HK40092785A - Novel flow manifold for cryoablation catheter - Google Patents

Description

Novel shunt manifold for cryoablation catheters

Cross-references to related applications

This application claims priority to U.S. Provisional Patent Application No. 63/065,892, filed on August 14, 2020, entitled “NOVEL FLOW MANIFOLD FORCRYOABLATION CATHETER”.

background

1. Field of Invention

Embodiments of the present invention relate to cryosurgery, and more specifically to cryoablation systems and catheters for treating heart disease.

2. Description of related technologies

Atrial flutter and atrial fibrillation are heart disorders in which one or the left or right atrium of the heart beats abnormally. Atrial flutter is characterized by a very fast but still regular atrial beat. Atrial fibrillation is characterized by a very fast but irregular atrial beat.

These conditions are typically caused by abnormal electrical behavior in a part of the atrial wall. Certain areas of the atrium or nearby structures (such as the pulmonary veins) may fail to generate or conduct the electrical signals that control cardiac contraction, creating abnormal electrical signals that cause the atria to contract between normal contractions caused by a normal cascade of electrical impulses. This can be caused, for example, by spots of ischemic tissue called ectopic lesions, or by electrically active fibers in the pulmonary veins.

Ventricular tachycardia (VT) is a regular and rapid heart rate caused by inappropriate electrical activity in the ventricles. In VT, abnormal electrical signals in the ventricles cause the heart to beat faster than normal, typically 100 times per minute or more, out of sync with the upper chambers. When this happens, because the chambers are beating too fast or out of sync with each other, they don't have time to fill properly, so the heart may not be able to pump enough blood to the body and lungs. Therefore, VT can lead to cardiac arrest and may develop into ventricular fibrillation.

Premature ventricular contractions (PVCs) are another cardiac condition related to the ventricles. PVCs are extra heartbeats that originate from one ventricle. These extra heartbeats disrupt the normal heart rhythm and can sometimes feel like the heart is throbbing or stopping. PVCs (especially when accompanied by another cardiac condition) can lead to more serious cardiac events.

Of the various heart conditions described above, atrial fibrillation is one of the most common. Untreated atrial fibrillation can lead to many adverse consequences, including palpitations, shortness of breath, weakness, and generally poor blood flow throughout the body.

Various techniques are used to treat atrial fibrillation. One technique for treating AF is pulmonary vein isolation (PVI). PVI is performed by creating lesions around the pulmonary veins. PVI is used to block erroneous or abnormal electrical signals.

However, a challenge in performing PVI is achieving persistent or permanent isolation of the pulmonary veins. Various studies have highlighted this limitation. In a long-term follow-up study investigating pulmonary vein reconnection rates after initial isolation, 53% of 161 patients did not have atrial fibrillation (AF). Repeat ablation was performed on recurrent arrhythmias in 66 patients. The pulmonary vein reconnection rate was as high as 94% (62 out of 66 patients). (Ouyang F, Tilz R, Chun J et al., Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up), Circulation, 2010; 122:2368-77.

One reason why some PVI treatments are not durable is due to the phenomenon of pulmonary venous (or electrical) reconnection. (Sawhney N, Anousheh R, Chen WC et al., Five-year outcomes after segmental pulmonary veinisolation for paroxysmal atrial fibrillation, Am J Cardiol, 2009; 104:366-72) (Callans DJ, Gerstenfeld EP, Dixit S et al., Efficacy of repeat pulmonary vein isolation procedures in patients with recurrent atrial fibrillation) (Efficacy of repeated pulmonary venous isolation in patients with recurrent atrial fibrillation, J Cardiovasc Electrophysiol, 2004; 15: 1050-5) (Verma A, Kilicaslan F, Pisano E et al., Response of atrial fibrillation to pulmonary veinantrum isolation is directly related to restoration and delay of pulmonary vein conduction, Circulation, 2005; 112: 627-35).

Pulmonary vein reconnection can be attributed to venous gaps and incomplete or discontinuous isolation. (Bunch TJ, Cutler MJ. Is pulmonary vein isolation still the cornerstone in atrial fibrillation ablation?, J Thorac Dis. 2015 Feb; 7(2): 132-41). Incomplete isolation is due to residual gaps within the lesion or the lack of transmural damage. (McGann CJ, Kholmovski EG, Oakes RS et al., New magnetic resonance imaging-based method for defining the extent of left atrial wall injury after the ablation of atrial fibrillation, J Am Coll Cardiol, 2008; 52:1) 263-71. (Ranjan R, Kato R, Zviman MM et al. Gaps in the ablation line as a potential cause of recovery from electrical isolation and their visualization using MRI, Circ Arrhythm Electrophysiol, 2011; 4:279-86).

Furthermore, early recurrence of AF after ablation may be an early marker of incomplete pulmonary vein isolation. This is supported by a study of 12 patients who underwent maze surgery after failed radiofrequency ablation. Notably, myocardial biopsy revealed anatomical gaps and/or non-transmural lesions in the reconnected pulmonary veins. (Kowalski M, Grimes MM, Perez FJ et al., Histopathological characterization of chronic radiofrequency ablation lesions for pulmonary vein isolation, J Am Coll Cardiol, 2012; 59:930-8).

A canine study further supports this, confirming endocardial conduction block and confirming the postoperative gap using MRI within the ablation line. Long-term follow-up data suggest that pulmonary veins with gaps confirmed by MRI are more likely to reconnect with symptom recurrence. (Ranjan R, Kato R, Zviman MM et al., Gaps in the ablation line as potential cause of recovery from electrical isolation and their visualization using MRI, Circ Arrhythm Electrophysiol, 2011; 4:279-86).

Various attempts to address these issues have included combining linear ablation with circumferential pulmonary vein isolation (CPVI). For example, a prospective randomized controlled trial in patients with paroxysmal atrial fibrillation (AF) compared the clinical outcomes of CPVI with additional linear ablation and CPVI alone. This study included 100 patients with paroxysmal AF who underwent radiofrequency circumferential ablation (RFCA) (75.0% male, 56.4 ± 11.6 years old) and were randomized to either the CPVI group (n = 50) or the catheter Dallas injury group (CPVI, posterior box-shaped injury and anterior linear ablation, n = 50). The catheter Dallas injury group required a longer procedure time (190.3 ± 46.3 min vs. 161.1 ± 30.3 min, P < 0.001) and ablation time (5345.4 ± 1676.4 s vs. 4027.2 ± 878.0 s, P < 0.001) than the CPVI group. The rate of complete bidirectional conduction block was 68.0% in the catheter Dallas lesion group and 100% in the CPVI group. There was no significant difference in the incidence of procedure-related complications between the catheter Dallas lesion group (0%) and the CPVI group (4%, P=0.157). During a follow-up period of 16.3±4.0 months, there was no significant difference in the clinical recurrence rate between the two groups, regardless of whether complete bidirectional conduction block was achieved after linear ablation. (Kim et al., Linear ablation in addition to circumferential pulmonary vein isolation (Dallas lesion set) does not improve clinical outcome in patients with paroxysmal atrial fibrillation: a prospective randomized study), Europace, March 2015; 17(3):388-95).

Therefore, based on the aforementioned reference studies, adding more ablation points around the vein inlet and/or attempting to increase linear damage through point-by-point ablation does not appear to be the optimal solution for preventing damage along the gap surrounding the lesion. Furthermore, adding multiple points and lines would unintentionally increase procedure time.

Given the aforementioned drawbacks, various ablation catheters, including flexible cryoprobes or cryocatheters, bipolar RF catheters, monopolar RF catheters (used as ground patches on the patient's skin), microwave catheters, laser catheters, and ultrasound catheters, have been proposed for lesion formation. For example, U.S. Patent No. 6,190,382 to Ormsby and U.S. Patent No. 6,941,953 to Feld describe RF ablation catheters for ablating cardiac tissue. These methods are attractive because they are minimally invasive and can be performed on a beating heart. However, these methods have a low success rate. This low success rate may be due to incomplete lesion formation. Complete transmural lesion requires ensuring complete isolation of the electrical pulses causing atrial fibrillation from the rest of the atrium, which is difficult to achieve with a beating heart.

Therefore, the challenge for surgeons is to place catheters/probes along the correct tissue contours so that the probes make full contact with the tissue. Due to the nature of the surgery and the anatomical location where damage must be caused, the catheters must be flexible and adjustable enough to match the shape and contour of the tissue to be ablated.

U.S. Patents 6,161,543 and 8,177,780, granted to Cox et al., describe malleable and flexible cryoprobes. The described probes have a malleable shaft. In embodiments, a malleable metal rod is co-extruded with a polymer to form the shaft. The malleable rod allows the user to plastically deform the shaft into the desired shape, enabling the tip to reach the tissue to be ablated.

U.S. Patent No. 5,108,390, issued to Potoky et al., discloses a highly flexible cryoprobe that can pass through blood vessels and enter the heart without any external guides other than the blood vessels themselves.

However, a challenge with some of the aforementioned devices is the need for continuous contact along anatomical surfaces, which can lead to progressive injury. This challenge is exacerbated by the varying contours and shapes of the target tissues due to their location within the body, as well as by variations in anatomical structures between patients. Consequently, different treatment procedures and patient anatomy require the design and use of different catheters. Another challenge is the ability to adjust the catheter shape in situ to accommodate these variations in anatomy and other factors.

Another challenge with some of the aforementioned devices is efficient heat transfer, i.e., cooling/heat transfer, between the internal cooling/heating elements and the external sheath/tube. Therefore, freezing and heating temperatures may need to be effectively transferred to the tissue to be ablated.

Therefore, there is a need for improved methods and systems to provide minimally invasive, shape-adjustable, safe, and effective tissue cryocooling. These improved systems include improved devices and methods to create continuous lesions in target tissues, regardless of changes in the disease being treated or the patient's anatomy.

There is also a need for improved devices and methods to treat AF, atrial flutter and VT, and to achieve more complete, durable and safe electrical signal isolation in the various chambers of the heart, including pulmonary vein isolation.

Overview

This invention relates to an ablation device for inducing damage in target tissue, comprising a handle, a flexible elongated shaft extending from the handle, and a distal ablation portion. The distal ablation portion includes a cryotherapy flow manifold that defines multiple fluid paths between the insert body and the tubular cannula. Cryotherapy circulates through the multiple fluid paths to induce damage in the target tissue.

In one embodiment, the insert body has a polygonal cross-section, such that multiple fluid paths are defined between the side of the insert body and the inner cavity of the sleeve. Optionally, the side of the insert body may vary along its circumference, such that a flat side is divided by an arcuate or curved side, corresponding to fluid paths with relatively high and low refrigerant flow rates, respectively. Not intended to be theoretically limited, the varying geometry and fluid paths are used to increase turbulence and improve cooling power efficiency.

In one embodiment, the handle includes an actuator assembly to bend the catheter shaft at an angle ranging from 0 to 180 degrees or greater, based on the amount of manipulation of the actuator assembly by the physician.

In one embodiment, the handle includes a friction braking assembly that the physician activates to bend and lock the catheter or set it at a desired angle. The brake is releasable, and the shaft angle can then be adjusted as needed.

