at tissue surface and lesion depth in the presence of forced cooling.</figref><figref num="36">A graph plotting power and temperature over time at tissue surface and lesion depth in the presence of forced cooling when utilizing algorithms that incorporate intermittent power delivery and cooling.</figref><figref num="37">A further representative embodiment of a closed circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="38">A further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="39">A further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="40">A further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="41">A further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="42">A further representative embodiment of an open circuit system for forcibly cooling the thermal heating element and / or the tissue in contact with it and its surroundings is shown.</figref><figref num="43">A to H use intravascular delivery, placement, deflection, rotation, retraction, repositioning, and use of therapeutic devices such as those shown in FIG. 5 to achieve heat-induced renal nerve regulation from within the renal arteries. Shown. I to K indicate the peripheral therapeutic effect resulting from the intravascular use of therapeutic devices such as those shown in FIG.</figref><figref num="43L">An alternative endovascular treatment approach using a therapeutic device such as that shown in Figure 5 is shown.</figref><figref num="44">An energy delivery algorithm corresponding to the energy generator of a system such as that shown in Figure 5 is shown.</figref><figref num="45">Shows multiple components of a system and treatment device packaged in a single kit.</figref><figref num="46">A to C show fluoroscopic images of treatment equipment, such as those shown in FIG. 5, at multiple treatment locations within the renal arteries of animals.</figref><figref num="46">D and E show fluoroscopic images of therapeutic instruments such as those shown in FIG. 5 at multiple therapeutic locations within the renal artery during human studies.</figref>

0009Although the disclosure herein is detailed and precise to allow one of ordinary skill in the art to practice the techniques disclosed, the physical embodiments disclosed herein are of the present invention. They merely illustrate various aspects, which may be embodied in other concrete structures. Although preferred embodiments are described, the details may be modified without departing from the invention as defined by the claims.

0010I. Related anatomy and physiology A. Sympathetic nervous system The sympathetic nervous system (SNS), along with the enteric and parasympathetic nervous systems, is a tributary of the autonomic nervous system. It is always active at the basal level (called sympathetic tone) and becomes more active during stress. Like the rest of the nervous system, the sympathetic nervous system operates through a series of interconnected neurons. Sympathetic neurons are often thought to be part of the peripheral nervous system (PNS), but many are within the central nervous system (CNS). Sympathetic neurons in the spinal cord, which are part of the CNS, communicate with peripheral sympathetic neurons via a series of sympathetic ganglia. Within the ganglia, spinal sympathetic neurons connect to peripheral sympathetic neurons through synapses. Spinal cord sympathetic neurons are therefore referred to as presynaptic (or preganglionic) neurons, while peripheral sympathetic neurons are referred to as postsynaptic (or postganglionic) neurons.

0011At synapses within the sympathetic ganglia, preganglionic sympathetic neurons release acetylcholine, a chemical messenger that binds to and activates nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulus, postganglionic neurons primarily release noradrenaline (norepinephrine). Sustained activation may elicit the release of adrenaline from the adrenal medulla.

0012Once released, norepinephrine and epinephrine bind to adrenergic receptors on peripheral tissues. Binding to adrenergic receptors provokes neuronal and hormonal responses. Physiological manifestations include pupil dilation, increased heart rate, occasional vomiting, and increased blood pressure. Increased sweating is also seen due to the binding of cholinergic receptors in the sweat glands.

0013The sympathetic nervous system is involved in ups and downs of many homeostatic mechanisms in living organisms. Fibers from SNS innervate tissues in almost any organ system and provide at least some regulatory function for a variety of things such as pupil diameter, intestinal motility, and urine output. This response also causes preganglionic sympathetic fibers ending in the adrenal medulla (but also all other sympathetic fibers) to secrete acetylcholine, thereby producing adrenaline (epinephrine) and, to a lesser extent, noradrenaline (norepinephrine). Because of its activation, it is also known as the body's sympathetic adrenal response. Thus, this response, which acts primarily on the cardiovascular system, is mediated directly via impulses transmitted through the sympathetic nervous system and indirectly via catecholamines secreted by the adrenal medulla.

0014Science typically considers SNS to be an autoregulatory system, a system that operates without the intervention of conscious thinking. Some evolutionists suggest that the sympathetic nervous system acted to maintain survival in early organisms because it is involved in prestimulating the body for activity. An example of this pre-stimulation is seen shortly before awakening, where sympathetic outflow spontaneously increases in preparation for activity.

00151. Sympathetic chain As shown in Figure 1, SNS provides a network of nerves that allows the brain to communicate with the body. The sympathetic nerves are thought to originate from the inside of the spinal column, head toward the middle of the spinal cord in the lateral cell column (or lateral corner) of the middle zone, start at the first thoracic segment of the spinal cord, and extend to the second or third lumbar segment. Has been done. SNS is said to have thoracolumbar outflow because its cells begin in the chest and lumbar region of the spinal cord. Axons of these nerves exit the spinal cord through the anterior roots / roots. They pass near the dorsal (sensory) ganglia, where they enter the anterior branch of the spinal nerve. However, unlike somatic innervation, they connect to either the paravertebral spine (near the spinal column) or the anterior ganglion (near the aortic bifurcation) that extends parallel to the spinal column. , Rapidly separate through the white rami connector.

0016To reach target organs and glands, axons must travel long distances throughout the body, and to accomplish this, many axons send their message a second through synaptic transmission. Relay to cells. The end of the axon crosses the crevice, synapse, and connects to the dendrites of the second cell. The first cell (presynaptic cell) sends neurotransmitters across the synaptic cleft, where it activates the second cell (postsynaptic cell). The message is then directed to the final destination.

0017In SNS and other components of the peripheral nervous system, these synapses are created at sites called ganglia. The cells that transmit the fibers of the cell are called preganglionic cells, while the cells in which the fibers of the cell leave the ganglion are called postganglionic cells. As mentioned above, the preganglionic cells of SNS are located between the 1st thoracic (T1) and 3rd lumbar (L3) segments of the spinal cord. Postganglionic cells have their cell bodies in the ganglia and send their axons to the target organ or gland.

0018The ganglia send sympathetic trunks as well as cervical ganglia (upper, middle, lower) that send sympathetic nerve fibers to the head and chest organs, and abdominal and mesenteric ganglia (send sympathetic nerve fibers to the intestine). Also includes).

00192. Innervation of the kidney As Figure 2 shows, the kidney is innervated by the renal plexus (RP), which is closely associated with the renal arteries. The renal plexus is the autonomic plexus that surrounds the renal arteries and is implanted in the adventitia of the renal arteries. The renal plexus extends along the renal arteries until it reaches the parenchyma of the kidney. The fibers that contribute to the renal plexus arise from the abdominal ganglion, superior mesenteric ganglion, aortic renal ganglion, and aortic plexus. The renal plexus (RP), also called the renal nerve, is mainly composed of sympathetic nerve components. There is no (or at least very minimal) parasympathetic innervation of the kidney.

0020The preganglionic neuron cell body is located in the lateral medial column of the spinal cord. The preganglionic axons pass through the paravertebral ganglia (they do not synapse) to the small visceral nerve, the minimal visceral nerve, the first lumbar splanchnic nerve, the second lumbar splanchnic nerve, and the peritoneal ganglion , To the superior mesenteric ganglion, and to the aortic synaptic ganglion. Postganglionic neuronal cell bodies exit from the peritoneal ganglion, superior mesenteric ganglion, and aortic renal ganglion into the renal plexus (RP) and are distributed to the renal vascular structure.

00213. Renal sympathetic nerve activity Messages move in a two-way manner through SNS. Efferent messages can simultaneously inspire changes in different parts of the body. For example, the sympathetic nervous system accelerates the heart rate, widens the bronchial passages, reduces the motility (movement) of the large intestine, constricts blood vessels, increases peristalsis in the esophagus, dilates the pupils, goose bumps, And causes perspiration (sweating) and also raises blood pressure. The afferent message carries signals from various organs and sensory receptors throughout the body to other organs, and especially to the brain.

0022Hypertension, heart failure, and chronic kidney disease are just a few of the many medical conditions that result from chronic activation of SNS, especially the renal sympathetic nervous system. Chronic activation of SNS is a maladaptated response that drives the progression of these pathologies. Pharmaceutical management of the renin-angiotensin-aldosterone system (RAAS) is a long-standing but less effective approach to reducing SNS overactivity.

0023As mentioned above, the renal sympathetic nervous system has been identified as a major contributor to the complex pathophysiology of hypertension, volume overload conditions (such as heart failure), and progressive renal disease, both experimentally and in humans. Has been done. Studies using a radioactive tracer dilution technique to measure the outflow of norepinephrine from the kidney to plasma have shown an increased renal norepinephrine (NE) overflow rate in patients with essential hypertension, especially in young hypertensive subjects. It was revealed that, in combination with increased NE overflow from the heart, it is typically seen in early hypertension and is characterized by increased heart rate, cardiac output, and renal vascular resistance. Consistent with the hemodynamic profile. Essential hypertension is generally neurogenic and is often not known to be associated with significant sympathetic overactivity.

0024Activation of cardiorenal sympathetic activity is even more pronounced in heart failure, as demonstrated by an excessive increase in NE outflow from the heart and kidneys to plasma in this group of patients. Total mortality and strong negative predictive value of renal sympathetic activation for heart transplantation in patients with congestive heart failure, independent of overall sympathetic activity, glomerular filtration rate, and left ventricular ejection fraction Recent proof of this is in line with this idea. These findings support the idea that therapeutic regimens designed to reduce renal sympathetic stimulation have the potential to improve survival in patients with heart failure.

0025Both chronic kidney disease and end-stage kidney disease are characterized by enhanced sympathetic nerve activation. Plasma levels of norepinephrine above median in patients with end-stage renal disease have been demonstrated to be predictive of total mortality and death from cardiovascular disease. This also applies to patients with diabetic nephropathy and contrast agent nephropathy. Sensory afferent signals emanating from the morbid kidney are major contributors to the induction and colonization of enhanced central sympathetic outflow in this group of patients: hypertension, left ventricular hypertrophy, ventricular arrhythmias, There is compelling evidence suggesting that it promotes the development of well-known adverse events of chronic sympathetic hypertension, such as sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

0026(i) Renal sympathetic efferent activity The sympathetic nerves to the kidney terminate in blood vessels, the juxtaglomerular apparatus, and renal tubules. Renal sympathetic stimulation causes increased renin release, increased sodium (Na +) reabsorption, and reduced renal blood flow. These components of the neuromodulatory regulation of renal function are significantly stimulated in conditions characterized by increased sympathetic tone and clearly contribute to elevated blood pressure in hypertensive patients. Reduced renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation is likely to be the cornerstone of loss of renal function in cardiorenal syndrome, as a progressive complication of chronic heart failure. Renal dysfunction, typically with a clinical course that varies with the patient's clinical condition and treatment. Pharmacological strategies for blocking renal efferent sympathomimetic events include central action sympathetic blockers, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptors. Body blockers (intended to block the effects of angiotensin II and aldosterone activation resulting from renin release), and diuretics (intended to counter renal sympathomimetic sodium and water retention) Is included. However, current pharmacological strategies have significant limitations, including limited efficacy, compliance issues, side effects, and more.

0027(ii) Renal sensory afferent nerve activity The kidney communicates with the integral structure in the central nervous system via the renal sensory afferent nerves. Multiple forms of "kidney injury" can induce activation of sensory afferent signals. For example, renal ischemia, reduced stroke or renal blood flow, or large amounts of adenosine enzymes can trigger activation of afferent nerve traffic. As shown in Figures 3A and 3B, this afferent traffic can be done from kidney to brain or from one kidney to the other (via the central nervous system). These afferent signals are centrally integrated and can result in increased sympathetic outflow. This sympathetic drive is directed to the kidney, thereby activating RAAS and inducing increased renin secretion, sodium retention, volume retention, and vasoconstriction. Central sympathetic hyperactivity also affects other organs and physical structures innervated by the sympathetic nerves, such as the heart and peripheral vasculature, resulting in the described adverse effects of sympathetic activation. Multiple aspects also contribute to the increase in blood pressure.

0028Physiology therefore states that (i) denervation of tissues with efferent sympathetic nerves reduces inappropriate renin release, salt retention, and reduction of renal blood flow, and (ii) afferent sensory nerves. It is suggested that denervation of tissues with is reduced systemic contribution to hypertension and other medical conditions associated with increased central sympathetic tone through its direct effect on the posterior hypothalamus and contralateral kidneys. To do. In addition to the central blood pressure lowering effect of afferent renal denervation, a desirable reduction in central sympathetic outflow to various other sympathetic innervated organs such as the heart and vasculature is expected.

0029B. Further clinical benefits of renal denervation As provided above, renal denervation includes hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic and end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death, etc. It is likely to be useful in the treatment of multiple clinical conditions characterized by increased overall sympathetic activity, and in particular increased renal sympathetic activity. Renal denervation may also be useful in treating other conditions associated with systemic sympathetic hyperactivity, as reduction of afferent nerve signals contributes to systemic reduction of sympathetic tone / drive. .. Therefore, renal denervation may also benefit other organs and physical structures innervated by the sympathetic nerves, including those identified in FIG. For example, reduced central sympathetic drive may reduce insulin resistance affecting people with metabolic syndrome and type II diabetes. In addition, patients with osteoporosis may also benefit from the downward regulation of sympathetic drive associated with renal denervation because they are sympathetic and activated.

0030C. Achieve intravascular access to the renal arteries According to the present invention, neural regulation of the left and / or right renal plexus (RP), which is closely related to the left and / or right renal artery, can be achieved through intravascular access. As Figure 4A shows, blood driven by the contraction of the heart is carried by the aorta from the left ventricle of the heart. The aorta descends through the chest and branches into the left and right renal arteries. Below the renal arteries, the aorta is bifurcated at the left and right iliac arteries. The left and right iliac arteries descend through the left and right legs, respectively, and join the left and right femoral arteries.

0031As Figure 4B shows, blood is collected intravenously, enters the iliac vein through the femoral vein, and into the inferior vena cava and returns to the heart. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends to carry blood into the right atrium of the heart. From the right atrium, blood is pumped through the right ventricle into the lungs, where it is oxygenated. From the lungs, oxygenated blood is carried into the left atrium. From the left atrium, oxygenated blood is carried back to the aorta by the left ventricle.

0032As described in more detail later, the femoral artery can be exposed and cannulated at the bottom of the femoral triangle, just below the midpoint of the inguinal ligament. A catheter can be percutaneously inserted into the femoral artery through this access site and routed into the iliac and aorta and into either the left or right renal artery. It comprises an intravascular route that presents minimally invasive access to each renal artery and / or other renal vessel.

0033The wrist, upper arm, and shoulder areas provide other places for the introduction of the catheter into the arterial system. Cathetering of any of the radial, brachial, or axillary arteries may be utilized in the alternative. Cauters introduced through these access points use standard angiography techniques through the left upper subclavian artery (or through the right upper subclavian and brachiocephalic arteries) and through the aortic arch. , It may be passed down the descending aorta and into the renal artery.

0034D. Characteristics and characteristics of renal vascular structure Since neural regulation of the left and / or right renal plexus (RP) can be achieved through intravascular access according to the present invention, the properties and characteristics of renal vasculature are devices for achieving such renal neural regulation. , System, and method design may be constrained and / or their design may be taught. Some of these characteristics and characteristics are within a particular patient population and / or over time, as well as hypertension, chronic kidney disease, vascular disease, end-stage kidney disease, insulin resistance, diabetes, metabolic syndrome. It may differ depending on the medical condition such as syndrome. These properties and characteristics may relate to the clinical safety and efficacy of the procedure, as well as the specific design of the intravascular device, as described below. The properties of interest may include, for example, material / mechanical, spatial, fluid mechanical / hemodynamic, and / or thermomechanical properties.

0035As mentioned above, the catheter can be percutaneously advanced into either the left or right renal artery via a minimally invasive intravascular route. However, minimally invasive renal artery access is such that the renal arteries are often highly meandering, can be relatively small in diameter, and can be relatively small compared to, for example, some other arteries accessed using catheters. / Or it can be relatively short, so it can be difficult. In addition, renal artery atherosclerosis is common in many patients, especially those with cardiovascular disease. The anatomy of the renal arteries can also vary considerably from patient to patient, further complicating minimally invasive access. For example, significant patient-to-patient variability may be seen in relative twist, diameter, length, and / or atherosclerotic burden, and in the exit angle at which the renal arteries diverge from the aorta. Devices, systems, and methods for achieving renal nerve regulation via intravascular access are these of the anatomical structure of the renal arteries and their variations across the patient population when the renal arteries are minimally invasively accessed. And other aspects must be considered.

0036In addition to complex renal artery access, the anatomical details of the kidney also complicate the establishment of stable contact between the neuromodulator and the luminal surface or wall of the renal artery. When the neuromodulator comprises an energy delivery element such as an electrode, consistent positioning and contact force application between the energy delivery element and the vessel wall is important for predictability and safety. However, diversion is hampered by tight gaps in the renal arteries, as well as arterial twists. In addition, the respiratory and / or cardiac cycle can cause significant movement of the renal arteries with respect to the aorta, and the cardiac cycle and / or the neuromodulator can transiently dilate the renal arteries for stable contact. Further complicate the establishment.

0037Even after accessing the renal arteries and facilitating stable contact between the neural regulator and the luminal surface of the artery, the nerves in and around the adventia of the artery are via the neural regulator. Must be adjusted safely. The safe application of heat treatment from within the renal arteries is not trivial given the potential clinical complications associated with such treatment. For example, the intima and media of the renal arteries are very vulnerable to thermal damage. As described in more detail below, the thickness of the intimal complex that separates the vascular lumen from its adventitia means that the target renal nerve can be a few millimeters away from the surface of the lumen of the artery. Sufficient thermal energy must be delivered to the target renal nerve to regulate the target renal nerve without overheating and drying the vessel wall. Another potential clinical complication associated with overheating is thrombus formation by coagulating blood flowing through the arteries. Considering that this thrombus can cause a renal infarction, which causes irreversible damage to the kidney, heat treatment from within the renal arteries must be applied carefully. Therefore, the complex hydrodynamic and thermomechanical pathologies present in the renal artery being treated, especially those that can affect the heat transfer dynamics at the treatment site, are important when applying heat treatment from within the renal artery. there is a possibility.

0038Because the location of treatment can also affect clinical safety and efficacy, neuromodulators may be configured to allow adjustable positioning and repositioning of energy delivery elements within the renal arteries. Also desirable. For example, considering that renal nerves can be peripherally separated around the renal artery, it may be attractive to apply treatment from within the renal artery to the entire circumference. However, perimeter lesions, which are likely to result from continuous perimeter treatment, may increase the risk of renal artery stenosis, thereby providing any possible therapeutic benefit of renal nerve regulation. Cancel. Therefore, the formation of more complex lesions along the longitudinal dimensions of the renal arteries and / or the repositioning of neuromodulators to multiple treatment sites may be desirable. In addition, variable positioning and repositioning of the neuromodulator is a treatment in certain locations when the renal arteries are particularly tortuous, or when there are proximal vessels branching from the major vessels of the renal arteries. It can prove to be useful in situations that increase the difficulty of.

0039To enable (1) renal artery intervention, (2) consistent and stable placement of energy delivery elements on the vessel wall, (3) safe application of heat treatment across the vessel wall, and (4) multiple treatment sites. Based on the above-mentioned tasks of positioning and repositioning of the therapeutic device, various independent and dependent properties of the renal vascular structure that may be of interest include, for example, vessel diameter, length, and intimal composite. Coefficients of body thickness, friction and twist; modulus of swelling, stiffness, and elasticity of vessel wall; peak contractile and end-diastolic blood flow velocity, and average contractile-diastolic peak blood flow velocity, mean / maximum volume measurement Blood flow; specific heat capacity of blood and / or vessel wall, thermal conductivity of blood and / or vessel wall, thermal convection and / or radiative heat transfer of blood flow past the vessel wall treatment site; and respiration and / or blood Includes pulsatile-induced renal movements into the aorta, as well as the angle of ejection of the renal arteries into the aorta. These properties are described in more detail with respect to the renal arteries. However, depending on the devices, systems, and methods utilized to achieve renal nerve regulation, such properties of the renal vein can also guide and / or constrain design features.

0040The device positioned within the renal artery must adapt to the shape of the artery. Renal artery vessel diameter, DRA, typically ranges from about 2-10 mm, with an average of about 6 mm. The renal artery vascular length, LRA, between its mitral at the aortic / renal arterial junction and its distal bifurcation is generally in the range of about 5 to 70 mm, and more generally in the range of about 20 to 50 mm. Because the target renal plexus is embedded within the adventitia of the renal artery, the complex intimal complex thickness, IMT (ie, radioactivity from the luminal surface of the artery to the adventitia containing the target neural structure). The outward distance) is also prominent, generally in the range of about 0.5-2.5 mm, with an average of about 1.5 mm. Some depth of treatment is important to reach the target nerve fibers, but the treatment is too deep (eg, of the renal arteries) to avoid non-target tissues and anatomical structures such as the renal veins. Should not be more than 5 mm from the inner wall).

0041Devices advanced within the renal arteries must also antagonize friction and twist. The coefficient of friction, μ (eg, static or dynamic friction) in the walls of the renal arteries is generally fairly low, for example, generally less than about 0.05, or less than about 0.03. The twist, τ, which is a measure of the relative kinks of curved segments, has been quantified in various ways. The arc-string ratio defines the twist as the length of the curve, the Lcurve divided by the chord, the Ccurve, and the ends of the curve connected (ie, the linear distance separating the ends of the curve): τ = Lcurve / Ccurve (1)

0042Renal artery twist, as defined by the arc-chord ratio, is generally in the range of about 1-2.

0043Pressure changes between diastole and systole change the luminal diameter of the renal arteries and provide information about the aggregate properties of blood vessels. The exponential coefficient, DC, which is a property that depends on the actual blood pressure, captures the relationship between pulse pressure and diameter change. DC = 2 * ((Dsys-Ddia) / Ddia) / ΔP = 2 * (ΔD / Ddia) / ΔP (2) In the equation, Dsys is the systolic diameter of the renal artery and Ddia is the diastolic diameter of the renal artery, ΔD (which is generally less than about 1 mm, eg, in the range of about 0.1 mm to 1 mm). Is the difference between the two diameters: ΔD = Dsys-Ddia (3)

0044The coefficient of renal artery dilatation is generally in the range of about 20-50 kPa-1 * 10-3.

0045Also, changes in luminal diameter during the cardiac cycle may be used to determine renal artery stiffness, β. Unlike the expansive coefficient, stiffness is a dimensionless property and is independent of actual blood pressure in normotensive patients: β = (ln [BPsys / BPdia]) / (ΔD / Ddia) (4)

0046Renal artery stiffness generally ranges from about 3.5 to 4.5.

0047The expansion modulus may be used in combination with other shape characteristics of the renal artery to determine the incremental modulus of elasticity of the renal artery, Einc: Einc = 3 (1+ (LCSA / IMCSA)) / DC, (5) In the formula, LCSA is the luminal cross-sectional area and IMCSA is the intima-media cross-sectional area: LCSA = π (Ddia / 2)² (6) IMCSA = π (Ddia / 2 + IMT)²-LCSA (7)

0048For the renal arteries, LCSA is in the range of about 7-50 mm2, IMCSA is in the range of about 5-80 mm2, and Einc is in the range of about 0.1-0.4 kPa * 103.

0049For patients without significant renal artery stenosis (RAS), peak renal artery systolic blood flow velocity, υmax-sys, is generally less than about 200 cm / s, while peak renal artery diastolic end-stage blood flow velocity, υmax-dia is generally less than about 150 cm / s, for example about 120 cm / s.

0050In addition to the renal artery blood flow velocity profile, volumetric flow rates are also of interest. Assuming a Poiseuille flow, the volumetric flow through the pipe, Φ (often measured at the outlet of the pipe), is defined as the average velocity of the fluid flow through the pipe, υavg, multiplied by the cross-sectional area of the pipe. Ru: Φ = υavg * πR2 (8)

0051By integrating over the velocity profile over the entire radius from 0 to R (as defined by Equation 8 above), the following can be shown: Φ = υavg * πR²= (πR4 * ΔPr) / 8η Δx (9)

0052As mentioned above, for renal artery purposes, η can be defined as η blood, Δx can be defined as LRA, and R can be defined as DRA / 2. Changes in pressure across the renal arteries, ΔPr, are measured at common points in the cardiac cycle (eg, via pressure-sensitive guide wires) to measure volumetric flow through the renal arteries at selected common points in the cardiac cycle. It may be determined (eg, during contraction and / or end diastole). Further or alternative, the volumetric flow rate may be measured directly or may be determined from a blood flow velocity measurement. Volumetric blood flow through the renal arteries is generally in the range of about 500-1000 mL / min.

0053The thermomechanical properties of the renal arteries are also of interest. Such properties include, for example, the specific heat capacity of the blood and / or vessel wall, the thermal conductivity of the blood and / or vessel wall, and the thermal convection of blood flow past the vessel wall treatment site. Thermal radiation can also be of interest, but the magnitude of conductive and / or convection heat transfer is expected to be significantly higher than the magnitude of radioactive heat transfer.

0054The heat transfer coefficient may be measured experimentally or calculated as a function of heat conductivity, vessel diameter, and Nusselt number. The Nusselt number is a function of the Reynolds number and the Prandtl number. The Reynolds number calculation considers flow velocity and flow rate, as well as fluid viscosity and fluid density, while the Prandtl number calculation considers specific heat, as well as fluid viscosity and thermal conductivity. The heat transfer coefficient of blood flowing through the renal arteries is generally in the range of about 500-6000 W / m2K.

0055A further property of the renal arteries that may be of interest is the degree of renal movement to the aorta, which is evoked by respiratory and / or blood pulsatileness. The patient's kidney, located at the distal end of the renal artery, can move about 5 cm cranial in the range of motion. This may give significant movement to the renal arteries that connect the aorta to the kidneys, thereby allowing the neuromodulator to maintain contact between the heat treatment element and the vessel wall during the respiratory cycle. Requires a unique balance between rigidity and flexibility. Moreover, the ejection angle between the renal arteries and the aorta can vary significantly between patients and can also vary dynamically within the patient, for example due to renal movement. The ejection angle can generally be in the range of about 30 ° to 135 °.

0056These and other properties of renal vascular structure impose constraints on the design of devices, systems, and methods for achieving renal nerve regulation via intravascular access, and / or design them. May be taught. Specific design requirements include access to the renal arteries, facilitating stable contact between the neural regulator and the lumen surface or wall of the renal artery, and / or renal nerves with the neural regulator. It may include safe adjustment.

0057II. Cathetering devices, systems, and methods for renal nerve regulation A. Overview FIG. 5 shows a system 10 for thermally inducing neural regulation of the left and / or right renal plexus (RP) through intravascular access.

0058As just mentioned, the left and / or right renal plexus (RP) surrounds the respective left and / or right renal arteries. The renal plexus (RP) is closely associated with each renal artery and extends into the parenchyma of the kidney. The system thermally induces neural regulation of the renal plexus (RP) by intravascular access into the respective left or right renal artery.

0059System 10 includes an endovascular treatment device 12. As shown in FIG. 6A, the therapeutic device 12 provides access to the renal plexus (RP) through the intravascular pathway 14 leading to each renal artery.

0060As shown in FIG. 5, the therapeutic device 12 includes an elongated shaft 16 having a proximal end region 18 and a distal end region 20.

0061The proximal end region 18 of the elongated shaft 16 is optionally connected to the handle assembly 200. The handle assembly 200 is sized and configured by the caregiver to be reliably or ergonomically held and manipulated outside the intravascular pathway 14 (eg, FIGS. 16A and 6A). Please refer to). By manipulating the handle assembly 200 from outside the intravascular pathway 14, the caregiver can advance the elongated shaft 16 through the meandering intravascular pathway 14 to remotely manipulate or activate the distal end region 20. .. Imaging guidance, such as CT, radiography, IVUS, OCT, or another preferred guidance mode, or a combination thereof, can be used to assist the caregiver's operation.

0062As shown in FIG. 6B, the distal end region 20 of the elongated shaft 16 can be flexed in a significant manner by manipulating the elongated shaft 16 to obtain entry into the respective left / right renal artery. .. As shown in FIGS. 28A and 28B, the distal end region 20 of the elongated shaft 16 can gain access to the renal artery via passage within the guide catheter 94. The distal end region 20 of the elongated shaft 16 comprises at least one energy delivery element 24 (eg, a radio frequency electrode, an electrode, a cooling radio frequency electrode, a thermal element, a thermal heating element, an electrical resistance heating element, a refrigeration cutting applicator, It carries a microwave antenna, an ultrasonic transducer, a high-density focal ultrasonic transducer, and a laser radiator). The energy delivery element 24 is also sized and configured for manipulation and use within the renal arteries.

0063As shown in FIG. 6B, once entry into the renal arteries is obtained, further manipulation of the distal end region 20 and the energy delivery element (s) 24 within each renal artery will result in each renal artery. The energy delivery element (s) 24 along the inner wall of the artery and proximal to the tissue, and the alignment between them are established. In some embodiments, manipulation of the distal end region 20 also facilitates contact between the energy delivery element 24 and the wall of the renal artery. In the context of this application, the phrase "contact between an energy delivery element and the wall of the renal artery" generally involves or does not involve non-traumatic swelling of the wall of the renal artery and punctures or perforates the wall of the renal artery. It means adjacent physical contact without the need for it.

0064In a typical embodiment of FIG. 6B, the thermal heating element 24 of the distal end region 20 is along the distal tip or end of the distal end region, eg, any third or distal flexion area 44. Positioned at the distal end of. However, it should be understood that the distal end region 20 may optionally include one or more additional thermal heating elements that are positioned relatively more proximally. When a large number of thermal heating elements are provided, the thermal heating elements may deliver power independently (ie, may be used in a unipolar fashion), either simultaneously or progressively. And / or power may be delivered between any desired combination of elements (ie, may be used in a bipolar fashion). In addition, caregivers optionally use which thermal heating element (s) for power delivery to form highly customizable lesions (s) in the renal arteries. It may be possible to mechanically select.

0065In one representative embodiment shown in FIG. 6C, one or more additional thermal heating elements 24a are optionally spaced longitudinally apart from the distal thermal heating element 24. Generally in an angular alignment position (s), proximal to the thermal heating element 24, eg, along a third flexure zone 44, to contact the inner wall of the renal artery. It may be positioned in the proximal region of any third flexure zone 44 and / or in the distal region of any second or intermediate flexure zone 34. The separation of the thermal heating elements 24 and 24a can be specified to provide the desired separation between the lesions formed when using the elements within the renal artery. In one typical embodiment, the thermal heating elements 24 and 24a are spaced up to about 1 cm. In other embodiments, the distance between the thermal heating elements 24 and 24a is in the range of about 2 mm to about 5 mm. In one typical embodiment, the thermal heating elements 24 and 24a are separated by about 5 mm. In another typical embodiment, the thermal heating elements 24 and 24a are separated by about 2 mm.

0066Further or alternatively, as shown in FIG. 6D, the one or more thermal heating elements 24b are longitudinally and angularly spaced (s) from the distal thermal heating elements 24. ) (For example, angularly opposite side (angular) In opposition)), it may be positioned relatively more proximally to contact the inner wall of the renal artery. Such a thermal heating element (s) 24b, for example, at the apex of the flexion formed during the deflection of any second flexure zone 34, in the proximal region of any second flexure zone 34, And / or may be positioned in the distal region of the first or proximal flexion area 32. The separation that separates the thermal heating element 24b from the thermal heating element 24 and / or from any thermal heating element 24a is, if desired, the desired length between lesions formed within the renal vascular structure. It can be specified to provide directional and angular separation. In one typical embodiment, the thermal heating elements 24 and 24b are separated by about 5 mm to about 25 mm. In another typical embodiment, the thermal heating elements 24 and 24b can be spaced up to about 30 mm. In another typical embodiment, the thermal heating elements 24 and 24b are separated by about 11 mm. In yet another typical embodiment, the thermal heating elements 24 and 24b are separated by about 17.5 mm.

0067As will be described in more detail later, the different compartments 16 of the elongated shaft perform different mechanical functions in use. The divisions are (i) percutaneous introduction into the femoral artery through a small diameter access site, (ii) through the tortuous intravascular route 14 through the iliac artery, into the aorta, and the respective left / right renal artery. For non-traumatic passage into the arteries, (iii) significant deflection near the junction of the left / right renal arteries and the aorta to obtain entry into the respective left or right renal arteries, (iv) Controlled translation, deflection, rotation, and / or activation within each renal artery to achieve access to the inner wall of each renal artery and desired alignment with them, (v) With at least one energy delivery element 24, in contact with tissue on the inner wall, (vi) during the movement of the renal arteries involved in the aorta due to respiration and / or pulsatile blood flow. Repositioning via receding and / or multidirectional deflection, and / or for (vii) subsequent treatment (s) to allow a substantially stable contact force with the inner wall. It is desirable to distinguish them in terms of their size, composition, and mechanical properties, including rotation within the renal arteries.

0068With reference to FIG. 5 again, the system 10 also includes an energy generator 26 (eg, a radio frequency generator). Under the control of the caregiver or automatic control algorithm 102 (described in more detail later), the generator 26 produces energy of selected morphology and magnitude. A cable 28 operatively attached to the handle assembly 200 electrically connects the energy delivery element 24 to the generator 26. At least one supply wire (not shown) that travels from the handle assembly 200 to the energy delivery element 24 along the elongated shaft 16 or through the lumen in the elongated shaft 16 transfers therapeutic energy to the energy delivery element 24. And carry. Control mechanisms, such as the Step 100, are intended to allow clinical operators to evoke, terminate, and optionally adjust various operational features of the generator, including, but not limited to, power delivery. , May be connected to the generator 26 (eg, aerated or electrically connected).

0069For systems that provide unipolar electric field delivery via the energy delivery element 24, a neutral or dispersive electrode 38 may be electrically connected to the generator 26 and attached to the outside of the patient. .. In addition, see one or more sensors 52 (eg, FIGS. 9A and 9B) such as one or more temperatures (eg thermocouples, thermistors, etc.), impedance, pressure, optics, flow rate, chemistry, or other sensors. ) Can be located close to or within the energy delivery element and connected to one or more of the supply wires. For example, a total of two supply wires can be included, where both wires can transmit signals from the sensor, and one wire serves a dual purpose and transfers energy to the energy delivery element. Can be carried again. Alternatively, both wires can transfer energy to the energy delivery element.