In one embodiment, a method includes advancing a distal ablation portion of a catheter into the ventricle of the heart, bending the shaft to a target angle in the range of 120 to 180 degrees, locking the shaft at the target angle, placing the distal ablation portion against target tissue, and circulating cryotherapy through multiple fluid paths in a shunt manifold of the distal ablation portion to induce damage in the target tissue.

The description, objects, and advantages of embodiments of the present invention will become apparent from the following detailed description together with the accompanying drawings.

Brief description of the attached diagram

The above-described aspects, as well as other features, aspects, and advantages of the present technology, will now be described with reference to the accompanying drawings and various embodiments. However, the illustrated embodiments are merely examples and not limiting. Throughout the drawings, similar symbols generally identify similar parts unless the context otherwise requires. Note that the relative dimensions in the following drawings may not be drawn to scale.

Figure 1 illustrates a typical refrigerant phase diagram;

Figure 2 is a schematic diagram of the cryogenic cooling system;

Figure 3 is the refrigerant phase diagram corresponding to the system shown in Figure 2, where the refrigerant is _N2 ;

Figure 4 provides a flowchart summarizing the various aspects of the cooling system in Figure 2;

Figure 5A is a perspective view of a cryoablation catheter according to an embodiment of the present invention;

Figure 5B is a cross-sectional view taken along line 5B-5B in Figure 5A;

Figure 6 is an illustration of a cryoablation system including a cryoablation catheter according to an embodiment of the present invention;

Figure 7 is an enlarged perspective view of the distal segment of the cryoablation catheter shown in Figure 6;

Figure 8 is a perspective view of another embodiment of a cryoablation catheter with a flexible distal treatment segment;

Figure 9A is a cross-sectional view of an embodiment of the catheter shown in Figure 8, taken along line 9A-9A in Figure 8;

Figure 9B is an enlarged view of one of the multilayer tubes shown in Figure 9A;

Figure 9C is a cross-sectional view of another embodiment of the cryoablation catheter;

Figure 10A is a partial cross-sectional view of an embodiment of the catheter shown in Figure 8;

Figure 10B is a partially exploded view of the proximal end of the tubular element and the distal end of the intermediate segment of the embodiment of the conduit shown in Figure 8.

Figure 11 is a perspective view of another embodiment of a cryoablation catheter with a flexible distal treatment segment;

Figure 12 is an enlarged view of a portion of the distal segment shown in Figure 11;

Figure 13 is a cross-sectional view of the conduit shown in Figure 12, taken along line 13-13 of Figure 12;

Figures 14-15 illustrate the sequential unfolding of the distal segment of the catheter shown in Figure 11 from the outer sheath components;

Figures 16-22 have been deliberately omitted;

Figure 24 is a side view of another embodiment of the cryoablation catheter;

Figure 25 is a cross-sectional view of the conduit shown in Figure 24, taken along line 25-25 of Figure 24;

Figure 26 is an enlarged view of a multilayer refrigerant delivery/return tube shown in Figure 25;

Figure 27 is a longitudinal sectional view of the distal region of the catheter shown in Figure 24;

Figure 28 is a cross-sectional view of the conduit shown in Figure 27, taken along line 28-28 of Figure 27;

Figure 29 is a perspective view of the insert shown in Figure 27;

Figure 30 is another longitudinal sectional view of the distal region of the catheter shown in Figure 24;

Figure 31A shows a side view of a handle for an ablation catheter according to an embodiment of the present invention;

Figure 31B illustrates a 180-degree bend in the guide shaft when the handle is activated according to an embodiment of the present invention;

Figure 32A shows a side view of the handle shown in Figure 31A, with the exterior removed;

Figure 32B shows a cross-section of a portion of the handle shown in Figure 31A;

Figure 33 is an illustration of the location of various injuries and the heart according to an embodiment of the present invention;

Figure 34 is an illustration of an embodiment of an intravascular catheter entering the heart;

Figures 35-36 are illustrations of a procedure for placing the distal segment of a cryoablation catheter against the endocardial wall in the left atrium according to an embodiment of the present invention, the procedure defining the left superior pulmonary vein inlet and the left inferior pulmonary vein inlet;

Figures 37-38 are schematic diagrams of a procedure for placing the distal segment of a cryoablation catheter against the endocardial wall within the left atrium according to an embodiment of the present invention, the procedure defining the right superior pulmonary vein inlet and the right inferior pulmonary vein inlet.

Figures 39-40 illustrate a method for generating a box-shaped injury according to an embodiment of the present invention, wherein the figures depict the left atrium as viewed from the back of a patient;

Figure 41 is a flowchart illustrating a method for generating a box-shaped lesion surrounding multiple PVs in the left atrium according to an embodiment of the present invention;

Figure 42 is a diagram of the heart showing the electrical activity of the mitral valve;

Figure 43A depicts the formation of damage that interrupts mitral valve electrical activity according to an embodiment of the present invention;

Figure 43B depicts the formation of damage that interrupts mitral valve electrical activity according to an embodiment of the present invention;

Figure 44 is a flowchart illustrating a method for generating a box-shaped lesion surrounding multiple PVs and lesion interrupting mitral valve electrical activity in the left atrium according to an embodiment of the present invention;

Figure 45 depicts the formation of damage caused by interrupted electrical activity in the right atrium according to an embodiment of the present invention; and

Figure 46 is a flowchart illustrating a method for inducing damage in the left or right ventricle according to an embodiment of the present invention.

Detailed description

It should be understood that, since various changes or modifications can be made to the described embodiments of the invention and equivalents can be substituted without departing from the spirit and scope of the embodiments of the invention, the embodiments of the invention described herein are not limited to the specific variations set forth herein. It will be apparent to those skilled in the art upon reading this disclosure that each of the various embodiments described and illustrated herein has discrete components and features that can be readily separated from or combined with features of any of the other several embodiments without departing from the scope or spirit of the embodiments of the invention. Furthermore, many modifications can be made to adapt particular circumstances, materials, composition of substances, processes, process actions, or steps to the purpose, spirit, or scope of the embodiments of the invention. All such modifications are intended to fall within the scope of the claims set forth herein.

Furthermore, although methods may be depicted in the accompanying drawings or described in the specification in a specific order, these methods do not need to be performed in the specific order shown or sequentially, and it is not necessary to perform all methods to obtain the desired result. Other methods not depicted or described may be incorporated into the example methods and processes. For example, one or more additional methods may be performed before, after, simultaneously with, or between any of the described methods. Furthermore, in other embodiments, these methods may be rearranged or reordered. Moreover, the separation of various system components in the embodiments described above should not be construed as requiring such separation in all embodiments, and should be understood as generally allowing the described components and systems to be integrated together in a single product or packaged into multiple products. Additionally, other embodiments are within the scope of this disclosure.

Unless otherwise specifically stated or otherwise understood in the context in which they are used, conditional terms such as “can,” “could,” “might,” or “may” are generally intended to indicate that certain embodiments include or exclude certain features, elements, and/or steps. Therefore, such conditional terms are not generally intended to imply in any way that features, elements, and/or steps are required in one or more embodiments.

Unless otherwise specified, connective language such as the phrase “at least one of X, Y, and Z” is generally understood in the context in which it is used to convey that an item, term, etc., can be X, Y, or Z. Therefore, such connective language is generally not intended to imply that some embodiments require the presence of at least one of X, at least one of Y, and at least one of Z.

References to a single item include the possibility of multiple identical items. More specifically, as used herein and in the appended claims, the singular forms “a,” “an,” “said,” and “the” include plural indicators unless the context clearly indicates otherwise. It should also be noted that claims may be designed to exclude any optional elements. Therefore, this statement is intended to serve as a preliminary basis for the use of such exclusive terms such as “merely,” “only,” and similar terms relating to the enumeration of claim elements, or the use of the restrictive term “negation.”

It should be understood that when an element is referred to as "connected" or "linked" to another element, it can be directly connected or linked to the other element, or there may be intermediate elements. Conversely, if an element is referred to as "directly connected" or "directly linked" to another element, there are no intermediate elements.

It should also be understood that although the terms first, second, etc., are used herein to describe various elements, these elements should not be limited by these terms. These terms are merely used to distinguish one element from another. Thus, a first element may be referred to as a second element without departing from the teachings of the invention.

The degree language used herein, such as the terms “approximately,” “about,” “roughly,” and “basically,” indicates a value, quantity, or characteristic that is close to the stated value, quantity, or characteristic, yet still performs the desired function or achieves the desired result. For example, the terms “approximately,” “about,” “roughly,” and “basically” can refer to quantities less than or equal to 10%, 5%, 1%, 0.1%, and 0.01% of the stated quantity. If the quantity is 0 (e.g., none), the above ranges can be specific ranges and not within a specific percentage of that value. Furthermore, numerical ranges include numbers that define the range, and any single value provided herein can serve as an endpoint of a range that includes other single values provided herein. For example, a set of values such as 1, 2, 3, 8, 9, and 10 is also a disclosure of numerical ranges such as 1-10, 1-8, 3-9, etc.

Several embodiments have been described in conjunction with the accompanying drawings. The drawings are drawn to scale, but this scale should not be limiting, as all dimensions and scales other than those shown are contemplated and within the scope of the disclosed invention. Distances, angles, etc., are merely illustrative and do not necessarily have an exact relationship to the actual size and layout of the illustrated device. Components may be added, removed, and/or rearranged. Furthermore, any particular feature, aspect, method, performance, characteristic, quality, attribute, element, etc., disclosed herein in conjunction with various embodiments may be used in all other embodiments set forth herein. Moreover, it should be recognized that any method described herein can be practiced using any device suitable for performing the steps.

While numerous embodiments and variations thereof have been described in detail, other modifications and methods of their use will be apparent to those skilled in the art. Therefore, it should be understood that various applications, modifications, materials, and substitutions may be equivalent without departing from the unique and inventive disclosure or scope of the claims herein.

All existing subjects mentioned herein (e.g., publications, patents, patent applications, and hardware) are incorporated herein by reference in their entirety, unless the existing subjects mentioned may conflict with the subject matter of this invention (in which case the content presented herein shall prevail).

Embodiments of the present invention utilize the thermodynamic process of using a refrigerant that provides cooling without encountering vapor lock.

Refrigerant phase diagram and near-critical point

This application uses phase diagrams to illustrate various thermodynamic processes. An example phase diagram is shown in Figure 1. This phase diagram includes axes corresponding to pressure P and temperature T, and a phase line 102 that depicts the trajectory of all (P, T) points where liquid and gas coexist. For (P, T) values to the left of phase line 102, the refrigerant is in a liquid state, typically obtained at higher pressures and lower temperatures, while (P, T) values to the right of phase line 102 define the region where the refrigerant is in a gaseous state, typically obtained at lower pressures and higher temperatures. Phase line 102 abruptly ends at a single point known as the critical point 104. In the case of nitrogen (N₂ ₎ , at the critical point, _Pc = 3.396 MPa and _Tc = -147.15 °C.

As the fluid exists in both liquid and gas phases during a gradual increase in pressure, the system moves upward along the liquid-gas line 102. In the case of _N₂ , the liquid at low pressure is up to two hundred times denser than the gas phase. The continued increase in pressure causes a decrease in liquid density and an increase in gas density until the liquid and gas densities are equal only at the critical point 104. The distinction between liquid and gas disappears at the critical point 104. Therefore, when the refrigerant flows under conditions around the critical point, defined herein as “near-critical conditions,” blockage of forward flow caused by gas expansion preceding the liquid refrigerant (“vapor plug”) is avoided. Factors allowing for greater deviations from the critical point while maintaining functional flow include greater refrigerant flow velocity, larger flow cavity diameter, and lower thermal loads based on heat exchangers or cryotherapy zones.

As the critical point is approached from below, the density of the gas phase increases and the density of the liquid phase decreases until the critical point is reached where the densities of the two phases are exactly equal. Above the critical point, the distinction between the liquid and gas phases disappears, leaving only a single supercritical phase, where the fluid simultaneously exhibits the properties of both liquids and gases (i.e., a dense fluid with no surface tension can flow without friction).

The van der Waals equation of state is the universally accepted equation describing gases and liquids:

(p + 3/ ^v² )(3v - 1) = 8t [Equation 1]

Where p = P/ _Pc , v = V/ _Vc , and t = T/ _Tc , and _Pc , _Vc , and _Tc are the critical pressure, critical molar volume, and critical temperature, respectively.

The variables v, p, and t are typically referred to as “corresponding molar volume,” “corresponding pressure,” and “corresponding temperature,” respectively. Therefore, any two substances with the same values of p, v, and t are in the same fluid thermodynamic state near their critical points. Equation 1 is thus known as embodying the “law of corresponding states.” This is described more fully in H.E. Stanley’s *Introduction to Phase Transitions and Critical Phenomena* (Oxford University Scientific Publications, 1971), the entire contents of which are incorporated herein by reference in their entirety for all purposes.

In embodiments of the invention, the contrast pressure p is fixed at a constant value of approximately one, and thus at a fixed physical pressure near the critical pressure, while the contrast temperature t varies with the thermal load applied to the device. If the contrast pressure p is a constant set through systems engineering, then the contrast molar volume v is an exact function of the contrast temperature t.

In other embodiments of the invention, the operating pressure p can be adjusted such that v remains below a certain maximum value during changes in the device temperature t, at which point vapor lock would occur. It is generally desirable to keep p at a minimum value, where it is reliable, because increasing the pressure to achieve a higher value for p may involve the use of more complex and expensive compressors, resulting in more expensive procurement and maintenance of the entire device support system and lower overall cooling efficiency.

The condition for v depends in a complex way on the volumetric flow rate dV/dt, the heat capacity of the liquid and gas phases, and transport properties such as thermal conductivity and viscosity in both liquids and vapors. This precise relationship is not obtained algebraically in a closed form, but can be numerically determined by integrating model equations describing mass and heat transport within a cooling device. Conceptually, vapor lock occurs when the heating rate at the end (or other equipment structure used to transport refrigerant and cooling components) generates a gas phase. The cooling capacity of this gas phase, proportional to the vapor flow rate multiplied by the vapor's heat capacity divided by its molar volume, cannot keep up with the heating rate at the end. When this occurs, more and more gas phase forms to absorb the excess heat that has converted to vapor in the refrigerant flow through the liquid phase. This creates an escape condition where the liquid transforms into a gas phase to fill the end, and due to the large pressure of this gas phase caused by the rapid increase in temperature and pressure of the heat flowing into the end, all refrigerant flow effectively stops. This condition is called "vapor lock".

According to one embodiment of the invention, the molar volumes of the liquid and gas phases are substantially the same. The cooling capacity is at a critical point, and the cooling system avoids vapor lock. Furthermore, the device can also avoid vapor lock under conditions slightly below the critical point.

Cryoablation system

Figure 2 provides a schematic diagram of the structural arrangement for a cryogenic system in one embodiment, and Figure 3 provides a phase diagram illustrating the thermodynamic path taken by the refrigerant when the system of Figure 2 is operated. The circled numerical identifiers in both figures correspond to each other, indicating in Figure 2 the physical location of the operating point determined along the thermodynamic path. The following description will therefore sometimes refer to both the structural diagram of Figure 2 and the phase diagram of Figure 3 when describing the physical and thermodynamic aspects of the cooling flow.

For illustrative purposes, Figures 2 and 3 specifically refer to nitrogen refrigerants, but this is not intended to be limiting. Embodiments of the invention can be used more generally with any suitable refrigerant, such as argon, neon, helium, hydrogen, and oxygen.

In Figure 3, the liquid-gas line is indicated by reference numeral 256, and the thermodynamic path followed by the refrigerant is indicated by reference numeral 258.

The cryogenic generator 246 is used to supply refrigerant at a pressure exceeding the critical point pressure _Pc at its outlet (indicated by reference numeral ① in Figures 2 and 3). While pressures close to the critical point pressure _Pc are advantageous, the cooling cycle can generally begin at any point in the phase diagram with pressures above or slightly below _Pc . The cooling efficiency of the process described herein is generally high when the initial pressure is close to the critical point pressure _Pc , allowing for increased energy demand at higher pressures to achieve the desired flow. Therefore, embodiments may sometimes include various higher upper boundary pressures, but generally begin near the critical point, for example between 0.8 and 1.2 times _Pc , and in one embodiment, at approximately 0.85 times _Pc .

As used herein, the term "near-critical" refers to the region close to the liquid-vapor critical point. This term is equivalent to "near the critical point," and it refers to a region where the liquid-vapor system is sufficiently close to the critical point, where the dynamic viscosity of the fluid is close to that of a normal gas and much smaller than that of a liquid; additionally, the density of the fluid is close to that of a normal liquid. The heat capacity of a near-critical fluid is even greater than that of its liquid phase. The combination of gaseous viscosity, liquid density, and very large heat capacity makes near-critical fluids highly effective coolants. The mention of the near-critical point refers to a region where the liquid-vapor system is sufficiently close to the critical point that the fluctuations in the liquid and gas phases are large enough to result in a significant increase in heat capacity above their background values. The near-critical temperature is the temperature within ±10% of the critical point temperature. The near-critical pressure is between 0.8 and 1.2 times the critical point pressure.

Referring again to Figure 2, the refrigerant flows through a pipe (at least a portion of which is surrounded by a reservoir 240 containing liquid refrigerant), lowering the refrigerant temperature without substantially changing its pressure. In Figure 2, the reservoir is shown as liquid _N₂ , with a heat exchanger 242 disposed within the reservoir 240 to extract heat from the flowing refrigerant. Outside the reservoir 240, insulation may be disposed around the pipe to prevent unwanted warming of the refrigerant as it flows from the refrigerant generator 246. At point ②, after being cooled by thermal contact with the liquid refrigerant, the refrigerant has a lower temperature but is essentially at its initial pressure. In some cases, as indicated in Figure 3 as a slight pressure drop, a pressure change may occur, provided that the pressure does not substantially drop below the critical point pressure _P₁ , i.e., not below a defined minimum pressure. In the example shown in Figure 3, the temperature drop is approximately 50°C as a result of the flow of liquid refrigerant.

The cryoprotectant is then supplied to the device for use in cryogenic applications. In the exemplary embodiment shown in FIG2, the cryoprotectant is supplied to the inlet 236 of the catheter 224, which may be used, for example, in medical cryogenic intravascular applications, but this is not necessary.

In fact, medical devices can take many forms and include, but are not limited to, instruments, appliances, catheters, devices, tools, apparatuses, and probes, regardless of whether such probes are short and rigid or long and flexible, and regardless of whether they are used in open, minimally invasive, non-invasive, manual, or robotic surgery.

In this embodiment, the cryoprotectant can be introduced by passing through the proximal portion of the catheter, continuing along the flexible middle section of the catheter, and entering the distal treatment section of the catheter. As the cryoprotectant is delivered through the catheter between reference numerals ② and ③ in Figures 2 and 3, and passes through the cryoablation treatment area 228, slight changes in the pressure and/or temperature of the cryoprotectant may occur as it moves across the interface with the device (e.g., the cryoablation area 228 in Figure 2). These changes typically manifest as a slight increase in temperature and a slight decrease in pressure. Assuming the cryoprotectant pressure remains above a defined minimum pressure (and associated conditions), the slight increase in temperature will not significantly affect performance, thus avoiding vapor lock, because the cryoprotectant only moves back towards the critical point without encountering the liquid-vapor line 256.

In the embodiments described, components including a check valve 216, flow resistance, and/or flow controller can be used to control the flow of refrigerant from the refrigerant generator 246 through conduit 224 or other devices. Conduit 224 itself may include a vacuum insulation 232 (e.g., a cover or jacket) along its length and may have a cold cryoablation zone 228 for cryogenic applications. Unlike Joule-Thomson probes, where the pressure of the working refrigerant changes significantly at the probe tip, these embodiments of the invention provide relatively small pressure variations throughout the device. Therefore, at point ④, the refrigerant temperature has risen to approximately ambient temperature, but the pressure remains elevated. Vapor plugging can be avoided by maintaining the pressure above or near the critical point pressure _Pc as the refrigerant is delivered through the conduit.

The refrigerant pressure returns to ambient pressure at point ⑤. The refrigerant can then be discharged through vent 204 under essentially ambient conditions.

Examples of cryoablation systems, their components, and various arrangements are described in the following commonly assigned U.S. patents and U.S. patent applications: U.S. Patent Application No. 10/757,768, filed January 14, 2004, entitled “CRYOTHERAPY PROBE,” by Peter J. Littrup et al., published August 12, 2008, as U.S. Patent No. 7,410,484; and U.S. Patent Application No. 10/757,769 ... August 12, 2008, by Peter J. Littrup et al. J. Littrup et al. filed on January 14, 2004, entitled "CRYOTHERAPY SYSTEM", which was published as U.S. Patent No. 7,083,612 on August 1, 2006; U.S. Patent Application No. 10/952,531, filed by Peter J. Littrup et al. on September 27, 2004, entitled "METHODS AND SYSTEMS FOR CRYOGENIC COOLIN". "G (Methods and Systems for Cryocooling)," was published as U.S. Patent No. 7,273,479 on September 25, 2007; U.S. Patent Application No. 11/447,356, filed by Peter Littrup et al. on June 6, 2006, entitled "CRYOTHERAPY SYSTEM," was published as U.S. Patent No. 7,507,233 on March 24, 2009; U.S. Patent Application No. 11/846,226, filed by P... Peter Littrup et al. filed on August 28, 2007, entitled "METHODS AND SYSTEMS FORCRYOGENIC COOLING", which was published as U.S. Patent No. 7,921,657 on April 12, 2011; U.S. Patent Application No. 12/018,403, filed by Peter Littrup et al. on January 23, 2008, entitled "CRYOTHERAPY". "PROBE (Cryotherapy Probe)," was published as U.S. Patent No. 8,591,503 on November 26, 2013; U.S. Patent Application No. 13/046,274, filed by Peter Littrup et al. on March 11, 2011, entitled "METHODS AND SYSTEMS FOR CRYOGENIC COOLING," was published as U.S. Patent No. 8,387 on March 5, 2013. Published 402; U.S. Patent Application No. 14/087,947, filed November 22, 2013 by Peter Littrup et al., entitled "CRYOTHERAPY PROBE", is pending; U.S. Patent Application No. 12/744,001, filed July 29, 2010 by Alexei Babkin et al., entitled "FLEXIBLE MULTI-TUBULAR CRYOPROBE". U.S. Patent No. 8,740,891, filed June 3, 2014, entitled "Expandable Multi-Tube Cryoprobe," filed July 29, 2010, by Alexei Babkin et al., entitled "Expandable Multi-Tube Cryoprobe," filed June 3, 2014, by Alexei Babkin et al., entitled "Endovascular Near-Critical Fluid-Based Cryoablation Catheter and Related Methods," is cited in its entirety in this document for all purposes.