0070Once the proximality between the energy delivery element 24 and the tissue, its alignment, and the contact between them are established within the respective renal arteries (as shown in Figure 6B), the energy delivery The deliberate application of energy from the generator 26 to the tissue by element 24 is the localized area of the renal arteries, and of the renal plexus (RP), which is located in close proximity to or adjacent to the adventitia of the renal arteries. Induces one or more desired neuromodulatory effects on adjacent regions. By deliberate application of accommodation effects, accommodation can be achieved along all or part of the RP.

0071Neuromodulatory effects can include both thermal resection, non-resectable thermal alteration or injury (eg, via continuous heating and / or resistance heating), and electromagnetic neuromodulation. The desired thermal heating effect raises the temperature of the target nerve fibers above the desired threshold to achieve non-resectable thermal alteration, or above higher temperatures to achieve resectable thermal alteration. May be included. For example, the target temperature may be above body temperature (eg, approximately 37 ° C) but below about 45 ° C due to non-resectable thermal alteration, or the target temperature may be of resectable thermal alteration. Therefore, it may be above about 45 ° C. The desired electromagnetic accommodation effect may include altering electrical signals transmitted within the nerve.

0072Further details of the particular size, configuration, and mechanical properties of the elongated shaft 16, the distal end region 20, and the energy delivery element 24, as well as other aspects of the system 10 are described. In yet another embodiment, the system 10 may have different configurations and / or include different features. Alternative multi-energy delivery element devices, such as, for example, multi-electrode baskets, helices or loops, or balloon dilation devices, with contact with the vessel wall to deliver neuromodulatory treatment intravascularly or. It may be implemented without it.

0073B. Size and construction of elongated shafts to achieve intravascular access to the renal arteries As mentioned above, intravascular access to the interior of the renal arteries can be achieved, for example, through the femoral artery. As shown in FIG. 6A, the elongated shaft 16 is specially sized to accommodate the passage of this intravascular route 14 from the percutaneous access site in the femoral artery to the target treatment site in the renal artery. It is configured that way. In this way, the caregiver is able to orient the energy delivery element 24 within the renal artery for its intended purpose.

0074For practical purposes, the maximum external dimension (eg, diameter) of any section of the elongated shaft 16 is a guide catheter or delivery that is the passage of the elongated shaft 16, including the energy delivery element 24 it carries. Determined by the inner diameter of the catheter. For example, an 8-French guide catheter (with an inner diameter of approximately 0.091 inches) is assumed to be likely to be the largest guide catheter used to access the renal arteries from a clinical point of view, and energy delivery. Allowing reasonable clearance resistance between the element 24 and the guide catheter, the maximum external dimension can be realistically expressed to be approximately 0.085 inches or less. However, the use of a smaller 5 French guide catheter 94 may require the use of a smaller outer diameter along the elongated shaft 16. For example, the energy delivery element 24 to be delivered within a 5 French guide catheter has an external dimension of 0.053 inches or less. In another example, the energy delivery element 24 to be delivered within a 6 French guide catheter has an external dimension of 0.070 inches or less.

00751. Force transmission classification As shown in FIG. 7A, the proximal end region 18 of the elongated shaft 16 is coupled to the handle assembly 200 and includes a force transfer section 30. Power transmission segment 30 is when it passes from the accessed femoral artery (left or right), through the respective iliac bifurcation artery, into the aorta, and proximally to the target renal artery (left or right). It is sized and configured to have selected mechanical properties, depending on the physical passage of the intravascular pathway 14 and the transmission of force within it. The mechanical properties of force transfer compartment 30 include at least the preferred effective length (represented in inches or centimeters). It should be understood that the term force transfer compartment can be used interchangeably with an elongated tubular shaft or proximal force transfer compartment.

0076As shown in FIG. 7A, the force transfer section 30 includes a preferred effective length L1. The preferred effective length L1 is a function of the anatomical distance within the intravascular pathway 14 between the access site and the location close to the junction of the aorta and renal arteries. The preferred effective length L1 is generally supplemented by the caregiver's knowledge of the target site and is guided to be derived from a human anatomy textbook or from a pre-analysis of the particular morphology of the target site. be able to. The preferred effective length L1 also depends on the length of the guide catheter used, if present. In a typical embodiment, for normal humans, the preferred effective length L1 comprises from about 30 cm to about 110 cm. If no guide catheter is used, the preferred effective length L1 comprises from about 30 cm to about 35 cm. When a 55 cm long guide catheter is used, the preferred effective length L1 comprises from about 65 cm to about 70 cm. When a 90 cm long guide catheter is used, the preferred effective length L1 comprises from about 95 cm to about 105 cm.

0077The force transfer section 30 also includes preferred axial stiffness and preferred torsional stiffness. Preferred axial stiffness represents the ability of force transfer compartment 30 to advance or withdraw along the length of the intravascular pathway 14 without buckling or substantial deformation. The preferred axial stiffness of the force transfer section is because some axial deformation is required for the force transfer section 30 to follow the meandering intravascular path 14 without providing excessive resistance. It should also provide this capability. The preferred torsional stiffness represents the ability of the force transfer section 30 to rotate the elongated shaft 16 along its longitudinal axis around its longitudinal axis without entanglement or permanent deformation. As described in more detail later, the ability to advance, retract, and rotate the distal end region 20 of the elongated shaft 16 within each renal artery is desirable.

0078The desired magnitude of axial stiffness and rotational stiffness for the force transfer section 30 is expressed in units of the desired elastic modulus (eg, Young's modulus (E)), which is an indicator of axial stiffness and torsional stiffness. ), And the construction of the force transfer type compartment and in terms of structural features including, for example, its inner diameter, outer diameter, wall thickness, and cross-sectional dimensions and shape. It can be obtained by selecting the configuration. Representative examples are described in more detail below.

00792. First flexure area As shown in FIGS. 7A and 7B, the distal end region 20 of the elongated shaft 16 is connected to the force transfer compartment 30. The length L1 of the force transfer compartment 30 generally serves to carry the distal end region 20 close to the junction of the respective renal and aortic arteries (as shown in Figure 6B). The axial and torsional stiffness of the force transfer region transfers the axial and rotational forces from the handle assembly 200 to the distal end region 20, as described in more detail later. It should be understood that the term first flexible zone can be used interchangeably with flexible tubular structures.

0080As shown in FIG. 7B, the distal end region 20 includes a first flexion area 32 close to the force transfer compartment 30. The first flexure zone 32 responds to significant flexure or flexion at a defined preferred access angle α1 during rotation without breakage, folding, substantial distortion, or significant kinking of the elongated shaft 16. It is sized and configured to have mechanical properties that provide torque transmission. The first flexion area 32 should accommodate sufficient flexure for the distal end region 20 to advance into the renal artery through the guide catheter without substantially aligning the guide catheter.

0081Angle α1 is advanced for the treatment device 12 to transition between the aorta (along which the force transmission compartment 30 is aligned) and the target renal artery (along which the distal end region 20 is aligned). It must be defined by the angular deviation (which is also shown in Figure 6B). This is because the force transmission section 30 of the elongated shaft 16 remains aligned with the natural axis of the aorta (as shown in FIG. 6B), while the first flexure zone 32 extends into the distal end region 20 of the elongated shaft 16. An angle that must be approximated to align with the target renal artery. The more tortuous the blood vessel, or the greater the angle of ejection between the renal artery and the aorta, the more flexion the first flexion area 32 should make in order for the distal end region of the treatment device to access the renal artery. It becomes larger and the angle α1 becomes smaller.

0082When the catheter is on the outside of the patient and the first flexion area 32 is in a substantially straight and non-deflected configuration, the angle α1 (as shown in FIG. 7B) is approximately 180 °. .. When the first deflection zone 32 is completely deflected, the angle α1 is reduced to any angle between about 30 ° and 180 °. In a typical embodiment, when fully deflected, the angle α1 is from about 30 ° to about 135 °. In another typical embodiment, when fully deflected, the angle α1 is about 90 °.

0083The first flexure area 32 is sized to have mechanical properties in response to significant abrupt flexure or flexion at a defined preferred access angle α1 near the junction of the aorta and renal arteries. It is composed of. Due to its size, configuration, and mechanical properties, the first flexure area 32 must eliminate these flexures or flexion forces without breakage, folding, strain, or significant kinking. Such flexion or flexion of the first flexure area can occur, at least in part, within the distal region of the guide catheter, without substantially aligning the guide catheter. Elimination of these flexures or flexions by the first flexure area 32 results in the distal end region 20 of the elongated shaft 16 getting into the target's left or right renal artery along the intravascular pathway 14. To enable.

0084The first flexure zone 32 is sized and configured such that length L2 is less than length L1 (see Figure 7A). It is the length of the aorta and renal arteries, where the distance between the femoral access site and the junction of the aorta and renal arteries (typically approximately 40 cm to about 55 cm) is less than about 7 cm. This is because it is generally larger than the length of the renal artery to and from the most distal treatment site along the canal. The preferred effective length L2 can be derived, generally supplemented by knowledge of the caregiver's site, as derived from a human anatomy textbook or from a pre-analysis of the particular morphology of the target site. For example, the length L2 can generally be less than about 15 cm, for example less than about 10 cm. In one typical embodiment, the length L2 can be about 9 cm.

0085Desirably, the length L2 allows a portion of the first flexion area 32 to rest partially in the aorta at or near the location of the first flexure area 32, as well as the rest of the first flexure area 32. It is selected to allow partial placement in the renal arteries (as shown in Figure 6B). In this way, the first flexion area 32 defines a transitional flexion that is supported and stable within the vascular structure.

0086In the deflected configuration of FIG. 7B, the first deflection zone 32 comprises a radius of curvature RoC1. In embodiments where the curvature of the first deflection zone 32 does not change or is consistent along the length L2, the length L2 and the deflection angle α1 may define the radius RoC1 of the curvature. It should be understood that the curvature of the first flexure zone 32, and thereby the radius RoC1 of the curvature of the first flexure zone, can instead vary along the length L2.

0087In embodiments such as when the curvature does not change, the length L2 may define a portion (180 ° -α1) / 360 ° of the outer circumference C1 of a circle with a radius RoC1 of equivalent curvature. Therefore, the circumference of such an equivalent circle is:<maths num="1"><img id="000003" he="12" wi="57" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (Ten) Solution for radius of curvature RoC1:<maths num="2"><img id="000004" he="11" wi="42" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (11)

0088Therefore, the first deflection when the curvature of the first deflection area does not change along the length L2, the length L2 is about 9 cm or less, and the angle α1 is about 30 ° to about 135 °. In a typical embodiment of area 32, the radius of curvature RoC1 is from about 3.5 cm to about 11.5 cm. Typical of the first flexure zone 32 when the curvature of the first flexure zone does not change along the length L2, the length L2 is about 9 cm or less, and the angle α1 is about 90 °. In the embodiment, the radius of curvature RoC1 is about 5.75 cm or less.

0089As is clear, equation (11) may be rearranged so that the length L2 and the radius RoC1 of curvature define the angle α1. Further, equation (11) may be rearranged such that the radius RoC1 of curvature and the angle α1 define the length L2. Therefore, in the embodiment where the curvature 34 of the first deflection zone does not change along the length L2, any one of the length L2, the angle α1 and the radius RoC1 of the curvature is the other two. It can be specified by specifying a variable.

0090As detailed below and shown in FIG. 6B, the length L2 of the first flexion zone 32 optionally does not extend to the full length of the target length of the renal artery. It is that the distal end region 20 of the elongated shaft 16 is optionally distal to the first flexion area 32 (towards the parenchyma of the kidney) to accommodate other different functions important for the therapeutic purpose of the therapeutic device 12. This is because it contains one or more additional flexure areas. As will be described later, the ability to transmit torque through the first flexure zone 32 allows the thermal heating device to rotate in order to properly position the energy delivery element in the renal artery for treatment. To do.

0091In terms of axial stiffness and torsional stiffness, the mechanical properties of the first flexure zone 32 may differ from the mechanical properties of the force transfer section 30, and are preferably different. This is because the first flexure zone 32 and the force transfer compartment perform different functions during use. Alternatively, the mechanical properties of the first flexure zone 32 and the force transfer compartment 30 may be similar.

0092The force transfer section 30 serves to transmit axial loads and torques over a relatively long length (L1) in the vascular pathway during use. In contrast, the first flexion area 32 needs to transmit axial load and torque over the shorter length L2 in or near the respective renal arteries. Importantly, the first flexion area 32 is the aorta and without straightening the guide catheter that is giving it breakage, folding, substantial distortion, or significant kinking, or access angle α1. It must suddenly adapt to the access angle α1 near the junction of each renal artery. This is a function that the force transmission area does not need to perform. Therefore, the first flexure zone 32 is sized and configured to be less rigid and more flexible than the force transfer compartment 30.

0093In addition, the first flexion area 32 allows the energy delivery element (s) 24 to maintain stable contact with the lining of the renal arteries as each kidney moves due to the patient's breathing. obtain. When the patient breathes, the kidneys may move, causing the renal arteries to swirl around the hilar, where the renal arteries join the aorta. Stable contact between the energy delivery element (s) 24 and the inner wall of the renal artery is desired during energy delivery. Therefore, the energy delivery element (s) 24 must move with respect to the aorta, along with the renal arteries. The mechanical properties of the first flexion zone 32, in response to significant, sudden flexion or flexion at an access angle α1 near the junction of the aorta and renal arteries, are also distal to the first flexure zone 32. The catheter compartment also allows it to orbit around the ventricle without significant obstruction, and the energy delivery element allows it to maintain stable contact with the lining of the renal arteries. In some embodiments, the deflectable compartment 34 distal to the first flexion zone 32 can be stiffer than the first flexure zone 32 when it is flexibly deflected. The additional stiffness of the deflectable compartment 34 helps maintain a stable contact force between the energy delivery element 24 and the inner wall of the renal artery, due to the flexible deformation of the catheter in the first flexion area 32. It allows the aorta to move with the renal arteries with sufficient freedom. The renal artery circles around the junction with the aorta so that the movement of the renal artery increases with distance from the junction with the aorta. The length of the distal end region 20 distal to the first flexure area 32 along the length of the first flexure zone 32 is such that the farther the treatment site is, the more the first flexure zone 32 is. The portion is configured to be positioned within the renal artery, between the energy delivery element 24 and the more distal treatment site on the inner wall of the renal artery, especially during increased exercise at the more distal treatment site. A sufficiently increased flexibility is provided in the area of the junction with the aorta to allow for stable contact force.

0094The desired magnitude of axial stiffness, rotational stiffness, and flexibility for the first flexure zone 32 is an indicator of flexibility, a unit of desired elastic modulus (eg, Young's modulus (E)). The selection of the constituents (s) to provide (represented by), as well as the construction and construction of the force transfer type compartment, eg, its inner diameter, outer diameter, wall thickness, and cross-sectional dimensions and shape. It can be obtained by selection in terms of structural features, including. A typical example will be described in detail below.

0095While it is desirable that the force transfer compartment 30 and the first flexure zone 32 have the stiffness and flexibility properties inherent in their respective functions, the force transfer compartment 30 and the first flexure zone 32 are force transfer. It is possible to have the same material, size, and shape configuration so that the compartment 30 and the first flexure zone 32 constitute the same compartment.

00963. Second flexure area As shown in FIGS. 7A, 7B, and 7C, the distal end region 20 of the elongated shaft 16 may also optionally include a second flexion zone 34 distal to the first flexure zone 32. Good. In some embodiments, the energy delivery element 24 may be supported by a second deflection zone 34. It should be understood that the term second flexure zone can be used interchangeably with a deflectable compartment or intermediate flexure zone or a deflectable tubular body or a multidirectionally deflectable assembly.

0097The second flexure zone 34, independent of the first flexure zone 32, responds to further flexure or flexion at a preferred contact angle α2, without breakage, folding, substantial distortion, or significant kinking. It is sized, so configured, and has such mechanical properties. The second flexion area 34 should also accommodate sufficient flexure for the distal end region 20 to advance into the renal artery through the guide catheter without aligning the guide catheter. The second deflection zone 34 may, in some embodiments, be configured for multi-directional controllable deflection.

0098The preferred contact angle α2 is defined by the angle at which the energy delivery element 24 can be radially deflected within the renal artery to establish contact between the energy delivery element 24 and the inner wall of each renal artery (FIG. FIG. As 6B shows). The magnitude of the contact angle α2 and the length of the second flexion zone L3 are preferably where the energy delivery element 24 is laid down and can vary between about 2 mm and about 10 mm of each renal artery. Based on the natural inner diameter, as well as the diameter of the energy delivery element 24. The diameter of the renal arteries most commonly varies between about 2 mm and about 8 mm, with an average diameter of about 6 mm.

0099The second flexion zone 34 extends distally from the first flexure zone 32 over a length L3 into the target renal artery (see Figure 6B). Desirably, the length L3 is to actively place the energy delivery element 24 (indicated at the end of the distal end region 20) at or near the target treatment site (as shown in FIG. 6B). ), The length L2 of the first flexion area 32 extending into the renal arteries, and the anatomical structure of each renal artery are selected. Length L3, taking into account length L2, is generally derived from a human anatomy textbook, along with knowledge of the caregiver's site, or from a pre-analysis of the specific morphology of the target site. Can be induced.

0100As shown in FIG. 7A, the second flexure zone 34 is preferably sized and configured such that length L3 is less than length L2. This is because, in terms of length, the distance required to actively deflect the energy delivery element 24 to contact the wall of the renal artery is elongated to gain access from the aorta into the renal artery. This is because it is significantly shorter than the distance required to bend the shaft 16. Therefore, the length of the renal artery is largely occupied by the second flexion zone 34 rather than the first flexure zone 32.

0101In a typical embodiment, L2 is about 9 cm or less and L3 is about 5 mm to about 15 mm. In certain embodiments, L3 can be about 20 mm or less, especially for treatment in relatively long blood vessels. In another typical embodiment, and as detailed below, L3 is about 12.5 mm or less. In another typical embodiment, the L3 is less than 3 mm, about 12.5 mm, especially if the second flexure area comprises a hinged joint.

0102When the catheter is on the outside of the patient and the second flexion area 34 is substantially in line, the non-deflected configuration, contact angle α2 (as shown in Figure 7C) is approximately 180 °. .. When the second flexure zone 34 is completely deflected, the angle α2 is reduced to any angle between about 45 ° and 180 °. In a typical embodiment, when fully deflected, the angle α2 is from about 75 ° to about 135 °. In another typical embodiment, when fully deflected, the angle α2 is about 90 ° or less.

0103In the deflected configuration of FIG. 7C, the second deflection zone 34 comprises a radius of curvature RoC2. In embodiments where the curvature of the second deflection zone 34 does not change or is consistent along the length L3, the length L3 and the deflection angle α2 may define the radius RoC2 of the curvature. It should be understood that the curvature of the second flexure zone 34, and thereby the radius RoC2 of the curvature of the second flexure zone, can instead vary along the length L3.

0104In embodiments such as when the curvature does not change, the length L3 may define a portion (180 ° -α2) / 360 ° of the outer circumference C2 of a circle with a radius RoC2 of equivalent curvature. Therefore, the circumference of such an equivalent circle is:<maths num="3"><img id="000005" he="11" wi="60" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (12)

0105Solution for radius of curvature RoC2:<maths num="4"><img id="000006" he="11" wi="43" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (13)

0106Therefore, when the curvature of the second flexure area does not change along the length L3, the length L3 is about 5 mm to about 20 mm, and the contact angle α2 is about 75 ° to about 135 °, the first In a typical embodiment of the deflection zone 34 of 2, the radius of curvature RoC2 is from about 3 mm to about 25 mm. When the curvature of the second deflection zone does not change along the length L3, the length L3 is about 12.5 mm, for example 12.5 mm or less, and the angle α2 is about 75 ° to about 135 °. In a typical embodiment of the second deflection zone 34, the radius of curvature RoC2 is from about 7 mm to about 16 mm, for example about 15 mm or less. Typical of the second flexure zone 34 when the curvature of the second flexure zone does not change along the length L3, the length L3 is about 12.5 mm, and the angle α2 is about 90 °. In the embodiment, the radius of curvature RoC2 is about 8 mm.

0107As is clear, equation (13) may be rearranged so that the length L3 and the radius RoC2 of curvature define the contact angle α2. Further, equation (13) may be rearranged such that the radius RoC2 of curvature and the angle α2 define the length L3. Therefore, in the embodiment where the curvature 34 of the second flexure area does not change along the length L3, any one of the length L3, the angle α2, and the radius RoC2 of the curvature is the other two. It can be specified by specifying a variable.

0108In the deflected configuration of FIG. 7C, the second flexure zone 34 dimensiones the energy delivery element 24 from the longitudinal axis A of the second flexure zone 34, just distal to the first flexure zone 32, in dimension Y. Position. Dimension Y can vary from about 2 mm to about 20 mm. In some configurations, given the dimensions of most renal arteries, the dimension Y can be from about 5 mm to about 15 mm. The average diameter of most renal arteries is generally less than 10 mm, and it may be desirable to have a dimension Y of 10 mm or less, as described below. For example, the Y dimension can be any length between and including 6 mm or 8 mm, or 6 mm to 10 mm.

0109As an example, the average diameter of the human renal artery is from about 2 mm to about 8 mm, but may range from about 2 mm to about 10 mm. Therefore, if the distal end of the first flexion zone 32 is positioned adjacent to the wall of the artery having a diameter of 8 mm, the second flexure zone 34 will have the energy delivery element 24 in contact with the opposite wall of the artery. It would be possible to be sufficiently biased to do so. However, in other embodiments, the dimension Y may have different values and may be oversized to facilitate contact within a straight or curved vessel. The second flexure zone 34 is also configured to position the energy delivery element 24 in dimension X from the distal end of the first flexure zone 32. Dimension X can vary based, for example, dimension Y and length L3.

0110As FIG. 7C shows, having first and second flexure areas 32 and 34, the distal end region 20 of the elongated shaft 16 is placed in the complex multiple flexion structure 36 during use. Can be done. The complex multi-bent structure 36 has one deflection region at access angle α1 over length L2 (first flexure area 32) and a second at contact angle α2 over length L3 (second flexure zone 34). It has two deflection regions. In complex multiple bends, both L2 and L3 and angles α1 and α2 can be different. It is specially sized and configured so that the angle α1 and length L2 gain access from the aorta into each renal artery through the femoral artery access point, and the angle α2 and length L3 This is because the energy delivery element 24 is specially sized and configured to align with the medial inner wall of the renal artery.

0111In an exemplary embodiment (see, eg, FIG. 7C), the second flexion area 34 is the kidney for the caregiver to contact and radially position the energy delivery element 24 with the inner wall of the renal artery. It is sized and configured to allow the second flexion area 34 to be remotely deflected within the artery.

0112In an exemplary embodiment, the control mechanism is connected to a second flexure zone 34. The control mechanism includes a control wire 40 attached to the distal end of the second flexion area 34 (typical embodiments are shown in FIGS. 12B and 12C and are detailed below). It should be understood that the term control wire can be used interchangeably with deflection control elements. The control wire 40 is passed proximally through an elongated shaft 16 and is connected to a trigger 260 (also called a deflection control device) on the handle assembly 200. Actuation of the motor 260 (eg, by the caregiver pulling proximally on the motor 260 or pushing it forward) pulls the control wire 40 back into the second flexion area 34 with compressive force and A flexing force is applied (as shown in Figures 7C and 12C) to result in flexion. A compressive force (described further below) combined with arbitrary directional biased stiffness of the second flexure zone 34 deflects the second flexure zone 34, thereby causing the energy delivery element 24 to renal. Move radially toward the inner wall of the artery (as shown in Figure 6B).

0113Desirably, as detailed below, the distal end region 20 of the elongated shaft 16 is sized and configured to vary the stiffness of the second flexure zone 34 around its perimeter. there is a possibility. The variable outer circumference imparts preferential and directional flexion to the second flexure area 34 (ie, directional biased stiffness). The second flexure zone 34 may be configured to bend in a single preferential direction in response to the actuation of the motor 260. Representative embodiments exemplifying this feature will be described in detail below. Further representative embodiments exhibiting multi-directional flexion are also detailed below.

0114The compressive and flexing forces, as well as the directional flexion resulting from the deflection of the second flexure zone 34, result in an event that alters the axial stiffness of the second flexure zone. The activation of the control wire 40 serves to increase the axial stiffness of the second flexure zone. As will be described later, the axial stiffness of the deflected second flexion area, in combination with the other flexible aspects of the distal end region of the catheter treatment device, provides favorable performance in renal arterial neuromodulation therapy. to enable.

0115In terms of axial stiffness and torsional stiffness, the mechanical properties of the second flexure zone 34 may differ from the mechanical properties of the first flexure zone 32, preferably different. This is because the first flexure zone 32 and the second flexure zone 34 perform different functions during use.

0116The first flexure zone 32 serves to transmit axial load and torque over a longer length (L2) than the second flexure zone 34 (L3). Importantly, the second flexion area 34 is also sized and so configured by the caregiver to be remotely deflected within the renal arteries. In this scheme, low resistance to deflection is desirable. This is a function that the first flexure zone 32 does not need to perform. Therefore, the second flexure zone 34 is preferably less rigid than the first flexure zone 32 (when the control wire 40 is not activated) and, importantly, the first flexure on at least one plane of motion. It is sized and configured to have higher flexibility than area 32.

0117Nevertheless, the second flexure zone 34 is also a preferred access angle because the second flexure zone 34, which is distal to the first flexure zone 32, precedes the first flexure zone 32 through the access angle access angle α1. At α1, it also includes the mechanical properties of the elongated shaft 16 to respond to its flexure or flexion without breakage, folding, substantial distortion, or significant kinking.

0118The desired magnitude of axial stiffness, rotational stiffness, and flexibility for the second flexure area 34 is an indicator of flexibility, a unit of desired elastic modulus (eg, Young's modulus (E)). The selection of constituents (s) to provide (represented by), and the construction and construction of the second flexure zone 34, eg, its inner diameter, outer diameter, wall thickness, and cross-sectional dimensions and shape. It can be obtained by selection in terms of structural features including. A typical example will be described in detail below. Axial stiffness, torsional stiffness, and flexibility are properties that can be measured and characterized by conventional methods.

0119As mentioned above, both the first and second flexure zones 32 and 34 preferably include the mechanical properties of axial stiffness sufficient to transfer the axial positioning force to the energy delivery element 24. .. By pulling on the handle assembly 200, the axial force is transmitted by the force transfer compartment 30, and the first and second flexure areas 32 and 34 move the energy delivery element 24 proximally in the renal artery ( Retreat (away from the kidneys). Similarly, by pushing forward on the handle assembly 200, axial force is transmitted by the force transfer compartment 30, and the first and second flexure areas 32 and 34 provide the energy delivery element 24 within the renal artery. Advance distally (towards the kidneys). Therefore, proximal retraction of the distal end region 20 and energy delivery element 24 within the renal artery can be achieved by the caregiver manipulating the handle assembly 200 or shaft from outside the intravascular pathway 14. ..

0120As mentioned above, both the first and second flexure zones 32 and 34 are also preferably such that the energy delivery element 24 is aligned with the outer circumference of the vessel wall when the second flexure zone 34 is deflected. Includes torsional strength characteristics that allow the transmission of sufficient rotational torque to rotate the distal end region 20 of the therapeutic device 12. Pull or push on the trigger to deflect the energy delivery element 24 to achieve vessel wall contact, then rotate the force transfer compartment 30, along with the first and second flexure areas 32 and 34. Thereby, the energy delivery element 24 can be rotated in the peripheral path within the renal artery. As will be described later, this rotational feature allows the clinical operator to maintain vessel wall contact when the energy delivery element 24 is relocated to another treatment site. By maintaining wall contact between treatments, clinical operators can achieve wall contact with greater confidence in orientation with inadequate visualization in subsequent treatments.

01214. Third flexure area As shown in FIGS. 7A, 7B, 7C, and 7D, the distal end region 20 of the elongated shaft 16 also optionally includes a third flexion zone 44 distal to any second flexure zone 34. But it may be. The third flexure zone may be used interchangeably with the distal flexure zone and force damping compartment. In this configuration, the length L3 of the second flexure zone 34 may be shortened by the length L4 having the length of the third flexure zone 44. In this configuration, the energy delivery element 24 is indicated at the end of the third flexure zone 44.

0122As shown in FIG. 7D, the third flexure zone 44 is sized to accommodate further flexure or flexion at the preferred treatment angle α3, independent of the first flexure zone 32 and the second flexure zone 34. It is so configured and has such mechanical properties. The third flexion area 44 is also sufficient for the distal end region 20 to advance into the renal artery through the guide catheter without straightening the guide catheter or causing damage to the blood vessels. Should respond to deflection. The treatment angle α3 provides significant deflection around the axis of the distal end region 20 (a typical embodiment is shown in FIG. 15C). The deflection in the third deflection zone, not under the direct control of the physician, is due to the contact between the energy delivery element 24 and the wall tissue caused by the radial deflection of the energy delivery element 24 in the second deflection zone 34. Occurs in response (see Figure 6B). Passive deflection of the third flexion area provides visible feedback to the clinical operator via fluoroscopy of vessel wall contact or other angiographic guidance (as shown in Figures 46A-46E). In addition, the third flexion zone preferably orients the area of tissue contact along one side of the energy delivery element 24, thereby increasing the area of contact. The third deflection zone 44 also biases the energy delivery element 24 against the tissue, thereby stabilizing the energy delivery element 24.

0123The function of the third deflection zone 44 provides additional benefits to the treatment. When the activation of the control wire 40 deflects the second flexion zone 34 and compresses the energy delivery element 24 against the inner wall of the artery, the third flexure zone is the contact between the energy delivery element 24 and the vessel wall. Effectively damps the force. This effect is particularly useful for renal artery treatment due to the movement of the renal arteries caused by respiratory and / or pulsatile flow. The flexibility of the first flexion area allows the distal end region of the treatment catheter to follow the movement of the renal arteries during breathing, while the increased axial direction of the deflected second flexure area. Rigidity provides integrity to the distal end region that helps maintain contact between the energy delivery element and the vessel wall. The third flexion area helps to relieve or buffer contact forces so that non-traumatic contact can be achieved or maintained, especially during renal artery operation. By attenuating this contact force, the third flexion area minimizes the chance of mechanical damage to the vessel wall and avoids excessive contact between the energy delivery element and the vessel wall (discussion of active surface area). See).

0124As shown in FIG. 7A, the third flexure zone 44 is preferably sized and configured such that length L4 is less than length L3. This is because, in terms of length, the distance required to align and stabilize the energy delivery element 24 in contact with the wall of the renal artery is the distance that causes the energy delivery element 24 to be radial within the renal artery. This is because it is significantly shorter than the distance required to deflect it. In some embodiments, the length L4 can be as long as about 1 cm. In other embodiments, the length L4 is from about 2 mm to about 5 mm. In one typical embodiment, the length L4 is about 5 mm or less. In another typical embodiment, the length L4 is about 2 mm or less. In another typical embodiment where the deflectable compartment 34 consists of a hinged joint, the length L4 is about 16 mm or less, and in this embodiment it is greater than the length L3 of the deflectable compartment 34. It can be long.

0125When the catheter is on the outside of the patient and the third flexion area 44 is substantially in line, the non-deflected configuration, treatment angle α3 (as shown in Figure 7D) is approximately 180 °. is there. When the third flexure zone 44 is fully deflected, the angle α3 is reduced to any angle between about 45 ° and 180 °. In a typical embodiment, when fully deflected, the angle α3 is from about 75 ° to about 135 °. In another typical embodiment, when fully deflected, the angle α3 is about 90 °.

0126In the passively deflected configuration of FIG. 7D, the third flexure zone 44 comprises a radius of curvature RoC3. In embodiments where the curvature of the third deflection zone 44 does not change or is consistent along the length L4, the length L4 and the deflection angle α3 may define the radius RoC3 of the curvature. It should be understood that the curvature of the third flexure zone 44, and thereby the radius RoC3 of the curvature of the third flexure zone, can instead vary along the length L4.

0127In embodiments such as when the curvature does not change, the length L4 may define a portion (180 ° -α3) / 360 ° of the outer circumference C3 of a circle with a radius RoC3 of equivalent curvature. Therefore, the circumference of such an equivalent circle is:<maths num="5"><img id="000007" he="11" wi="59" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (14)

0128Solution for radius of curvature RoC2:<maths num="6"><img id="000008" he="11" wi="43" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (15)

0129Therefore, when the curvature of the third flexure area does not change along the length L4, the length L4 is about 2 mm to about 5 mm, and the contact angle α3 is about 75 ° to about 135 °, the third In a typical embodiment of the deflection zone 44 of 3, the radius of curvature RoC3 is from about 1 mm to about 6 mm.

0130As is clear, equation (15) may be rearranged so that the length L4 and the radius RoC3 of curvature define the contact angle α3. Further, equation (15) may be rearranged such that the radius RoC3 of curvature and the angle α3 define the length L4. Therefore, in the embodiment where the curvature 44 of the third deflection area does not differ along the length L4, any one of the length L4, the angle α3, and the radius RoC3 of the curvature is the other two. It can be specified by specifying a variable.

0131The mechanical properties of the third flexure zone 44 and the second flexure zone 34 may be comparable in terms of axial stiffness, torsional stiffness, and flexibility. However, the third flexure zone 44 is sized and configured to be less rigid and, more importantly, more flexible than the second flexure zone 34.

0132In the embodiment just described (and as shown in FIG. 7D), the distal end region 20 is the first or proximal flexion zone 32, the second flexure zone 34, and the third flexure zone. 44 may be provided. The first, second, and third flexure areas are independent of each other so that the distal end region 20 of the elongated shaft 16 can be placed in the more complex multiple flexion structure 36 during use. And work. The complex multi-bent structure 36 of the composite has a first deflection region at an access angle α1 over length L2 (first flexure zone 32) and a contact angle α2 over length L3 (second flexure zone 34). It comprises a second deflection region of the, and a third deflection region at a treatment angle α3 over length L4 (third deflection zone 44). In the complex multi-bent structure 36 of the composite, all lengths L2, L3, and L4, and all angles α1, α2, and α3 can be different. It is specially sized so that the angle α1 and length L2 gain access from the aorta into each renal artery through the femoral artery access point, and the angle α2 and length L3 are configured as such. The energy delivery element 24 is specially sized and configured to align with the medial inner wall of the renal artery, and the angle α3 and length L4 optimize contact between the tissue and the energy delivery element. This is because it is specially sized and constructed as such.