A method for cooling a target tissue is illustrated using the flowchart in Figure 4, wherein the refrigerant follows a thermodynamic path similar to that shown in Figure 3. At block 310, the refrigerant is generated at a pressure exceeding the critical point pressure and close to the critical point temperature. The temperature of the generated refrigerant is reduced at block 314 by heat exchange with a substance having a lower temperature. In some cases, this can be conveniently achieved by using heat exchange with a refrigerant in liquid form at ambient pressure; however, this heat exchange can occur under other conditions in different embodiments. For example, in some embodiments, different refrigerants can be used, such as by providing heat exchange with liquid nitrogen when the working fluid is argon. Furthermore, in other alternative embodiments, heat exchange can be performed using a refrigerant at a pressure different from ambient pressure, for example by providing a refrigerant at a lower pressure to create a cooler environment.

Additional refrigerant is supplied at block 318 to a cryogenic application device that can be used for cooling applications at block 322. Cooling applications may include chilling and/or freezing, depending on whether the target application involves freezing. As a result of the refrigerant application, the refrigerant temperature increases, and the heated refrigerant at block 326 flows to the control console. While some variation is possible, throughout blocks 310-326, the refrigerant pressure is generally maintained above the critical point pressure; at these stages, the primary change in the thermodynamic properties of the refrigerant is its temperature. At block 330, the pressure of the heated refrigerant is then allowed to drop to ambient pressure, allowing the refrigerant to be discharged or recirculated at block 334. In other embodiments, the remaining pressurized refrigerant at block 326 may also return along the path to block 310 for recirculation instead of being discharged at ambient pressure.

Cryoablation catheter

Embodiments of the cryoablation device of the present invention can have various configurations. For example, one embodiment of the present invention is a flexible conduit 400 as shown in FIG. 5A. The conduit 400 includes a housing or connector 410 disposed proximal to a fluid source (not shown) adapted for fluid connection.

Multiple fluid transfer tubes 420 are shown extending from connector 410. These tubes include a set of input fluid transfer tubes 422 for receiving input flow from connector 410 and a set of output fluid transfer tubes 424 for discharging flow from connector 410.

In this embodiment, each fluid transfer tube is formed of a material that maintains structural and mechanical integrity over the entire temperature range from -200°C to ambient temperature. In this embodiment, the fluid transfer tube 420 is formed of annealed stainless steel or a polymer (such as polyimide). In this configuration, the material can remain flexible near its critical temperature. In this embodiment, each fluid transfer tube has an inner diameter in the range of about 0.1 mm to 1 mm (preferably between about 0.2 mm and 0.5 mm). Each fluid transfer tube may have a wall thickness in the range of about 0.01 mm to 0.3 mm (preferably between about 0.02 mm and 0.1 mm).

End cap 440 is positioned at the end of a fluid transfer tube to provide fluid transfer from an input fluid transfer tube to an output fluid transfer tube. End cap 440 is shown as having a damage-resistant end. End cap 440 can be any suitable element for providing fluid transfer from an input fluid transfer tube to an output fluid transfer tube. For example, end cap 440 can define an inner chamber, cavity, or channel for fluid connection tubes 422, 424.

Referring to Figure 5B, the outer sheath 430 is shown surrounding the tube bundle 420. The outer sheath is used to hold the tubes in the tubular arrangement and to protect the structure from penetration or damage by foreign objects and obstacles.

Temperature sensor 432 is displayed on the surface of the distal segment. The temperature sensor may be a thermocouple to sense the temperature corresponding to adjacent tissue and transmit the signal back to the control console for processing via wires in the tubing. The temperature sensor may be placed elsewhere along the axis or within one or more fluid transfer tubes to determine the temperature difference between inflow and outflow.

There are many configurations for the arrangement of the pipes. In one embodiment, the fluid transfer pipes are formed in a circular array, wherein the set of input fluid transfer pipes includes at least one input fluid transfer pipe 422 defining a central region of the circle, and wherein the set of output fluid transfer pipes 424 includes a plurality of output fluid transfer pipes spaced in a circular pattern around the central region. In the configuration shown in FIG. 5B, the fluid transfer pipes 422, 424 fall within this type of embodiment.

During operation, refrigerant/refrigeration fluid is supplied from a suitable refrigerant source via a supply line to the conduit at a temperature close to -200°C. The refrigerant circulates through a multi-tubular freezing zone provided by exposed fluid transfer tubing and returns to the connector. Refrigerant flows into the freezing zone through inlet fluid transfer tubing 422 and out of the freezing zone through outlet fluid transfer tubing 424.

In the embodiments, the nitrogen flow does not form gaseous bubbles in the small-diameter tube under any thermal load, so as not to create vapor lock that restricts flow and cooling capacity. By operating under near-critical conditions for at least the initial period of energy application, vapor lock is eliminated as the distinction between the liquid and gas phases disappears. After initial operation under near-critical conditions (e.g., for nitrogen, at a temperature close to the critical temperature of -147.15°C and a pressure close to the critical pressure of 3.396 MPa), the operating pressure can be reduced as disclosed and described in commonly assigned U.S. Patent Application No. 14/919,681, filed October 21, 2015, entitled “PRESSURE MODULATED CRYOABLATION SYSTEM AND RELATED METHODS”, the contents of which are incorporated herein by reference in their entirety for all purposes.

Multi-tube designs are preferable to single-tube designs because the additional tubes can significantly increase the heat exchange area between the cryopropellant and the tissue. Depending on the number of tubes used, cryostats can increase the contact area several times greater than previous designs with a single shaft/tube of similar diameter. However, embodiments of the invention are not intended to be limited to single-tube or multi-tube designs, unless specifically stated in the appended claims.

Cryoablation Control Console

Figure 6 illustrates a cryoablation system 950 with a cart or console 960 and a cryoablation catheter 900 detachably connected to the console via a flexible elongated tube 910. The cryoablation catheter 900, which will be described in more detail below with reference to Figure 7, comprises one or more fluid delivery tubes for removing heat from the tissue.

The control console 960 may include or house various components (not shown), such as generators, controllers, tanks, valves, pumps, etc. A computer 970 and a display 980, shown in Figure 6, are positioned on top of the trolley for easy user operation. The computer may include a controller, timer, or components (e.g., pumps, valves, or generators) that communicate with an external controller to drive the cryoablation system. Input devices such as a mouse 972 and a keyboard 974 may be provided to allow the user to input data and control the cryoablation equipment.

In this embodiment, as described herein, computer 970 is configured or programmed to control refrigerant flow rate, pressure, and temperature. Target values and real-time measurement results can be sent to and displayed on display 980.

Figure 7 shows an enlarged view of the distal segment 900 of the cryoablation device. The distal segment 900 is similar to the design described above, except that the treatment area 914 includes a flexible protective cover 924. The cover is used to contain leakage of cryotherapy material in the event of a rupture in one of the fluid delivery lines. While leakage in either of the fluid delivery lines is undesirable or unplanned, the protective cover provides an additional or redundant barrier that the cryotherapy material would have to penetrate to flow out of the catheter during the procedure. In an embodiment, the protective cover may be formed of metal.

Furthermore, a heat-conducting fluid can be disposed within the space or gap between the delivery pipe and the inner surface of the cover to improve the thermal cooling efficiency of the device during treatment. In this embodiment, the heat-conducting fluid is water.

The cover 924 is shown to be tubular or cylindrical and terminates at a distal end 912. As described herein, the cooling zone 914 includes a plurality of fluid delivery tubes and fluid return tubes to deliver cooling fluid through the treatment zone 914, resulting in heat transfer/removal from the target tissue. In embodiments, the cryoprotectant is delivered through the tube bundle under physical conditions of a fluid critical point in the adjacent phase diagram. Among other things, the cover helps to contain the cooling fluid and prevent its escape from the conduit in the event of a leak in one of the delivery tubes.

Although a cover is shown in Figures 6 and 7, the invention is not intended to be limited to such a extent as described in the appended claims. The device may or may not have a protective cover and is used to cool target tissue.

tube-in-tube

Figure 8 shows a partial view of a cryoablation catheter 1010 according to another embodiment of the invention, which has a protective device to mitigate leakage in the event of leakage of cooling fluid/crystal from the cryosurface described above. Specifically, the catheter 1010 includes a plurality of flexible multilayer cryoenergy transfer tubes or a bundle 1012 of flexible multilayer cryoenergy transfer tubes, each comprising two tubes arranged coaxially, i.e., a tube-within-a-tube configuration.

Figure 9A shows a cross-sectional view taken along line 9A-9A of Figure 8. The bundle 1012 of multilayer tubes is shown having fluid delivery tubes 1014 and fluid return tubes 1015 assembled in a parallel arrangement. The tube bundle 1012 is shown to have 12 tubes/lines, including four (4) fluid return tubes 1015a-1015d and eight (8) fluid delivery tubes 1014a-1014h. The fluid delivery tubes 1014a-1014h form a perimeter surrounding the fluid return tubes 1015a-1015d. This arrangement ensures that the cooler delivery fluid/cryotherm is adjacent to the tissue to be ablated/frozen, and the warmer return fluid/cryotherm is isolated from the tissue to be ablated/frozen.

Figure 9B shows an enlarged cross-sectional view of the fluid delivery tube 1014d of Figure 9A. The first tube or inner tube 1013 is shown as being coaxially surrounded by the second tube or outer tube 1018. As described herein, the space or gap 1020 between the outer surface of the inner tube 1013 and the inner surface of the outer tube 1018 can be filled with a heat-conducting medium 1021. In an embodiment, the gap 1020 has an annular shape. All fluid delivery tubes 1014 and fluid return tubes 1015 can have similar tubes within the tube structure.

During use, if the cooling fluid 1016 leaks or the inner tube 1013 ruptures, the cooling fluid 1016 is contained within the gap 1020 between the inner tube 1013 and the outer tube 1018. This tube-within-a-tube feature adds an extra safety element to the device because any leaked fluid/crystal 1016 is confined within the catheter and prevented from entering the patient's body. In some embodiments, a pressure sensor/device or pressure gauge may be incorporated to monitor the pressure of the heat-conducting medium 1021 in the gap 1020. Therefore, if the fluid/crystal 1016 ruptures the inner tube 1013 and leaks into the gap 1020, the pressure in the gap 1020 will increase, and consequently, the pressure of the heat-conducting medium 1021 will also increase. If the pressure change exceeds a threshold limit, the system can be programmed to stop ablation, thereby preventing potential harm to the patient and/or notifying the user/physician of the pressure change.

The inner tube 1013 may be made or fabricated from materials as described herein in relation to other flexible tubes used for conveying cooling fluids.

As disclosed herein, the material of the outer tube 1018 should also be flexible to allow the distal treatment segment to deflect elastically, thereby allowing the distal treatment segment to change its shape. In some embodiments, the outer tube is non-inflate, non-expandable, and non-inflatable, such that the size and shape of the outer tube are substantially unaffected by the presence of the contained thermally conductive medium 1021. Non-limiting exemplary materials for the outer tube 1018 include polymers and metals or alloys. Examples of materials for the outer tube 1018 are nitinol or polyimide.

The number of tubes forming the tubular bundle 1012 can vary considerably. In some embodiments, the tubular bundle 1012 includes 5-15 tubes, more preferably 8-12 tubes, including a fluid delivery tube 1014 and a fluid return tube 1015.

The cross-sectional profile of the tube bundle 1012 can also vary. While Figure 9A shows a generally circular profile, in embodiments, the profile can be rectangular, square, cross-shaped, or T-shaped, annular, or circumferential, or another shape profile, including some of the arrangements described above. The tubes can also be braided, woven, twisted, or otherwise wound together, as depicted in commonly assigned U.S. Patent Application No. 14/915,632, filed September 22, 2014, entitled “ENDOVASCULAR NEARCRITICAL FLUID BASED CRYOABLATION CATHTER AND RELATED METHODS” by Alexei Babkin et al., the entire contents of which are incorporated herein by reference for all purposes.

The diameter of the frozen segment or tubular bundle can vary. In embodiments, the bundle diameter ranges from about 1 mm to 3 mm, and is preferably about 2 mm. In embodiments, the diameter of the frozen segment is between 2.5 mm and 3 mm.

Figure 9C shows a cross-section of a cryoablation catheter with another tubular arrangement 1017. Eight (8) tubular elements (1019a-1019d and 1023a-1023d) are circumferentially spaced or distributed around the core element 1025. Preferably, as shown, the fluid delivery elements/tubes (1019a-1019d) and fluid return elements/tubes (1023a-1023d) alternate along the circumference of the catheter.

As shown with reference to FIG9B, each internal tubular element (e.g., 1019a) includes an external tubular element (e.g., 1027a) coaxially surrounding the internal tubular element, thereby creating a space or gap that can be filled with a heat-conducting medium/fluid.

Actuating elements, sensors, and other functional components can be integrated into the conduit. In an embodiment, the actuating elements are integrated into a mechanical core, such as the mechanical core 1025 shown in FIG9C.

Figure 10A shows an enlarged cross-sectional view of the catheter at detail 10A in Figure 8, illustrating the tubular bundle 1012 fluidly connected to the end portion 1040 of the intermediate section of the catheter 1010.

Figure 10B shows an exploded view of the intermediate section 1040 of the catheter and the proximal section of the tubular bundle 1012. The tubular bundle 1012, having external tubular elements/covers 1018a-1018d extending beyond the fluid delivery line 1014 and internal tubular elements 1013a-1013d, can be inserted into the intermediate section 1040 of the catheter.

Referring to Figures 10A-10B, fluid delivery lines 1014 are shown bundled together and inserted/connected to main line 1032. Adhesive plugs 1042 or seals, gaskets, or stops may be applied to help and ensure a fluid seal between the pipe components. Cooling capacity fluid (CPF) is delivered from fluid delivery main line 1032 to fluid delivery line 1014.

The proximal ends of the outer tubular elements/covers 1018a-1018d, offset from the proximal ends of the inner tubular elements 1013a-1013d, are shown inserted into the intermediate section 1040 of the conduit, such that the thermally conductive fluid (TCF) within the cavity 1050 can fill the gaps 1020 of each of the multilayer cryogenic tubular elements (Figure 9B). An adhesive plug 1044 (welded or bonded) can be applied to facilitate a fluid-tight and robust connection. As is known to those skilled in the art, press-fitting, heating, and other manufacturing techniques can be applied to join the components.

Figure 11 shows another cryoablation catheter 500, which includes a distal treatment segment 510, a handle 520, and an umbilical cord 530. The proximal end of the umbilical cord 530 terminates at a connector 540, which is inserted into a socket port 560 on a console 550.

One or more auxiliary connector lines 570 are shown extending proximally from the handle 520. The tubular lines 570 may be used to provide a variety of functions, including but not limited to (a) flushing; (b) vacuum; (c) thermally conductive liquid as described above; and/or (d) temperature and pressure sensor conductors.

The catheter 500 is also shown having an electrical connector 580 extending proximally from the handle 520. The electrical connector 580 can be coupled to an EP recording system for analyzing electrical information detected in the distal treatment segment 510. Examples of systems for analyzing electrical activity include, but are not limited to, the GE Healthcare CardioLab II EP Recording System manufactured by GE Healthcare and the LabSystem PRO EP Recording System manufactured by Boston Scientific Inc. (Marburg, MA). The recorded electrical activity can also be used to assess or verify persistent contact with target tissue, as described in co-assigned international patent application PCT/US16/51954, filed September 15, 2016, entitled “TISSUE CONTACT VERIFICATION SYSTEM” by Alexei Babkin et al., the entire contents of which are incorporated herein by reference for all purposes.

Figure 12 shows an enlarged view of a portion of the distal segment 510 of the conduit 500. Annular electrodes 602, 604 are arranged circumferentially around axis 606. Although two electrodes are shown, more or fewer electrodes may be present on the axis for sensing electrical activity. In embodiments, up to 12 or more electrodes are provided on the axis. In one embodiment, eight electrodes are axially spaced along axis 606.

Figure 13 is a cross-section of the conduit shown in Figure 12, taken along line 13-13. The conduit axis is shown as having a mechanical core 620 extending along a central axis, and a plurality of energy delivery tube structures 630 extending in parallel and arranged circumferentially around the mechanical core.

Each tube configuration 630 is shown as having a double layer as described above in conjunction with Figures 9-10 and a thermally conductive liquid layer disposed therebetween.

Tubular wire 624 is shown as a conductor 626 for housing the various sensors described herein.

The mechanical core 620 can be configured to provide a predetermined shape to the distal treatment segment of the catheter. Referring to Figure 13, the mechanical core includes a metallic tubular member 622 having a predetermined shape. The predetermined shape matches the target anatomy for continuous contact with the target anatomy. An exemplary material for the predetermined tubular member 622 is nitinol. Figure 13 also shows an outer layer or covering concentrically surrounding the nitinol tube. The outer covering can be a flexible polymer, such as PET. The inner PET layer 620 and the outer axial layer 606 together form a fluid-sealed annular chamber to accommodate a plurality of tubular structures 630.

Referring to Figures 14-15, the catheter 608 is shown unfolded from the outer sheath 642. Initially, the distal segment 606 of the catheter is disposed within the lumen of the outer sheath 642 and is prevented from presenting its predetermined shape. The distal segment 606 and the outer sheath 642 are axially movable relative to each other. For example, the catheter can be ejected from the sheath. Once the catheter is unrestrained, it presents the predetermined shape shown in Figure 15.

The mechanical core assembly biases the shape of the distal segment 608 of the catheter, forcing the energy delivery element into a curved shape. In embodiments, the catheter shape is adapted to create lesions in the right atrium for treating atrial flutter. For example, the shape shown in Figure 15 is a single loop or ellipse shape with curvature matching the target area of tissue in the right atrium for treating atrial flutter. The additional device and method for treating atrial flutter are described in U.S. Patent Application No. 61/981,110, filed April 17, 2014, and International Patent Application No. PCT/US2015/024778, filed October 21, 2015, entitled “ENDOVASCULAR NEAR CRITICAL FLUID BASED CRYOABLATION CATHETER HAVING PLURALITY OF PREFORMED TREATMENT SHAPES”, the contents of which are incorporated herein by reference in their entirety for all purposes.

Refrigerant split manifold

Figure 23 illustrates a cryoablation catheter 3000 according to another embodiment of the present invention, which includes an elongated shaft 3010, a handle 4000, and an umbilical cord cord 530. The proximal end of the umbilical cord cord cord 530 terminates at a connector 540, which can be inserted into a socket port, such as a socket port 560 on a console 550 described above in conjunction with Figure 11.

The catheter 3000 is also shown having an electrical connector 580. The electrical connector 580 can be coupled to an EP recording system for analyzing electrical information detected in the distal treatment segment, as described above in conjunction with Figure 11.

Figure 24 is an enlarged view of the distal segment of the ablation catheter 3000 shown in Figure 23. In the embodiment shown in Figure 24, the ablation catheter 3000 has an elongated shaft 3010, which includes a distal ablation portion 3020 and a distal end 3030. The proximal region of the shaft can be coupled to a handle 4000 for manipulating the catheter and selectively bending the catheter shaft, as further described herein in conjunction with Figures 31-32.

In embodiments, the flexibility of the shaft can vary along its length. For example, in embodiments, the proximal or first shaft portion can be flexible, semi-flexible, semi-rigid, or rigid. In some embodiments, the first or proximal shaft portion is less flexible than the middle portion of the shaft; however, the first shaft portion is still flexible enough to be delivered to the target tissue via the body's vascular/venous system.

The ablation catheter shown in Figure 24 also includes a plurality of electrodes 3040 axially spaced along the distal ablation portion 3020. These electrodes can be used to detect electrical activity in the target tissue to assess or verify continuous contact between the distal ablation portion and the target tissue, as described in the commonly assigned international patent application No. PCT/US16/51954 entitled “TISSUE CONTACTVERIFICATION SYSTEM” filed by Alexei Babkin et al. on September 15, 2016, the entire contents of which are incorporated herein by reference for all purposes. In some embodiments, the electrodes may be included on the distal ablation tip 3030, or the ablation tip 3030 itself may function as an electrode.

Referring to Figure 25, a cross-sectional view of the ablation catheter 3000 taken along line 25-25 of Figure 24 is shown. The ablation shaft 3010 includes a multilayer cryoprotectant delivery tube/lumen 888 for delivering cryoprotectant to the distal ablation section 3020 and a multilayer cryoprotectant return tube/lumen 889 for delivering cryoprotectant away from the distal ablation section. The cryoprotectant delivery tubes 888/889 are fluidly connected to the distal segment inlet port 3052 and the distal segment outlet port 3050 to allow cryoprotectant circulation through the distal ablation cryoprotectant manifold, as further described herein.

Multiple service tubes/lumens 891 are also shown, which may include conduit electrode wires 892, thermocouple wires 3892, or any other elements that may be desired.

Cross-sectional Figure 25 also illustrates a number of optional elements for manipulating the shape of the catheter, in particular one or more control lines 3052, 3053, an open directional biasing lumen 3054, and a pull ring 3060 arranged and operable to cause bidirectional deflection. These features can be coupled to a handle to selectively bend the distal segment of the catheter, as described herein.

Figure 25 also shows one or more outer tubular sheaths 3065 and thermal insulation members 3070. Preferably, the outer diameter of the distal segment is substantially constant along its length, and again referring to Figure 24, there is a smooth transition between the intermediate portion 3014 and the distal segment 3020.

In addition, areas or spaces not occupied by working parts can be filled with material or bushing 3062 to facilitate bending flexibility.