0133The combined lengths of L2, L3, and L4 in the first, second, and third flexure areas of the distal end region 20, respectively, are the length L1 of force transfer compartment 30 and the energy delivery element 24. Specify the working length of the elongated shaft 16 of the treatment device 12 along with the length L5 (see Figure 8A) (ie, a composite length equal to L1 + L2 + L3 + L4 + L5). In some typical embodiments, this working length is from about 40 cm to about 125 cm. In a typical embodiment where a guide catheter is not used, this working length may be from about 40 cm to about 50 cm. Alternatively, if a 55 cm long guide catheter is used, this working length may be from about 70 cm to about 80 cm. Alternatively, if a 90 cm long guide catheter is used, this working length may be from about 105 cm to about 115 cm.

0134C. Size and composition of energy delivery elements to achieve neural regulation in the renal arteries In some patients, it may be desirable to create a large number of focal lesions that are peripherally spaced along the longitudinal axis of the renal artery. However, a single focal lesion with the desired longitudinal and / or peripheral dimensions, one or more circumferential lesions, a large number of peripherally spaced focal lesions in common longitudinal positions, It should be understood that a large number of longitudinally spaced focal lesions may be created as and / or alternative or even in common peripheral positions.

0135Creating a large number of focal lesions that are peripherally spaced along the longitudinal axis of the renal artery avoids the creation of all-around lesions, thereby reducing the risk of vascular stenosis, while still It provides an opportunity to peripherally treat the renal plexus, which is distributed around the renal arteries. It is desirable for each lesion to cover at least 10% of the vessel perimeter to increase the likelihood of acting on the renal plexus. However, it is important that each lesion is not too large (eg, more than 60% of the vessel circumference) so that the risk of stenotic effects (or other unwanted healing responses such as thrombus formation or incidental injury) does not increase. is there. In one embodiment, the energy delivery element 24 is configured to produce lesions in at least 30% (ie, 30% or more) of the perimeter of the blood vessel. In another embodiment, the energy delivery element 24 is configured to produce lesions that are greater than or equal to 30% of the perimeter of the vessel but less than 60%. It is also important that each lesion is deep enough to penetrate into and beyond the adventitia and thereby act on the renal plexus. However, lesions that are too deep (eg, greater than 5 mm) run the risk of interfering with non-target tissue and tissue structures (eg, renal veins), so heat treatment at a controlled depth is desirable.

0136As described in more detail below, the energy delivery element 24 is the first in the renal artery so that the energy delivery element 24 is positioned in contact with the inner wall of the artery to treat the renal plexus. It may be delivered to the treatment site (see Figure 43C). Once positioned within the artery as desired, energy may be delivered via an energy delivery element to create a first focal lesion at this first treatment site (see Figure 43D). I want to be). The first focal lesion is not completely continuous around the perimeter of the renal artery in a radial plane or cross section perpendicular to the wall or the longitudinal axis of the artery, the first treatment area 98a. Create (ie, the first focal lesion does not extend throughout the perimeter of the vessel wall). As a result, there is a separate untreated area around the outer circumference of the artery in the radial plane of the first treated area perpendicular to the longitudinal axis of the artery.

0137After the formation of the first focal lesion in the first treatment area 98a, the energy delivery element 24 may optionally be angularly repositioned with respect to the renal arteries (FIGS. 43E and 43F). Please refer to). This angular repositioning can be achieved, for example, by angularly rotating the elongated shaft 16 of the treatment device 12 via the handle assembly 200 (see FIG. 16A). ). In addition to the angular repositioning of the energy delivery element 24, the energy delivery element may optionally be repositioned along the longitudinal or longitudinal dimensions of the renal artery (see Figure 43E). I want to be). This longitudinal repositioning can be achieved, for example, by translating the elongated shaft 16 of the treatment device 12 through the handle assembly 200, prior to the angular repositioning of the energy delivery element 24. It can occur later or at the same time.

0138By repositioning the energy delivery element 24 in both longitudinal and angular dimensions, the energy delivery element is in contact with the inner wall of the renal artery at the second treatment site to treat the renal plexus. Deployed (see Figure 43E). Energy may then be delivered via an energy delivery element to form a second focal lesion at this second treatment site, thereby providing a second treatment area 98b and a second untreated area. (See Figure 43F).

0139Like the first treatment area created by the first focal lesion, the second treatment area is not continuous around the complete perimeter of the renal artery. However, the first and second treated areas (and the first and second untreated areas) are angularly and longitudinally from each other around the angular and longitudinal dimensions of the renal arteries, respectively. It is located offset in the direction (see Figure 43G). Overlapping the first and second treatment areas, which are positioned along different cross-sections or radial planes of the renal arteries around a common cross-section, is more of an artery than covering either treatment area individually. It provides a complex treatment area that covers a large area of the perimeter. Because this complex treatment area is not continuous (ie, it is formed from multiple longitudinal and angularly separated treatment areas), it is at a single treatment site (ie, a single longitudinal of the renal arteries). Peripheral arterial wall while reducing the risk of vascular stenosis compared to the formation of a single focal lesion covering an equivalent portion of the arterial perimeter (in a directional position or around a single cross section) It is expected that larger parts of the can be treated.

0140Optionally, one or more at one or more angularly and longitudinally spaced treatment sites to create an angularly and longitudinally spaced treatment area. Further focal lesions may form (see Figures 43G-43K). In one typical embodiment, the superposition of all or part of the treatment area is discontinuous (ie, subdivided along the longitudinal dimensions or longitudinal axes of the renal arteries). It still provides a complex treatment area that is substantially peripheral (ie, extends substantially throughout the perimeter of the renal artery over the longitudinal segment of the artery). This superimposed treatment area beneficially does not produce a continuous peripheral lesion along any individual radial plane or cross section perpendicular to the artery, which causes such a continuous peripheral lesion. The risk of acute or late-onset stenosis formation may be reduced compared to the peripheral treatment that produces.

0141Discontinuous perimeter treatment by positioning the energy delivery element (s) in different angular orientations along multiple longitudinal locations is an anatomy that substantially propagates along the longitudinal dimensions of the artery. It can act preferentially on the anatomical structure. Such anatomical structures can be nerve fibers and / or structures that support nerve fibers (eg, renal plexus). Moreover, such discontinuous perimeter treatment can reduce or reduce potentially unwanted effects induced in structures such as smooth muscle cells that propagate around the angular dimension of the artery. If continuous peripheral lesions are formed alternative, angular or peripheral orientation of smooth muscle cells with respect to the artery can increase the risk of acute or delayed stenosis or acute vasospasm.

0142In multiple energy delivery element configurations (eg, multiple electrode configurations), such as those in Figures 6C and 6D, multiple discontinuous peripheral treatment areas are created during a single catheter placement within the renal artery. be able to. Numerous energy delivery elements are such that they are longitudinally and angularly separated from each other, and that they are longitudinally offset, creating treatment areas that are angularly opposed or offset. They may be separated and so located. The retraction and rotation of the treatment device 12 can reposition the energy delivery element to create a further longitudinally and angularly isolated treatment area, thereby a single catheter for the practitioner. Allows the ability to create multiple treatment areas per placement, and multiple treatment areas through only two catheter placements.

0143In some embodiments, as described below with respect to FIG. 26, the distal end region 20 of the therapeutic device 12 has a spirally deflected configuration in which a large number of thermal heating elements are positioned along their length. You may prepare. When positioned in a spirally deflected configuration within the renal artery, a number of thermal heating elements 24 are peripherally along the longitudinal length of the distal end region in contact with the arterial wall. It may be separated. In some embodiments, discontinuous perimeter treatment may be achieved via a single catheter placement without angular or longitudinal repositioning of the distal end region 20.

0144As described (and as shown in FIG. 8A), the energy delivery element 24 is sized and configured to contact the lining of the renal arteries during use. In an exemplary embodiment (see Figure 8A), the energy delivery element 24 is sized and configured to apply an electric field with radio frequency (RF) energy from the generator 26 to the vessel wall. It takes the form of an electrode 46. In an exemplary embodiment, the electrode 46 is operated in monopolar or unipolar mode. In this scheme, the return path for the applied RF electric field is established by, for example, a dispersive electrode (shown as 38 in FIG. 6A), also referred to as an indifferent or neutral electrode. The unipolar application of RF electric field energy serves to ohm-heat or resistance-heat the tissue in the vicinity of the electrode 46. The application of RF electric fields causes thermal damage to tissues. The therapeutic objective is to thermally induce neural regulation (eg, necrosis, thermal alteration, or excision) in the target nerve fibers. Thermal damage forms a lesion in the vessel wall, which is shown, for example, in FIG. 9B. Alternatively, the RF electric field can deliver tissue with vibrational intensity that does not cause thermal damage, whereby neural regulation in the target nerve is achieved by electromodification of neural signals.

0145The active surface area (ASA) of the contact between the energy delivery element 24 or electrode 46 and the vessel wall is the heat across the vessel wall to thermally act on the target nerve fibers in the renal plexus (RP). It has a great deal to do with the efficiency and control of energy field transfer. The active surface area of the energy delivery element 24 and the electrode 46 is defined as the energy transfer area of the element 24 or the electrode 46, which can be placed in close contact with the tissue. Excessive contact and / or excessive power between the energy delivery element and the vessel wall can create unreasonably high temperatures at or around the interface between the tissue and the energy delivery element, thereby this. It produces excessive heat generation at the interface and / or contraction and contraction of the vessel wall. This excessive heat can also create lesions that are too large on the periphery, increasing the risk of stenosis. This excessive heat can also lead to unwanted thermal damage to the vessel wall, which stiffens and dries the vascular tissue, making it more sensitive to puncture and perforation. In addition, tissue drying (ie, dehydration) reduces the electrical and thermal conductivity of the tissue. Reduced conductivity can potentially create lesions that are too shallow to reach nerve fibers, and can also result in excessive heat buildup, increased against the vessel wall and undesirable. Causes damage and increases the likelihood of thrombus formation. Although there is a high risk of excessive wall contact and heating, too little contact between the energy delivery element and the vessel wall can compromise the effectiveness of the treatment. For example, too little contact can result in superficial heating of the vessel wall, thereby causing lesions that are too small (eg, less than 10% of the perimeter of the vessel) and / or too shallow to reach the target renal nerve fibers. produce.

0146The active surface area (ASA) and total surface area (TSA) of the energy delivery element 24 and electrode 46 are important for creating lesions of the desired size and depth, while the active surface area (ASA) of the energy delivery element 24 and electrode 46 is important. The ratio between and is also important. The ASA to TSA ratio affects lesion formation in two ways: (1) the degree of resistance heating through the electric field, and (2) blood flow or other convective cooling such as injectable or infused saline. The effect of the element. As mentioned above, the RF electric field causes lesion formation through resistance heating of the tissue exposed to the electric field. The higher the ASA to TSA ratio (ie, the larger contact between the electrode and the tissue), the greater the resistance heating. As described in more detail below, the flow of blood over the exposed portion of the electrode (TSA-ASA) provides conductive and convective cooling of the electrode, thereby causing excess thermal energy between the vessel wall and the electrode. Carry away from the interface. If the ratio of ASA to TSA is too high (eg 50%), resistance heating of the tissue may be too aggressive, not enough excess heat energy carried away, excessive heat generation, and stenosis damage. , Thrombosis, and increased potential for unwanted lesion size. If the ratio of ASA to TSA is too low (eg, 10%), the resistance heating of the tissue will be too low, resulting in superficial heating and smaller, shallower lesions.

0147Various size constraints on the energy delivery element 24 may be imposed for clinical reasons by the maximum desired dimensions of the guide catheter, as well as by the size and anatomy of the renal artery itself. Typically, the maximum outer diameter of the electrode 46 (or the dimensions of the cross section for a non-circular cross section) comprises the maximum diameter encountered in the handle assembly 200 along the length of the distal elongated shaft 16. Therefore, the outer diameters of the force transfer compartments 30, 1, 1, 2, and 3 flexure zones 32, 34, and 44 are equal to or (preferably) less than the maximum outer diameter of the electrode 46. Is.

0148In a typical embodiment shown in FIG. 8A, the electrode 46 takes the form of a right cylinder with a length L5 larger than its diameter. The electrode 46 further preferably comprises a distal region rounded to form a non-traumatic end surface 48. In a typical embodiment shown in FIG. 8B, the electrode 46 has a spherical shape such that the length L5 is equal to the diameter of the electrode. The sphere also presents a non-traumatic surface at the tissue interface.

0149As shown in FIGS. 8A and 8B, the angle α3 and length L4 of the distal flexion area 44 give the activity of contact between the tissue and each electrode 46 (ASA) given the TSA of each electrode. It is specially sized and configured to optimize surface area. The angle α3 and length L4 of the distal flexion area 44 allow the quadrant 50 on at least one side of the electrode 46 to be placed closer to the tissue (see Figure 8C), but the electrode 46 It should be understood that prior to power delivery, the quadrant 50 on one side does not necessarily have to be positioned to be closer to the tissue. In a typical embodiment, the active surface area of the electrode 46 in contact with tissue (ASA) can be expressed as ASA 0.25 TSA and ASA 0.50 TSA.

0150With a reduced power delivery profile, ASA to TSA ratios greater than 50% can be effective. Alternatively, higher ASA to TSA ratios can be compensated by increasing the conductive or convective cooling of the electrodes (eg, via forced cooling). As detailed below, this may be achieved by injecting or injecting a cooling fluid, such as saline solution (eg, room temperature saline solution or cold saline solution), onto the electrodes and into the bloodstream. There is.

0151The stiffness of each of the second and third flexure areas 34 and 44 is also selected to apply a stabilizing force that almost certainly contacts and positions the electrode 46 with the vessel wall tissue via the electrode. This stabilizing force also affects the amount of wall contact achieved by the energy delivery factor (ie, ASA to TSA ratio). With a greater stabilizing force, the energy delivery element has more wall contact, and with less stabilizing force, less wall contact is achieved. Further advantages of stabilizing force are: (1) softening the contact force between the distal end 20 and the vessel wall to minimize the risk of mechanical damage to the vessel wall, (2) ) Consistent positioning of the electrode 46 with respect to the vessel wall, and (3) stabilizing the electrode 46 with respect to the vessel wall. As mentioned above with respect to the combined effect of the first flexure zone and the second / second flexure zone, this stabilizing force is exerted by the catheter treatment device, even during the operation of the renal arteries during breathing. It makes it possible to maintain consistent contact with the vessel wall. The stabilizing force also allows the electrode to return to its neutral position after it has been removed from contact with the wall.

0152As mentioned above, for clinical reasons, the maximum outer diameter (or cross-sectional dimension) of the electrode 46 is constrained by the maximum inner diameter of the guide catheter, which is the passage of the elongated shaft 16 to pass through the intravascular path 14. To. 8 French Guide Catheter 94 (with an inner diameter of approximately 0.091 inches) is assumed to be the largest desired catheter used to access the renal arteries from a clinical point of view, and with electrodes 46 and a guide catheter. Allowing reasonable clearance tolerance between, the maximum diameter of electrode 46 is constrained to about 0.085 inches. When a 6 French guide catheter is used instead of an 8 French guide catheter, the maximum diameter of the electrode 46 is constrained to about 0.070 inches. When a 5 French guide catheter is used, the maximum diameter of the electrode 46 is constrained to about 0.053 inches. Based on these constraints and the power delivery considerations described above, the electrode 46 preferably has a maximum outer diameter of about 0.049 to about 0.051 inch. The electrode 46 also preferably has a minimum outer diameter of about 0.020 inches to provide sufficient cooling and lesion size. In some embodiments, the electrode 46 (ie, the energy delivery element 24) may have a length of about 1 mm to about 3 mm. In some embodiments where the energy delivery element is a resistance heating element, it may have a maximum outer diameter of about 0.049 to 0.051 inches and a length of about 10 mm to 30 mm.

0153D. Applying energy to tissues through energy delivery elements With reference to FIG. 5 again, in an exemplary embodiment, the generator 26 may supply a pulsed or continuous RF electric field to the electrode 46. Continuous delivery of RF energy is desirable, but the application of thermal energy in pulses is relatively more controlled with higher energy levels (eg, higher power), longer or shorter total duration, and / or better. It may enable the application of intravascular renal nerve regulation therapy. Pulse energy may also allow the use of smaller electrodes.

0154Thermotherapy was collected by one or more sensors 52, such as temperature sensors (eg thermocouples, thermistas, etc.), impedance sensors, pressure sensors, optical sensors, flow sensors, chemical sensors, force sensors, strain sensors, etc. It may be monitored and controlled via data (see Figures 9A and 9B). The sensor (s) 52 may be incorporated in or above the electrode 46 and / or in or above the adjacent region on the distal region 20.

0155Advantageously, the second flexion area 34 is deflected in a controlled manner so that the surface of the electrode 46 that comes into contact with the tissue during treatment can be known. Therefore, the sensor (s) 52 is incorporated into the electrode in a manner that specifies whether the sensor (s) are in contact with tissue and / or face blood flow at the treatment site. May be good. The ability to specify sensor placement for tissue and blood flow is very significant because the temperature gradient from the side facing the blood flow to the electrodes in contact with the vessel wall can be up to about 15 ° C. is there. Significant gradients across electrodes in other sensitive data (eg, flow, pressure, impedance, etc.) are also expected.

0156The sensor (s) 52 may be incorporated, for example, during power and energy delivery, on the side surface of the electrode in contact with the vessel wall at the treatment site (see Figure 9B) or in the tip of the electrode. It may be incorporated during energy delivery on the opposite side of the electrode facing the blood flow (see Figure 9A) and / or within certain regions of the electrode (eg, distal). , Proximal, quadrant, etc.). In some embodiments, multiple sensors may be provided along the electrodes and / or at multiple positions relative to blood flow. For example, multiple peripherally and / or longitudinally spaced sensors may be provided. In one embodiment, the first sensor may contact the vessel wall during treatment and the second sensor may face blood flow.

0157Further or alternative, various microsensors can be used to obtain data corresponding to blood flowing across energy delivery elements, vessel walls, and / or energy delivery elements. For example, a number of microthermocouples and / or impedance sensors can be implemented to acquire data along with energy delivery elements or other parts of the therapeutic device. Sensor data can be acquired or monitored prior to, at the same time as, or after the delivery of energy, or, where applicable, between pulses of energy. The monitored data may be used in a feedback loop to better control the treatment, eg, to decide whether treatment should be continued or discontinued, and it has been increased or decreased. It can promote controlled delivery of power, or longer or shorter duration therapies.

0158Non-target tissue may be protected by blood flow (F) within its respective renal arteries, which acts as a conductive and / or convective heat sink that carries away excess thermal energy. For example (as shown in Figures 9A and 9B), blood flow (F) is not blocked by the elongated shaft 16 and the electrodes 46 it carries, so that the natural circulation of blood in each renal artery is excessive. It serves the function of removing thermal energy from non-target tissues and energy delivery elements. Removal of excess thermal energy by the bloodstream also allows for higher power treatment, where additional power can be delivered to the target tissue as the thermal energy is carried away from the electrodes and non-target tissue. .. In this way, intravascularly delivered thermal energy heats the target nerve fibers located close to the vessel wall in order to regulate the target nerve fibers, while the blood flow (F) in each renal artery. ) Protects non-target tissue of the vessel wall from excessive or unwanted thermal damage. When energy is delivered in pulses, the time interval between the delivery of thermal energy pulses is that of the non-target tissue of the vessel wall compared to applying continuous thermal energy of comparable magnitude or duration. Further convective cooling or other cooling may be promoted.

0159It may also be desirable to provide enhanced cooling by inducing additional innate blood flow across the energy delivery element. For example, caregivers can implement techniques and / or techniques to increase perfusion through the renal arteries or to the energy delivery element itself. These techniques include positioning a partial shielding element (eg, a balloon) within an upstream vessel, such as the proximal portion of the aorta or renal artery, to improve flow across the energy delivery element. Further or alternately, autologous blood from another region of the vascular structure is siphoned and redirected into the renal arteries to increase the volumetric flow and / or velocity of blood flowing through the arteries. May be good.

0160In addition, or as an alternative, forced cooling may be provided to remove excess thermal energy and protect non-target tissue in order to passively utilize blood flow (F) as a heat sink. For example, the thermofluid infusion may be injected, injected, or delivered into the blood vessel in an open circuit system. Further or alternatively, the energy delivery element 24 (eg, electrode 46) heats in a closed circuit system (ie, without delivering any drug into the bloodstream) to remove excess thermal energy. The fluid infusion (eg, cold or cold fluid) may be forcibly cooled by circulating it within the distal end region 20, or by some other mechanism, and the like.

0161Thermofluid infusions used for forced cooling include, for example, saline (room temperature or cold) or some other biocompatible fluid. The thermofluid infusion (s) may be introduced through the therapeutic device 12, for example, through one or more infusion lumens and / or ports. When introduced into the bloodstream, the thermofluid infusion solution (s) are introduced through a guide catheter, for example, upstream of the energy delivery element 24 or electrode 46, or elsewhere for tissues that require protection. May be done. Delivery of the thermofluid infusion near the treatment site (via an open circuit system and / or via a closed circuit system) may allow, for example, increased / higher power application, during energy delivery. Can allow the maintenance of lower temperatures on the blood vessel wall, can promote the creation of deeper or larger lesions, can help reduce treatment time, can allow the use of smaller electrode sizes, and rapidly It can compensate for the reduced blood flow and can compensate for the anatomical features that result in relatively low blood flow at the treatment site, or a combination thereof.

0162Much of what is described herein relates to electrical systems configured for the delivery of RF energy, but the desired treatment is by other means, for example, coherent or non-coherent light; direct heat. Modifications (eg, using heated or cooled fluids or resistance heating elements); microwaves; ultrasound (including high-density focused ultrasound); diode lasers; radiation; tissue heating fluids; and / or cold fluids Is intended to be achieved by.

0163III. Typical embodiments A. First representative embodiment (first, second, and third flexure areas with distally indicated energy delivery elements) Figures 10A-15H are representative of elongated shafts 16 including force transfer compartments 30, and first, second, and third flexure zones 32, 34, and 44, having the physical and mechanical features described above. Embodiment is shown. In this embodiment, the thermal heating element 24 is directed distal to the third flexure zone 44 (see, eg, FIG. 11A).

01641. Force transmission classification In an exemplary embodiment, as shown in FIGS. 10A and 10B, the force transfer section 30 comprises a first elongated, preferably tubular structure, which, for example, takes the form of a first tubular structure 54. be able to. The first tubular structure 54 is preferably made of a metallic material, such as stainless steel, or, as already described, to have the axial stiffness and torsional stiffness required for the force transfer compartment 30. A shape memory alloy, such as a hypo tube made of nickel titanium (also known as Nitinol or NiTi). As already described, the force transfer section 30 is most rigid along the elongated shaft 16 in order to facilitate the axial movement of the elongated shaft 16 as well as the rotational operation of the elongated shaft 16 within the intravascular path 14. It has the division of. Alternatively, the first tubular structure 54 is a hollow coil, hollow cable, solid cable (with embedded wire), braided or braided reinforcing shaft, coil reinforced polymer shaft, metal / polymer composite. Etc. may be provided.

0165Rigidity is created by microengineering, machining, cutting, and / or skiving the hypotube material to provide material choice, as well as desired axial stiffness and torsional stiffness characteristics. It is a function of structural features such as inner diameter, outer diameter, wall thickness, shape, and other features. For example, the elongated shaft can be a hypo tube that is laser cut into various shapes and cross-sectional shapes to achieve the desired functional properties.

0166When the first tubular structure 54 is made of a conductive metal material, the first tubular structure 54 may include a sheath 56 or cover made of an electrically insulating polymer material (s). It is placed over the outer diameter of the underlying tubular structure. The polymeric material can also be selected to have the desired durometer (representing the degree of stiffness or lack thereof) so as to contribute to the desired overall stiffness of the first tubular structure 54. Candidate materials for polymeric materials include, but are not limited to, polyethylene terephthalate (PET); Pebax® materials; nylon; polyurethanes, Grilamid® materials, or combinations thereof. The polymeric material can be laminated, dip coated, spray coated or deposited / adhered to the outer diameter of the tube.

01672. First flexure area As shown in FIGS. 11A, 11B, and 11C, the first flexure area 32 comprises a second elongated, preferably tubular structure, which may take the form of, for example, a second tubular structure 58. it can. The second tubular structure 58 may be made from the same or different material as the first tubular structure 54. The axial stiffness and torsional stiffness of the second tubular structure 58 have the axial stiffness and torsional stiffness required for the first flexure zone 32, as already described. As already described, the first flexion area 32 is less rigid than and less rigid than the force transmission section 30 in order to undergo intense flexion at and before the aorta and the junction of the respective renal arteries. Can be flexible. The second tubular structure is preferably a hypo tube, but can optionally include hollow coils, hollow cables, braided shafts, and the like.

0168It may be desirable for the first and second tubular structures 54 and 58 to share the same material. In this case, the morphology and physical characteristics of the second tubular structure 58 may be varied compared to the first tubular structure 54 to achieve the desired stiffness and flexibility differences. For example, the inner diameter, outer diameter, wall thickness, and other machined features of the second tubular structure 58 may be tailored to provide the desired axial stiffness and torsional stiffness as well as flexibility features. it can. For example, the second tubular structure 58 may be laser cut along its length to provide a bendable spring-like structure. Depending on the ease of manufacture, the first and second tubular structures may be produced from the same piece of material or from two separate pieces. If the first tubular structure and the second tubular structure are not made of the same material, the outer diameter of the second tubular structure 58 is the rigidity between the first and second tubular structures 54 and 58. It may be less than the outer diameter (or have a smaller wall thickness) of the first tubular structure 54 to create the desired distinction in.

0169When the second tubular structure 58 is made of a conductive metal material, the second tubular structure 58, like the first tubular structure 54, is an electrically insulating polymer material, as already described. Includes sheath 60 (see Figures 11B and 11C) or cover made from one or more). The sheath 60 or cover can also be selected to have the desired durometer to contribute to the desired distinction in stiffness and flexibility between the first and second tubular structures 58.

0170The second tubular structure 58 comprises a different material than the first tubular structure 54 to provide the desired distinction in stiffness and flexibility between the first and second tubular structures 58. be able to. For example, the second tubular structure 58 may include a cobalt-chromium-nickel alloy instead of stainless steel. Alternatively, the second tubular structure 58 may comprise a less rigid polymer, braided or braided reinforcing shaft, coil reinforced polymer shaft, metal / polymer composite, nitinol, or hollow cable-like structure. it can. In addition to material selection, the desired distinction in stiffness and overall flexibility is machined, as already described, the inner diameter, outer diameter, wall thickness, and other work of the second tubular structure 58. It can be achieved by selecting features. In addition, as mentioned above, the sheath 60 or cover made from an electrically insulating polymer material also has a second tubular to provide the desired distinction between the first and second tubular structures 54 and 58. It can also be placed so as to cover the outer diameter of the structure 58.

01713. Second flexure area As shown in FIGS. 12A, 12B, 12C, and 12D, the second flexure area 34 comprises a third elongated, preferably tubular structure, which takes the form, for example, a third tubular structure 62. be able to. The third tubular structure 62 can be made from the same or different material as the first and / or second tubular structures 54 and 58. The axial stiffness and torsional stiffness of the third tubular structure 62 have the axial stiffness and torsional stiffness required for the second flexure area 34, as already described. As already described, the second flexion zone 34 is less rigid than the first flexure zone 32 in order to promote the controlled deflection of the second flexure zone 34 within each renal artery. , Can be more flexible than that.

0172When the second and third tubular structures 58 and 62 share the same material, the morphology and physical characteristics of the third tubular structure 62 are first to achieve the desired stiffness and flexibility differences. Can be varied compared to 2 tubular structure 58. For example, the inner diameter, outer diameter, wall thickness, and other machined features of the third tubular structure 62 can be tailored to provide the desired axial stiffness and torsional stiffness as well as flexibility features. it can. For example, the third tubular structure 62 is more flexible than the second tubular structure 58 and may be laser cut along its length to provide a more spring-like structure. is there.

0173When the third tubular structure 62 is made of a conductive metallic material, the third tubular structure 62 is also made of an electrically insulating polymer material (s), as already described. It may include 64 (see Figures 12B, 12C, and 12D) or a cover. The sheath 64 or cover can also be selected to have the desired durometer to contribute to the desired distinction in stiffness and flexibility between the second and third tubular structures 62.

0174The third tubular structure 62 comprises a different material than the second tubular structure in order to provide the desired distinction in stiffness and flexibility between the second and third tubular structures 62. Can be done. For example, the third tubular structure 62 can contain a nitinol substance to provide the desired distinction in stiffness between the second and third tubular structures 58 and 62. In addition to material selection, the desired distinction in stiffness and overall flexibility is machined, as already described, the inner diameter, outer diameter, wall thickness, and other work of the third tubular structure 62. It can be achieved by selecting features.

0175For example, in terms of diameter, the outer diameter of the third tubular structure 62 is preferably less than the outer diameter of the second tubular structure 58. The reduction in outer diameter or wall thickness affects the desired distinction in stiffness between the second and third tubular structures 58 and 62.

0176As described in more detail above, preferential deflection of the second deflection zone is desirable. This can be achieved by making the third tubular structure 62 compressible in the desired deflection direction and elastic against compression on the opposite side of the deflection direction. For example, as shown in FIGS. 12B and 12C, the third tubular structure 62 (unlike the second tubular structure 58) may include a laser cutting pattern, including a back 66 with connecting ribs 68. it can. The pattern biases the deflection of the third tubular structure 62 in the desired direction in response to a pull on the control wire 40 connected to the distal end of the third tubular structure 62. The control wire 40 is attached with solder 130 to the distal end of the deflectable section. When the control wire is pulled, the third tubular structure compresses on the compressible flanks and biases the deflection in the direction of the compressible flanks. The benefits of preferential bias within the renal arteries have already been described.

0177As also shown in FIG. 12D, the flat ribbon material 70 (eg, nitinol, stainless steel, or spring stainless steel) can be attached to the third tubular structure 62. The flat ribbon, which serves to reinforce the deflectable third tubular structure 62 when the pulling force is removed from the control wire 40, elastically aligns the deflectable third tubular structure 62.

0178In addition, as mentioned above, the sheath 64 (see Figures 12B, 12C, and 12D) or cover, made from an electrically insulating polymer material and having the desired durometer, is also a first and second tubular structure 54. The outer diameter of the second tubular structure 58 can be placed over the outer diameter to provide the desired distinction between and 58.

0179In the embodiments of FIGS. 12B-12D, the width of the back 66 (ie, the length of the radial arc of the back 66 in the region along the longitudinal axis of the third tubular structure 62, not including the rib 68). ) Acts on the relative stiffness and elasticity of the third tubular structure 62. It should be understood that the width of the dorsal 66 can be specified to provide a third tubular structure 62 with the desired relative stiffness and / or elasticity. In addition, the width of the dorsal 66 can vary along the longitudinal axis of the third tubular structure 62, thereby having a relative stiffness and / or elasticity that varies along its length. Provide a tubular structure. Such fluctuations in the width of the back 66 can be gradual, continuous, sudden, intermittent, or a combination thereof.

0180The length L3 of the deflectable section 34 is between about 5 mm and 20 mm, for example, about 12.5 mm or less. As the distal end region 20 advances from the guide catheter into the renal artery, the energy delivery element 24 contacts the upper surface of the renal artery wall. The length L3 is a deflectable segment for the energy delivery element 24 to contact the dorsal, ventral, and medial surfaces of the renal artery wall within a short distance, as long as a portion of the deflectable compartment 34 projects from the guide catheter. Allows to be manipulated through 34 deflections. Therefore, the length L3 of the deflectable compartment 34 is selected to be specifically suitable for use in the renal arteries.

0181The width of the ribs 68 (ie, the distance each rib extends along the longitudinal axis of the third tubular structure 62), and the distance between the ribs 68 (ie, the back 66 is the third tubular between adjacent ribs 68). The distance (distance extending along the longitudinal axis of the member 62) can optionally act on the maximum preferential deflection achievable by the second flexure zone 34 before the adjacent ribs 68 contact each other, ie. It may limit the maximum amount of compression with respect to the sides of the third tubular structure that is compressible. Such contact between adjacent ribs 68 may optionally define the radius and / or angle α2 of the curvature of the deflectable section 34 under such maximal preferential deflection (see Figure 7C). The deflectable compartment is configured to be in the maximum deflection state, where the maximum deflection state is such that the deflectable body separates the energy delivery element from the axis of the elongated tubular body by a predetermined distance. Achieved when moving. Maximum deflection avoids the risk of causing trauma to the renal artery wall, which can occur if the deflectable compartment 34 of length L3 is significantly deflected by the diameter of the renal artery. As described in detail below, the force damping section 44 is configured to dampen the force exerted on the arterial wall when the deflectable section 34 is deflected. A stable contact force between the energy delivery element 24 and the inner wall of the renal artery can be created by exerting a force greater than an unstable force and less than a traumatic force. The force damping section 44 provides stable contact force, even when the deflectable section 34 moves the energy delivery element 24 away from the axis of the elongated tubular body by a distance greater than the diameter of the renal artery. However, it is attenuated while still being kept within the non-traumatic range. For example, the force damping section 44 may be sufficiently deflected so that the deflectable section 34 is configured to be in a state of maximum deflection such that the predetermined distance is approximately 4 mm greater than the diameter of the renal artery. In one embodiment, the distal assembly 53 has a length of about 3 mm to 6 mm (eg, 5 mm or less) and the deflectable compartment 34 has a length of about 8 mm to 15 mm (eg, 12. It has a length L3 (less than 5 mm) and has the maximum deflection that shifts the energy delivery element 24 by a predetermined distance of about 10-14 mm. Alternatively or further, the predetermined distance is adjusted by a deflection limiter on the handle 200, which limits the actuating device 260 to shift the control wire by a maximum amount and thus limits the deflection to the adjusted maximum deflection state. There is a possibility that

0182It should be understood that the width and / or spacing of the ribs 68 can be optionally specified to achieve the desired maximal preferential deflection. In addition, the width and / or spacing of the ribs 68 can vary along the longitudinal axis of the third tubular structure 62, thereby causing such maximal preferential deflection to the second flexure area 34. Provides the radius of curvature that changes below. Such variations in the width and / or separation of ribs 68 can be gradual, continuous, abrupt, intermittent, or a combination thereof.