It should be understood that although Figure 25 depicts one (1) multilayer cryotherapy delivery tube 888, one (1) multilayer cryotherapy return tube 889, and two (2) service tubes/lumens 891, the embodiments of the present invention are not intended to be so limited. Rather, any number of multilayer cryotherapy delivery tubes 888, multilayer cryotherapy return tubes 889, and service tubes/lumens 891 may be included depending on the desired ablation power of the catheter or the conditions under which the catheter will be used for treatment. Furthermore, although Figure 25 depicts a specific configuration of the multilayer cryotherapy delivery tubes 888, multilayer cryotherapy return tubes 889, and service tubes/lumens 891, particularly the paired multilayer cryotherapy delivery tubes 888 and multilayer cryotherapy return tubes 889 positioned adjacent to each other and the service tubes/lumens 891 being separate, the embodiments of the present invention are not intended to be so limited, and any number of different configurations for the multilayer cryotherapy delivery tubes 888, multilayer cryotherapy return tubes 889, and service tubes/lumens 891 may be included.

Figure 26 shows an enlarged cross-sectional view of the multilayer refrigerant delivery tube 888 and multilayer refrigerant return tube 889 of Figure 25. A first tube or inner tube 893 is shown as being coaxially surrounded by a second tube or outer tube 894. The cavity 895 of the inner tube 893 is designed to receive the flow of refrigerant. The inner tube 893 and outer tube 894 are arranged such that a space or gap 896 is formed between the outer surface of the inner tube 893 and the inner surface of the outer tube 894. This gap 896 can be emptied, filled with gas or air, or can be filled with a heat-conducting medium as described herein. In some embodiments, the gap 896 has an annular shape. All multilayer refrigerant delivery tubes 888 and multilayer refrigerant return tubes 889 can have similar tube-in-tube structures.

During use, if the cryoprotectant flowing through cavity 895 leaks or the inner tube 893 ruptures, the leaked cryoprotectant is contained within the gap 896 between the inner tube 893 and the outer tube 894. This tube-in-tube structure adds an extra safety element to the device because any leaked fluid/cryoprotectant is contained within the catheter and prevented from entering the patient's body. In some embodiments, a pressure sensor/device or pressure gauge may be incorporated to monitor the pressure in gap 896. Therefore, if fluid/cryoprotectant ruptures the inner tube 893 and leaks into gap 896, the pressure in gap 896 will increase. If the pressure change exceeds a threshold limit, the system can be programmed to (a) stop ablation to prevent potential harm to the patient and/or (b) notify the surgeon of the pressure change.

The inner tube 893 can be prepared and fabricated from materials described herein related to other flexible tubes used for conveying refrigerant/cooling fluid. The outer tube 894 can also be made from a flexible material such that the flexible shaft portion and the distal ablation portion 3020 of the ablation conduit 3000 can be elastically deflected, thereby allowing these portions to change their shape as disclosed herein. In some embodiments, the outer tube 894 is non-fillable, non-expandable, and non-inflatable, such that the size and shape of the outer tube are substantially unaffected by the presence of the heat-conducting medium contained therein. Non-limiting exemplary materials for the outer tube 894 include polymers and metals or alloys. An example of a material for the outer tube 894 is polyimide.

The diameter of the distal ablation portion 3020 can vary. In some embodiments, the outer diameter of the distal ablation portion ranges from about 1 mm to 3 mm, and is preferably about 2 mm.

Figure 27 is a longitudinal sectional view of the distal ablation region 3020 of the catheter shown in Figure 24, with one or more external components removed to facilitate understanding of the invention. In the embodiment shown in Figure 27, the distal ablation region 3020 has a cryomanifold assembly 3022, which includes a tubular sheath 3032 and a body 3080 inserted into the sheath, and are arranged together to define a plurality of small fluid paths in the space between the sheath and the insertion, which will be discussed further herein.

A cryoprotectant delivery tube 888 is shown fluidly connected to an inlet port 3052 of the insert 3080, and a cryoprotectant return tube 889 is shown fluidly connected to an outlet port 3050 of the insert 3080. In operation, after the distal ablation segment is positioned to contact the target tissue, cryoprotectant circulates from the inlet port 3052 along the insert channel 3082 through the cryoprotectant manifold 3022 into the end space 3086 (where the fluid changes direction), and is distributed to multiple discrete fluid flow paths arranged around the circumference or periphery of the insert, ultimately being collected by the outlet port 3088 and entering the return delivery tube 889. As the cryoprotectant circulates through the cryoprotectant manifold, heat is transferred from the target tissue to the cryoprotectant, thereby cooling the tissue and causing damage.

Figure 28 is an enlarged cross-sectional view of the refrigerant manifold assembly 3022 shown in Figure 27, taken along line 28-28. The body 3080 is shown having an octagonal cross-sectional shape and is inserted into the circular cavity 3034 of the sleeve 3032. Four fluid paths 3092 are defined between a flat side 3096 and the inner surface 3034 of the sleeve. The flat side 3096 is separated by a low-flow (bow-shaped) section 3094 of the body, which extends to or nearly matches the inner diameter (ID) of the sleeve. In an embodiment, the effective diameter of the fluid paths 3092, i.e., the distance between the sleeve and the body along the flat side 3096, is in the range of 0.05 to 1 mm. Along the low flow section 3094, the distance between the sleeve and the body is less than the distance of the fluid path, and can be in the range of 0 to 0.30 mm, and more preferably in the range of 0.05 to 0.15 mm, and in some low flow areas, it can be zero or zero gap.

Figure 29 is a perspective view of the insert shown in Figures 27 and 28, with the cannula removed for ease of understanding of the invention. The embodiment shown in Figure 29 has arrows indicating the direction of fluid flow. Specifically, fluid is shown exiting the central channel outlet 3084, moving along the fluid path 3092, and being collected in the outlet port 3088. As described above, the collection port 3088 connects the fluid to the return tube 889 (not shown in Figure 29). The insert body 3080 shown in Figure 29 also includes a hub portion 3086 adapted to mate with the outer sheath 3070 of the conduit shaft (not shown in Figure 29).

Figure 30 is another longitudinal sectional view of the distal region of the catheter shown in Figure 24. Figure 30 illustrates the arrangement of thermocouple wires 3892 and electrode wires 892 with the cryomanifold assembly. Thermocouple wires 3892 are nested in cavities that are in thermal communication with the insert body 3080. As described herein, measuring the temperature of the catheter ablation region can be used to control the amount of power supplied to the catheter. Each electrode wire 892 extends and connects to a separate annular electrode 3040. Optionally, the spacers between the electrode rings are filled with an electrically insulating but semi-thermally conductive material. An example of an electrically insulating but semi-thermally conductive material is a ceramic-filled thermoplastic elastomer (e.g., a boron nitride-filled polyether block amide).

As described herein, electrode 3040 can be used during surgery to determine tissue contact and location information, as well as to estimate treatment effectiveness. The distal end 3030 may also be covered with an electrically insulating but thermally conductive material. An example of an electrically insulating but thermally conductive material is a ceramic-filled thermoplastic elastomer (e.g., a boron nitride-filled polyether block amide). Electrical insulation prevents crosstalk between electrodes and provides a more accurate signal profile from the tissue.

Although the insert body 3080 is generally shown with an octagonal cross-section, the invention is not intended to be limited to this extent except as described in the appended claims. The cross-sectional shape of the insert body can vary widely. Exemplary cross-sectional shapes include any type of polygon, such as, but not limited to, triangles, quadrilaterals, pentagons, hexagons, decagons, nonagons, hectogons, and other shapes, whether symmetrical or not, that differ from the shape of the sleeve cavity. Each side of the polygon can be straight, or the side can be modified to extend to the inner surface of the sleeve, as described above with reference to edge 3094 shown with reference to FIG. 28. In a preferred embodiment, the sides of the polygon alternate between straight edges and curved or outwardly arched edges. Not intended to be theoretical, various discrete fluid paths are defined along the axial cut of the insert body for generating turbulent flow and improving heat transfer efficiency.

The material of the refrigerant manifold can vary. In this embodiment, the insert body and outer sheath are made of a thermally conductive material such as aluminum or steel. These components can be joined together using adhesives, press fittings, and other joining techniques known to those skilled in the art.

Handle actuator for bidirectional shaft bending

Figure 31A shows a side view of a handle 4000 for an ablation catheter according to an embodiment of the present invention; the handle 4000 shown in Figure 31A includes a proximal handle 4002, a distal handle 4004, and an actuator assembly 4006 located between the proximal and distal handles. In general, the handle has an ergonomic, slender, dagger-like appearance.

The actuator assembly 4006 has two levers or finger holders 4010, 4012 that can rotate in either direction (R or F), causing the elongated shaft to bend to a desired angle based on the rotation level of the finger holders. In an embodiment, the bending of the shaft is bidirectional and up to (or greater than) 180 degrees, as shown in Figure 31B. Once the physician has reached or achieved the desired level of bending (possibly by visualizing the shaft with fluoroscopy or another imaging technique), the brake 4020 can be set to hold the bending at the desired level. In the embodiment shown in Figure 31A, the brake 4020 is a variable friction brake and is set by rotating the cover 4021 clockwise until the finger is tightened, as further described herein.

Referring to Figures 32A and 32B, the handle 4000 is shown with its exterior removed to facilitate understanding of additional details of the embodiments of the invention. More specifically, the cooperation of the control lines 3052, 3053 and the actuator assembly is visible. As described above, the control lines 3052, 3053, extending to the distal ablation segment of the catheter and coupled to the pull ring, are mechanically coupled to the pulley assembly 4036. Optionally, and as shown in Figures 32A and 32B, the control lines are secured to flexible filaments 4022, 4023 (e.g., sutures, nylon, etc.) via loop couplers 4024, 4025. Thus, when the pulley is rotated by manipulating the finger holder or the levers 4010, 4012, the control lines and the distal segment of the final catheter shaft are bent to the level at which the finger holder is manipulated. In the embodiments shown in Figures 32A and 32B, the movement generated from the actuator mechanism 4006 is bidirectional. In other words, when the actuator assembly 4006 is actuated, the catheter shaft is forced to bend only in one direction (or the opposite direction) from its axis. However, the physician can gain additional degrees of freedom by manually rotating the entire handle 4000 around its longitudinal axis.

As described herein, the catheter can be operated to bend and lock at a desired angle via friction. In the embodiments shown in Figures 32A and 32B, the braking assembly 4020 includes a knob or button 4021 threadedly engaged with a gasket 4014 via a member 4016, the gasket 4014 compressing the pulley assembly 4036 when the knob is turned. Once the knob 4021 is pressed against or tightened by hand, the pulleys and finger levers 4010, 4012 may not be further actuated due to the friction between the plate 4014 and the pulleys and arms 4036.

The brake can be released by unscrewing knob 4021, which is used to loosen or release the pulley. Once the pulley is free, the finger lever can be rotated forward or backward as needed to bend the guide shaft to the corresponding level. It should be understood that although specific types of components are shown and described in the handle, actuator, and braking assembly, the invention is not intended to be so limiting, except as specifically stated in the claims.

application

The embodiments of cryoablation devices (catheters, probes, etc.) described herein have a wide range of diagnostic and therapeutic applications, including, for example, intravascular cardiac ablation, and more specifically, intravascular cardiac ablation treatment of atrial fibrillation.

Figure 33 illustrates an example of targeted ablation lesions during pulmonary vein isolation (PVI) surgery for the treatment of atrial fibrillation.

The basic structure of the heart 1 is shown in Figure 33, including the right atrium 2, left atrium 3, right ventricle 4, and left ventricle 5. The blood vessels include the aorta 6 (entering via the femoral artery), the superior vena cava 6a (entering via the subclavian vein), and the inferior vena cava 6b (entering via the femoral vein).