0183As mentioned above, the preferential deflection of the deflection direction from the reduced stiffness can be achieved in a number of different ways. For example, as shown in FIG. 13B, the third tubular structure 62 has segments with different stiffnesses D1 and D2 where D1&gt; D2 (ie, the segment of D1 is more mechanical than the segment of D2). It can be rigid), tubular polymer or metal / polymer composite. The third tubular structure 62 can also take the form of an elliptical, rectangular, or flattened metal coil or polymer with segments with different stiffnesses D1 and D2, D1&gt; D2. Yes (as shown in Figure 13C). In either scheme, the segment with the lower stiffness D2 is oriented onto a third tubular structure 62 on the same side surface to which the motor wire is attached.

0184Alternatively, as shown in FIGS. 14B and 14C, the third tubular structure 62 can comprise an eccentric polymer or metal / polymer composite that may be braided or coiled. The third tubular structure 62 can also take the form of an elliptical, rectangular, or flattened metal coil or polymer (as shown in FIG. 14C). In both schemes, the thinner (lower rigid) wall segment 76 is oriented onto a third tubular structure 62 on the same side as the side to which the motor wire is attached.

01854. Third flexure area As shown in FIGS. 15A-15H, the third flexure zone 44 comprises a flexible tubular structure 74. The flexible structure 74 can comprise a metal, polymer, or metal / polymer composite. The physical and physical characteristics of the flexible structure 74 are that the third flexion area 44 applies a pressure where (1) the energy delivery element 24 is less than the pressure at which there is a high risk of causing trauma to the inner wall of the renal artery. When it is elastic and flexible enough to deform, (2) the contact force or pressure between the energy delivery element 24 and the inner wall of the renal artery, which allows for energy delivery and stable contact. Selected to be rigid enough to produce. The flexibility of the third flexure zone 44 is the force applied to the arterial wall by the energy delivery element 24 so that the force remains in this preferred range when the second flexure zone 34 is extensively deflected. Attenuate. Further, by elastically deforming, the third flexure zone 44 aligns the energy delivery elements 24 such that one side thereof is in contact with the arterial wall, as described above.

0186The physical and physical characteristics of the flexible structure 74 are that, optionally, the axial stiffness and torsional stiffness of the flexible structure 74 is less than or equal to the axial stiffness and torsional stiffness of the third tubular structure 62. Can be selected to be. The overall flexibility of the flexible structure 74 is optionally greater than or equal to the flexibility of the third tubular structure 62 when the third tubular structure is not deflected by the control wire 40. ..

0187As part of the third flexure zone 44, the flexible structure 74 can be connected to the second flexure zone as described above. Alternatively, in embodiments that do not provide a second flexion zone, the third flexure zone can be connected to the first flexure zone. As shown in FIG. 15B, the energy delivery element 24 is directed to the distal end of the flexible structure 74 for tissue-contacted placement along the vessel wall of each renal artery.

0188The material selected for the flexible structure 74 can be radiation opaque or non-radiation opaque. For example, radiation opaque materials such as stainless steel, platinum, platinum iridium, or gold can be used to enable visualization and image guidance. When using a non-radiation opaque material, the material may optionally be supplemented with a radiation opaque material such as barium sulphate to facilitate visualization and image guidance.

0189The configuration of the flexible structure 74 can be different. For example, in the embodiments shown in FIGS. 15B and 15C, the flexible structure 74 comprises a thread 104 boxed or covered in a polymer coating or packaging 110. The thread 104 is fed through a proximal mooring 108 attached to the distal end of the second flexion area 34 and a distal mooring 106 fixed or integrated within the heating element 24 / electrode 46. The distal mooring 106 may be secured within the heating element 24 / electrode 46 using, for example, solder. Alternatively, the distal mooring 106 and the heating element 24 / electrode 46 may be made as a single piece or unit structure.

0190In order to have a flexible structure 74 that securely connects to the second flexure area 34 and the energy delivery element 24, various types of materials can be used to construct the above-mentioned structures, but yarn. It is desirable that 104 is made of Kevlar or similar polymer yarn and proximal mooring 108 and distal mooring 106 are made of stainless steel. The coating 110 may consist of any electrical insulating material, in particular those listed later with respect to the sheath 80, while the structure of the flexible structure 74 is as low as the carbothane laminate 110. It is desirable to be boxed / coated / covered with a durometer polymer. As shown in FIG. 15C, one or more feed wires 29 may run in parallel with or within the flexible structure 74. As mentioned above, these wires may provide the energy delivery element 24 with current / energy from the generator 26 or may carry a data signal acquired by the sensor 52. As shown in FIG. 15C, the control wire 40 extending from the handle trigger 260 may be formed into a proximal mooring 108 and attached to an elongated shaft using solder 130.

0191One advantage of the above configuration of the flexible structure 74 is that the flexible structure 74 creates an area of electrical separation between the energy delivery element and the rest of the elongated shaft. Both the Kevlar yarn 104 and the laminate 110 are electrically insulating, thereby providing the feed wire (s) 29 as the only means for electrical connectivity. Therefore, the outer surfaces of the flexible structure 74 and the third flexure zone 44 are electrically inert.

0192As shown in FIGS. 15D-15F, the flexible structure 74 allows considerable passive deflection of the third flexure zone 44 when the energy delivery element 24 is brought into contact with the vessel wall. As already described, this flexibility has multiple potential benefits. One such benefit is that if the third flexion zone 44 is removed and the energy delivery element is directly connected to the distal end of the second flexure zone 34, then the second flexure zone When the 34 is deflected against the force or stress applied to the vessel wall during the deflection of the second flexure zone 34, or at the same time, the third flexure zone 44 is with the energy delivery element 24 and the vessel wall. It can be the ability to reduce the force or stress applied during. This can reduce the risk of trauma. In addition, the forces or stresses applied to the vessel wall by the energy delivery element 24 are in a consistent range during the deflection of the second flexure zone 34, especially during the movements caused by respiration and / or pulsatile flow. It may be maintained, which may promote consistent and / or controlled lesion formation.

0193The size and composition of the flexible structure 74 is that the energy delivery element is deflected in many directions because the third flexion zone can bend by an angle Θ in any plane through the axis of the distal end region. To enable. For treatment in peripheral blood vessels such as the renal arteries, the angle Θ is preferably 90 degrees or less. Optionally, the flexible structure 74 is less elastic, i.e., does not provide significant restoration or alignment power when deflected.

0194The energy delivery element 24 may preferably provide omnidirectional delivery of energy in substantially any or all directions. When the third flexion area 44 passively deflects at the treatment site at an angle Θ appropriate for the anatomy of a given patient, any portion of the energy delivery element 24 energizes the target renal nerve. It may be aligned with the lining of the renal artery for delivery. Blood flow can remove heat during such energy delivery, thereby making the third flexion area 44 undesirably stiffer or bulkier, shielding the energy delivered to the target renal nerves, Or reduce or mitigate the need for other prioritized orientations. Such omnidirectional energy delivery, without shielding / preferred orientation, is compared to shielding or oriented energy delivery elements, such as energy delivery elements with microwave or radioactive power sources. It may facilitate simpler or safer positioning of the energy delivery element 24 at the treatment site.

0195In an alternative embodiment of the third flexure zone 44, the flexible structure 74 may take the form of a tubular metal coil, cable, braid, polymer or metal / polymer composite, as shown in FIG. 15H. it can. Alternatively, the flexible structure 74 can take the form of an elliptical, rectangular, or flattened metal coil or polymer, as shown in FIG. 15G. In an alternative embodiment, the flexible structure 74 may include other mechanical structures or systems that allow the energy delivery element 24 to swivel in at least one plane of operation. For example, the flexible structure 74 may include hinges, or ball / socket combinations.

0196If the flexible member comprises a conductive material in whole or in part, the third flexure area 44 is preferably an outer sheath covering the flexible structure 74 made of an electrically insulating polymer material. Includes 80 (see Figures 15G and 15H) or cover. The polymeric material also has the desired durometer due to the flexibility of the flexible member (eg, 25D-55D).

0197Candidate materials for polymeric materials include polyethylene terephthalate (PET); Pevacs; polyurethane; urethane, carbothane, tecothane, low density polyethylene (LDPE); silicone; or a combination thereof. The polymeric material may be laminated, dip coated, spray coated or deposited / applied on the flexible structure 74. Alternatively, a thin film of polymeric material (eg, PTFE) can be wrapped around the flexible structure 74. Alternatively, the flexible structure 74 is essentially insulated and may not require a separate sheath 80 or cover. For example, the flexible structure can include a polymer coated coiled wire.

0198Optionally, the third flexure zone 44 can include a sensor 42 indicating the amount of deflection of the third flexure zone 44, as shown in FIG. 16A. The sensor 42 may be, for example, a piezoresistive element that is the overall length or partial length of the third flexure zone 44 and can be mounted on one side of the third flexure zone. A pair of conductors (not shown) running through the elongated shaft 16 connects the sensor 42 to an electrical source and sensitive circuit (not shown). When the third flexion zone 44 is deflected by the inner wall of the renal artery in response to the force applied to the energy delivery element 24 or a portion of the third flexure zone 44, the sensor 42 quantifies the amount of deflection. Deliver a signal to When the sensor 42 is a piezoresistive element, its resistance changes in proportion to its constraints. The amount of deflection in the third flexion area 44 is an indicator of contact force with the inner wall of the renal artery.

01995. Rotation control device As detailed below, it is desirable to rotate the device within the renal artery after the energy delivery element has contacted the vessel wall. However, or the clinical practitioner rotating the entire handle assembly at the proximal end of the device can be cumbersome and cumbersome, especially considering the dimensions of the renal anatomy. In one typical embodiment, the proximal end of the shaft 16 is connected to the handle assembly 200 by a rotor 230, as shown in FIGS. 16A and 16B.

0200The proximal end of the force transfer compartment 30 is attached to the stationary coupler 88 on the rotor 230. The rotation of the rotor 230 (as shown in FIG. 16A) thereby rotates the force transfer section 30 and, along with it, the entire elongated shaft 16 without the rotation of the handle assembly 200. As shown in FIG. 16A, the caregiver thereby holds the proximal portion of the handle assembly 200 rotationally stationary with one hand, and with the same or different hands, a torsional force to rotate the elongated shaft 16. Can be applied to the rotor 230. This allows the trigger to remain easily accessible for controlled deflection.

0201Unnecessary entanglement of these wires due to the presence of cables and wires running from the handle assembly through the shaft of the equipment (eg, control 40, electrical transmission wires, and / or sensors / thermocouple wires (s) 29, etc.) And to avoid kinking, it is desirable to limit the rotation of the shaft with respect to these wires. To address this issue, rotation limiting elements may be incorporated into the handle assembly and rotor. The rotor 230 and handle assembly may be configured to allow the optimum number of turns for the shaft given such structural or dimensional constraints (eg, wire). The components of the handle assembly may be configured, for example, to allow a finite number of rotations (eg, 2) of the shaft independent of the handle assembly. Limiting the rotation of the shaft to the optimum number of rotations can be achieved by any number of commonly known mechanical features.

0202As described and detailed below, intravascular access allows the caregiver to operate the handle assembly 200 to position the distal end region 20 of the elongated shaft 16 within each renal artery. be able to. The caregiver can then activate the motor 260 on the handle assembly 200 to deflect the energy delivery element 24 around the second flexion zone 34 (see Figures 16A and 16B). The caregiver can then actuate the rotor 230 on the handle assembly 200 to apply a rotational force along the elongated shaft 16 (see Figures 16A and 16B). The rotation of the elongated shaft 16 when the second flexion area 34 is deflected within each renal artery causes the energy delivery element 24 to rotate within each renal artery, achieving contact with the vessel wall, It simplifies the determination of the presence of wall contact, especially in planes where angiographic visualization is inadequate.

0203In a further aspect of the disclosed technology, the handle assembly 200 may be configured to minimize its handling by the operator / caregiver while the device is inside the patient. For example, as shown in FIG. 16B, the handle assembly also comprises one or more surfaces 243 that are substantially adapted to the subsurface (eg, operating table). This surface 243, which appears to be substantially flat in FIG. 16B, may be optionally curved, molded, or angled, depending on the composition and / or shape of the underlying surface. There is. The adaptive surface 243 allows the clinical operator to keep the handle assembly 200 stable when the treatment device 12 is inside the patient. To rotate the device when it is inside the patient, the operator can simply dial the rotor 230 without any need to lift the handle assembly. When the operator wishes to retract the device for subsequent treatment, the operator can simply slide the handle assembly along the underlayer to the next position. Again, this reduces the risk of damage due to operator error or excessive handling of the treatment equipment. Further or alternative, the lower surface can engage the surface of the underlying layer using clips, woven fabrics, adhesives and the like.

0204Further enhancements to the rotating mechanism disclosed herein include tactile and / or tactile on rotating instruments so that the operator can exercise greater control and attention as he rotates the device. Includes providing visible feedback. The rotor 230 can also selectively lock to the handle assembly if the operator wishes to hold the treatment device in a position at a particular angle, thereby preventing further rotation. Another optional enhancement includes providing a distance marker along the shaft / handle assembly to allow the operator to measure the distance when retracting the treatment device.

0205B. Second representative embodiment (third flexible area comprises a flexible thermal heating element) 17A and 17B show typical embodiments of the elongated shaft 16 including a force transfer section 30, a first or proximal flexion zone 32, a second flexure zone 34, and a third flexure zone 44. In this embodiment, the materials, sizes, and configurations of the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34 are described in the first representative embodiment, respectively. It is about the same as the corresponding product.

0206In this embodiment, however, the third flexure zone 44 is sized and configured to serve itself as a flexible energy delivery 90. In diameter, the flexible energy delivery element 90 is sized and configured such that it is greater than or equal to the second flexure zone 34. The total surface area TSA of the flexible thermal heating element 90 is thereby increased, and as a result, the potentially active surface of the product electrode 46 is also increased.

0207Also, in this scheme, the overall length of the flexible thermal heating element 90 shares the flexibility properties of the third flexure zone 44, as described above. The flexible thermal heating element can be an active flexible electrode. In addition to imparting the desired flexibility, materials that are also conductive are selected. Active flexible electrodes can be made from flexible conductive wires or tubes, laser-cut conductive tubes, coiled conductors, or multiple filament brush electrodes. Alternatively, the flexible thermal heating element 90 is a flexible thermal heating element that may be made from an electrically insulating resistant metal that heats when delivered through an electric current. The flexible thermal heating element 90 is sufficiently flexible along its entire length to adapt closely to the vessel wall, thereby further increasing the active surface area of the thermal heating element that may be possible. increase. The flexible thermal heating element 90 also deflects more easily away from the vessel wall when engaging the vessel wall head-on, thereby causing the flexible thermal heating element 90 to side with the vessel wall. The force exerted on the vessel wall when placed in a square relationship can be minimized. The flexible thermal heating element 90 is thereby considered to be more non-traumatic.

0208In an exemplary embodiment, the active flexible electrode 90 further comprises a tapered distal region, preferably to form a smooth non-traumatic end surface 48. The end surface 48 can be formed from metallic material by laser, resistance welding, or machining techniques. The end surface 48 may also be formed from a polymeric material by bonding, laminating, or insert molding.

0209C. Third Representative Embodiment (Third flexure area includes a substantially spherical active electrode) 18A-18C show a representative embodiment of an elongated shaft 16 including a proximal force transfer section 30, a first flexure zone 32, a second flexure zone 34, and a third flexure zone 44. .. In this embodiment, the material, size, and composition of the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34 are with their respective counterparts in the first and second embodiments. It is about the same.

0210In this embodiment, however, the third flexure area 44 is sized to carry at least one substantially spherical active electrode 92 at a location more proximally spaced from its distal end. It is configured that way. Alternatively, the at least one active electrode 92 may optionally have a substantially cylindrical configuration such that the active electrode is a strip electrode, while the preferred substantially spherical of the at least one active electrode 92. The configuration is expected to advantageously reduce the electrical edge effects that may be encountered during the more abrupt transitions present at the relatively sharp edges of the periphery of the cylindrical electrode. For the purposes of the present invention, substantially spherical electrodes include electrodes that project outward from an elongated shaft 16 and have rounded edges. Thus, a substantially spherical electrode can be spherical, oblong, ellipsoidal, cylindrical with rounded edges, complex contouring, and the like.

0211In this embodiment, the third flexion zone 44 shares the flexibility features of the third flexure zone 44 described for the previous embodiment. In terms of diameter, the third flexure zone 44 of the third representative embodiment shown in FIG. 18 is sized to be less than or approximately equal to the diameter of the second flexure zone 34, as such. It may be configured. In diameter, the at least one spherical active electrode 92 is sized larger than the diameter of the third flexure zone 44. Therefore, the deflection of the third deflection area 44 allows the spherical electrode 92 to be placed in contact with a larger tissue area, thereby increasing the active surface area (ASA) of the electrode.

0212In an exemplary embodiment, the third flexion area 44 preferably comprises a tapered distal region to form a smooth non-traumatic end surface 48. The end surface 48 can be formed from metallic material by laser, resistance welding, or machining techniques. The end surface 48 may also be formed from a polymeric material by bonding, laminating, or insert molding.

0213At least one spherical electrode 92 may be attached to the distal flexion area 44 by, for example, crimping, heat shrinkage, molding, spot welding, laser welding, or soldering techniques. The placement of at least one spherical electrode 92 along the length of the third flexure zone 44 can be different. It may be placed, for example, in the approximately intermediate region of the third flexion area 44, closer to the distal end than to the proximal end, or vice versa.

021418A and 18B illustrate a third embodiment having a single spherical electrode 92. However, if desired, any number of additional spherical electrodes 92 may be provided along the third deflection zone 44. For example, FIG. 18C illustrates a third embodiment having three spherical electrodes 92 positioned along the length of the third flexure zone 44. In some embodiments, the one or more spherical electrodes 92 can be further or alternatively placed along the second flexure zone 34, as described herein below.

0215D. Fourth Representative Embodiment (Third flexure area includes a substantially hemispherical active electrode) 19A-19C show a representative embodiment of an elongated shaft 16 including a proximal force transfer section 30, a first flexure zone 32, a second flexure zone 34, and a third flexure zone 44. .. In this embodiment, the material, size, and composition of the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34 are the first, second, and third embodiments, respectively. It is about the same as the corresponding product of.

0216In this embodiment, however, the third flexure zone 44 is sized to carry at least one substantially hemispherical active electrode 92a at a location more proximally spaced from its distal end. , So configured. The hemispherical active electrode is attached to the third flexion zone 44 so that it is directed towards the target tissue in the deflected configuration of the third flexure zone. While the at least one active electrode 92a may optionally include a substantially semi-cylindrical configuration, the preferred substantially hemispherical configuration of the at least one active electrode 92a is advantageously semi-hemispherical. It is expected to reduce the electrical edge effects that may be encountered at the relatively sharp edges of the periphery of the cylindrical electrode. For the purposes of the present invention, substantially hemispherical electrodes include electrodes that project outward from one side of the elongated shaft 16 and have rounded edges. Thus, a substantially spherical electrode can be hemispherical, semi-elliptical, semi-ellipoid, semi-cylindrical with rounded edges, complex contouring along one side of the shaft 16 and the like.

0217In this embodiment, the third flexure zone 44 shares the flexibility features of the third flexure zone 44 described with respect to the previous embodiment. In terms of radius, the third flexure zone 44 of the third representative embodiment shown in FIG. 19 is sized and configured to be approximately equal to the radius of the second flexure zone 34. At a radius (ie, from the center of the cross section of the third flexure zone 44), at least one hemispherical active electrode 92a is sized larger than the radius of the third flexure zone 44. Thus, the deflection of the third deflection area 44 allows the hemispherical electrode 92a to be placed in contact with a larger tissue area, thereby increasing the active surface area (ASA) of the electrode. The use of the hemispherical electrode 92a, rather than the use of the spherical electrode 92, is expected to increase the ASA to TSA ratio of the electrode.

0218In an exemplary embodiment, the third flexion area 44 preferably comprises a tapered distal region to form a smooth non-traumatic end surface 48. The end surface 48 can be formed from metallic material by laser, resistance welding, or machining techniques. The end surface 48 may also be formed from a polymeric material by bonding, laminating, or insert molding.

0219At least one hemispherical electrode 92 may be attached to the distal flexion area 44, for example, by spot welding, laser welding, or soldering techniques. The placement of at least one spherical electrode 92 along the length of the third flexure zone 44 can be different. It may be placed, for example, in the approximately intermediate region of the third flexion area 44, closer to the distal end than to the proximal end, or vice versa.

022019A and 19B illustrate a fourth embodiment having a single hemispherical electrode 92. However, if desired, any number of additional hemispherical electrodes 92 may be provided along the third flexure zone 44. For example, FIG. 18C illustrates a fourth embodiment having three hemispherical electrodes 92 positioned along the length of the third flexure zone 44. Several embodiment mounds, one or more hemispherical electrode 92, as will be described later herein, it can be further or alternatively arranged along a second flexure zone 34.

0221E. Fifth Representative Embodiment (Third flexure area includes a multifilament brush active electrode) 20A and 20B show typical embodiments of the elongated shaft 16 including the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34, and the third flexure zone 44. .. In this embodiment, the material, size, and composition of the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34 are comparable to their respective counterparts in the aforementioned embodiments. ..

0222In this embodiment, however, the third flexure zone 44 is sized and configured to carry a brush active electrode 96 having a plurality of filaments at its distal end. In diameter, the brush electrode 96 is sized and configured such that it is greater than or equal to the second flexion zone 34. The diameter of the brush electrode 96 and the large number of filaments increase the total surface area TSA of the brush electrode 96 so that the potential active surface area of the electrode 46 is increased as well.

0223Also, in this scheme, the overall length of the brush electrode 96 shares or is more flexible than the flexibility property of the third flexure zone 44, as described above. In addition to imparting the desired flexibility, materials that are also conductive are selected. The brush electrode 96 is thereby sufficiently flexible along its entire length to adapt closely to the vessel wall, of which the individual filaments of the electrode are independently deflected and adapted to the wall. And thereby further increasing the potential active surface area of the electrode.

0224Compared to the aforementioned embodiment of the electrode 46, the filament of the brush electrode 96 can more easily deflect away from the vessel wall when engaging the vessel wall head-on, thereby causing the electrode 96 to deflect away from the vessel wall. Reduces the force exerted on the vessel wall when placed in contact. The multifilament brush electrode 96 can thereby be considered non-traumatic and can reduce the need for a third flexure zone 44 (eg, if a third flexure zone 44 is not provided, the brush electrode 96 will Can be connected to the distal end of 2 flexion areas 34). In addition, the increased TSA of the brush electrode 96 may enhance heat transfer due to active (eg, via injected thermal fluid) or passive (eg, via blood flow) cooling of the electrode. , It may facilitate the delivery of higher power electric fields through the electrodes, while reducing damage to non-target tissues of the renal vasculature due to heat-induced regulation of the target renal nerve.

0225F. Sixth Representative Embodiment (Third flexure area includes off-axis force redistribution) 21A, 21B, and 21C show typical embodiments of the elongated shaft 16 including a force transfer section 30, a first flexure zone 32, a second flexure zone 34, and a third flexure zone 44. .. In this embodiment, the material, size, and composition of the proximal force transfer compartment 30, the first flexure zone 32, and the second flexure zone 34 are comparable to their respective counterparts in the aforementioned embodiments. ..

0226In this embodiment, however, the third flexion zone 44 buckles or buckles in the first and / or second flexure zone while reducing vessel wall contact force as compared to some of the aforementioned embodiments. It is sized and configured to encourage bending. This can be achieved by an off-axis flexion 49 that positions the normal force vector applied between the third flexion area and the vessel wall, off-axis from the longitudinal axis of the elongated shaft 16. Off-axis flexion 49 is applied to i) shift the axial load on the catheter strut to an eccentric and / or lateral load, ii) to promote buckling of the catheter shaft. Trauma by means of reorienting forces, iii) reducing the pressure exerted on the renal artery wall by increasing the surface area, and / or iv) facilitating diversion around sharp flexions. The risk can be reduced. It should be understood that the term off-axis flexion can be used interchangeably with force turning elements, or preformed shapes.

0227For example, as shown in FIG. 21, the flexible structure 74, polymer coating or packaging 110 of the third flexure zone 44 can include an off-axis bend 49 in an unconstrained configuration. The physical and physical characteristics of the flexible structure 74 are that the axial and torsional stiffness of the flexible structure 74 is less than or equal to the axial and torsional stiffness of the third tubular structure 62. The overall flexibility of the flexible structure 74 is at least equal to, preferably it, the flexibility of the third tubular structure 62 when the third tubular structure is not deflected by the control wire 40. Selected to be greater than. Alternatively, the force diversion element 49 is made from a wire or tube with the desired flexibility incorporated into the force damping section 44 using material selection and dimensions, a third flexure zone 44. May be a bend in. For example, force damping compartment 44 may be made from nitinol wire with a diameter of about 0.10 to 0.20 mm.

0228Curvature or off-axis flexion of the flexible structure 74 in an unconstrained configuration (as shown in FIGS. 21A and 21B) causes the third flexure area 44 to vascularize as the catheter advances within the renal artery. The normal force vector exerted when engaging the walls is positioned misaligned with the axes of the first flexure zone 32 and / or the second flexure zone 34. It is expected that this positioning of the normal force vector may reduce the vascular contact force required to cause buckling or flexion of the first and / or second flexion areas, which also to the vessel wall. The risk of applying traumatic force can be reduced. Further / alternative, such a second flexion area establishes contact and treatment on the angularly opposed luminal surface of the renal artery without the need for rotation of the elongated shaft 16. Can be promoted.

0229A simplified example (as shown in FIG. 21D) with a virtually rigid and straight catheter 300 follows for the purpose of considering the force interactions between the catheter and the arterial wall. As detailed below, variables such as catheter flexibility, dimensions, and shape represented by the present invention modify force interactions. Every force has both magnitude and direction. The magnitude of the force applied by the virtually rigid, straight catheter to the arterial wall is essentially equal to the force applied by the caregiver to advance the catheter into the body. In this example, an essentially straight and rigid catheter advances into the renal artery by pushing the proximal end of the catheter, and therefore the catheter's forward trajectory is translational along the axis of the catheter. Therefore, the direction of force applied by the catheter to the arterial wall is forward along the axis of the catheter. In this simplified example, the arterial wall is represented by an elastic wall with maximum dilation and wall strength. The forces exerted by the arterial wall are characterized by their ability to withstand swelling and puncture of the arterial wall (a function of elasticity and strength), the normal force, which is a component perpendicular to the surface, and the arterial wall and catheter. Includes components parallel to the arterial wall surface, characterized by friction with the surface.

0230A straight catheter shaft is similar to a strut that can withstand a significant load along its axis before deformation. The load applied to the sides of the stanchion bends it with less force than the axial load. A load that is parallel to the strut but applied at a distance from its axis, an eccentric load, buckles the strut with a load less than the axial load. The more eccentric the load, the less force is required to buckle the stanchions. A specially constructed force that redirects element 49 so that the load applied to all parts of the distal end region 20 is eccentric as the distal tip advances into the renal artery wall. , Pull the distal tip of the catheter off the axis. In particular, the load applied to the force damping section 44 forms an angle with the axis, thereby facilitating deformation or buckling of the force damping section 44, and the load applied to the deflectable section is eccentric. , Buckle it as shown in Figures 21F and 21G. Therefore, the distal end region 20 is configured to deform under a load that is less than the pressure that can be applied to the arterial wall that causes excessive trauma, thereby reducing the risk of trauma to the renal artery wall. .. Examples of distal end regions 20 with different embodiments of force diversion elements 49 are shown in FIGS. 21H-21L.

0231In addition, the pressure applied to the arterial wall by the catheter is the force divided by the area of contact. As long as the tip of the catheter touches the arterial wall, the pressure is equal to the force divided by the contact surface area of the tip. As shown in FIG. 21F, when the catheter contacts the arterial wall over a large contact surface area SA, such as along the sides of the energy delivery element 24 and force damping compartment 44, the pressure is divided by the area where the force is much larger. Therefore, it is greatly reduced. For example, the pressure exerted by a catheter with a 0.049 "diameter tip is approximately 75% greater than the pressure exerted by the force diversion element 49 distributed over the length of the distal assembly.

0232In some embodiments, the force diversion element 49 and the force damping section 44 have the same structure, where the force diversion element is flexed in the force damping section 44, as shown in FIGS. 21H and 21J. Or it is curved. Alternatively, the force diversion element can be two bends or curves that occur in the two force damping compartments 44, as shown in Figures 21I and 21K, or the force diversion element can be in Figure 21L. As shown in, the distal tip 57 of the energy delivery element 24 can be flexed or curved in any number and combination that pulls it away from the axis of the elongated body 16.

0233In other embodiments, the force diversion element 49 and the force damping section 44 can comprise separate structures. For example, as shown in FIG. 21N, the force diversion element 49 is a wire or tube with an angular bend performed. The force diversion element may be connected to a separate force damping section 44, which is a spring coil in FIG. 21N.

0234Referring to FIG. 21H, the force diversion element 49 is between about 135 ° and 170 °, eg, an angular bend with an angle α4 of about 160 ° or less, and between about 0 mm and 1 mm. For example, a radius RoC4 with a curvature of about 0.25 mm or less can be provided. The force diversion element 49 may be positioned along the force damping section 44 within about 0 mm to 2 mm, eg, about 0.25 mm or less, from the proximal end of the force damping section 44. The length of the distal assembly 53 distal to the force diversion element 49 can be between 3 mm and 10 mm, for example about 5 mm or less.

0235Referring to FIG. 21I, the force diversion element 49 has a first angular bend with an angle α5 and a radius of curvature RoC5, and a second angular bend with an angle α6 and a radius of curvature RoC6. An angular bend can be provided, where the angles α5 and α6 are between 135 ° and α6, for example about 145 ° or less, and the radii of curvature RoC5 and RoC6 are between 0 mm and 2 mm. For example, it is about 0.25 mm or less.

0236As shown in FIGS. 21J and 21K, the force turning element 49 of the first representative embodiment can comprise one or two curves. The force turning element 49 may be a bending force damping section 44.

0237As shown in FIG. 21K, the force diversion element 49 comprises any preformed shape that positions the distal end of the catheter with respect to the axis of the deflectable section 34 at an initial set angle α7 and a distance L7. Here, the initial setting angle α7 is between about 15 ° and 45 °, for example, about 20 ° or less, and the distance L7 is between about 1 mm and 6 mm, for example, about 2 mm or less.

0238The force diversion element described above can be oriented such that the energy delivery element 24 is offset in a direction approximately opposite and in the same plane as the deflection of the deflectable compartment 34 with a predetermined bias. There is sex. Alternatively, the force diversion element can be oriented such that the energy delivery element 24 is offset in a direction that is approximately the same direction and plane as the deflection of the deflectable compartment 34 that has been given a predetermined bias. There is.

0239G. Seventh Representative Embodiment (Second flexure area includes preformed form) 22A-22K are representative of a seventh embodiment having an elongated shaft 16 including a force transfer section 30, a first flexure zone 32, a second flexure zone 34, and any third flexure zone 44. Embodiment is shown. In these embodiments, the material, size, and composition of the force transfer section 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments, respectively. It is about the same as the corresponding product of.

0240In these embodiments, however, the second flexure zone 34, in an unconstrained configuration, has a preformed or shaped force diversion element 49 that is off-axis or deflected from the longitudinal axis of the elongated shaft 16. A third tubular structure 62 may be provided (see, eg, FIGS. 22A and 22B), which may facilitate the positioning of the energy delivery element 24 in contact with the therapeutic site within the renal artery. The length and diameter of the second flexure zone 34 may be comparable to that described in any of the previous embodiments of the second flexure zone 34. In one embodiment, the preformed form of the third tubular structure 62 has a radius RoC2 and an angle α2 (see FIG. 7C) of desired curvature, such as those described above, in the second flexure zone 34. Can be specified to provide. In other embodiments, the preformed form can take other morphological and dimensional forms. The third tubular structure 62 may be made from a shape memory material such as, for example, a nickel-titanium alloy (ie, nitinol) or from spring steel to provide a preformed form.

0241The second flexion area 34 may be positioned within a guide catheter, such as a guide catheter 96, when advanced in and withdrawn from the renal artery via an intravascular route. During intravascular delivery and recovery, the third tubular structure 62 may be substantially aligned or constrained. After advancing the second flexion area 34 distal to the guide catheter, the third tubular structure 62 was off-axis, for example, to carry the energy delivery element 24 in contact with the wall of the renal artery. The preformed form may be exhibited again. The second flexure zone 34 can optionally be actively deflected in addition to the passive deflection provided by the preformed form of the third tubular structure 62 (eg, as described above, the handle invoker. (Via control wire 40 attached to 260). Alternatively, the deflection of the second flexure zone 34 is completely passive (ie, may be entirely due to the preformed form of the third tubular structure), with respect to the wire 40 and the trigger 260. The need can be reduced.

02421. Active deflection in the direction of the preformed form When the second flexure zone 34 is configured for both active and passive deflection, the third tubular structure 62 will have the active deflection of the second flexure zone of the third tubular structure. It may be configured to be urged in the direction of the preform. This can be achieved by making the third tubular structure 62 compressible in the direction of the preformed form of the structure and elastic against compression on the opposite side of the preformed form of the structure. In such a configuration, active deflection complements and extends the passive deflection provided by the preformed form of the third tubular structure.

0243FIG. 22C provides a representative embodiment of a second flexure zone 34 having a preformed form and configured for active deflection in the direction of the preformed form. In FIG. 22C, the third tubular structure 62 comprises a laser cutting pattern, including a back 66 with connecting ribs 68. The dorsal 66 comprises a preformed form that positions the second flexure zone 34 in an unconstrained configuration so as to be off-axis or deflected from the longitudinal axis of the elongated shaft 16. The preformed orientation is a third towards the preformed orientation in response to a pull on the control wire 40 where the laser cutting pattern is connected to the distal end of the third tubular structure 62. The direction is such that it biases the active deflection of the tubular structure 62. The control wire 40 is attached with solder 130 to the distal end of the second flexion area.

02442. Active deflection in the opposite direction of the preform for bidirectional deflection via a single control wire As an alternative to the embodiment of FIG. 22C, when the second flexure zone 34 is configured for both active and passive deflection, the third tubular structure 62 is active in the second flexure zone. The target deflection may be configured to be urged in a substantially opposite direction to the preformed form of the third tubular structure. This can be achieved by making the third tubular structure 62 compressible in the direction opposite to the preformed form of the structure and elastic with respect to compression in the direction of the preformed form of the structure. it can. In such a configuration, active deflection reduces or reverses the passive deflection provided by the preformed form of the third tubular structure.