Exemplary target lesions for PVI surgery include lesions 8 surrounding and isolating all left pulmonary veins (PV) and 9 surrounding and isolating all right pulmonary veins (PV). As further described herein, the invention may include the application or generation of additional lesions to increase the effectiveness of treatment. Furthermore, it should be understood that although the following discussion focuses primarily on embodiments for performing PVI, the techniques and procedures described herein for generating these lesions can be used to generate other lesions in and around the heart and other organs, such as those described in International Patent Applications Nos. PCT/US2012/047484 and PCT/US2012/047487 by Cox et al., which correspond to International Publications Nos. WO2013/013098 and WO2013/013099, respectively, the contents of which are hereby incorporated herein by reference in their entirety.

Figure 34 illustrates a technique for reaching the left atrium using the distal treatment segment of a catheter. This procedure can be performed under conscious sedation or, if necessary, under general anesthesia.

Peripheral veins (e.g., femoral vein FV) are punctured with a needle. The puncture wound is enlarged using a dilator to a size sufficient to accommodate an introducer sheath, and the introducer sheath, having at least one hemostatic valve, is positioned within the enlarged puncture wound while maintaining relative hemostasis.

Once the guide sheath is in place, the guide catheter 10 or sheath is introduced through the hemostatic valve of the guide sheath and advanced along a peripheral vein to the target cardiac region (e.g., the vena cava and into the right atrium 2). Fluorescence imaging can be used to guide the catheter to the selected site.

Once in the right atrium 2, the distal end of the guiding catheter is positioned against the fossa ovalis in the septum of the atrium. A needle or cannula is then advanced distally through the guiding catheter until it pierces the fossa ovalis. A separate dilator can also be used, with a needle advanced through the fossa ovalis to prepare an access port for placement of the guiding catheter through the septum. Subsequently, the guiding catheter, instead of the needle that has pierced the septum, is placed through the fossa ovalis in the left atrium, thus providing an entry point for the device to pass through its own cavity and into the left atrium.

The placement of the aforementioned instruments may be performed under one or more of the following guidance: fluoroscopy, intracardiac pressure, transesophageal echocardiography (TEE), and intracardiac echocardiography (ICE).

Figures 35-38 illustrate methods for deploying a loop catheter in the left atrium and around the pulmonary vein inlet for the treatment of various cardiac conditions, such as atrial fibrillation.

Referring first to Figure 35, the cross-sectional view of the heart includes the right atrium RA2, the left atrium LA3, the left superior pulmonary vein LSPV entrance, and the left inferior pulmonary vein LIPV entrance. The guiding catheter 2100 is shown extending through the septum and into the left atrium.

Although not shown, the mapping catheter can be located at the LSPV inlet in the left atrium for monitoring cardiac electrical signals. The mapping catheter can be placed in other locations, such as the coronary sinus (CS). Examples of mapping catheters include a bidirectional CS catheter and a CS catheter, both manufactured by Biosense Webster Inc. (Diamond Bar, CA 91765, USA). Another example of a mapping and cryotreatment system is described in Mihalik's U.S. Patent Publication No. 2015/0018809.

Optionally, an esophageal warming balloon can be placed in the esophagus to mitigate collateral damage caused by the formation of the lesion. The esophageal warming balloon prevents low temperatures from reaching the inner lining of the esophageal cells and can prevent, for example, the formation of an atrial-esophageal fistula. Examples of suitable esophageal warming balloon devices that can be used are described in commonly assigned U.S. Patent Application No. 15/028,927, filed October 12, 2014, entitled “ENDOESOPHAGEAL BALLOON CATHTER, SYSTEM, AND RELATED METHOD” by Alexei Babkin et al., the contents of which are incorporated herein by reference in their entirety for all purposes.

Figure 36 shows the distal segment of the cryoablation catheter 2116 advanced through the guide sheath 2100. The energy element 2118 is shown as having a circular shape as disclosed and described herein and is pushed toward the endocardium. As described herein, the shape can be adjusted to make continuous contact with tissue and form a continuous elliptical or circular lesion (e.g., lesion 8 shown in Figure 33) that surrounds all left PV entrances.

In embodiments, the shape is modified by reducing the diameter of the ring, the middle section of the hinge axis, and rotating or manipulating the distal section of the catheter. In general, the steps of unfolding, diameter control, manipulation, and hinge allow the entire circumference of the ring to remain in continuous contact with the endocardial tissue. When energy is applied to the distal treatment segment, for example by allowing cryotherapy to flow through it, a continuous, elongated ring-shaped injury (frozen tissue) is formed, such as injury 8 shown in Figure 33, surrounding all the left pulmonary vein inlets.

Figure 37 illustrates the formation of a ring-shaped lesion around the entrances of the right superior pulmonary vein (RSPV) and the right inferior pulmonary vein (RIPV), such as lesion 9 shown in Figure 33. In contrast to the slightly linear (straight shot) localization shown in Figures 35-36, the catheter neck region 2116 shown in Figure 37 is deflected nearly 180 degrees to target the right pulmonary vein. The energy element portion 2118 is located around the entrances of the RSPV and RIPV.

Figure 37 illustrates the energy element 2118, which unfolds in a circle and contacts the endocardium. As described herein, the shape can be adjusted for better tissue contact, thereby forming an elongated, continuous annular lesion that surrounds or encloses the RSPV and RIPV entrances.

Similar elongated, continuous ring-shaped lesions can be formed around the entrances of the left superior pulmonary vein (LSPV) and the left inferior pulmonary vein (LIPV).

Figure 38 shows catheter 2116 deflected to target the posterior wall of the left atrium. The energy element portion 2118 is manipulated to form a loop and pushed toward the posterior wall, overlapping the previously formed right and left lesions.

Optionally, and not shown, a guidewire may be advanced from the guide sheath and used to guide the catheter treatment segment into place.

The shape and pattern of the lesion may vary. In an embodiment, referring to Figure 39, a “box-shaped” lesion 900 is shown surrounding multiple pulmonary vein inlets during a PVI procedure. The box-shaped lesion surrounds the pulmonary vein inlets on both sides of the left atrium.

Box-shaped damage 900 can be formed in various ways. In some embodiments, box-shaped damage is formed by overlapping combinations of damages, which may have similar or different shapes (e.g., oval, elliptical, ring-shaped, etc.) to form a larger overall continuous damage, which may have a box shape 900 as shown in FIG39.

Referring to the illustration shown in Figure 40 and the corresponding flowchart shown in Figure 41, a method 1000 for forming a box-shaped lesion surrounding/enclosing the entrances of all pulmonary veins (RSPV, RIPV, LSPV, and LIPV) in the left atrium is described.

Step 1010 describes advancing the cryoablation catheter into the left atrium, for example, this can be done using a guide sheath.

Step 1020 describes guiding the therapeutic segment (energy element portion 2118) of the catheter to one side of the left atrium and into the sinuses of the superior and inferior pulmonary veins on that side of the atrium.

Step 1030 describes manipulating the treatment section (energy element portion 2118) of the catheter to form a ring shape and adjusting the size of the ring to achieve full circumferential tissue contact with the tissue surrounding the superior and inferior venous inlets on that side of the atrium.

Step 1040 describes the verification of tissue contact. This step can be performed using, for example, electrodes mounted on the distal treatment segment, as disclosed and described in commonly assigned international patent application PCT/US16/51954 entitled “TISSUE CONTACTVERIFICATION SYSTEM” filed by Alexei Babkin et al., September 15, 2016, all contents of which are incorporated herein by reference for all purposes. An EP recording system can be used to display a tissue electrocardiogram (ECG).

Optionally, an esophageal balloon (EBB) (as described above) is advanced into the esophagus near the heart. During ablation treatment, the EBB is inflated, and a thermally conductive fluid is circulated within the balloon. As described herein, by heating the tissue during the ablation cycle, the EEB minimizes collateral damage to tissues near the ablation zone.

Step 1050 describes performing ablation by freezing the tissue to create a first successive injury surrounding/around the pulmonary vein inlet on a first side of the left atrium, for example, left-side injury 901 in Figure 40. The duration of tissue freezing can be up to 3 minutes or longer, typically in the range of about 1 to 3 minutes, preferably about 2 minutes. In embodiments, the freezing step comprises a single application of uninterrupted ablation energy.

In some embodiments, the duration of energy application ranges from about 10 seconds to 60 seconds, and sometimes is less than or equal to about 30 seconds.

The duration of a freeze cycle can vary. A physician or electrophysiologist may choose to terminate the freeze cycle as needed (e.g., before or after the expected time period has elapsed). Examples of reasons for early termination include: wanting to reposition the catheter, wanting to improve catheter-tissue contact, or for safety reasons.

Step 1060 states that the ablation has been confirmed as complete. Electrical activity from the electrodes on the distal treatment segment can be monitored. During freezing, the electrocardiogram (ECG) will show abnormal signals due to the freezing of tissue and blood in contact with the frozen end. However, after freezing is complete, the ECG should not show any signal or evidence of voltage potential in the tissue due to tissue necrosis.

However, if an ECG signal/signature reappears after the freezing step, it indicates that electrical activity remains in the tissue, suggesting that ablation was incomplete and PVI may not have been achieved. If PVI was not achieved, the applicable steps described above can be repeated.

In some embodiments, another freezing can be initiated at the same location. Alternatively, the catheter can be repositioned or otherwise adjusted to better contact the target tissue. Additional freezing can then be performed.

Performing additional freezing may be beneficial, especially when the distance between pulmonary veins is abnormally large. Isolating the pulmonary vein inlets with only a single, continuous lesion is challenging when the distance between pulmonary veins is abnormally large. In a subgroup of patients with abnormally large hearts, the formation of additional lesions around the pulmonary vein inlets increases the likelihood of complete and persistent PVI.

Furthermore, in some cases, it may be desirable to reduce the size of the ablation ring to accommodate a single vein. In an embodiment, the method involves performing a single vein isolation around the ostium of a single vein. The diameter of the catheter ring is reduced from a relatively large size used for isolating multiple veins to a suitable size for a single vein. In an embodiment, a single vein isolation is performed after a larger multi-vein isolation.

Step 1070 describes the steps to be repeated for the pulmonary veins on the other side of the left atrium. That is, for example, after the left sinus venosus is isolated, the catheter loop will be guided to the right sinus venosus, and all relevant steps should be repeated to create a second right-sided lesion (e.g., lesion 902 in Figure 40).

Step 1080 describes repeating the applicable steps above for posterior wall injuries (injury 903 in Figure 40). Once the LSPV sinus and LIPV sinus, as well as the RSPV venous sinus and RIPV venous sinus, are isolated, the annular treatment segment of the catheter is guided to the posterior wall of the left atrium.

Optionally, the EBB is infused into the esophagus and activated prior to posterior wall ablation. For posterior lesions, the other applicable steps for placing left and right lesions are repeated. Posterior lesion 903 is located in a more central position and is shown in Figure 40 as overlapping with the left and right sinus lesions (901 and 902, respectively). Lesion 903 is also shown as extending from the base to the top of the left atrium.

Although this method describes a specific sequence in which damage to the left pulmonary vein, right pulmonary vein, and posterior wall is produced, embodiments of the invention are not intended to be so limited, unless specifically stated in the appended claims. The order in which damage is produced may differ. For example, in embodiments, right-sided or posterior damage may occur before left-sided damage.