0245FIG. 22D provides a representative embodiment of a second deflection zone 34 having a preformed form and configured for active deflection in the opposite direction of the preformed form. In FIG. 22D, the third tubular structure 62 again comprises a laser cutting pattern, including a back 66 with connecting ribs 68. As in the embodiment of FIG. 22C, the dorsal 66 preforms to position the second flexure zone 34 in an unconstrained configuration so as to be off-axis or deflected from the longitudinal axis of the elongated shaft 16. Have a shape. However, in contrast to the embodiment of FIG. 22C, the preformed orientation responds to a pull on the control wire 40 where the laser cutting pattern is connected to the distal end of the third tubular structure 62. , A direction away from the preformed direction that biases the active deflection of the third tubular structure 62.

0246As shown in FIGS. 22E-22G, when the second flexure zone 34 has a preform and is configured for active deflection in the opposite direction of the preform, the second The flexure area can preferably achieve bidirectional flexion via a single control wire 40. As shown in FIG. 22E, in an unconstrained configuration of the second flexure zone 34 without active deflection (eg, when the control wire 40 is not pulled in tension), the second flexure zone 34 exhibits a preformed form of its third tubular structure 62. As shown in FIG. 22F, the tension applied to the control wire 40 partially or completely aligns the bend in the second flexure zone 34. As shown in FIG. 22G, in some embodiments, further pulling of the control wire 40 (ie, proximal retraction) directs the second flexion area to the opposite side of its preform. It can be deflected, thereby providing bidirectional bending of the second flexion area by a single control wire 40.

0247Optionally, the control wire 40 delivers / recovers the preformed form of the second flexion area 34 during delivery and / or recovery of the energy delivery element 24 within the renal artery, as shown in FIG. 22F. Can be under tension to align at least partially in. When positioned within the renal artery, tension forces the energy delivery element 24 to contact the wall of the renal artery, so that the second flexion area is oriented in its preformed form, as shown in FIG. 22E. It may be removed from the control wire 40 to deflect it. Further or alternately, the control wire 40, as shown in FIG. 22G, to carry the energy delivery element 24 in contact with the opposing wall of the renal artery without requiring the rotation of the elongated shaft 16. The second flexure area may be pulled more proximally to deflect it in the opposite direction of its preform. As mentioned above, the third flexion area 44 is preferably passively deflected in response to contact with any wall of the renal artery to bring the energy delivery element 24 to at least a portion of the wall of the artery to be contacted. It is held so that it aligns with the other, thereby responding to the bidirectional deflection of the second flexure area 34.

02483. Active deflection in any desired direction in combination with the preformed form Figures 22C-22G exemplify a representative embodiment of the second flexure zone 34, which is configured for both active and passive deflection of the second flexure zone, where the active deflection is It is either in the direction of passive deflection (ie, the direction of the preformed form of the second flexure zone) or in opposition to it. However, in other contemplated embodiments, the active deflection of the second flexion zone may be in any plane (s), if desired, in the preformed direction or in the preformed form. It should be understood that it is not limited to active deflection in the opposite direction of.

02494. Active deflection that deviates from the preformed form in the longitudinal direction In FIGS. 22C-22G, the active and passive deflections of the second deflection zone occur along a common longitudinal segment. Active and passive deflections can be alternative / further longitudinally separated or offset from each other. For example, the second flexion area 34 may comprise a more proximal section configured for active deflection, a more distal section having a preformed form, or vice versa. Active deflection can occur in the direction of the preform, in the opposite direction of the preform, or in any other direction, if desired.

0250FIG. 22H illustrates a representative embodiment of a second flexion zone 34 having a more proximal section configured for active deflection and a more distal section having a preformed form. The more proximal section of the second flexion area 34 is exemplifiedly constructed for active deflection in the opposite direction of the preform form of the more distal section. However, it should be understood that the preformed form may be alternatively directed in the direction of active deflection or in any other direction.

0251As shown in FIG. 22H, the third tubular structure 62 comprises a laser cutting pattern, including a dorsal 66 with connecting ribs 68. In contrast to the embodiments of FIGS. 22A-22G, the solder 130 places the control wire 40 into a third tubular structure 62 proximal to the distal end of the second flexion area, eg, a third tubular. Connect at the distal end of the more proximal section of structure 62 and / or at the proximal end of the more distal section of the third tubular structure. Distal of the attachment of the control wire 40 to the third tubular structure 62, the dorsal 66 comprises a force diversion element 49 with a preformed off-axis shape. The laser cutting pattern of the third tubular structure is on the opposite side of the preformed form in response to a pull on the control wire 40 connected to the third tubular structure 62 proximal to the preformed form of the dorsal. Toward, bias the active deflection of the third tubular structure 62.

0252Then referring to FIGS. 22I-22K, the second flexure zone 34 has a more proximal section configured for active deflection in the opposite direction of the preform form of the more distal section. When, the second flexion zone can facilitate buckling in the first or second flexure zone, preferably while reducing the contact force applied to the vessel wall by the energy delivery element 24, which is traumatic. It can provide lower treatment and / or reduce the need for any third flexion area 44. Further / alternative, such a second flexion area establishes contact and treatment on the angularly opposed luminal surface of the renal artery without the need for rotation of the elongated shaft 16. Can be promoted.

0253As shown in FIG. 22I, in an unconstrained configuration of the second flexure zone 34 without active deflection (eg, when the control wire 40 is not pulled in tension), the second flexure zone The 34 more distal compartments exhibit the preformed form of its third tubular structure 62. As mentioned above, when positioned within the renal artery, the first flexion area 32 may be located along or near the surface of the upper wall of the renal artery (see, eg, FIG. 7E). .. As shown in FIG. 22J, when not actively deflected, the preformed form of the more distal segment second flexion zone has the energy delivery element 24 and any third flexure zone 44 on its wall surface. Can be encouraged to contact with. The aforementioned passive deflection of any third flexure zone can align the energy delivery element 24 with the top wall surface at least in part, as shown.

0254As shown in FIG. 22K, the tension applied to the control wire 40 makes the more proximal section of the second flexure area 34 in the opposite direction of the more distal preform, eg, Bend towards the inner kidney of the artery. The preformed form allows the energy delivery element 24 to contact the inner surface at a lower contact angle (ie, less than perpendicular to the surface) than would otherwise be contacted without the preformed form. , Thereby reducing the buckling force applied to the heating element (eg, to the heating element and / or to any third flexion area 44), and the puncture force applied to the vessel wall, which is less Traumatic treatment may be provided and / or the need for any third flexion area 44 may be reduced. The aforementioned passive deflection of any third flexure zone can align the energy delivery element 24 with the surface of the inferior wall at least partially, as shown. Figures 22J and 22K illustrate the establishment of contact and treatment at the angularly opposed luminal surface of the renal artery without the need for rotation of the elongated shaft 16.

0255H. Eighth Representative Embodiment (The force diversion element is configured to facilitate multi-directional access) 23A-23G show a representative embodiment of an eighth embodiment having an elongated shaft 16 including a force transfer section 30, a first flexure zone 32, and a force damping section 44 with a force diversion element. .. In these embodiments, the material, size, and configuration of the force transfer section 30, the first flexure zone 32, the force damping section 44, the force diversion element 49, and the energy delivery element 24 are any of the previous embodiments. It is comparable to their respective counterparts described in.

0256However, in the eighth representative embodiment, the force damping section 44 and the force diversion element 49 are arranged so that the energy delivery element 24 can be placed in contact with the inner wall of the renal artery at various locations. It is configured to deflect 24 in multiple directions. In such an embodiment, the force diversion element 49 comprises a number of (ie, more than one) bends. For example, flexions 49'and 49'' are separated along the axis of the catheter, as shown in FIG. 23D. The eighth embodiment is configured to advance into the renal artery while being retracted in the delivery sheath 95. When the distal assembly is retracted in the delivery sheath, the force damping compartment 44 and the force diversion element 49 are flexible and adapt to the delivery sheath (see Figure 23B). When the distal assembly advances to the desired depth in the renal artery, the delivery sheath is elastically deformed to deflect the force damping compartment 44 at the first angle α8, the first of the force diversion elements 49. To expose the bend 49', it is pulled towards and pulls the energy delivery element 24 away from the axis of the elongated tubular body 16 in the first direction (see Figure 23C). When the delivery sheath is pulled toward to further expose the second bend 49'', the second bend elastically deforms, deflecting the force damping section 44 at the second angle α9 and delivering energy. Pull the element 24 away from the axis of the elongated tubular body 16 in a second direction (see Figure 23D).

0257When the force diversion element 49 is deployed in the renal artery, as shown in FIG. 23A, the energy delivery element 24 projects a force diversion from the delivery sheath, as shown in FIGS. 23E and 23F. Depending on the part of element 49, it may be composed of multiple angles α8 and α9 so that it is placed in multi-directional contact with the inner wall of the renal artery. The angles α8 and α9 can be greater than 90 ° to less than 180 °, such that the first angle α8 minus the second angle α9 is greater than 0 ° to less than 90 °, eg, the first angle. α8 can be between about 130 ° and 150 °, for example 140 ° or less, and the second angle α9 can be between about 90 ° and 130 °, for example about 110 ° or less. There is. The length of the force damping compartment 44 and the position of the force diversion element 49 are configured such that the energy delivery element 24 is placed in contact with the inner wall of the renal artery with a stable contact force. For example, the length of the energy delivery element 24 from the distal end can be approximately 8 mm to 11 mm (eg, 9.5 mm or less) up to the first flexion 49'including the force damping section 44. The first angle α8 can be about 130 ° to 150 ° (eg, 140 ° or less), and the length between the first and second angles is about 1.25 mm to 3 mm (eg, 1.5). The second angle α9 can be about 90 ° to 130 ° (eg, 110 ° or less).

0258Alternatively, the force diversion element 49, as shown in FIG. 23G, has a large number of three-dimensional force decay compartments 44, depending on the proportion of the force diversion element 49 protruding from the delivery sheath. It may be composed of a gradual curvature such as a spiral shape so that it is deflected in the direction. The force diversion element 49 in combination with the force damping compartment 44 is elastically deformed as the force diversion element 49 advances from the delivery sheath in its flexible and adapted retracted state, resulting in the force damping compartment 44. An energy delivery element 24 mounted on the distal end is configured to be placed in contact with the inner wall of the renal artery. For example, the force diversion element 49 has a spiral angle between about 20 ° to 50 ° (eg, 30 ° or less), a diameter of about 2 mm to 4 mm (eg, 3 mm or less), and about 0.5 to 3 turns. It can comprise a helical structure with (eg, one or less turns), and the force diversion element 49 is positioned approximately 7 mm to 11 mm (eg, less than 9.5 mm) from the distal end of the energy delivery element 24. There is a possibility of being

0259I. Ninth representative embodiment (the length of the force attenuation section may be adjusted by the telescope method) 24A-24D show a representative embodiment of a ninth embodiment having an elongated shaft 16 including a force transfer section 30, a first flexure zone 32, a force turning element 49, and a force damping section 44. .. In these embodiments, the material, size, and configuration of the force transfer section 30, the first flexure zone 32, the force turning element 49, the force damping section 44, and the energy delivery element 24 are any of the previous embodiments. It is comparable to their respective counterparts described in.

0260However, in a ninth representative embodiment, the force diversion element 49 is connected to the first flexure zone 32, and the force damping section 44 passes through the force diversion element 49 and the elongated tubular body 16, a tube. It comprises an elongated flexible wire or tube that is slidably housed in the lumen 17, so that the force damping section 44 advances the proximal end of the force damping section 44 through the lumen 17 to the lumen. It is pulled away from the distal opening of 17 in a telescopic manner. Similar to the previous embodiment, the force diversion element 49 is configured to flexibly adapt to the inner lumen of the guide catheter and elastically deflect to a predetermined angle when not constrained by the guide catheter. The force diversion element 49 is such that the force damping compartment 44 and the elongated tubular body buckle when the catheter is advanced along an axial trajectory and force is applied to the energy delivery element 24 by the contacting internal arterial wall. The energy delivery element 24 is provided with the above-mentioned angle that pulls the energy delivery element 24 away from the axis of the elongated tubular body 16 so that the orbit is modified to flow through the artery. The telescopically adjustable length of force attenuation compartment 44 may be shortened while the distal assembly 53 is advanced through the renal arteries. When the distal assembly advances to the desired distance in the renal artery, the force attenuation section 44 is extended in a telescope manner to facilitate contact between the energy delivery element 24 and the inner wall of the renal artery. there is a possibility.

0261The force direction change element 49 can deflect the force damping division 44 at an angle similar to the angle in the previous embodiment (angle α4 or the like shown in FIG. 7B). For example, the angle of the force turning element 49 can be between about 130 ° and 170 ° (eg, 160 ° or less). The minimum length of the force damping section 44 protruding distally from the bend of the force turning element 49 is also similar to the length L4 of the force damping section 44 in the previous embodiment (as shown in FIG. 7A). It may be. For example, the minimum protrusion length of the force damping section 44 may be between about 2 mm and 5 mm. The length of the force damping section 44 protruding from the distal opening of lumen 17 can be increased in a telescopic manner to a maximum between about 5 mm and 30 mm (eg, 20 mm below). Alternatively, the combination of angle α4 and length of the force damping section 44 protruding in a telescope manner can separate the energy delivery element 24 by a distance between about 1 mm and 15 mm from the axis of the elongated tubular body 16. ..

0262As shown in FIG. 24D, the force damping section 44 is such that when the force damping section 44 is advanced in a telescope manner, the load created by contact with the arteries is pulled away from the axis of the force damping section 44. A second force diversion element 49'that pulls the distal tip of the energy delivery element 24 away from the axis of the force damping compartment 44 can be further provided to facilitate buckling of the force damping compartment 44.

0263The force attenuation section 44 may consist of electrically insulated nitinol wires and conductors that carry, for example, energy and sensor signals to and from the energy delivery element 24, and the generator 26 may consist of electrically insulated nitinol wires and nitinol wires. May be held in the gap between and. The proximal end of the force damping compartment 44 may extend through the lumen to the proximal opening in the lumen of the elongated tubular body, where it is the force protruding from the distal opening of the lumen 17. The distal portion of attenuation compartment 44 may be manipulated to extend in a telescope manner. Alternatively, the proximal end of force damping compartment 44 may be operated by a trigger 260 in the handle 200.

0264J. Tenth Representative Embodiment (Second flexure zone promotes controlled multi-directional deflection) Figures 25A-25W typically have an elongated shaft 16 that includes a force transfer section 30, a first flexure zone 32, a second flexure zone 34, an energy delivery element 24, and any third flexure zone 44. An embodiment is shown (see Figure 25A). In these embodiments, the material, size, and composition of the force transfer section 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments, respectively. It is about the same as the corresponding product of. Further, the length and diameter of the second flexure zone 34 in the embodiment of FIG. 25 may be comparable to that described in any of the previous embodiments of the second flexure zone 34. Also, the controlled flexion of the second flexure zone 34 may provide the second flexure zone with a radius RoC2 and an angle α2 (see FIG. 7C) of desired curvature, such as those described above. Good.

0265However, in this embodiment of the invention, the second flexure zone 34 can facilitate controlled deflection in many different directions, eg, the second flexure zone can be controlledly deflected in many different directions. A large number of control wires 40 may be provided for this purpose. The controlled multi-directional flexion of the second flexion area may facilitate the placement of the energy delivery element 24 in stable contact with one or more treatment sites within the renal artery. Such control over the placement of energy delivery elements can be particularly useful in patients with relatively meandering blood vessels. For example, if the arrangement of the energy delivery element 24 in contact with the therapeutic site of the renal artery is less than optimal under the controlled flexion of the second flexion zone in the first direction, the second flexure zone is the energy. The delivery element can be controllably deflected in a second direction for more optimal placement in contact with the treatment site or alternative or additional treatment site. In addition, stable contact and energy delivery may be achievable at multiple treatment sites via controlled multidirectional deflection of the second flexion area.

0266In some typical embodiments, the second flexion area may have a center-positioned spine connected to a rib or surrounded by a coil, the center-positioned spine being controlled. It may have a shape that promotes the multi-directional bending. The second flexure area may include a number of peripherally positioned dorsal, connected by ribs, or a centrally positioned dorsal to facilitate controlled multidirectional flexion.

02671. Centered spine Figures 25B-25M provide a representative embodiment having a central dorsal and a second flexion zone 34 configured for controlled multi-directional flexion with a large number of control wires.

0268In the embodiments of FIGS. 25B and 25C, the second flexure zone is configured for controlled bidirectional flexion. As shown in the cross section of FIG. 25B, the third tubular structure 62 of the second flexure area 34 is a substantially flat or ribbon that substantially divides the third tubular structure in half. It has a shape (ie, the width of the back is significantly greater than its depth) and has a centered back 66. The diameter of the central lumen below the depth of the dorsal may be formed through the center of the dorsal 66 for the passage of the electrical transmission wire (s) and / or the sensor / thermocouple wire (s) 29. Alternatively, the wire (s) 29 can pass through a lumen defined by a centered spine 66 and rib 68.

0269The third tubular structure 62 may be made, for example, through electrical discharge machining (EDM), microfabrication, and / or extrusion to form a tube with a ribbon having a lumen, where the ribbon is , Divide the tube into two, as shown in Figure 25B. As shown in FIG. 25C, the laser cutting pattern is then spaced along the length of the tube extending over the opposite side of the dorsal 66 around the perimeter of the third tubular structure 62. In order to form the connecting ribs 68a and 68b at, the section of the ribbon-shaped tube can be removed along its length. The control wires 40a and 40b are attached with solder 130 to the distal end of the second flexion area on the opposite side of the spine 66 and are radially positioned between the spine 66 and the rib 68 in a third tubular structure. Move along the length of your body.

0270Alternatively, the deflectable compartment 34 may have a centered back 66 that is elastic to compression and is surrounded by a third tubular structure 62. The third tubular structure is compressible and may include a laser-cut hypo tube, a hollow coil with a loose pitch, a hollow cable, a braided shaft, and the like. The dorsal may be connected to 62 along the length of the third tubular structure, may be connected to the structure in only one or a few places (eg, at its distal end), or It may float or be friction-fitted within the coiled third tubular structure.

0271The shape of the dorsal 66, in combination with the shape of the ribs 68a and 68b and the distal mounting location of the control wires 40a and 40b, responds to, for example, pulling the wire 40a or 40b into a plane perpendicular to the width of the back. Promotes controlled bidirectional flexion of the second flexure area 34 by substantially constraining buckling or flexion of the dorsal 66. The second deflection zone deflects in the first direction in response to pull on the control wire 40a while the control wire 40b is not under significant tension (see Figure 25C). The second deflection zone deflects in the second opposing direction in response to the pull on the control wire 40b while the control wire 40a is not under significant tension.

0272Although FIGS. 25B and 25C illustrate an embodiment of bidirectional bending of the second flexion area 34, the third tubular structure 62 promotes bending in any number of directions as desired. , May be manufactured with a centered spine. Figures 25D-25J exemplify an embodiment of a second flexion zone with a centered back configured for controlled quadrulateral deflection. As shown in FIGS. 25G-25I, the third tubular structure 62 is arranged at an angle of about 90 ° from each other in an alternating pattern along the length of the third tubular structure. It comprises a centrally positioned back 66 with width, longitudinally spaced back ribbon compartments 66a and 66b. The centrally positioned lumen extends through the ribbon compartment along the length of the third tubular structure for the passage of the electrical transfer wire (s) and / or the sensor / thermocouple wire (s) 29. ing. Between each pair of back ribbon compartments 66a and 66b, the spine 66 extends radially outward to form a back ribbon connector compartment 66c connecting the pairs of back ribbon compartments.

0273In the embodiments of FIGS. 25G-25I, each connector compartment 66c has four sides or extensions extending to the outer circumference of the third tubular structure 62. The four sides or extensions have radial-most points that are located approximately 45 ° apart from the width of the ribbon compartments 66a and 66b. Connecting ribs 68a, 68b, 68c, and 68d connect each of the four sides or extensions of each connector compartment 66c at radial-most points to the level of each connector compartment 66c. To form an outer ring or loop.

0274The third tubular structure 62 therefore comprises a series of repeating segments along the length of the structure. Each repeating segment features a rib 68, a first connector section 66c; subsequently longitudinally, at an angle of 45 ° from the radial-most point of the side or extension of the first connector section 66c. Ribbon compartment 66a with widths that are staggered; subsequently, in the vertical direction, a second connector compartment 66c with ribs 68 (this second connector compartment is 45 ° angular from the width of the ribbon compartment 66a). Radial-most offset to and angularly aligned with the radial-most point of the side or extension of the first connector compartment 66c. Has a side or extension with a point); subsequently, longitudinally, the radial-most of the side or extension of the second connector compartment 66c. Ribbon compartment 66b with a width that is 45 ° angularly offset from point) and 90 ° angularly offset from the width of ribbon compartment 66a; subsequently in the vertical, repeating first connector. It has a category 66c; etc. The third tubular structure 62 of FIG. 25G may be made, for example, from a combination of EDM, micromachining, and / or extrusion, laser cutting with rib 68, 45 ° angularly from the width of ribbon section 66b. Radial-most points that are offset and angularly aligned with the radial-most points of the side or extension of the second connector section 66c. The same applies to the repeating first connector section; etc., which has a side or extension portion provided with).

0275Ribbon compartments 66a and 66b are preferably each connector such that the shape of the repeating segment of the third tubular structure 62 forms four longitudinal voids along the length of the third tubular structure. At the level of compartment 66c, it has a width that is less than the diameter of the third tubular structure 62 (eg, less than the diameter of the ring formed by the ribs 68). Two of the voids are substantially aligned with the width of the back ribbon compartment 66a, but are positioned outward in their radial direction, while the remaining two voids are substantially aligned with the width of the back ribbon compartment 66b. However, it is positioned outward in the radial direction. Therefore, the four voids are located approximately 45 ° apart from the radial-most point of the side or extension of the connector compartment 66c, i.e. the void is its side or extension. Extends to the outer circumference of the third tubular structure 62 and occupies the gap between the sides or extensions where the ribs 68 connect.

0276The control wires 40a, 40b, 40c, or 40d are positioned inside each of the voids along the length of the third tubular structure and are attached with solder 130 to the distal end of the second flexion area. Pulling over any one of the control wires while the other three control wires are not under significant tension is the controlled deflection of the second flexure area 34 in the direction of the wire being pulled. (Alternatively, any three control wires may provide a controlled deflection of the second deflection area in the opposite direction of the unpulled control wire. The control wire may be pulled while it is not under significant tension). In this aspect, the second flexure zone 34 is configured for controlled quadrulateral flexion in four directions, either arranged approximately 90 ° out of phase with each other or out of phase. May be done.

0277For example, as shown in FIG. 25H, the pull on the wire 40a buckles or bends the ribbon section 66a, which has a width in a plane perpendicular to the plane of the wire 40a, in the direction of the wire 40a. Provides a controlled bend in the direction of the wire 40a of the third tubular structure 62 and the second flexure area 34. Similarly, as shown in FIG. 25I, pulling on the wire 40b buckles or bends the ribbon compartment 66b in the direction of the wire 40b, in the second flexure zone 34 towards the wire 40b. Provides controlled bending. Conversely, pulling on wire 40c buckles or bends the ribbon compartment 66a (and thereby the second flexure zone 34) in the direction opposite to the direction achieved by wire 40a (not shown). ), The pull on the wire 40d buckles or bends the ribbon compartment 66b (and thereby the second flexure zone 34) in the direction opposite to the direction achieved by the wire 40b (not shown).

0278In some multidirectional deflection embodiments, such as those shown in FIGS. 25G-25J, the pulling on any two adjacent control wires is such that the remaining control wires are not under significant tension. A controlled deflection of the second deflection zone 34 may be provided that deviates from the direction achieved by pulling on any single control wire 40 or further out of phase. Virtually all of the alternating ribbon compartments 66a and 66b are expected to buckle or bend when the two adjacent wires are pulled. Ribbon compartments 66a are expected to bend in the direction of tension applied by the first control wire in their flexible and biased planes, while alternative ribbon compartments 66b are them. It is expected to bend in the direction of tension applied by the second adjacent control wire in the flexible and biased plane of. The alternating ribbon compartments bend in a direction that deviates from each other by about 90 °. The amount of bending of the alternating ribbon compartments 66a and 66b is proportional to the amount of tension applied by each respective control wire. The cumulative effect of bending both alternating ribbon compartments along the total length of the second flexure area 34 would be a bend in the direction between the two flexible and biased planes. In this mode, the second flexure zone 34 is further by pulling two adjacent control wires 40 in four directions by pulling one of the four control wires 40 and in equal or disproportionate tension. It may be configured for directional, controlled deflection.

0279As shown in FIG. 25D, the third tubular structure may be manufactured with a cross section of the back connector compartment 66c via EDM, microfabrication, and / or extrusion. As shown in FIG. 25F, the first side cross section of the third tubular member 62 is arranged at an angle of about 45 ° from the point where the inside of the third tubular structure connects to the outside of the tubular. Laser cutting in a plane can form a narrowing of the diameter at the level of the back ribbon section 66a, as well as the back ribbon section 66b. Similarly, as shown in FIG. 25E, the second of the third tubular member 62, perpendicular to the first side cross-sectional plane (ie, placed 90 ° angularly offset from it). Laser cutting in the lateral cross-sectional plane can form diameter narrowing at the levels of the back ribbon section 66b and the back connector section 66c, as well as the back ribbon section 66a. This provides four sides to the back connector compartment 66c, as shown in Figure 25G.

0280Next, referring to FIG. 25J, an alternative configuration of a third tubular structure configured for quadrudirectional controlled deflection (and, as mentioned above, when two adjacent control wires are pulled). Deflection in further directions) is described. In FIG. 25J, each of the back ribbon compartments 66a and 66b extends outward in the radial direction and extends along the back along only two sides or extensions extending to the outer circumference of the third tubular structure 62. Connect to connector compartment 66c. The two sides or extensions each have a radial-most point that is substantially aligned with the width of each of the ribbon compartments 66a and 66b. Connecting ribs 68a and 68b, 68c and 68d connect each of the four sides or extensions found in each connector compartment 66c (two such sides or extensions are the ribbon compartments 66a, respectively). And emanates from each of 66b and is approximately 90 ° out of phase with the other two sides or extensions), forming an outer ring or loop at the level of each connector compartment 66c.

0281The third tubular structure 62 therefore comprises a series of repeating segments along the length of the structure. Each repeating segment comprises a rib 68, a first connector section 66c; subsequently vertically, two of the lateral-most points of the side or extension of the first connector section 66c. Ribbon section 66a that is at an angle and has a width that is approximately 90 ° out of phase with the other two sides or extensions of the first connector section; followed by a second connection with rib 68 in the vertical direction. Child compartment 66c (this second connector compartment has four sides or extensions with four radial-most points, two of which are again with the width of ribbon compartment 66a. Aligned, the two are approximately 90 ° out of phase with the ribbon section 66a); then in the vertical direction, two radial directions of the side or extension of the second connector section 66c aligned with the width of the ribbon section 66a. Has a width that is 90 ° angularly offset from the radial-most point of, and is angular with the remaining two radial-most points of the second connector compartment 66c. Aligned to (angularly) Ribbon compartment 66b with aligned width; subsequently in the vertical direction, a repeating first connector compartment 66c with ribs 68 (this repeating first connector compartment has four radial-most radial-most). It has four sides or extensions with point), two of which are again aligned with the width of the ribbon section 66b and two are about 90 ° out of phase with the ribbon section 66b); etc.

0282In the embodiment of FIG. 25J, the two lumens extend near both ends of the width of each ribbon compartment and extend through each ribbon compartment 66a and 66b, respectively (ie, centered for the passage of wire 29). In addition to the lumens, a total of four such lumens). The control wire 40, as described above, has a controlled four-way deflection of the second flexure area 34 (and, as described above, a further directional deflection when the two adjacent control wires are pulled). May be sent through these lumens.

028325B and 25C illustrate a second flexure zone 34 with a centered back 66 configured for bidirectional controlled deflection, while FIGS. 25G-25I are quadrupedal. A second deflection zone with a centrally positioned back 66 configured for controlled deflection (and, as described above, further deflection when the two adjacent control wires are pulled). 34 is illustrated. The second deflection zone may optionally include a center-positioned back 66 configured for any number of further directional deflections, if desired. For example, additional ribbon compartments may be provided at additional angular deviations and connected by back connector compartments with additional sides (eg, 6-way flexion, as shown in FIG. 25K). For, three alternating back ribbon compartments are provided at a 60 ° angle shift and may be connected by a back connector compartment with six sides or extensions, the radial-most point of which. ) Is angularly aligned with the edge of the back ribbon section (in angular) alignment) extends to the outer circumference of the third tubular structure 62, resulting in six voids that deviate about 30 ° from the width of any back ribbon section). When combined with the appropriate ribs 68 and control wire 40, controlled deflection in any number of directions can be achieved. However, it is expected that the second flexure zone 34 may become increasingly rigid as the number of alternating ribbon compartments increases, which may impose a practical limit on the achievable number of controlled deflection directions. ..

0284Then, referring to FIGS. 25L and 25M, as an alternative to the second flexion area 34 with a third tubular structure 62 with a centered spine, combined with a laser cutting pattern forming connecting ribs. The second flexure zone 34 may include a center-positioned spine 66 surrounded by coiling a third tubular structure 62. The coiled third tubular structure can increase the flexibility of the second flexure area 34. The coiled third tubular structure may include a laser cutting hypo tube, a hollow coil, a hollow cable, a braided shaft, and the like. The dorsal may be connected to a coiled third tubular structure 62 along its length, or may be connected to the structure in only one or a few places (eg, at its distal end). Well, it may float or be friction-fitted within a third tubular structure that is coiled.

0285The spine 66 may have any of the spines found in FIGS. 25B-25K (eg, may be flat or ribbon-like, as shown in FIGS. 25B and 25C, or as shown in FIGS. 25G-25K. As desired, it may be provided with alternating ribbons that are angularly offset), or optionally, optionally, to facilitate controlled deflection in any number of directions. It may be provided with a further number of alternating ribbons. The spine may be made, for example, via EDM, micromachining, and / or extrusion, and may be provided with a laser cutting pattern that increases flexibility along its length. The spine may alternate along its length, for example, in a spiral laser cutting pattern.

0286In FIGS. 25L and 25M, the second deflection zone 34 is exemplarily constructed for controlled bidirectional deflection. The spine 66 has a flat or ribbon-shaped spine, and a coiled third tubular structure 62 surrounds the spine. The control wires 40a and 40b are attached with solder 130 to the distal end of the second flexion area on the opposite sides of the back 66. As in the embodiments of FIGS. 25B and 25C, while the control wire 40b is not under significant tension, the pull on the control wire 40a (see FIG. 25M) first sets the second flexure area 34. Deflection in the direction of. The second deflection zone deflects in the second opposing direction in response to the pull on the control wire 40b while the control wire 40a is not under significant tension.

0287The multi-directional deflection, including embodiments, may further include a third flexion zone 44 comprising the flexible structure 74 described above.

0288The alternative multi-directional motor 260 may include a multi-directional joystick connected to a large number of control wires, as shown in FIG. 25W. Alternatively, one or more bidirectional triggers may be provided, each for triggering in two directions in a given plane.

02892. Externally positioned spine Figures 25N-25S show an elongated shaft 16 comprising a proximal force transfer section 30, a first or proximal flexion zone 32, a second or intermediate flexure zone 34, and any third or distal flexure zone 44. A typical embodiment of the second embodiment is shown. In these embodiments, the material, size, and configuration of the proximal force transfer compartment 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments. It is comparable to their respective counterparts.

0290In these embodiments, however, the second flexion zone 34 may comprise a third tubular structure 62 having two or more peripherally positioned backs 66. As described in more detail above, a multi-directional preferential deflection of the second deflection zone is desirable. This can be achieved by making the third tubular structure 62 compressible in the desired deflection direction and elastic against compression along a plane perpendicular to the deflection. In this embodiment, such variable compressibility is elastic to compression, but still flexible enough to bend in the biased compressible direction, two. This is achieved by the above-mentioned externally positioned spine. The two externally positioned spines that are elastic to compression form a plane that is elastic to compression and passes through the two externally positioned spines. 25N-25S have a second deflection area 34 with a large number of externally positioned backs and control wires 40 configured for controlled multi-directional bending, a second embodiment. A typical embodiment of the above is illustrated.

0291In the embodiments of FIGS. 25N and 25O, the second flexure zone 34 is configured for controlled bidirectional flexion. As can be seen in the cross section of FIG. 25N, the third tubular structure 62 of the second flexure area 34 has the outer circumference of the third tubular structure on both sides of the third tubular structure and around the outer circumference. Positioned at, divided into halves connected by connecting ribs 68a and 68b, respectively, angularly opposed (ie, arranged approximately 180 ° angularly offset), perimeter It comprises a laser cutting pattern that forms the positioned dorsal 66a and 66b. The connecting ribs 68a and 68b each span an arched segment of approximately 180 ° around the perimeter of the third tubular structure. The control wires 40a and 40b are arranged angularly offset from the backs 66a and 66b on the opposite sides of the third tubular structure 62, respectively, and are attached with solder 130a and 130b to the distal ends of the second flexure area. Be done.

0292The width of each dorsal 66a and 66b limits the deflection in the dorsal direction (ie, limiting the deflection in the plane containing the two dorsals), while limiting the deflection in the rib 68a and 68b directions of the third tubular structure 62. Each cannot be significantly greater than the depth of each back (eg, the width of each back can be less than or equal to that depth) to facilitate bidirectional deflection towards. Optionally, ribs 68a on the first side of the third tubular structure 62 may alternate with ribs 68b on the opposite side of the third tubular structure along the length of the structure. Well, it can increase flexibility and / or promote controlled deflection of the second flexure area 34.

0293The shapes of the dorsal 66a and 66b, as well as the ribs 68a and 68b, combined with the distal angularly offset mounting locations of the control wires 40a and 40b, both controlled in the second flexure area 34. Promotes directional flexion. The second deflection zone deflects in the first direction in response to pull on the control wire 40a while the control wire 40b is not under significant tension (see Figure 25O). The second deflection zone deflects in the second opposing direction in response to the pull on the control wire 40b while the control wire 40a is not under significant tension.

029425N and 25O illustrate an embodiment of bidirectional bending of the second flexion area 34, where the third tubular structure 62 facilitates bending in any number of directions, if desired. It may be made by adding additional peripherally positioned spines connected by ribs and by adding additional control wires. For example, FIGS. 25P and 25Q exemplify an embodiment of a second deflection zone configured for controlled tridirectional deflection. In FIGS. 25P and 25Q, the third tubular structure 62 of the second flexure area 34 is positioned around the outer circumference of the third tubular structure, respectively, connecting ribs. It comprises a laser cutting pattern that forms an angularly offset, perimeterly positioned dorsal 66a, 66b, and 66c that are divided into three equal parts connected by 68a, 68b, and 68c. The dorsal can be placed around the perimeter of the third tubular structure at an angle of about 120 ° from each other.

0295The dorsal is provided with longitudinally spaced extension elements 67, such as slow wave or S-shaped elements, that resist compression of the dorsal during compressible flexion while promoting modest elongation of the dorsal during tensile flexion. When the back 66 bends in a stretched manner (eg, placing the back in a stretched state), the expansion element 67 is at least partially aligned to accommodate such back stretch. Conversely, when the back 66 bends in a manner that shortens the back (eg, puts the back in a compressed state), the expansion element 67 has a shape that resists such back compression. In this aspect, the extension element 67 allows the back 66 to respond to a controlled deflection in the desired direction while resisting the deflection in the other direction. Optionally, the expansion element 67 (as well as the back 66 or third tubular structure 62) is from a shape memory alloy such as nitinol so that the expansion element regains their slow wavy shape after removing tension from the back 66. It may be manufactured.

0296In each one-third arc segment of the outer circumference of the third tubular structure 62 positioned between the spines, the control wires 40a, 40b, or 40c are soldered 130 to the distal end of the second flexion area. It is attached. The control wires 40a, 40b, and 40c are placed relative to the dorsal 66a, 66b, and 66c by, for example, a separation element (not shown) that can be a flexible extruded polymer tube with a lumen for the control wire. Can be held in. Pulling over any one of the control wires while the other two control wires are not under significant tension is the controlled deflection of the second flexure area 34 in the direction of the wire being pulled. May be provided. For example, when the control wire 40c is pulled, the two adjacent backs 66c and 66b resist compression and provide bending power. The third tubular structure 62 compresses on the side surface of the bending power to which the control wire 40c is pulled and expands on the opposite side surface of the bending power. Substantially angularly opposite to the control wire 40c being pulled (angular) The extension element 67 of the back 66a, positioned at opposition), expands (at least temporarily) at least partially to accommodate the flexion of the third tubular structure. In this aspect, the second flexure zone 34 is configured for controlled tridirectional flexion in three directions, either arranged approximately 120 ° out of phase with each other or out of phase. May be done.

0297Figures 25R and 25S exemplify an embodiment of a second deflection zone configured for controlled four-way deflection. In FIGS. 25R and 25S, the third tubular structure 62 of the second flexure zone 34 has an expansion element that positions the outer circumference of the third tubular structure around the outer circumference of the third tubular structure. Forming quadrants connected by connecting ribs 68a, 68b, 68c and 68d, respectively, angularly offset, peripherally positioned backs 66a, 66b, 66c, and 66d. , Equipped with a laser cutting pattern. The dorsal can be placed approximately 90 ° angularly offset around the perimeter of the third tubular structure.

0298In each quadrant segment of the outer circumference of the third tubular structure 62 positioned between the spines, the control wires 40a, 40b, 40c, or 40d are soldered 130 to the distal end of the second flexure area. Be done. Pulling over any one of the control wires while the other three control wires are not under significant tension is the controlled deflection of the second flexure area 34 in the direction of the wire being pulled. May be provided. In this aspect, the second flexure zone 34 is configured for controlled quadrulateral flexion in four directions, either arranged approximately 90 ° out of phase with each other or out of phase. May be done.

0299Figures 25N-25S exemplify a second flexion zone 34 with an externally positioned spine configured for bidirectional, ternary, or quadrudirectional controlled deflection. As will be apparent to those skilled in the art, the laser cutting pattern of the third tubular structure 62 has an expansion element 67 and, if desired, any number of arc segments (eg, half, three minutes,) on the outer circumference. Any number of externally positioned, connected by connecting ribs 68 around the outer circumference of the structure to divide into quarters, five minutes, six minutes, seven minutes, eight minutes, nine minutes, ten minutes, etc.) It may be equipped with a back 66. When combined with the appropriate control wire, controlled deflection in any number of directions can be achieved. However, the second flexure area 34 was expected to become increasingly rigid as the number of arc segments around its perimeter (ie, the number of dorsal positions positioned perimeter) increased, which was controlled. It may impose a practical limit on the achievable number of deflection directions.

03003. Center-positioned spine combined with externally positioned spine Figures 25T-25U are configured for controlled multi-directional deflection with a centrally positioned spine 66 combined with a number of peripherally positioned spines 66 and a large number of control wires 40. A typical embodiment of the eighth embodiment having the second bending area 34 is illustrated.

0301In the embodiments of FIGS. 25T and 25U, the second flexure zone 34 is exemplary and is configured for controlled bidirectional deflection. The centered spine 66a is substantially flat or ribbon-shaped, while the third tubular structure 62 of the second flexure zone 34 is angularly oriented with the edge of the centered spine 66a. An angularly aligned dorsal 66b and 66c are formed (ie, the dorsal 66b and 66c can be offset by about 180 ° around the outer circumference of the third tubular structure. ), And with a laser cutting pattern forming ribs 68a and 68b (see Figure 25T). The centrally positioned dorsal 66a and the perimeterly positioned dorsal 66b and 66c, connected by the connecting ribs 68a and 68b, bisect the outer circumference of the third tubular structure. The control wires 40a and 40b are solder 130 attached to the distal end of the second flexion area on the opposite side of the centered back 66a and angularly from the peripherally positioned backs 66b and 66c. They are placed out of alignment.

0302The width W of the center-positioned back 66a is substantially larger than the thickness T of the center-positioned back 66a. The shape of the center-positioned back 66a and the peripherally positioned back 66b and 66c is parallel to the direction of the externally positioned back 66b and 66c (ie, the width of the centrally positioned back 66a). ), While promoting bidirectional deflection of the third tubular structure 62 in the direction of ribs 68a and 68b (ie, perpendicular to the width of the centered back 66a). To do.

0303The edges of the centrally positioned dorsal 66a are peripherally positioned along all or part of their length (eg, at the distal end of the centrally positioned dorsal 66a), the dorsal 66b and 66c The spine 66a, which may be attached to or centered on, may be substantially floating within the third tubular structure 62. Alternatively, the centered edge of the dorsal 66a is centered while facilitating variation in longitudinal alignment (which can enhance the flexibility of the second flexure area 34). Formed by, or proximal to, externally positioned dorsal 66b and 66c to maintain angular alignment between the externally positioned backs and the edges of the externally positioned backs 66b and 66c. It may be positioned in a channel or detent (not shown).

0304The centrally positioned spine 66a and the peripherally positioned spine 66b and 66c shapes, as well as the connecting ribs 68a and 68b shapes, are placed in an angularly offset distal position of the control wires 40a and 40b. In combination with, promotes controlled bidirectional flexion of the second flexure area 34. The second deflection zone deflects in the first direction in response to the pull on the control wire 40 while the control wire 40b is not under significant tension (see Figure 25U). The second deflection zone deflects in the second opposing direction in response to the pull on the control wire 40b while the control wire 40a is not under significant tension.

0305The second flexure zone 34 of FIGS. 25T and 25U is exemplifiedly configured for controlled bidirectional deflection, while having a centrally positioned back and a large number of externally positioned backs. The second flexion area has an alternative, by increasing the number of back ribbon segments that are alternately angularly offset around the centered back length, and with an extension element 67. And, if desired, controlled deflection in any further number of directions by increasing the number of externally positioned backs aligned with the centered back back ribbon segment. It should be understood that it may be configured for. See, for example, the center-positioned spine and the peripherally-positioned spine described above with respect to FIGS. 25G-25K and 25P-25S. For example, the dorsal centered in the four directions of FIGS. 25G-25J is the four perimeters of FIGS. 25R and 25S to achieve the controlled four-way deflection of the second flexure area 34. It may be used in combination with a positioned spine. Further directional control may be provided, if desired.

03064. Handle trigger for controlled multi-directional deflection In one typical embodiment, as shown in FIG. 25V, the motor 260 of the handle assembly 200 terminates proximally at the motor and distally in the second flexion area. A ball socket joint for a controlled multi-directional deflection of a second flexure area 34, via a controlled pull on one or more control wires 40. FIG. 25V exemplifies four control wires 40 that are circumferentially spaced around the handle assembly 200 and extend outwardly to a second flexion zone. The motor 260 could turn in all directions with respect to the handle assembly, any wire (s) were pulled in tension and, if desired, a second flexure area 34 was controlled. It makes it possible to deflect in multiple directions in a mode.

0307The alternative multi-directional motor 260 may include a multi-directional joystick connected to a large number of control wires, as shown in FIG. 25W. Alternatively, one or more bidirectional triggers may be provided, each for triggering in two directions in a given plane.

0308K. Eleventh Representative Embodiment (Second Flexure Area Constructed for Spiral Deflection) Figures 26A-26L have an elongated shaft 16 that includes a proximal force transfer compartment 30, a first flexure zone 32, a second or intermediate flexure zone 34, and any third or distal flexure zone 44. A typical embodiment of the eleventh embodiment is shown (see FIG. 26A). In these embodiments, the material, size, and configuration of the proximal force transfer compartment 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments. It is comparable to their respective counterparts. Further, the length and diameter of the second flexure zone 34 in the embodiment of FIG. 26 may be comparable to that described in any of the previous embodiments of the second flexure zone 34.

0309However, in the eleventh embodiment of the present invention, the second flexure zone 34 is configured for spiral deflection. The helical deflection of the second flexion area can facilitate the establishment of complete or partial peripheral contact between the second flexure area and the inner wall of the renal artery. This can reduce the angle of contact between the thermal element 24 and the inner wall of the artery, which can reduce the force applied to the vessel wall by the thermal element and can provide a less traumatic treatment. , Can reduce the risk of acute dissection of the arterial wall, can provide better juxtaposition between one aspect of the thermal element and the vascular wall, and / or thermally over the duration of treatment and throughout the cardiac cycle. The element can be stationaryly stabilized against the vessel wall. In addition, the helix may provide longitudinally spaced ring strength along its contact path with the inner wall of the renal artery, which risks luminal narrowing and blood flow blockage due to vasospasm during treatment. Can be reduced.

0310In some typical embodiments of the eleventh embodiment, the helical deflection of the second flexure zone 34 may reduce the need for any third flexure zone 44.

0311In some typical embodiments of the eleventh embodiment, one or more thermal elements 24 are spirally deflected along the length of a second flexion zone 34 and / or its distal end. It may be positioned with. When a large number of thermal elements are provided, the longitudinal and / or perimeter spacing of the thermal elements in the deployed configuration avoids the rotation and / or longitudinal repositioning of the thermal elements altogether. , Or reduced, may be designated to facilitate the creation of treatment areas within the renal arteries with the desired longitudinal and / or peripheral spacing.

0312In some typical embodiments of the eleventh embodiment, one or more substantially spherical, cylindrical, hemispherical, or semi-cylindrical electrodes (as described above) have a second deflection. It may be positioned along the length of the area.

0313In some typical embodiments of the eleventh embodiment, the long, substantially continuous thermal element may be positioned along the length of the second deflection zone that deflects spirally. .. Thermal elements of the tissue, such as through injection of thermal fluid into the second flexure zone and / or through resistance heating, or through Pelche cooling of the spiral second flexure zone, etc. It may be configured for direct thermal modification. Direct heating of the thermal element 24 can facilitate the creation of a longer treatment area than would be achievable by the electrodes, eg, a spiral that provides a longitudinally spaced peripheral treatment area within the renal artery. Can facilitate the creation of treatment areas.

0314Direct heating can also promote renal nerve regulation through energy delivery at relatively low energy densities over a relatively longer period of time than would be achievable by electrode-based thermal elements. This may allow blood flow to remove excess thermal energy from the lining of the renal arteries, thereby targeting renal nerves (in response to direct thermal modification applied via the thermal element 24). Reduces the risk of damage to non-target wall tissue while facilitating changes in temperature to a temperature sufficient to achieve the desired renal neuroregulation.

0315Any of the thermal elements 24 described above, as well as the spiral embodiment of the thermal element, may be long, continuous and / or configured for direct thermal modification of the tissue. It should be understood that it may be. For example, the flexible electrode 90 of the second representative embodiment seen in FIG. 17 may optionally include a thermal element configured for direct thermal reforming of the tissue.

0316When the second flexion zone 34 is configured for spiral deflection, the spiral properties are appropriate for placement in target vessels such as the renal arteries and for the creation of the desired treatment zone. Should be. For example, the spiral is similar in diameter and longitudinal length to that described in any of the previous embodiments of the second flexure zone 34, and / or longitudinal length is described above. Should be configured for delivery in a low profile configuration, comparable to the length of the renal arteries in (eg, 5-8 diameters configured for placement within a French guide, L3 length is about 5 mm. Between ~ 30mm, for example, about 10 ~ 30mm in length L3). In addition, the helix is for deployment to an extended configuration in which the diameter is suitable for establishing partial or complete peripheral contact with the inner wall of the vessel along the desired longitudinal length. Should be configured. As mentioned above, the innate medial diameter of the renal artery can vary between about 2 mm and about 10 mm, i.e., the innate medial radius of the renal artery can vary between about 1 mm and 5 mm. It is most common for the diameter of the renal arteries to vary between about 2 mm and about 8 mm, i.e., for the radius of the renal arteries to vary between about 1 mm and about 4 mm.

0317The radius of the spiral (ie 1/2 diameter), rHelix, is defined as:<maths num="7"><img id="000009" he="15" wi="47" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (16) In the equation, LArc is the arc length along the spiral and tHelix is the elongated shaft along the longitudinal length of the spiral surrounded by an arcuate angle (ie, along the longitudinal length of the spiral). The angle of rotation around 16 axes), where PHelix is the pitch of the spiral. The spiral pitch is defined as the longitudinal distance between two points on the helix, separated by a single full rotation of the helix. The longitudinal length of the spiral, LLong, is therefore defined as:<maths num="8"><img id="000010" he="11" wi="34" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (17)

0318By replacing equation (17) with equation (16), the following can be shown:<maths num="9"><img id="000011" he="14" wi="35" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (18)

0319In the delivery configuration, the radius of the first spiral of the second flexure zone, rHelix1, and the length of the first longitudinal direction, LLong1 is due to the appropriate diameter (radius) described above and the length of the second flexure zone 34. And / or constrained by the length of the renal artery. In addition, the radius of the deflected helix of the second flexion area in the deployed configuration, rHelix2, is constrained by the inner diameter (radius) of the renal artery to be treated. As specified in equation (18), the radius of the spiral in the second deflection zone is from rHelix1k to rHelix2 by reversibly varying the spiral tHelix, LArc or LLong (or PHelix), or a combination thereof. Can be reversibly extended to. Further, from equation (17), the longitudinal length of the helix may change as the helix PHelix and / or tHelix changes.

0320When the spirally deflected second flexure zone comprises a number of thermal elements 24 positioned along its length, the thermal element is that of the thermal element in the expanded configuration of the second flexure zone. To provide the desired longitudinal and / or peripheral separation (eg, at the maximum expected renal artery radius, to provide the minimum desired longitudinal and / or peripheral separation of the thermal element. In), it may be positioned along the unfolded pitch PHelix2 of the spiral in the second flexure zone. This may facilitate the creation of a therapeutic area within the renal artery with the desired perimeter and longitudinal spacing without the need for rotational or longitudinal repositioning of the thermal element after initial deployment.

0321In some typical embodiments of the eleventh embodiment, the spiral in the second flexure zone deviates the longitudinal length of the spiral from the first longitudinal length, LLong1. The length of tHelix and LArc remain constant (ie, by reducing the pitch of the spiral from PHelix1 to PHelix2), while extending from rHelix1 to rHelix2 by reducing the length to LLong2. In some typical embodiments of the eleventh embodiment, the second flexure area has a spiral bow angle, from the first bow angle, tHelix1, to a deflected bow angle, tHelix2. L Long and L Arc remain constant (ie, by increasing the pitch of the spiral from PHelix 1 to PHelix 2), while spiraling from rHelix 1 to rHelix 2 by reducing to. In some typical embodiments of the eleventh embodiment, the second flexure zone extends the arc length of the spiral from the first arc length, LArc1, to the deflected arc length, LArc2. , THelix and LLong (and hence PHelix) remain constant, while spiraling from rHelix1 to rHelix2. In some typical embodiments of the eleventh embodiment, the second flexure area is the reduction of the longitudinal length of the helix, the reduction of the arcuate angle of the helix, and / or the arc length of the helix. It spirals from rHelix1 to rHelix2 through a combination of expansions.

03221. Radial expansion of the spiral through longitudinal length reduction The delivery conditions for the spiral of the second flexure zone, i.e. rHelix1, LLong1, tHelix1, and LArc1, are specified or known. For example, rHelix1 and LLong1 are specified by the constraints that guide catheter delivery and renal anatomy impose on the second flexion area 34 in the delivery configuration, respectively, while tHelix1 and LArc1 are the second flexure. It can be selected to provide the area with the desired deployment conditions. In this embodiment, the second flexure area is from rHelix1 to rHelix2 by reducing the longitudinal length of the spiral from LLong1 to LLong2 (ie, by reducing the pitch of the spiral from PHelix1 to PHelix2). While spirally expanding to (eg, to the inner diameter of the renal artery), tHelix and LArc remain constant (ie, tHelix1 = tHelix2 = tHelix, and LArc1 = LArc2 = LArc).

0323By rearranging equation (18), the following can be shown:<maths num="10"><img id="000012" he="15" wi="42" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (19)

0324Since LArc and tHelix (and hence the LArc / tHelix ratio) remain constant during the radial expansion of the helix, the spiral delivery and deployment conditions are relevant:<maths num="11"><img id="000013" he="14" wi="60" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (20)

0325Therefore, the longitudinal length in the extended configuration, LLong2, is defined as:<maths num="12"><img id="000014" he="9" wi="62" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (21)

0326For example, an initial radius of 0.5 mm rHelix1, a desired final radius of 4 mm rHelix2 (eg for use in an 8 mm diameter renal artery), a first longitudinal length of 27 mm LLong1, and a desired arch of 2π. Given the angle tHelix (eg, 360 ° of the spiral or one complete rotation to achieve peripheral contact within the renal artery), the spiral in the second flexion area slightly exceeds 10 mm. Should be shortened to the unfolded longitudinal length LLong2.

0327Conversely, equation (21) may be rearranged and utilized to select tHelix (and thereby L Arc) that provides the desired rHelix2 and LLong2 in the expanded configuration:<maths num="13"><img id="000015" he="14" wi="39" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (22)

0328For example, an initial radius of 0.5 mm rHelix1, a desired final radius of 4 mm rHelix2 (eg for use in an 8 mm diameter renal artery), a first longitudinal length of 27 mm L Long1, and a desired final length of 10 mm. Given a directional length L Long2 (eg, to achieve a distance of about 5 mm between a number of thermal elements 24 positioned at the proximal, midpoint, and distal ends of the helix), its longitudinal direction. The arcuate angle tHelix surrounded by the spiral along the length of the spiral should be equal to slightly greater than 2π (ie, slightly greater than 360 ° of the spiral or one complete rotation of the spiral).

0329Advantageously, the unfolded radius rHelix2 of the expanding helix, through the longitudinal shortening of the second flexure area 34 from LLong1 to LLong2, is the maximum, unfolded longitudinal length of the helix. LLong2 may be mechanically varied up to a maximum radius equal to zero:<maths num="14"><img id="000016" he="12" wi="20" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (23)

0330This may facilitate the establishment of at least partial peripheral contact with the inner wall of the renal artery, which has various radii up to the maximum radius.

0331Equations (16)-(23) are the expanded configurations of the second flexure zone when the spirally deflected second flexure zone comprises a number of thermal elements 24 positioned along its length. May be utilized to provide the desired longitudinal and / or peripheral spacing of the thermal elements in. For example, the thermal element may be optionally positioned along the unfolded pitch PHelix2 of the spiral in the second flexure zone. This may facilitate the creation of a therapeutic area within the renal artery with the desired perimeter and longitudinal spacing without the need for rotational or longitudinal repositioning of the thermal element after initial deployment.

0332In a representative embodiment of FIGS. 26B-26G, the third tubular structure 62 of the second flexure area 34 comprises a laser cutting pattern forming a spiral spine 66 with connecting ribs 68. The control wire 40 is attached with solder 130 to the distal end of the second flexure area 34. The spiral spine responds to the proximal retraction of the control wire 40 with the radius rHelix1 of the first spiral (rHelix1 is approximately 1/2 diameter of the third tubular structure 62) and the first longitudinal direction. From a substantially linear configuration with a length of LLong1 (see Figures 26B and 26C), a shorter diameter in the longitudinal direction, with a deflected spiral radius rHelix2 and a deflected longitudinal length LLong2. Bias the deflection of the third tubular structure 62 into a wider spiral configuration in the direction (see figure 26D).

0333The arc length L Arc of the spiral dorsal 66 and the arched angle tHelix are specified to achieve the desired deployment conditions, and they do not change during the radial expansion of the helix through longitudinal shortening. However, the arc length LArc and / or arched angle tHelix of the dorsal 66 is specified by a relatively large value, so that the second flexion area is spirally contacted with the inner wall of the patient's renal artery. The tensile force applied to the control wire 40 (eg, the force expected to provide a spiral radius in the range of about 1-5 mm) that would be required to deflect the back arc length LArc and / Or the arched angle tHelix is expected to increase compared to when specified with a relatively small value.

0334The spirally deflected second flexure zone 34 may be positioned proximal to the thermal heating element 24 indicated by the third flexure zone 44. Alternatively, as shown in FIG. 26E, one or more thermal elements 24, such as the substantially spherical electrode 92 or the substantially hemispherical electrode 92a described above, are the second deflection areas 34. It may be positioned along the length of. In FIG. 26E, a third flexion zone 44 is provided as a non-traumatic distal tip, but an elongated shaft 16 may be provided as an alternative without the third flexure zone 44. Should be understood.

0335In FIG. 26F, the long, substantially continuous thermal element 24 is positioned along the length of the spirally deflected second flexion zone 34. The thermal element 24 of FIG. 26F is via injection of thermal fluid into the second flexion zone, through resistance heating, and / or through Pelche cooling in the spiral second flexure zone, etc. , May be configured for direct thermal modification of the tissue. The thermal elements 24 in FIG. 26F are shown to be long and substantially continuous, but the thermal elements may optionally include a large number of thermal elements closely spaced together. Should be understood. Further, in FIG. 26F, the elongated shaft 16 is exemplified without a third flexure zone 44, although a third flexure zone may be provided as an alternative.

0336In FIG. 26G, the control wire 40 is externally positioned with respect to the third tubular structure 62 along the second flexion zone. For example, the control wire may exit the elongated shaft at or near the proximal end of the second flexion zone 34, for example, through a lateral port or through a longitudinal gap between connecting ribs 68. Good. Positioning the control wire 40 outward along its length relative to the second flexion area is applied to the control wire 40, which is necessary to spirally deflect the second flexure area. The tensile force can be reduced. As is apparent, the control wire (s) 40 may optionally be in the second flexure zone in any of the second flexure zones described above, such as in any of the second flexure zones that flex in a plane. On the other hand, it may be positioned to the outside.

0337Referring to FIG. 26H, another embodiment of the second flexure zone 34 is described in which the second flexure zone 34 is an elastic or hyperelastic material such as nitinol or a wire. In FIG. 26H, the second flexure zone 34 is such that the proximal retraction of the control wire shortens the second flexure zone longitudinally into an unfolded configuration with a radially extended spiral. , Connected distally to the control wire 40 and proximally to the first flexure zone 32. Removal of tension from the control wire causes the second flexion zone to regain a substantially straight delivery configuration.

0338The second flexure zone 34 in FIG. 26H may optionally include a plastically deformable material, such as a polymer or metal wire or coil. In such an embodiment, the proximal retraction of the control wire 40 can plastically deform the second flexure area during longitudinal shortening and radial expansion of its spiral. The control wire 40 is sufficiently rigid so that the second flexure area is extended by pushing the wire distally longitudinally and its spiral is radially folded for delivery and / or recovery. obtain. Alternatively, by advancing the sheath, such as a guide catheter, over the elongated shaft 16 and the extended second flexion zone 34, the second flexure zone can be straightened and extended, thereby causing its spiral. Folded radially for delivery and / or recovery.

03392. Radial expansion of the spiral through reduction of bow angle As mentioned above, the delivery conditions for the second deflection zone spiral, i.e. rHelix1, LLong1, tHelix1, and LArc1, are specified or known. For example, rHelix1 and LLong1 are specified by the constraints that guide catheter delivery and renal anatomy impose on the second flexion area 34 in the delivery configuration, respectively, while tHelix1 and LArc1 are the second flexure. It can be selected to provide the area with the desired deployment conditions. In this embodiment, the second flexure area is from rHelix1 by reducing the arched angle surrounded by the spiral from tHelix1 to tHelix2 (ie, by increasing the pitch of the spiral from PHelix1 to PHelix2). While spirally expanding to rHelix2 (eg, to the inner diameter of the renal artery), LLong and LArc remain constant (ie, LLong1 = LLong2 = LLong, and LArc1 = LArc2 = LArc).

0340By rearranging equation (18), the following can be shown:<maths num="15"><img id="000017" he="7" wi="42" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (24)

0341Since LArc and LLong (and hence LArc2-LLong2) are held constant during the radial expansion of the helix, the spiral delivery and deployment conditions are relevant:<maths num="16"><img id="000018" he="5" wi="47" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (25)

0342Therefore, the bow angle in the delivery configuration, tHelix1, is defined as:<maths num="17"><img id="000019" he="12" wi="35" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (26)

0343For example, an initial radius of 0.5 mm rHelix1, a desired deployed radius of 4 mm rHelix2 (eg for use in an 8 mm diameter renal artery), a fixed delivery and a deployed longitudinal length (eg, for example). LLong = 20mm), as well as the desired expanded arched angle tHelix2 of 2π (ie, 360 ° or one complete rotation of the spiral to achieve peripheral contact within the renal artery). The arched angle tHelix1 of the second flexion area during delivery should be about 16π (ie about 2880 ° or 8 rotations). When the desired deployed bow angle tHelix2 is reduced to π (ie 180 ° or half-turn), the bow angle tHelix1 in the second flexion area during delivery is about 8π (ie about 1440). It is reduced proportionally up to ° or 4 rotations).

0344Advantageously, the expanded radius rHelix2 of the expanding spiral through the reduction of the arched angle mechanically by reducing the expanded arched angle tHelix2 to increase the radius. It may be changed. This may facilitate the establishment of at least partial peripheral contact with the inner walls of renal arteries of varying radii.

0345Equations (16)-(18) and (24)-(26) are in the second, when the spirally deflected second deflection zone comprises a number of thermal elements 24 positioned along its length. May be utilized to provide the desired longitudinal and / or peripheral spacing of the thermal elements in the unfolded configuration of the flexure zone. For example, the thermal element may be optionally positioned along the unfolded pitch PHelix2 of the spiral in the second flexure zone. This may facilitate the creation of a therapeutic area within the renal artery with the desired perimeter and longitudinal spacing without the need for rotational or longitudinal repositioning of the thermal element after initial deployment.

0346Then, referring to FIGS. 26I and 26J, the second flexure zone 34 may spirally wrap around a control wire or shaft 40 that is positioned externally to the second flexure zone. The control wire is connected to the distal end of the second flexion area via solder 130 and can be relatively rigid compared to the control wire 40 described above, at least in the vicinity of the second flexure area 34.

0347As shown in FIG. 26I, in the delivery configuration, the second flexure area wraps around the control wire relatively tightly during delivery (eg, rHelix1 is relatively similar to the diameter of the control wire. is there). As shown in FIG. 26J, the second deflection zone spirally extends from the delivery radius rHelix1 to the unfolded radius rHelix2 along its longitudinal axis through the rotation of the control wire 40. And it eliminates the twist of the spiral. LArc and LLong remain constant during such expansion, while the spiral bow angle is reduced from tHelix1 to tHelix2.

03483. Radial expansion of the spiral through expansion of arc length As mentioned above, the spiral of the second flexion zone of the delivery condition, i.e. rHelix1, LLong1, tHelix1, and LArc1, is specified or known. In this embodiment, the second flexion area spirally extends from rHelix1 to rHelix2 (eg, to the inner diameter of the renal artery) by increasing the arc length of the spiral from LArc1 to LArc2. Llong and tHelix (and hence PHelix) remain constant (ie, LLong1 = LLong2 = LLong, and tHelix1 = tHelix2 = tHelix).

0349By rearranging equation (18), the following can be shown:<maths num="18"><img id="000020" he="7" wi="42" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (27)

0350Therefore, the arc length of the spiral is defined as:<maths num="19"><img id="000021" he="8" wi="46" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (28)

0351Furthermore, since LLong and tHelix are held constant during the radial expansion of the helix, the delivery and deployment conditions of the helix are relevant as follows:<maths num="20"><img id="000022" he="6" wi="67" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (29)

0352Therefore, the arc length, LArc1, in the delivery configuration is defined as:<maths num="21"><img id="000023" he="8" wi="71" file="JP2016214902A_D0001.tif" img-format="tif" img-content="drawing" /></maths> (30)

0353For example, a desired extended radius of 4 mm rHelix2 (eg, for use in an 8 mm diameter renal artery), a fixed delivery of 15 mm and an expanded longitudinal length LLong, and a desired delivery of 2π and Given the unfolded arched angle tHelix (ie, 360 ° or one complete rotation of the spiral to achieve peripheral contact within the renal artery in the unfolded configuration), use the unfolding condition. The desired developed arc length LArc2 from equation (28) is slightly over 29 mm. Therefore, given a delivery radius of 0.5 mm, rHelix1, the arc length LArc1 of the second flexure zone during delivery from equation (28) or equation (30) should slightly exceed 15 mm. When the desired deployed bow angle tHelix is increased to 4π (720 ° or 2 turns), the deployed arc length LArc2 in the second flexure zone is increased to about 52.5 mm while , Delivery arc length LArc1 is increased to just over 16 mm.

0354Advantageously, the expanded radius rHelix2 of the expanding spiral through the expansion of the arc length mechanically changes to increase the radius as the expanded arc length LArc2 of the spiral increases. You may be forced to. This may facilitate the establishment of at least partial peripheral contact with the inner walls of renal arteries of varying radii.

0355Equations (16)-(18) and (27)-(30) are second when the second deflection zone, which deflects in a spiral, comprises a number of thermal elements 24 positioned along its length. May be utilized to provide the desired longitudinal and / or peripheral spacing of the thermal elements in the unfolded configuration of the flexure zone. For example, the thermal element may be optionally positioned along the delivery and unfolded pitch PHelix of the spiral in the second flexure zone. This may facilitate the creation of a therapeutic area within the renal artery with the desired perimeter and longitudinal spacing without the need for rotational or longitudinal repositioning of the thermal element after initial deployment.

0356Then, referring to FIGS. 26K and 26L, the second flexure zone 34 may spirally wrap around a control wire or shaft 40 that is positioned externally to the second flexure zone. The control wire is connected to the distal end of the second flexion area via solder 130 and can be relatively rigid compared to the control wire 40 described above, at least in the vicinity of the second flexure area 34.

0357The second flexion area may wrap around the control wire relatively tightly during delivery (eg, rHelix1 is relatively similar to the diameter of the control wire). As shown in FIG. 26K, when positioned at the treatment site, the distal end of the second flexion area may be positioned at the desired longitudinal distance LLong from the guide catheter 94. As shown in FIG. 26L, the elongated shaft 16 may be advanced distally to the control wire 40 and the guide catheter 94 while keeping the LLong and tHelix (and hence PHelix) constant. This increases the arc length LArc of the second deflection zone from the delivery arc length LArc1 to the unfolded arc length LArc2, causing a radial extension of the spiral from the delivery radius rHelix1 to the unfolded radius rHelix2. ..

03584. Radial extension of the spiral through a combination of longitudinal length reduction, bow angle reduction, arc length extension, and / or pitch change As mentioned above, the spiral of the second flexion zone of the delivery condition, i.e. rHelix1, LLong1, tHelix1, and LArc1, is specified or known. Spiral dilation from the delivery radius rHelix1 to the unfolded radius rHelix2 (eg, to the inner diameter of the renal artery) reduces the longitudinal length of the helix LLong, reduces the spiral arch angle tHelix, spirals. It can be achieved through a combination of expansion of the arc length Larc and / or modification of the spiral pitch PHelix. Equations (16)-(30) have been utilized to achieve the desired expansion conditions rHelix2, LLong2, tHelix2, and LArc2, where appropriate (given the specific mechanism of radial expansion). May be good. In addition, when a large number of thermal elements 24 are positioned along the length of the second flexure zone, the desired longitudinal and / or perimeter spacing of the thermal elements in the expanded configuration of the second flexure zone. If appropriate, those equations may be used to provide. For example, the thermal element may be optionally positioned along the unfolded pitch PHelix2 of the spiral in the second flexure zone. This may facilitate the creation of a therapeutic area within the renal artery with the desired perimeter and longitudinal spacing without the need for rotational or longitudinal repositioning of the thermal element after initial deployment.

0359Various combinations of reduction of the longitudinal length LLong of the helix, reduction of the arcuate angle tHelix of the helix, expansion of the arc length Larc of the helix, and / or modification of the pitch Phelix of the helix, extend the radial of the helix. May be used to achieve. For example, in the embodiments of FIGS. 26I and 26J, the control wire 40 reduces the longitudinal length of both helices and the arcuate angle of the helix to achieve the desired radial extension of the helix. May be rotated and translated proximally during deployment to reduce. As another example, in the embodiments of FIGS. 26K and 26L, the control wire 40 reduces the longitudinal length of the helix and reduces the arc length of the helix in order to achieve the desired radial extension of the helix. To increase, the elongated shaft 16 may be advanced distally and retracted proximally when the guide catheter 94 is held in place. Yet another example, in the embodiments of FIGS. 26K and 26L, the control wire 40 reduces the spiral arch angle and the spiral arc length to achieve the desired radial extension of the helix. As the elongated shaft 16 advances, it may be rotated about its longitudinal axis so as to increase. Still further, in the embodiments of FIGS. 26K and 26L, the control wire 40 reduces the arcuate angle of the helix and reduces the longitudinal length of the helix in order to achieve the desired radial extension of the helix. And as the elongated shaft 16 advances distally and the guide catheter 94 is held stationary, it is rotated about its longitudinal axis and proximally to increase the arc length of the spiral. It may be translated.