As can be seen from Figures 39 and 40, multiple independent lesions (901, 902, 903) collectively form a complex, box-shaped, continuous lesion 900 (Figure 39), which surrounds all pulmonary vein entrances on all sides (left, right, top, and bottom) of the left atrium. In this embodiment, the sum of the sub-lesions forms a box-shaped, square, or rectangular shell. Performing ablation to form this complex, continuous lesion 900 effectively electrically isolates all pulmonary vein entrances in the left atrium.

In patients with atrial flutter in addition to paroxysmal atrial fibrillation and in patients with non-paroxysmal atrial fibrillation, in addition to the lesions (901, 902, 903) discussed above with reference to Figures 39-41, it is necessary to form additional lesions to isolate the mitral valve. In these patients, as shown in Figure 42, there is electrical activity/current 950 flowing around the mitral valve 960. Therefore, in order to treat these patients, the flow of this electrical activity/current 950 must be interrupted and stopped/blocked. Examples of lesions that can be formed to interrupt the flow of current 950 are depicted in Figures 43A and 43B. As can be seen from the figures, the mitral valve lesion 975 is connected to a box-shaped lesion 900 formed by the left pulmonary vein lesion 901, the right pulmonary vein lesion 902, and the posterior wall lesion 903.

As shown in Figure 43A, in one embodiment, a mitral valve injury 975 extends from near the mitral valve 960 (mitral annulus) and intersects the flow paths of current 950 and injury 900. In this and other embodiments, it is important that the mitral valve injury 975 intersects at least the flow paths of current 950 and injury 900. Therefore, the mitral valve injury 975 can be formed at different locations within the left atrium, as long as it intersects the flow path of current 950 and connects to injury 900. This type of injury can be formed by altering the shape of the treatment segment of the catheter.

In the embodiment shown in Figure 43B, the same annular treatment segment of the catheter used to generate left pulmonary vein injury 901, right pulmonary vein injury 902, and posterior wall injury 903 can be used to generate mitral valve injury 975. As shown in Figure 43B, generating annular or circular mitral valve injury 975 causes injury 975 to intersect with the flow paths of current 950 and injury 900 at multiple points (A, B, C, D), thereby increasing the likelihood of surgical success.

If necessary, a mitral valve injury 975 can be created after the formation of the box-shaped injury 900 as shown in FIG41. A method for performing the procedure is illustrated in the flowchart shown in FIG44, which includes creating the mitral valve injury 975 as step 1090 after the formation of the box-shaped injury 900. It will be apparent to those skilled in the art that, as long as this procedure is followed, the steps used in creating the left pulmonary vein injury 901, right pulmonary vein injury 902, posterior wall injury 903, and mitral valve injury 975 can be performed in any order, isolating all pulmonary vein inlets and interrupting the flow path of the current 950.

In another embodiment, linear lesion in the right atrium 2 may be necessary in some patients with persistent atrial fibrillation. As depicted in Figure 45, this linear lesion 2500 is created to connect the inlet of the inferior vena cava (IVC) 6b to the annulus of the tricuspid valve (TV) 2510 and extends through the cava-tricuspid isthmus (CTI) 2520. This CTI lesion serves to prevent/interrupt most potential reentry circuits in the right atrium, such as right atrial flutter and/or other arrhythmias originating from the right atrium. This type of injury is described in U.S. Patent Application No. 15/304,524, filed October 15, 2016, by Alexei Babkin et al., entitled “ENDOVASCULAR NEAR CRITICAL FLUID BASED CRYOABLATION CATHETERHAVING PLURALITY OF PREFORMED TREATMENT SHAPES”, the contents of which are incorporated herein by reference in their entirety for all purposes.

In some embodiments, for certain patients, in addition to forming the injuries (901, 902, 903) discussed above with reference to Figures 39-41, it is also necessary to form the CTI injury 2500 discussed above with reference to Figure 45. It will be apparent to those skilled in the art that, provided the procedure is followed, the steps used in forming the left pulmonary vein injury 901, the right pulmonary vein injury 902, the posterior wall injury 903, and the CTI injury 2500 can be performed in any order, isolating all pulmonary vein inlets and interrupting/blocking most potential re-entry circuits in the right atrium.

In some embodiments, for certain patients, in addition to forming the injuries (901, 902, 903) discussed above with reference to Figures 39-41 and the mitral valve injury 975 discussed above with reference to Figures 43A, 43B, and 44, it is also necessary to form the CTI injury 2500 discussed above with reference to Figure 45. It will be apparent to those skilled in the art that, provided the procedure is followed, the steps used in forming the left pulmonary vein injury 901, right pulmonary vein injury 902, posterior wall injury 903, mitral valve injury 975, and CTI injury 2500 can be performed in any order, isolating all pulmonary vein inlets, interrupting the flow path of the current 950, and interrupting/blocking most of the potential reentry circuits in the right atrium.

Treatment of ventricular tachycardia

In another embodiment, in some patients with ventricular tachycardia, it may be desirable to produce one or more linear or focal lesions in the ventricles.

Referring to Figure 46, a method 5000 for treating VT is described according to an embodiment of the present invention. Initially, as described above, the ablation catheter can be introduced by either retrograde or antegrade methods.

Step 5010 describes advancing the ablation catheter into the ventricle. The catheter is inserted into either the left or right ventricle.

Step 5020 describes guiding the treatment segment to the target location. Electrodes on the catheter can be used to guide and identify the location requiring ablation. Referring to Figure 33, examples of ideal locations for treating VT include the RV diaphragm 13, LV diaphragm 15, LV lateral wall 17, and LV apex 19.

Next, according to step 5030, the catheter will be positioned to contact the target ablation site. As described herein, in embodiments, the catheter may be deflected up to 180 degrees and rotated to strike the desired ablation site for effective treatment of VT.

Step 5040 describes the verification of tissue contact. As described herein, tissue contact can be verified using an electrogram obtained from an electrode on the treatment segment of the catheter.

Step 5050 describes the execution of the treatment. The treatment will be delivered to the target tissue.

Step 5060 inquires whether ablation is complete. An electrogram can be obtained from the electrodes on the distal segment of the catheter to observe whether the ablation was effective as described herein. If ablation is not complete, the treatment segment can be further guided or adjusted for better contact or positioning, as shown in steps 5020 or 5030, if necessary.

If ablation is complete (as verified by electrography or other means), the procedure proceeds to step 5070, and new damage can be created at another target location, or the procedure can be terminated.

Based on the teachings above, many modifications and variations of the invention are possible. Therefore, it should be understood that the invention can be practiced in ways other than those specifically described within the scope of the appended claims.

For example, while the devices described herein can be used as cryoablation catheters to create damage by freezing tissue with a suitable cryotherapy agent, these devices can be used in combination with other non-cryotherapy ablation energies, such as radiofrequency, microwave, laser, high-frequency ultrasound (HIFU), and pulsed field ablation (PFA). In fact, combined types of damage can be produced, whether continuous and elongated or inherently more concentrated, such as one or more points.

Claims (24)

1. An ablation device for creating damage in target tissue, the ablation device comprising: An elongated shaft, the elongated shaft comprising a proximal portion, a middle portion, and a distal ablation portion; A first ablation fluid delivery chamber, extending through the shaft to the distal ablation portion, is used to deliver fluid along a first direction; and A second ablation fluid delivery chamber, extending through the shaft to the distal ablation portion, is used to deliver fluid along a second direction; and wherein the distal ablation portion includes: A sleeve, the sleeve defining an inner surface having a first cross-sectional shape; and An insert, disposed within the sleeve, the insert comprising: main body, A channel extending through the body of the insert and including a proximal port and a distal port, wherein the proximal port of the channel is in fluid communication with the first ablation fluid delivery cavity. The outer surface defines a second cross-sectional shape that is different from the first cross-sectional shape; Multiple discrete fluid paths are defined between the cannula and the insert, wherein the multiple discrete fluid paths are in fluid communication with the distal port of the channel and with the second ablation fluid delivery chamber, such that fluid can circulate between the first and second ablation fluid delivery chambers through the multiple discrete fluid paths to deliver ablation energy to the target tissue, thereby causing the damage. 2. The ablation device according to claim 1, wherein the first cross-sectional shape is circular, and the second cross-sectional shape is polygonal. 3. The ablation device according to claim 2, wherein the polygon has a plurality of flat sides and a plurality of arcuate sides. 4. The ablation device of claim 3, wherein each of the plurality of fluid paths defined between the flat edge of the insert and the curved inner surface of the sleeve has an effective gap in the range of 0.05 mm to 1 mm. 5. The ablation device according to claim 1, wherein the ablation portion has a length in the range of 5 mm to 25 mm. 6. The ablation device according to claim 1, wherein the ablation portion has an outer diameter of 1 mm to 5 mm. 7. The ablation device according to claim 1, wherein the ablation portion is rigid and straight. 8. The ablation device of claim 1, wherein the cannula further includes a dome-shaped distal end and defines space for the distal port of the plurality of fluid paths and the channel for fluid connection. 9. The ablation device according to claim 1, wherein the first ablation fluid delivery chamber and the second ablation fluid delivery chamber each include an inner tube, the inner tube having an outer tube surrounding the inner tube, thereby defining a gap between the inner tube and the outer tube. 10. The ablation device according to claim 9, wherein the gap is empty or under vacuum. 11. The ablation device according to claim 1, further comprising a plurality of axially spaced electrodes along the outer surface of the ablation portion. 12. The ablation device according to claim 1, further comprising a semi-thermally insulating and electrically insulating material between the electrodes. 13. The ablation device of claim 12, further comprising a distal end and a non-thermally insulating and electrically insulating material on the distal end. 14. The ablation device of claim 13, further comprising a heat insulation body surrounding the intermediate portion of the axis. 15. The ablation device of claim 1, wherein the refrigerant circulates through the plurality of discrete fluid paths. 16. The ablation device according to claim 15, wherein the refrigerant is nitrogen. 17. The ablation device according to claim 16, wherein the nitrogen is near-critical nitrogen. 18. The ablation device of claim 1, wherein the shaft has a shape and flexibility sufficient to be manipulated from an inlet in the patient's blood vessels, through the patient's vascular system and into a chamber in the patient's heart. 19. The ablation device according to claim 1, further comprising a temperature sensor located in the ablation portion. 20. The ablation device of claim 1, further comprising a control line extending through the shaft from the proximal portion to the ablation portion, and the control line being operable to bend the shaft to a target angle of up to 180 degrees when the control line is manipulated from the proximal region of the control line. 21. The ablation device of claim 20, further comprising a handle having an actuator connected to the proximal region of the control line and adapted to progressively bend the shaft by an amount corresponding to the degree or amount to which the actuator is adjusted. 22. The ablation device of claim 21, wherein the handle further includes a brake lock for holding the ablated portion at the target angle. 23. A method for treating ventricular tachycardia, atrial fibrillation, atrial flutter, and PVCs, comprising using an ablation device according to any one of claims 1-22. 24. An ablation system comprising a cryoablation catheter, the cryoablation catheter including a cryogen manifold according to any one of claims 1-22, a fluid source in communication with the cryoablation catheter, and a controller operable to control the amount of cooling power delivered from the cryoablation catheter to the tissue.