0360L. 12th representative embodiment (second flexure area configured for complex deflection) Figures 27A-27D show an elongated shaft 16 containing a proximal force transfer section 30, a first or proximal flexion zone 32, a second or intermediate flexure zone 34, and any third or distal flexure zone 44. A representative embodiment of the twelfth embodiment having the above is shown (see FIG. 27A). In these embodiments, the material, size, and configuration of the proximal force transfer compartment 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments. It is comparable to their respective counterparts. Further, the length and diameter of the second flexure zone 34 in the embodiment of FIG. 27 may be comparable to that described in any of the previous embodiments of the second flexure zone 34.

0361However, in the twelfth embodiment of the present invention, the second flexure zone 34 is configured for spiral deflection. Complex deflections may include, for example, multi-directional deflection in a single plane, multi-directional deflection in multiple planes, planar deflection in combination with helical deflection, and the like. The complex deflection of the second flexion zone 34 is positioned along the length of the second flexure zone so that it contacts the inner wall of the renal artery at the desired longitudinal and / or perimeter position (s). And / or may facilitate the placement of one or more thermal elements 24, which may be connected to any third flexure zone 44.

0362In a typical embodiment of FIG. 27B, the third tubular structure 62 of the second flexure area 34 comprises a laser cutting pattern including a dorsal 66 with connecting ribs 68. The control wire 40 is attached with solder 130 to the distal end of the second flexion area. The dorsal 66 is longitudinally spaced apart and angularly opposed (ie, placed approximately 180 ° apart from each other) in the first segment 66'and the second segment 66''. , As well as angularly opposed to the second segment 66'', but angularly opposed to the first segment 66'. aligned) Includes a third segment 66'''. In response to pull on the control wire 40, the positioning of the first and second segments of the dorsal is in a plane where the laser cutting pattern of the third tubular structure is orthogonal to the first and second segments of the dorsal. , It is like biasing the deflection of the third tubular structure back and forth, so that the second deflection zone has an "S" shape in the deflected configuration of FIG. 27C. As shown, the thermal element 24 optionally, in a deflected configuration, is at the apex of flexion where the thermal element is longitudinally separated and can contact the inner wall of the renal artery in a position that is peripherally opposed. It may be positioned along the length of the second flexion zone and at the distal end of the third flexure zone 44 so that it can be positioned.

0363In a typical embodiment of FIG. 27D, the dorsal 66 is longitudinally spaced, angularly opposed to the first segment 66'and the second segment 66'', as well as longitudinally separated. , Angularly opposed to each other The third segment 66'''' and the fourth segment 66'''' and the fourth segment 66'''' which are orthogonal to the first segment 66'and the second segment 66'' (that is, are arranged at an angle of about 90 °). It has a segment 66'''''. In response to the pull on the control wire 40, the positioning of the first and second segments of the dorsal is that the laser cutting pattern of the third tubular structure has a third tubular structure in each of the two orthogonal planes. It is like biasing the body deflection back and forth, so that the second flexion area has a "U" shape in the deflected configuration of FIG. 27E. As shown, the thermal element 24 is optionally located on the inner wall of the renal artery in a longitudinally spaced peripheral position where the thermal element is located approximately 90 ° angularly offset in a deflected configuration. It may be positioned along the length of the second flexure zone 34 and at the distal end of the third flexure zone 44 so that it is positioned at the apex of the bend that can be touched.

0364The complex deflection of the second deflection zone 34 can optionally be achieved using a large number of control wires 40. For example, in the embodiment of FIG. 27B, the first control wire may be attached distally to the distal end of the first back segment 66'and the second control wire may be attached to the second back segment 66. It may be attached distally to the distal end of the'', and the third control wire may be attached distally to the distal end of the third back segment 66'''. A pull on the first control wire will deflect only the first back segment, while a pull on the second control wire will deflect both the first and second back segments, and the second The pull on the control wire of 3 deflects all 3 back segments (as shown in Figure 27B). The use of multiple pull wires can thereby facilitate partial or all deflection of the second flexure area 34, if desired.

0365M. Thirteenth Representative Embodiment (Second Deflection Zone Constructed for Electrically Induced Deflection) Figures 28A and 28B show an elongated shaft 16 comprising a proximal force transfer section 30, a first or proximal flexion zone 32, a second or intermediate flexure zone 34, and any third or distal flexure zone 44. A representative embodiment of the thirteenth embodiment is shown (see FIG. 28A). In these embodiments, the material, size, and configuration of the proximal force transfer compartment 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments. It is comparable to their respective counterparts. Further, the length and diameter of the second flexure zone 34 in the embodiment of FIG. 28 may be comparable to that described in any of the previous embodiments of the second flexure zone 34.

0366However, in the thirteenth embodiment of the present invention, the second flexure zone 34 is configured for electrically evoked deflection. In a typical embodiment of FIG. 28B, the third tubular structure 62 of the second flexure area 34 comprises a laser cutting pattern including a back 66 with connecting ribs 68, but with a mechanism other than laser cutting or laser cutting. It should be understood that other patterns that bias the spine or other structural design formed by the may be used in an alternative manner. The control wire 40 is attached with solder 130 to the distal end of the second flexion area. As in the previous embodiment, in response to the control wire 40 pulled proximally on the distal end of the second flexion area, the laser cutting pattern of the third tubular structure is a plane orthogonal to the dorsal. Bias the deflection of the third tubular structure in. However, unlike the case of the above-described embodiment, the control wire 40 is due to the electrically evoked shortening of the control wire rather than the mechanically evoked tension along its length. Pull on the distal end of the flexion area of 2.

0367As shown in FIG. 28B, the control wire 40 is also attached via solder 130'to the proximal end of the second flexion zone. Unlike in the previous embodiment, the control wire 40 does not extend to the handle assembly 200 through the elongated shaft 16 in the proximal of the second flexion area. Rather, the electrical supply wire 29 travels from the handle 200 through an elongated shaft and is electrically connected to the control wire 40 at the solder joints 130 and 130'. The motor 260 in the handle assembly 200 applies a current to the supply wire 29, which transfers the current to the control wire 40. The control wire 40 is shortened in response to the current, which causes the deflection of the second deflection zone 34.

0368In contrast to this thirteenth embodiment, some of the aforementioned embodiments of the present invention have one or more control wires 40 extending through the entire elongated shaft 16 to the handle assembly 200. The tension is applied to the control wires (s) 40 via the trigger 260 along their overall length to pull over the second flexure area 34 and cause its deflection. To facilitate such deflections, the elongated shaft 16 proximal to the second flexion zone is compressed along its length when tension is applied to the control wire (s) 40. Due to its placement, it is relatively resistant to buckling. Therefore, the elongated shaft 16 can be relatively rigid, which can be more rigid during deflection of the second flexion zone. In the thirteenth embodiment, the control wire 40 does not extend proximal to the second flexion zone, so the more proximal section of the elongated shaft 16 needs to be uncompressed and less aggressively resist buckling. There is no. Therefore, the elongated shaft may be made in a manner that provides greater flexibility, which may enhance deliverability and / or reduce catheter flexibility during rotation. The electrically induced change or shortening of the control wire shape may be utilized in combination with any of the above-mentioned second flexure areas 34 and control wire 40.

0369In one typical embodiment of the thirteenth embodiment, the control wire 40 comprises a shape memory material such as nitinol. Prior to its attachment to the second deflection zone, the temperature of the control wire depends on its transformation temperature (eg, the relative proportions of nickel and titanium in the alloy, because it places nitinol in the austenite phase. It can be increased to above (in the range of about 20 ° C to 60 ° C). The control wires are straightened and cooled to below their transformation temperature so that the wires are placed in the martensite phase. The control wire is then attached to the proximal and distal ends of the second flexion area under significant elastic deformation (eg, strain in the range of about 6-10%). The electricity applied to the feed wire 29 heats the control wire 40 resistantly until it exceeds its transformation temperature, transforming the control wire back into the austenite phase, which is a substantially strain-free austenite configuration. Regain the previous heat set. This shortening of the control wire causes deflection in the second deflection area. The control wire or the third tubular structure 62, which can optionally be heated with resistance through the supply wire 29, instead has a bending austenite shape that pulls the second bending area in the direction of bending. You may prepare.

0370In one typical embodiment of the thirteenth embodiment, the control wire 40 comprises an electroactive polymer commonly referred to as an artificial muscle. The electricity applied to the electroactive polymer control wire shortens the control wire and causes deflection in the second deflection zone. When the electricity is turned off, the control wire regains its original shape and straightens (or allows it to be straightened) the second flexion area.

0371N. 14th Representative Embodiment (Second Flexure Area Constructed for Deflection in Fittings) FIGS. 29A-29E have a 14th elongated shaft 16 including a proximal force transfer section 30, a first or proximal flexion zone 32, a joint 35, and any third or distal flexure zone 44. A typical embodiment of the embodiment is shown (see FIG. 29A). In these embodiments, the material, size, and configuration of the proximal force transfer compartment 30, the first flexure zone 32, and any third flexure zone 44 are described in any of the previous embodiments. It is comparable to their respective counterparts.

0372However, in a fourteenth embodiment of the invention, the second flexure zone 34 is replaced by one or more joints 35 to facilitate deflection of the third flexure zone 44. The fitting 35 can provide accurate deflection control because the fitting can exhibit consistent deflection dynamics. In addition, the fitting may provide a sharper bend than would be achievable by some of the aforementioned embodiments of the second deflection zone, as the fitting represents a turning point relative to the radius of curvature. .. Therefore, the length of the second flexion zone with the joint can be less than the length of the second flexure zone of the biased back mentioned above. This can promote thermal neuromodulation in the shorter renal arteries and / or, as shown in FIG. 29E, the use of a longer third flexion zone 44. The longer third flexion area dissipates vascular contact force over its longer length and elastically applies pressure to the vascular wall to provide stable electrode contact during pulsatile blood flow and respiratory movements. obtain. Also, the longer third flexure area may be easier to visualize by fluoroscopy. The third flexure area 44 can be between about 6 mm and 16 mm in length, eg, about 9.5 mm or less, which may be suitable to provide sufficient flexure in the renal arteries.

0373Referring to FIG. 29B, in one typical embodiment of the fourteenth embodiment, a hinge joint 35 connecting the first flexure zone 32 to the third flexure zone 44. The control wires 40a and 40b are attached to both sides of the joint 35, distal to the axis R for rotating the force damping compartment 44 around the axis R of the hinge joint. Alternatively, one control wire is attached to one side of the joint 35, distal to the axis R for rotating the force damping compartment 44 around the axis R of the hinge joint , and the spring controls. When the tension on the wire is reduced, the force damping section 44 is rotated back to its unbiased state.

0374Alternatively, a large number of third flexure areas may be connected to the first flexure area via one or more fittings. Each distal flexion area can be attached to or provided with electrodes. Each distal flexion area can be triggered to rotate around the fitting, either independently or with a single control wire. Alternatively, the springs can be positioned in the fitting to push open the distal flexion area and they can be closed by retracting into the delivery sheath. When the distal flexion area opens, the electrodes move away from each other and are placed in contact with the vessel wall.

0375The force damping section 44 comprises a force diversion element 49 along its longitudinal length, which provides the energy delivery element 24 with a force damping section at an angle and distance similar to that described in the previous embodiment. Pull away from the 44 axis. The longer force damping section 44 is more susceptible to buckling, especially when the applied load is pulled away from its axis, because the slenderness ratio (length: diameter) is greater for the longer force damping section 44. .. When the distal assembly 53 advances into the renal artery and the energy delivery element 24 contacts the renal artery wall, the load applied to the energy delivery element 24 is disengaged from the axis of force damping compartment 44 and is a traumatic load. Lower loads can cause buckling in force damping compartment 44. The force diversion element 49 may be longitudinally located on the force damping section 44 at approximately midpoint. For example, on a 9.5 mm long force damping section 44, the force diversion element 49 can be about 4-5 mm proximal to the distal end. With reference to FIG. 29C, in one typical embodiment of the fourteenth embodiment, the second flexure zone 34 comprises a first hinge joint 35 and a second hinge joint 35'. Control wires 40a and 40b are attached to both sides of the joint 35 to rotate the distal flexion area around the axis R of the hinge joint 35, while control wires 40c and 40d are the axes of rotation of the hinge joint 35'. Attached to both sides of the second fitting 35'to rotate the third flexure area around R'. The rotation axis R'of the hinge joint 35'is preferably orthogonal to the rotation axis R of the hinge joint 35 to provide deflection for the distal flexion area 44 in two orthogonal planes.

0376With reference to FIG. 29D, in one typical embodiment of the fourteenth embodiment, the second flexure zone 34 joins the proximal and distal flexure zones and has any radius of curvature RoC of about zero. It is equipped with a ball socket joint 35 that promotes rotation on a flat surface. Any number of control wires 40 (exemplarily four control wires) may be provided to deflect the second flexure zone 34.

0377O. Fifteenth Representative Embodiment (Forced Cooled Energy Delivery Element) 1. Applying energy to intravascular tissue in combination with forced cooling When used in a unipolar fashion, the aforementioned energy delivery element 24 is an electrode that conducts RF current from the electrode through the tissue to the return electrode, such as the neutral electrode 38, which is positioned on the patient's skin. May be provided. When used in a bipolar fashion, the thermal heating element 24 may also include an electrode that conducts RF current from the active electrode 24 through the tissue to the return electrode, which is also positioned on the elongated shaft 16. Good. RF currents are conducted along the parallel tissue circuit through the tissue from the active electrode to the return electrode.

0378The RF current is most concentrated in the tissue near the surface of the active electrode. The simplified relationship of current densities in uniform tissue for relatively spherical electrodes explains that the current densities decay at a rate of r4 with distance from the active electrode surface. This relationship becomes more complex in environments with substantial differences in electrical and thermal properties, especially in impedance, heat capacity, and convection, and as the electrode shape deviates from the spherical shape.

0379Rapid alternating current, such as RF, oscillates ions in tissue to generate heat. The heating effect is proportional to the current density and the rate of heat transfer due to conduction, convection, and / or radiation in tissues and blood. Generally speaking, the hottest tissue is at or near the surface of the electrode, and the temperature decreases rapidly with distance.

0380With respect to FIGS. 30B-30D, it may be beneficial to forcibly cool the thermal heating element and / or non-target tissue in the vicinity of the thermal heating element. Such cooling is enhanced safety (eg, lower intraluminal tissue surface temperature), enhanced efficacy, shorter (or longer) than that would be achievable in the absence of cooling. ) With duration, higher power, higher depth, and / or larger size, it can promote lesion formation. As shown in FIG. 30A, when the intravascular treatment device 12 is equipped with open circuit forced cooling, the system 10 pumps thermal fluid from the fluid source 11a through the fluid delivery tube 11b and through the lumen of the treatment device 12. A fluid pump 11 may be provided for pumping fluid to its distal end region 20 in the vicinity of the thermal heating element 24. When the intravascular treatment device 12 is equipped with closed circuit forced cooling, the system 10 further returns the thermal fluid to the fluid source for recirculation, or recirculates the thermal fluid, for example, as shown in FIGS. 30C and 30D. It may be provided with a fluid return tube (not shown) and a fluid return tube 45b of the therapeutic device that communicates with the fluid to be disposed of outside the patient.

0381The rate, volumetric flow rate, and total volume of the thermal fluid pump feed through the fluid pump 11 may be controlled manually by the caregiver or by algorithm 102, as shown in FIG. 30A. Good. The therapeutic device 12 is provided with sufficient strength against rupture to facilitate safe injection or delivery of thermal fluid through the pump 11. In addition, the therapeutic device and its distal end region 20 have physical and mechanical properties for maintaining the position of the thermal heating element 24 while the infusion is being injected or delivered.

0382For example, infusions such as thermofluid infusions (eg, room temperature or cold saline), during power or energy delivery, to act as conductive and / or convective heat sinks that remove thermal energy. It may be injected into the patient's bloodstream near the treatment site (open circuit system) (see Figure 30B). Injectable injections (eg, continuous infusion injections) provide more or faster heat transfer, as well as more uniform and / or predictable, compared to the pulsating blood flow provided by passive cooling. It can provide heat transfer mechanics. Injectable injection or blood proteins can be removed from the thermal heating element, thereby reducing the risk of clot formation. Infusion In addition to or as an alternative to injection, forced cooling removes heat indirectly from thermal heating elements and from non-target tissues during power or energy delivery, circulating or static coolant (eg,). It may have a closed circuit system with cold fluid, cold saline, etc. (see Figures 30C and 30D).

0383Energy is defined as power x time. When closed-circuit or open-circuit forced cooling is provided, the energy delivered is also not changed if the power and time to deliver energy is not changed compared to when forced cooling is not provided. Therefore, as shown in FIGS. 31A and 31B, forced cooling further maintains the desired tissue temperature TLESION at the desired therapeutic depth dLESION within the target tissue TiTARGET from the vessel surface of the vessel wall. Target tissue TiNON-TARGET can be protected from thermal damage at or near the vessel wall, eg, the surface temperature of the vessel wall during power delivery TSURF-ACTIVE compared to treatment TSURF-INACTIVE without forced cooling. Can be reduced.

0384However, if forced cooling is provided in combination with increased power but a consistent duration of power delivery, the energy delivered is increased, accompanied by forced cooling that protects non-target tissue in the vessel wall. It can facilitate the safe creation of deeper or larger lesions than would be feasible without. Similarly, providing forced cooling in combination with an increased duration of power delivery but with a consistent magnitude of power level will increase the energy delivered and again potentially forced cooling. Promotes the safe creation of deeper or larger lesions than would be feasible in the absence of. For example, as shown in Figures 32A and 32B, increased energy delivery in the presence of forced cooling maintains a consistent surface temperature Ts consistent with that achieved by lower energy in the absence of forced cooling. Treatments that reach the target temperature TLESION compared to the depth of treatment that reaches the target temperature when utilizing lower energy in dLESION-INACTIVE in the absence of forced cooling while gaining (or reducing the surface temperature) Increases the depth dLESION-ACTIVE of.

0385Forced cooling can also facilitate the delivery of energy through increased power levels, combined with a reduced power delivery duration. As shown in Figures 33A and 33B, this can facilitate faster lesion formation, which is the desired lesion depth dLESION at which the target temperature TLESION is achieved, as well as surfaces at or below the desired level. The time until power delivery is turned off, tFINISH, may shorten the duration of power delivery while maintaining tissue temperature Ts. Depending on the relative degree of increase in power magnitude and decrease in power duration, such changes can also facilitate the delivery of more energy in less time, which in less time. Can facilitate the safe creation of deeper or larger lesions. For example, FIG. 33A shows temperature vs. time at a distance from the thermal heating element 24 within the target tissue TTARGET. By cooling the surface of the treatment site, the power can be increased at a faster rate and the temperature of the target tissue can rise faster until it exceeds the target temperature TLESION, the temperature of the target tissue. Can be held above the target temperature for equal duration and power can be turned off faster, resulting in an end time without cooling tFINISH-NON-COOLED compared to , Brings an earlier end time tFINISH-COOLED. Therefore, the duration of treatment may be reduced. In a different algorithm, the duration of treatment is higher over a shorter duration, as shown in Figure 33B, which shows the temperature vs. time at a distance from the thermal heating element within the target tissue. It may be reduced by providing equivalent heat irradiation.

0386The three effects of cooling mentioned above (lower surface temperature, larger / deeper lesions, and faster lesions) were simplified by keeping the variables constant for the purposes of consideration. Variations or combinations of these effects can be achieved by varying variables, including: power, rate of power increase, duration of power delivery, and rate of cooling. Algorithms such as Algorithm 102 may optionally be used to control these variables.

03872. Capacity and rate of injectable solution during open circuit forced cooling When forced cooling is achieved via an open circuit system that utilizes intravascular injection (eg, saline) injection (see, eg, Figure 30B), attention should be paid to the volume and rate of injection. Is. Intravascular infusion is performed, for example, before power delivery, then during power delivery for about 0-10 seconds (eg, about 5 seconds), and after power delivery for about 0-10 seconds (eg, about 5 seconds), at the treatment site. Provided in the vicinity of. Intravascular infusion of significant saline volume can induce pulmonary edema or heart failure in some patients, and in some patient groups there may be a higher risk of such complications. These higher-risk patient groups include, for example, patients with a history of heart failure or heart disease, renal dysfunction, and / or diabetes, who have been shown to be therapeutically indicated for renal neuromodulation. It can be.

0388Advantageously, according to the embodiments described in this application, the magnitude of the maximum power delivered during renal neuromodulatory therapy is, for example, the power utilized in electrophysiological therapy to achieve cardiac tissue resection. Relatively low (eg, less than about 15 watts, eg, less than about 10 watts or less than about 8 watts) compared to levels (eg, power levels greater than about 15 watts, eg, greater than about 30 watts). .. In addition, the relative volume of the electrode or thermal heating element 24 described in the embodiments of the present application, configured for use in the renal vascular structure for renal nerve regulation, achieves cardiac tissue resection. It is expected to be significantly lower than the capacitance of the electrodes used to do this (eg, about 10% relative capacitance).

0389Thermal heating elements and / or non-target tissues are kept below the desired temperature during power delivery (eg, because relatively low power levels can be utilized in combination with relatively small electrodes to achieve renal nerve regulation (eg,). The flow rate and / or total volume of intravascular infusion injection required to maintain, eg, at about 50 ° C or less, for example, at about 45 ° C or less, is also used, for example, in electrophysiological therapy. It can be relatively lower than what is needed at higher power levels (eg, power levels above about 15 watts). This relative reduction in intravascular infusion flow rate and / or total volume is advantageous in favor of higher power levels, and therefore correspondingly higher infusion rates / volumes. If so, it may facilitate the use of intravascular infusions in contraindicated, higher risk patient populations (eg, patients with heart disease, heart failure, renal dysfunction, and / or diabetes).

0390When the intravascular infusion comprises saline, 1 liter of saline may comprise about 9 grams of sodium chloride, including about 3.6 grams of sodium. 3.6 grams of sodium is about 150% of the recommended daily allowance for patients with heart failure or hypertension. Each liter of saline solution may also contain approximately 1,000 units of anticoagulant heparin. In addition, saline injection increases venous pressure, and thereby capillary pressure, which increases the amount of fluid leaving the vascular structure. If lymphatic and renal excretion (urine output) cannot maintain homeostasis, fluid can accumulate and cause pulmonary edema or heart failure.

0391Based on the above, it may be desirable to limit the saline (eg, room temperature saline) infusion to less than about 1 liter, such as less than about 500 mL, less than about 250 mL, or less than about 100 mL. Such limits on saline infusion volume may facilitate infusion in higher risk patient groups, such as those with heart disease, heart failure, diabetes, and / or renal dysfunction. When the maximum power level does not exceed about 15 watts, for example, about 10 watts, the injection rate of about 15 mL / min or less, for example about 10 mL / min or less, keeps the thermal heating element below the desired temperature. For example, below about 50 ° C, it is expected that it will be sufficient to maintain, for example, below about 45 ° C. For treatment times of 2 minutes or less, these infusion rates facilitate treatment at multiple sites while maintaining a total infusion volume below approximately 1 liter, 500 mL, 250 mL and / or 100 mL. A control algorithm, such as Algorithm 102, or a manual controller may be provided to control the injection rate and / or total injection volume, while the fluid pump is desired (eg, controlled) through an elongated shaft 16. ) May be provided to propel the infusion at a rate.

0392As an example, if saline solution is injected before and after treatment for 5 seconds and during 2 minutes of treatment (ie, if saline solution is injected for about 130 seconds per treatment site). Each treatment at an infusion rate of 15 mL / min would result in a total infusion volume of approximately 32.5 mL. Therefore, treatment is performed at about 3 treatment sites while maintaining a total infusion volume of less than about 100 mL, and at more than 7 treatment sites while maintaining a total infusion volume of less than about 250 mL, with a total infusion volume of less than about 500 mL. It may be performed at about 15 treatment sites while maintaining and at more than 30 treatment sites while maintaining a total infusion volume of less than about 1 liter. Treatment for less than 2 minutes can promote even lower total infusion volumes for a given number of treatment sites and / or treatment at additional sites while maintaining a total infusion volume below the desired threshold. Can be promoted.

0393Similarly, if saline solution is injected before and after treatment for 5 seconds and during 2 minutes of treatment (ie, if saline solution is injected for about 130 seconds per treatment site). Each treatment at an infusion rate of 10 mL / min would result in a total infusion volume of approximately 21.7 mL. Therefore, treatment is performed at more than 4 treatment sites while maintaining a total infusion volume of less than about 100 mL, and at more than 11 treatment sites while maintaining a total infusion volume of less than about 250 mL, with a total infusion volume of less than about 500 mL. It may be performed at about 23 treatment sites while maintaining and at about 46 treatment sites while maintaining a total infusion volume below about 1 liter. Treatment for less than 2 minutes can promote even lower total infusion volumes for a given number of treatment sites (and / or treatment at additional sites while maintaining a total infusion volume below the desired threshold. Can be promoted).

0394Urethral catheterization may be provided in addition to or as an alternative to limiting the volume of injectable fluid injected intravascularly during renal nerve regulation to remove excess fluid load. .. Also, an open and closed hybrid cooling system is circulated through the closing components of the cooling system (eg, through coolant as shown in Figures 30C and 30D) to reduce or limit the volume of the injectate. ), May be provided by removing at least a portion of any excess thermal energy.

0395Still as an alternative, rather than injecting saline solution, the infusion solution may comprise blood, either from an in-house or external donor. When autologous, blood can be arterial or venous and can be taken from any other point in the vascular structure, such as at or near the femoral artery access point for injection within the renal artery. In this mode, the total fluid volume in the patient is unchanged, while the flow rate and volume through the renal arteries (and thereby the rate of heat transfer from the thermal heating element and / or non-target wall tissue). Is increased.

03963. Effect of open circuit cooling on thermal heating element contact stability, and its mitigation Forced cooling via infusion injection from an infusion electrode, such as that shown in FIG. 30B, may destabilize stable contact at the interface between the tissue and the electrode 46 at the treatment site. When the fluid flows out of the electrode through port 47, eg, radially and / or vertically from the electrode, the fluid may prompt the electrode to move away from the treatment site tissue.

0397As shown in FIGS. 34-34L, various embodiments of the perfused electrode 46 and / or port 47 are provided that can enhance or facilitate the maintenance of stable contact between the treatment site tissue and the electrode. May be done. In these embodiments, port 47 is configured to direct the thermofluid infusion away from the tissue / electrode interface and / or to direct the injectate with a lower force vector oriented perpendicular to the interface. Will be done. What is achieved when the injectate is directed perpendicular to the interface along a common cross section because the injectate is not directed at the tissue / electrode interface (or is not directed at the interface with similarly large force). Cooling at the interface may be lower than that. However, the flow of fluid through the electrodes will still draw heat from the tissue into the blood through the electrodes.

0398With reference to FIG. 34A, the irrigation port 47 of the electrode 46 may be positioned on the side surface of the electrode that does not contact the tissue in order to direct the thermofluid infusion away from the tissue / electrode interface. Further or alternately, one or more irrigation ports 47 may be provided at the tip of the electrode 46, as shown in FIG. 34B (eg, irrigation electrode tip). In a further embodiment seen in FIG. 34C, the electrode 46 is wider in diameter than the more proximal portion of the distal end region 20 of the elongated shaft 12, and the proximal facing port (s) 47 is with the elongated shaft. Positioned along the proximal surface of the electrode between the outer diameter of the electrode. In FIG. 34D, the electrode 46 has a contour with at least one reduced diameter lumbar or groove positioned along the length of the cylindrical electrode, and the port 47 is in the groove. Positioned and recessed from the tissue / electrode interface.

0399In FIGS. 34E-34H, the irrigation port (s) 47 directs the flow at a smaller angle to the electrode surface so that the normal force vector at the tissue / electrode interface is smaller. In FIG. 34E, the port 47 is angled to deliver fluid directed distally (ie, in the forward or direction of blood flow) to the vessel wall at an acute angle. In Figure 34F, port 47 is angled to deliver fluid directed proximally (ie, in the opposite direction or in the opposite direction of blood flow) to the vessel wall at an acute angle. Can be attached. In FIG. 34G, the port (s) 47 are angled to deliver the fluid at an acute angle to the vessel wall in the circumferential direction (ie, neither forward nor reverse). In FIG. 34H, the port 47 is angled and recessed with respect to the outermost diameter of the electrode 46 to deliver the fluid at an acute angle to the vessel wall. As will be apparent, any combination of fluid infusions that are sharp with respect to the vessel wall and are directed distally, proximally, and / or peripherally may be provided.

0400Optionally, the port 47 may be utilized to draw blood into the thermal heating element 24 in order to increase the heat transfer from the thermal heating element to the blood. Blood is drawn to a syringe or blood reservoir located outside the body, eg, through one or more ports 47, such as one or more tip ports, and through an elongated shaft 12, as shown in FIG. 34B. May be good. Blood may optionally be redeposited into the patient's bloodstream during or after treatment at the same or different locations. Further or alternately, blood drawn through the port (s) 47 may be pumped back from the renal arteries to a more hypotensive location such as the femoral artery or vein.

0401As shown in FIGS. 34I-34L, the irrigation port (s) 47 optionally allows the fluid infusion to flow over the electrodes in the direction of renal blood flow rather than flowing out of the electrodes. It may be located proximal to the electrode 46 rather than inside or above the electrode itself. Blood flow through the renal arteries can be substantially layered, with much less flow over the electrodes positioned on the wall than through the center of the blood vessel. Therefore, the infusion delivered through the irrigation port 47, which is positioned proximal to the electrode 46 (eg, located along a third flexure zone 44 or a second flexure zone 34), is a fluid flowing over the electrode. The temperature can be reduced and / or the flow at the wall can be increased.

0402In FIG. 34I, the port (s) 47, positioned proximal to the electrode 46, are oriented radially to deliver the injectate substantially perpendicular to the elongated shaft 12. In Figure 34J, the port (s) are at an acute angle (distal and / or proximal) with respect to the elongated shaft 12 to deliver the infusion solution at an acute angle to the shaft. , Acute in the radial direction. In FIG. 34K, the port 47 is generally oriented away from the tissue / electrode interface and towards the center of the vessel. In FIG. 34L, the port (s) are directed outwardly with respect to the vessel, which can establish a vortex in the vicinity of the electrode 46 and / or divert blood flow towards the treatment site.

0403Additional techniques for directing the thermo-fluid infusion away from the tissue / electrode interface and / or directing the infusion perpendicular to the interface, with a lower force vector, may be port 47. It may be provided with varying speed or pressure injection through. For example, a relatively large number of ports may be provided in all directions so that the volumetric flow through each port is less for a given volumetric flow rate, which is each port. The speed or pressure of flow through can be reduced. Further or alternatively, the port (s) positioned on the interface side surface of the electrode 46 and / or the elongated shaft 12 can be relatively smaller than the port positioned on the blood flow facing side surface of the electrode. In addition, the volumetric flow rate may be controlled to provide the minimum flow required to achieve the desired cooling effect, as described above. A cooling electrode 46 with an open-circuit and closed-circuit hybrid cooling system can also reduce the volumetric flow rate of the injection required to achieve the desired cooling effect.

0404Maintaining stable contact between the treatment site tissue and the electrodes during delivery of the infusion through port 47 also provides sufficient mechanical stabilization for the distal end region 20 and its complex flexion configuration. Can be achieved by Mechanical stabilization may be designed in the equipment to compensate for any destabilization induced by irrigation. For example, a large force applied over a large surface area applies a lower pressure while providing stabilization. This is achieved by making the contact between the contact catheter and the arterial wall over a large surface area similar to longitudinal contact, spiral contact, multipoint contact with flexion, deployable contact, etc. can do. In addition, contact or stabilization feedback may be provided to inform the caregiver whether tissue / electrode interfacial stability is insufficient for effective resection (eg, one or more sensors (eg, one or more sensors). Multiple) via 52). Such feedback may include, for example, feedback of impedance or pressure measurements at or near the interface. Still further, the fluid flowing through the lumen 45 during open-circuit cooling can stiffen the distal end region 20 of the elongated shaft 12, which offsets any instability induced by such fluid injection. Can be done.

0405The irrigation-induced orthogonal force pushing the electrode 46 away from the vessel wall may optionally be utilized to assist delivery of the electrode in stable contact with the vessel wall. For example, such forces can potentially reduce traumatic forces as the electrodes and / or distal end region 20 advance into the arterial wall. In addition, the force and injectate can establish a smooth layer that assists in electrode placement and / or reduces friction or scraping during electrode placement, repositioning, and / or withdrawal. When the irrigation or infusion is directed in the opposite direction at an acute angle to the vessel wall (see Figure 34F), the infusion solution pushes the electrode away from the vessel wall and propels the electrode forward into the vessel. , It may assist in the delivery and placement of the electrodes.

04064. Impact of forced cooling on temperature measurement and its mitigation When utilizing forced cooling, temperature measurements may be less accurate or useful than when cooling is not provided. As shown in FIG. 35, the temperature sensor 52 (eg, thermocouple) is in or on the electrode because the electrodes and tissue surface are cooled (directly in the open circuit system and indirectly in the closed circuit system). When provided to, a significant increase in tissue temperature at lesion depth from the lumen surface Tlesion can only correspond to a small increase in electrode and / or surface temperature TS (and hence the temperature sensor temperature monitored). .. There may be a correlation between cooling electrode temperature and this deeper lesion tissue temperature, but such a correlation is expected to be significantly less accurate in the presence of forced cooling.

0407Complex algorithms, such as embodiments of Algorithm 102, to enhance the accuracy of the correlation between electrode temperature and deep tissue temperature to illustrate the reduced accuracy or usefulness of temperature measurements at the treatment site. May be provided. The algorithm can model complex hydromechanical and thermomechanical environments in the vicinity of temperature sensors and / or treatment sites. Variables used in such algorithms include, for example, flow rate, infusion or coolant temperature, blood flow, blood temperature, tissue temperature, tissue electrical and thermal characteristics, coolant and blood temperature downstream of the treatment site. Etc. may be included. Additional and alternative variables may be used. Additional sensors may be provided to measure one or more of these variables.

0408Alternatively, other than temperature, therapeutic efficacy and safety indicators may be utilized. For example, relative changes in impedance measurements at the electrodes over time as lesions are being created may be used as indicators of lesion formation. Typically, when the tissue heats, its impedance decreases up to some temperature threshold, and when the tissue properties change with increasing temperature, the impedance then increases. A suitable lesion size can correlate with, for example, a relative decrease in impedance, a relative change in the slope of the impedance curve, and / or a relative increase following a decrease in impedance as measured by the impedance sensor 52. ..

0409The placement of the temperature sensor (s) 52 relative to the electrodes 46 and / or the irrigation port (s) 47 allows for forced cooling, surface temperature TS measurement accuracy and / or when assessing lesion temperature Tlesion at the desired depth. It can be specified to reduce or mitigate its impact on usefulness. The temperature sensor (s) 52 is such that the temperature sensor (s) is not cooled or is less likely to be cooled by the delivery of the injectate or coolant, eg, electrodes 46 and / or ports 47. On the other hand, it may be arranged externally or remotely. For example, a protruding temperature sensor that projects from the electrodes and expands or inserts into the tissue may be provided. Further or alternately, the stylus temperature sensor may be deployed from the device to the target depth. When the irrigation is directed away from the tissue / electrode interface (see, eg, FIG. 34A), the temperature sensor (s) 52 may be located on the side of the electrode in contact with the tissue.

0410In addition, as described in more detail below with respect to FIG. 36, energy can be delivered by algorithms incorporating intermittent power delivery and cooling, which can facilitate more accurate and / or useful temperature measurements. ..

04115. Control system for energy delivery during forced cooling As mentioned above, it may be desirable to reduce, control, or minimize the volume of injectable solution delivered during open circuit cooling. Control algorithms, such as Algorithm 102 above, have one or more monitored parameters of power delivery, such as power magnitude, duration of power delivery, temperature, flow, pressure, and / or impedance measurement. One or more control loops may be provided to control or change the volumetric flow of the infusion infusion in response to the effect of delivery on sensor measurements, etc.). For example, a relatively low volumetric flow rate infusion may be provided to reduce / control saline infusion into the patient's interior during idle conditions (ie, while energy is not being delivered). (For example, a rate sufficient to prevent blood coagulation within the port (s) 47 and / or the lumen (s) 45). Optionally, a low power pretreatment energy pulse may be provided in the presence of a low flow injection relative to the measured impedance and / or relative impedance to verify stable contact at the electrode / tissue interface. When activating energy delivery, the power may be given a gradient while maintaining a relatively low injectable flow rate until a higher injectable flow rate is required. For example, if the measured temperature is below a predetermined power level and increases above a predetermined level, for example, if it is 5 W or less and increases by 5 ° C or more from the baseline, the injectable flow rate may be increased. This first phase of energy delivery with a low injectable flow rate can provide more accurate temperature measurements compared to a higher injectable flow rate. This temperature measurement can be compared to the energy delivered to indicate whether blood flow is sufficient, too low, or inadequate contact with tissue. For example, a high temperature rise can show low blood flow, cooling can be increased, an ideal temperature rise can show sufficient blood flow, and a low temperature rise can be May indicate inadequate contact with tissue. The indication of blood flow is in the subsequent phase of energy delivery. , Can be incorporated into energy delivery algorithms. For example, low blood flow may be compensated for by increased or decreased power, and ideal blood flow may result in maintenance of low injectable flow, which is inadequate. Tissue contact can provide a message to reconfirm electrode contact and position.

0412As mentioned above, the dimensions of the electrodes are used in an environment where the active surface area to total surface area ratio (ASA: TSA) is in the appropriate range of volumetric blood flow when placed in contact with the inner wall of the renal artery. It may be configured so that it can result in a lesion of suitable size. Volumetric measurements If blood flow is below the appropriate range, heat convection from the electrodes and tissue surface may not be sufficient, causing blood coagulation and / or excessive tissue damage on the surface of the vessel wall, and / Or it results in a higher surface temperature that can interfere with the ability to effectively raise the temperature of the target tissue. Electrodes provide an appropriate ASA: TSA with a given power delivery profile to produce effective lesions with minimal or low forced cooling in the majority of patients with renal artery volume measurement blood flow within range. May be configured to have. Forced cooling can be triggered or increased as needed if volumetric blood flow in each renal artery is below range. For example, volumetric blood flow in a treated renal artery is very short, when the artery is narrowed, when more than one major renal artery replenishes the same kidney, When blood flow is divided between tributaries, it can fall below range. In these situations and the like, forced cooling can be increased manually or automatically when the volumetric blood flow is lower than the range in which the electrodes are constructed. The automatic increase in forced cooling can be triggered by a control algorithm that responds to the monitored parameters described above.

0413Irrigation or infusion may also be used in conjunction with an algorithmic control loop that regulates flow rates to compensate for sudden changes in electrode contact and / or renal blood flow. For example, sudden changes in renal blood flow can be caused by acute contraction of the renal arteries, changes in heart rate, and changes in renal vascular structure resistance. Forced cooling can be triggered or increased manually or automatically in response to sudden changes in renal blood flow.

0414After the power delivery reaches steady state, the flow rate and / or power is optionally only a measurable amount above normal blood temperature, but blood coagulation or excessive tissue, to increase the practicality of temperature measurement. It may be temporarily adjusted within the initial set range to allow the temperature to rise to the extent that it is not high enough to cause potential heating problems such as damage. Allowing the temperature to rise may provide further feedback that effective lesions have been created. After the temperature rise is detected, the flow rate and / or power may then return to levels where the measured temperature does not rise or falls again to baseline.

0415Algorithm 102 may optionally incorporate intermittent power delivery and forced cooling (open or closed). As shown in FIG. 36, when cooling, or power and cooling, is intermittently stopped or reduced over a short period of time, heat is conducted from the tissue at lesion depth to the tissue surface and temperature sensors. The surface temperature TS better approximates or correlates with the lesion temperature Tlesion during such an intermittent idle period. Therefore, the information gathered during the idle period may be used to calculate a more accurate representation of the lesion temperature Tlesion.

04166. Further representative embodiments i. Open circuit embodiment When a large number of irrigation ports 47 and a large number of temperature sensors 52 (eg, a large number of thermocouples) are incorporated into the electrode 46, to each port (or to each group of ports connected to a common injection lumen 45). ) The flow rate may be adjusted based on local temperature measurements. For example, a temperature sensor that measures a lower temperature may indicate that that portion of the electrode is relatively far from the tissue / electrode interface. Therefore, the irrigation flow to the port (s) 47 in the vicinity of the temperature sensor may be reduced to reduce the amount of saline infusion in the patient and / or to improve susceptibility to changes in temperature. ..

0417Similarly, a temperature sensor that measures warmer temperatures can indicate that that portion of the electrode is relatively close to the tissue / electrode interface, and the irrigation flow to the port (s) in the vicinity of the warmer temperature sensor is tissue. / May be increased to increase heat transfer in the vicinity of the electrode interface. Reducing irrigation or infusion on the side of the electrode facing blood flow facilitates delivery of further irrigation on the tissue / electrode interface side of the electrode while maintaining a total infusion volume below the desired threshold. obtain.

0418ii. Closed circuit embodiment FIG. 37 illustrates a further embodiment of the present invention. In FIG. 37, the distal end region 20 of the elongated shaft 12 comprises a balloon catheter 300 having one or more electrodes 46 coupled, connected, or laminated inside or outside an expandable balloon. Electrical connections to each electrode 46 may be provided by wires 29 or electrical traces on the surface of the balloon catheter 300. The wire / electric trace is electrically connected to the generator 26.

0419The balloon catheter 300 is flexible and can adapt to the range of anatomical structures expected upon dilation within the renal arteries. The fluid used to inflate the balloon may provide a thermal sink for closed circuit cooling of the electrode (s) 46 and / or the tissue being contacted. Optionally, the fluid may be circulated to enhance convective cooling and / or to maintain the temperature of the fluid at the desired level.

0420Because the balloon 300 blocks blood flow, accurate modeling of complex thermomechanical and fluid mechanical environments during treatment can be more controllable, which gives better control of treatment and lower risk. It can promote treatment and / or more effective treatment.

0421When a large number of electrodes 46 are provided, the longitudinal and / or perimeter separation of the electrodes, as shown in FIG. 37, does not require repositioning of the distal end region 20, if desired. It can be specified to facilitate treatment in multiple longitudinal / peripheral positions.

0422iii. Open circuit embodiment using an occlusion balloon FIG. 38 shows a further embodiment of the present invention. In FIG. 38, the distal end region 20 of the elongated shaft 12 comprises a distal occlusion balloon 301 mounted on a catheter, proximal to the distal occlusion balloon 301, which is a tube that communicates fluid with the source of the infusion. There is a pumping mechanism with an infusion port 49a connected to the cavity and a flow monitor. Proximal to the injection port 49 is one or more electrodes 46 located on a mechanically dilated or self-expanding member 35. The electrode 46 may include a temperature sensor. A temperature sensor may be included to measure the temperature of the injectate. For example, a thermocouple or thermistor can be used in an injectable lumen (not shown) in an extended shaft, at the opening of an injectable port 49, in an injectable source, and / or in a pumping mechanism. May be placed in. The flow rate of the injectate may be monitored by a flow meter or flow sensor, or controlled by the speed of the pumping mechanism.

0423Blood flows from the aorta to the kidney through renal artery flow, in other words, towards the distal end of the extended shaft 12. In this embodiment, the distal occlusion balloon temporarily slows or stops the flow, and the infusion of the infusion solution through the infusion port 49 flows in the opposite direction across the electrode 46 into the aorta. ..

0424Accurate modeling of complex thermomechanical and fluid mechanical environments during treatment can be more controllable because the flow rate and temperature of the infusion is known, which is better control of treatment, better of risk. May promote lower treatment and / or more effective treatment.

0425FIG. 39 illustrates an embodiment of the invention having an occlusion balloon 301 mounted on a balloon catheter 13 introduced through a lumen 51 in an excision catheter. The excision catheter comprises one or more electrodes 46 that are placed on a mechanical or self-expanding member 35.

0426Similar to the embodiment of FIG. 38, the injectate is pumped into the renal artery and flows in the opposite direction across the electrode 46 into the aorta. In the embodiment of FIG. 39, the infusion port 51 may be the same port as the passage through which the balloon catheter 13 is delivered, or it may be a separate lumen and port.

0427FIG. 40 illustrates an embodiment of the invention having an occlusion balloon 301 mounted on the distal end of the guide catheter 95. The excision catheter may be the embodiment shown in FIGS. 5-34L with or without port 47. The guide catheter 95 of FIG. 40 comprises the internal volume of the balloon 301 and an dilation lumen communicating with an dilation port (not shown) on the proximal end of the guide catheter 95. The guide catheter 95 also comprises a lumen 96, which is the passage through which the excision catheter is introduced into the renal artery.

0428Similar to the embodiment of FIG. 38, the injectate is pumped into the renal artery. However, in the embodiment of FIG. 40, the injectate is delivered through lumen 96 and flows forward into the kidney over electrode 46. The occlusive balloon 301 limits or stops blood flow from entering the artery.

0429FIG. 41 illustrates an embodiment comprising a distal occlusion balloon 301a and a proximal occlusion balloon 301b mounted on a distal and proximal extending shaft 12 on one or more electrodes 46, respectively. The extended shaft 12 further includes an injection port 49 and a suction port 53, which are located distally and proximally to the electrode 46, respectively. The injection port 49 fluidly communicates the length of the extended shaft with a supply lumen (not shown) that travels to the infusion supply connector on the proximal end of the catheter. The suction port 53 is fluid with a suction lumen (not shown) that travels the length of the extended shaft to the suction connector on the proximal end of the catheter. One or more electrodes 46 are arranged on a mechanical or self-expanding member 35.

0430The injectable feed is mechanically pumped into the supply connector and the suction injectable is disposed of or collected in a collection vessel. The injectate flows over the electrode 46 and is removed from the artery through the suction port 53.

0431iv. Embodiment of an open circuit having a Weeping Balloon / mesh FIG. 42 shows a further embodiment of the present invention. In FIG. 42, the distal end region 20 of the elongated shaft 12 has one or more electrodes 46 coupled or laminated inside or outside an expandable weeping balloon. ) 302 is provided. Electrical connections to each electrode 46 may be provided by wires 29 on the surface of the weeping balloon 302 or by electrical traces. The wire / electric trace is electrically connected to the generator 26.

0432The weeping balloon 302 is flexible and adapts to the range of anatomical structures expected during dilation within the renal arteries. The weeping balloon 302 includes a hole 303 that allows fluid inside the balloon to pass through. The hole 303 is positioned near or proximal to the electrode (s) 46. A fluid, such as saline solution, used to expand the weeping balloon passes through hole 303 and heat sinks and / or convection of the (s) and / or contacted tissues of electrode 46. May provide sex cooling. In addition, the fluid can be cooled.

0433Since the weeping balloon 302 blocks blood flow, accurate modeling of complex thermomechanical and fluid mechanical environments during treatment can be more controllable, which can lead to better control of treatment. , Lower risk treatment, and / or may promote more effective treatment.

0434When a large number of electrodes 46 are provided, the longitudinal and / or perimeter separation of the electrodes, as shown in FIG. 42, does not require repositioning of the distal end region 20, if desired. It can be specified to facilitate treatment in multiple longitudinal / peripheral positions.

0435Alternatively, expandable braids, meshes, or fabrics may be used in place of the Weeping balloon. Expandable braids, meshes, or fabrics can be expanded by injecting fluid into it. Alternatively, it may be extended by mechanical means such as pull wires that reduce the length of the braid, or the expandable braid may be self-expanding.

0436IV. Using the system A. Intravascular delivery, deflection, and placement of treatment equipment Any one of the 12 embodiments of the therapeutic device described herein can be delivered over a guidewire using conventional over-the-wire techniques. When delivered in this manner (not shown), the elongated shaft 16 comprises a passage or lumen that accommodates the passage of the guide wire.

0437In one exemplary approach, a guide wire (not shown) is inserted through the access site and using image guidance, through the femoral artery, into the iliac and aorta, and either left or right. It is passed through the renal artery. The guide catheter may be routed over the guide wire into the renal artery being accessed. The guide wire is then removed.

0438In the second exemplary approach, the first guide catheter is placed at the entrance of the renal artery (with or without a guide wire). The second guide catheter is routed through the first guide catheter (with or without the assistance of a guide wire) into the renal artery. The treatment device is then delivered into the renal artery via a second guide catheter. Once the therapeutic device is properly positioned within the renal artery, the second guide catheter is retracted, leaving the first guide catheter at the entrance to the renal artery. In this approach, the first and second guide catheters should be sized and configured to accommodate passage within the first guide catheter of the second guide catheter (ie, first). The inner diameter of the guide catheter should be larger than the outer diameter of the second guide catheter). For example, the first guide catheter can be 8 French in size and the second guide catheter can be 5 French in size.

0439In the third exemplary approach, and as shown in FIG. 43A, the renal guide catheter 94 (eg, 6 French renal guide catheter) is positioned within the abdominal aorta just proximal to the entrance of the renal artery. .. The therapeutic device 12 described herein is then routed through a guide catheter 94 into the renal artery being accessed, as shown in FIG. 43B. The elongated shaft makes a non-traumatic passage of the guide catheter 94 in response to the force applied to the force transfer compartment 30 through the handle assembly 200. The first or proximal flexion area 32 responds to significant flexure at the junction of the left / right renal artery and the aorta to obtain entry into the respective left or right renal artery through the guide catheter 94 (Figure). As 43B shows).

0440As shown in FIG. 43C, the second flexion area 34 on the distal end of the elongated shaft 16 is then axially translated into each renal artery and approaches the inner wall of each renal artery. And remotely deflected within each renal artery in a controlled manner to achieve the desired alignment with them (eg, plane deflection or flexion, but alternative, spiral Any other aforementioned deflection, such as a shape deflection, may be provided) and / or may be rotated. As further shown in FIG. 43C, any third flexure zone 44 bends to place the thermal energy heating element 24 in contact with the tissue on the inner wall (alternatively or additionally, one or more energies). The delivery element 24 may be positioned along the length of the second flexure zone 34 and carried in contact with the tissue on the inner wall during remote deflection of the second flexure zone).

0441B. Creation of thermally affected tissue areas As mentioned above (and as shown in FIG. 43B), the energy delivery element 24 flexes along the first flexion area 32 at the first desired axial location within each renal artery. May be positioned by. As shown in FIG. 43C, the energy delivery element 24 may be radially positioned by the deflection towards the vessel wall of the second flexion area 34. As also shown in FIG. 43C, the energy delivery element 24 may be placed in optimal surface area contact conditions with the vessel wall due to further deflection of the third flexure zone 44.

0442Once the energy delivery element 24 is positioned in the desired location by a combination of deflection of the second flexion zone 34, deflection of the third flexure zone 44, and / or rotation of the catheter, treatment can be performed. Optionally, the infusion solution, such as saline solution, of the treatment site before, during, and / or after treatment to provide conductive and / or convective cooling beyond that provided by the bloodstream. It may be delivered in the vicinity (eg, through an energy delivery element, as shown in Figure 30B). By applying energy through the energy delivery element 24, a first thermally acted tissue region 98 (a) can be formed, as shown in FIG. 43D. In an exemplary embodiment, the thermally acted area 98 (a) takes the form of a lesion on the vessel wall of the respective renal artery.

0443After forming the first thermally actuated tissue region 98 (a), the catheter may optionally be repositioned for another heat treatment. As described in more detail above, it is desirable to create a large number of focal lesions that are peripherally spaced along the longitudinal axis of the renal artery. To achieve this result, the catheter may optionally be retracted and optionally rotated to position the energy delivery element proximally along the longitudinal axis of the vessel. Rotation of the elongated shaft 16 from the outside of the access site (see Figure 43E) may reposition the energy delivery element 24 peripherally around the renal arteries. Once the energy delivery element 24 is isolated from the axial position of the first description, as shown in FIG. 43E (eg, 98 (b)), the second axial and the second axial and Once positioned in the outer peripheral location, another focal treatment may be the treatment to be given (with or without saline infusion). By repeating the operational steps described immediately before (shown in Figures 43F-43K), the caregiver can perform multiple thermally actuated tissues on the axially and peripherally spaced vessel walls. Regions 98 (a), 98 (b), 98 (c), and 98 (d) can be created, of which the first thermally acted tissue region 98 (a) is the most distal. Yes, the subsequent thermally affected tissue area is more proximal. FIG. 43I provides a cross-sectional view of a lesion formed by multiple layers of the renal artery to be treated. This figure shows that multiple peripheral and axially spaced treatments (eg, 98 (a) -98 (d)) provide a substantially peripheral range of application, and thus nerves to the renal plexus. Shows that it can cause a regulatory effect. Clinical studies show that each lesion covers approximately 20 to 30 percent of the perimeter area surrounding the renal arteries. In other embodiments, the peripheral coverage of each lesion can be as much as 50 percent.

0444In an alternative therapeutic approach, therapeutic instruments can be applied to create complex patterns / numerous thermally acted tissue areas along the walls of the renal arteries. As Figure 43L shows, this alternative therapeutic approach provides multiple perimeter treatments at each axial site along the renal artery (eg, 98, 99, and 101). Using this approach to increase the density of thermally affected tissue regions along the walls of the renal arteries increases the likelihood of thermal blockage of nerve fibers within the renal plexus.

0445The rotation of the energy delivery element 24 within the renal artery, as seen in Figure 43G, may improve treatment certainty and consistency. Since angiographic guidance such as fluoroscopy only provides visualization in two dimensions, it is generally common to obtain a visible confirmation of wall contact at the top (apex) and bottom (bottom) of the renal artery. It is only possible in the front / rear image. For anterior and posterior treatments, catheters so that confirmation of contact at the upper and lower locations is first obtained and then the energy delivery element moves peripherally along the vessel wall until the desired treatment location is reached. It may be desirable to rotate. Physiological data such as impedance may be monitored simultaneously to ensure that wall contact is maintained or optimized during catheter rotation. Alternatively, the C-shaped arm of the fluoroscope can be rotated to achieve a better angle to determine wall contact.

0446FIG. 43 shows a number of longitudinally and peripherally spaced nests created by repositioning the energy delivery element 24 through a combination of deflection of the second flexion zone and rotation and / or translation of the elongated shaft. Illustrative lesions. In some of the aforementioned embodiments of the therapeutic device, such a large number of focal lesions may be created by a large number of energy delivery elements 24 positioned along the length of the distal end region 20. Further or alternatively, in some of the aforementioned embodiments of the therapeutic device, such multiple focal lesions occur only through a second flexion zone deflection in multiple planes, only through the translation of an elongated shaft. Created by repositioning the energy delivery element (s) 24 only through the rotation of the elongated shaft, or only through deflection of the second flexure zone, translation of the elongated shaft, and only any subset of the rotation of the elongated shaft. May be good.

0447Figures 46A-46C provide fluoroscopic images of therapeutic devices in the renal arteries during animal studies. FIG. 46A shows the positioning of the therapeutic device and energy delivery element 24 at the distal treatment site. The second flexion zone 34 is deflected to position the energy delivery element 24 in contact with the vessel wall and to cause flexure in the third flexure zone 44. FIG. 46A also shows the contact area 124, where the apex of the flexion of the second flexure zone 34 is radially opposite or angularly opposite to the contact between the energy delivery element and the vessel wall. (angular In opposition), it is in contact with the blood vessel wall. FIG. 46B shows the placement of treatment equipment at a more proximal treatment site following perimeter rotation and axial retraction. FIG. 46C shows the placement of treatment equipment at a treatment site just distal to the aortic and renal artery junctions. Figures 46D and 46E provide similar fluoroscopic images showing therapeutic equipment positioned for treatment within the human renal artery. FIG. 46D shows a treatment device advanced to a distal treatment site similar to that described above with respect to FIG. 46A. FIG. 46E shows a treatment device in a proximal treatment position similar to that described above with respect to FIG. 46C.

0448Angiographic visualization is used because both the energy delivery element 24 and the solder 130 at the distal end of the second flexion area 34 can be radiation opaque, as shown in Figures 46A-46C. The operator can use the image corresponding to the first treatment location to relatively position the treatment device for the second treatment. For example, in an average length renal artery, it is desirable for the clinical operator to treat approximately every 5 mm along the length of the major artery. In an embodiment where the length of the third flexure zone 44 is 5 mm, the operator aligns the device with the current position of the energy delivery element 24 in the longitudinal direction with the position of the solder 130 in the previous treatment. It can simply be set back.

0449In another embodiment, different types of radiation opaque markers can replace the solder 130. For example, a platinum band may be attached to the distal end of the second flexion area to act as a radiation opaque marker.

0450Angiographic visualization of the vasculature generally requires the contrast agent to be injected into the renal arteries, so the lumen for injecting the contrast agent into the bloodstream in or in parallel with the treatment device. It may be desirable to include and / or ports. Alternatively, the contrast agent can be delivered into the blood in parallel with the therapeutic device in the annular gap between the therapeutic device and the guide catheter, which is the passage through which the device is delivered.

0451Exposure to thermal energy (heat) above body temperature of about 37 ° C but below temperature of about 45 ° C is through moderate heating of the target nerve fibers, or of the vascular structure that perfuse the target fibers. Can induce thermal alteration. When the vascular structure is acted upon, the target nerve fibers are deperfused, resulting in necrosis of nerve tissue. For example, it can induce non-resectable thermal alterations in fibers or structures. Exposure to heat above a temperature of about 45 ° C, or above about 60 ° C, can induce thermal alteration through substantial heating of the fibers or structures. For example, such higher temperatures can thermally excise target nerve fibers or vascular structures. In some patients, the target nerve fibers or vascular structures are thermally excised, but at temperatures below about 90 ° C, or less than about 85 ° C, or less than about 80 ° C, and / or less than about 75 ° C. It may be desirable to achieve this. Reduced renal sympathetic nerve activity (RSNA) is expected, regardless of the type of heat exposure used to induce thermal neuromodulation.

0452C. Control of applied energy In the treatments disclosed herein for delivering treatment to target tissue, it may be beneficial for energy to be delivered in a controlled manner to the target neural structure. Controlled delivery of energy allows the area of heat treatment to extend into the renal fascia while reducing unwanted energy delivery or thermal effects to the vessel wall. Controlled delivery of energy can also result in more consistent, predictable, and efficient overall treatment. Therefore, the generator 26 preferably includes a programmed instruction with an algorithm 102 (see FIG. 5) for controlling the delivery of power and energy to the thermal heating device. Algorithm 102, whose typical embodiment is shown in FIG. 44, can be implemented as a conventional computer program for execution by a processor coupled to generator 26. Caregivers using step-by-step instructions can also manually implement Algorithm 102.

0453Working parameters monitored by the algorithm may include, for example, temperature, time, impedance, power, flow rate, volumetric flow rate, blood pressure, heart rate and the like. Individual values of temperature may be used to inspire changes in power or energy delivery. For example, high temperature values (eg, 85 ° C) can indicate tissue dryness, in which case the algorithm has power and energy to prevent unwanted thermal effects on targeted or non-targeted tissue. Delivery can be reduced or stopped. Time may be used further or as an alternative to prevent unwanted thermal alteration to non-target tissue. For each treatment, a set time (eg, 2 minutes) is checked to prevent infinite delivery of power.

0454Impedance may be used to measure tissue changes. Impedance indicates the electrical characteristics of the treatment site. When a heat-induced electric field is applied to the treatment site, the impedance decreases as the tissue cells become less resistant to current flow. When excessive energy is applied, tissue drying or coagulation can occur near the electrodes, because the cells lose water retention and / or the electrode surface area is reduced (eg, through the accumulation of blood clots). ) Increase impedance. Therefore, an increase in tissue impedance can be an indicator or prediction of undesired thermal alteration for target or non-target tissue.

0455Further or alternative, power is an effective parameter for monitoring in controlling the delivery of therapies. Power is a function of voltage and current. The algorithm may tailor the transfer and / or current to achieve the desired power.

0456Derivatives of the above parameters (eg, rate of change) may also be used to inspire changes in power or energy delivery. For example, the rate of change in temperature may be monitored so that the power output is reduced if a sudden rise in temperature is detected. Similarly, the rate of change in impedance may be monitored so that the power output is reduced if a sudden rise in impedance is detected.

0457As shown in FIG. 44, when the caregiver evokes treatment (eg, via a tread), algorithm 102 gives the generator 26 its power output during the first period t1 (eg, 15). Instruct to step up to the first power level P1 (eg 5 watts) over seconds). The power increase during the first period is generally linear. As a result, the generator 26 generally increases its power output at a constant rate of P1 / t1. Alternatively, the power increase can be non-linear (eg, exponential or parabolic) with a variable rate of increase. Once P1 and t1 are achieved, the algorithm can be held in P1 for a new time t2 over a predetermined period of time t2-t1 (eg, 3 seconds). At t2, power is increased by a given increment (eg, 1 watt) up to P2 over a given period of time, t3-t2 (eg, 1 second). This power lamp in a given increment of about 1 watt over a given period of time can continue until the maximum power PMAX is achieved or some other condition is met. In one embodiment, the PMAX is 8 watts. In another embodiment the PMAX is 10 watts. Optionally, power may be maintained at maximum power PMAX for a desired period of time, or up to a desired total treatment time (eg, up to about 120 seconds).

0458In FIG. 44, algorithm 102 exemplifies a power control algorithm. However, it should be understood that algorithm 102 may optionally include a temperature control algorithm. For example, the power may be increased stepwise over a desired duration (duration) until the desired temperature (s) is obtained. In another embodiment, combinatorial power control and temperature control algorithms may be provided.

0459As discussed, algorithm 102 includes monitoring certain operating parameters (eg, temperature, time, impedance, power, flow rate, volumetric flow rate, blood pressure, heart rate, etc.). Operating parameters may be monitored continuously or periodically. Algorithm 102 checks the parameters being monitored against a given parameter profile to determine if the parameters, individually or in combination, fall within the range set by the given parameter profile. Treatment can be continued with the commanded power output if the monitored parameters fall within the range set by the predetermined parameter profile. If the parameter being monitored falls outside the range set by the predetermined parameter profile, Algorithm 102 adjusts the commanded power output accordingly. For example, if a target temperature (eg, 65 ° C.) is achieved, power delivery is kept constant until the total treatment time (eg, 120 seconds) expires. If the first temperature threshold (eg 70 ° C) is achieved or exceeded, the power is reduced by a given increment (eg 0.5 watts, 1.0 watts, etc.) until the target temperature is achieved. Will be done. Power delivery may be terminated if a second power threshold (eg, 85 ° C) is achieved or exceeded, which indicates undesired conditions. The system may be fitted with various audible and visible alarms that warn the operator of certain conditions.

0460The following is a non-exhaustive list of events in which Algorithm 102 can adjust and / or terminate / interrupt the commanded power output: (1) The measured temperature exceeds the maximum temperature threshold (for example, about 70 ° C to about 85 ° C). (2) The average temperature derived from the measured temperature exceeds the average temperature threshold (for example, about 65 ° C). (3) The rate of change of the measured temperature exceeds the rate of change of the threshold value. (4) While the generator 26 has a non-zero output, the temperature rise over a period of time falls below the minimum temperature change threshold. Inadequate contact between the energy delivery element 24 and the arterial wall can cause such conditions. (5) The measured impedance exceeds the impedance threshold (eg, less than 20 ohms or more than 500 ohms). (6) The measured impedance exceeds the relative threshold (eg, the impedance decreases from the starting or baseline value and then rises above this baseline value). (7) The measured power exceeds the power threshold (eg, greater than 8 watts or greater than 10 watts). (8) The measured duration of power delivery exceeds the time threshold (eg, greater than 120 seconds).

0461V. Prepackaged kits for distribution, transportation and sale of disclosed equipment and systems As shown in FIG. 45, one or more component systems 10 shown in FIG. 5 can be packaged together for convenient delivery to customers / clinical operators and their use. it can. Suitable components for packaging include a therapeutic device 12, a cable 28 for connecting the therapeutic device 12 to the generator 26, a neutral or dispersive electrode 38, and one or more guide catheters 94 (eg, one or more guide catheters 94). Renal guide catheter) is included. Cable 28 can also be integrated into the treatment device 12 so that both components are packaged together. Each component may have its own sterilization package (for components that require sterilization). Alternatively, the component may have its own sterile compartment within the kit package. The kit also provides the operator with technical product features and technical product features for using System 10 and Therapeutic Equipment 12, including all methods of insertion, delivery, placement, and use of the Therapeutic Equipment disclosed herein. It may include step-by-step instructions 126 for use that provide operating instructions.

0462VI. Further clinical use of disclosed devices, methods, and systems Much of the disclosure herein relates to at least partially denervating a patient's kidney to block afferent and / or efferent nerve traffic from within a renal vessel (eg, a renal artery). The devices, methods, and systems described herein may also be used for other endovascular treatments. For example, the catheter system described above, or a selected embodiment of such a system, is placed in other peripheral blood vessels to deliver energy and / or electric fields, and nerves in close proximity to these other peripheral blood vessels. The neuromodulatory effect can be achieved by changing. There are several arterial blood vessels originating from the aorta that migrate to the target organ in parallel with a rich group of nerves. Accessing these nerves and utilizing the arteries to regulate them may have obvious therapeutic potential in some medical conditions. Some examples include nerves surrounding the abdominal trunk, superior mesenteric artery, and inferior mesenteric artery.

0463The sympathetic nerves that approach or surround the arterial blood vessels, known as the abdominal trunk, pass through the abdominal ganglia and follow the tributaries of the abdominal trunk, including the stomach, small intestine, abdominal blood vessels, liver, bile ducts, gallbladder, pancreas, and adrenal glands. , And can innervate the kidneys. Global (or partial) regulation of these nerves can result in diabetes, pancreatitis, obesity, hypertension, obesity-related hypertension, hepatorenal syndrome, hepatorenal syndrome, gastric ulcer, gastric dyskinesia, and irritable bowel syndrome. It may enable the treatment of pathological conditions, including (but not limited to) syndromes and autoimmune disorders such as Crohn's disease.

0464The sympathetic nerves that approach or surround the arterial blood vessels, known as the inferior mesenteric artery, pass through the inferior mesenteric ganglion and follow the tributaries of the inferior mesenteric artery to the colon, rectum, bladder, and genitals. , And can innervate the external genitalia. Global (or partial) regulation of these nerves can result in GI dyskinesia, colitis, urinary retention, overactive bladder, incontinence, infertility, polycystic ovary syndrome, premature ejaculation, It may allow treatment of conditions including, but not limited to, erectile dysfunction, dyspareunia, and vaginismus.

0465Although arterial access and treatment are the focus of attention herein, the devices, methods, and systems disclosed can also be used to deliver treatment from peripheral veins or lymphatic vessels.

0466VII. Conclusion The above details of embodiments of the invention are neither exhaustive nor intended to limit the invention to the exact embodiments disclosed above. Specific embodiments of the invention, and examples thereof, will be described above for illustrative purposes, but as will be appreciated by those skilled in the art, various equivalent modifications are possible within the scope of the invention. For example, the steps may be presented in a given order, while alternative embodiments may perform the steps in a different order. Further embodiments can also be provided by combining the various embodiments described herein.

0467From the above, specific embodiments of the invention are described herein for illustrative purposes, but well-known structures and functions unnecessarily obscure the description of embodiments of the invention. It is understood that it is neither shown nor described in detail to avoid doing so. Where the context allows, the singular or plural terms may also include the plural or singular terms, respectively. For example, much of the disclosure herein describes the energy delivery element 24 or electrode 46 in the singular. It should be understood that this application does not exclude more than one energy delivery element or electrode.

0468The energy delivery element 24 includes an electrode, a radio frequency electrode, a cooling radio frequency electrode, a thermal element, a thermal heating element, an electric resistance heating element, a refrigeration cutting applicator, a microwave antenna, an ultrasonic transducer, and a high-density focused ultrasonic wave. It should also be understood that it may be an oscillator, or a laser emitter.

0469In addition, other terms used herein may be expressed in different and interchangeable ways. For example, the force transfer section may also be a proximal force transfer section, an elongated tubular shaft, and the first flexure area may also be a flexible tubular structure, a deflectable section. Can also be an intermediate flexion zone or a second flexure zone, as well as a deflectable tubular body, the control wire can be a flexure control element, and the force damping section is a third flexure zone. Alternatively, it may be a distal flexion area, or a passive flexible structure, and the force diversion element may be a preformed shape.

0470In addition, the word "or" refers to a list of two or more items and is "unless otherwise explicitly limited to mean a single item that is exclusive from other items" in such a list. The use of "or" shall be construed to include (a) any single item in the list, (b) all of the items in the list, or (c) any combination of items in the list. In addition, the term "comprising" means at least a list of features (s) that are not excluded so that any larger number of the same features and / or other features of further types are not excluded. Used throughout as it does. Although specific embodiments are described herein for illustrative purposes, it is also understood that various modifications may be made without departing from the present invention. Therefore, the present invention is not limited except as limited by the appended claims.