Regulating pressure to lower temperature in a cryotherapy balloon catheter

A cryotherapy catheter can include an elongate member and an inflatable balloon at a distal end of the elongate member, the elongate member having lumens formed therein to supply cryogenic fluid to a chamber of the balloon and to channel exhaust from the balloon chamber; and a controller programmed to control a first rate at which the cryogenic fluid is supplied to the balloon chamber and a second rate at which exhaust is channeled from the balloon chamber, wherein the controller is programmed to a) develop, during a first phase of a cryotherapy procedure, a first pressure inside the balloon chamber at a value that is greater than an ambient pressure outside and adjacent to a proximal end of the elongate member, and b) develop, during a second phase of the cryotherapy procedure, the first pressure at a value that is less than the ambient pressure.

BACKGROUND

A number of serious medical conditions may be treated in a minimally invasive manner with various kinds of catheters designed to reach treatment sites internal to a patient's body. One such medical condition is atrial fibrillation—a condition that results from abnormal electrical activity within the heart. This abnormal electrical activity may originate from various focal centers of the heart and generally decreases the efficiency with which the heart pumps blood. It is believed that some of these focal centers reside in the pulmonary veins of the left atrium. It is further believed that atrial fibrillation can be reduced or controlled by structurally altering or ablating the tissue at or near the focal centers of the abnormal electrical activity.

One method of ablating tissue of the heart and pulmonary veins to treat atrial fibrillation is cryotherapy—the extreme cooling of body tissue. Cryotherapy may be delivered to appropriate treatment sites inside a patient's heart and circulatory system by a cryotherapy catheter. A cryotherapy catheter generally includes a treatment member at its distal end, such as an expandable balloon having a cooling chamber inside. A cryogenic fluid may be provided by a source external to the patient at the proximal end of the cryotherapy catheter and delivered distally through a lumen to the cooling chamber where it is released. Release of the cryogenic fluid into the chamber cools the chamber (e.g., through the Joule-Thomson effect), and correspondingly, the balloon's outer surface, which is in contact with tissue that is to be ablated. Gas resulting from release of the cryogenic fluid may be exhausted proximally through an exhaust lumen to a reservoir or pump external to the patient.

SUMMARY

In a cryotherapy balloon catheter in which cryogenic fluid is delivered to and released in a balloon portion, where it undergoes a phase change that cools the balloon portion by the Joule-Thomson effect, pressure inside the balloon can affect the boiling point of the cryogenic fluid, and thus the temperature to which the balloon portion can be cooled. In some implementations, lowering the pressure inside the balloon portion results in a lower temperature, which can accelerate a cryotherapy procedure. Some cryotherapy procedures include two phases: an initial treatment phase during which the cryotherapy balloon is inflated against body tissue that is to be treated (e.g., the ostium of a pulmonary vein) and cooled enough to cause its surface to be frozen to the body tissue; and a second treatment phase during which the pressure can be lowered inside the balloon, resulting in a lower surface temperature of the balloon, which may accelerate the cryotherapy procedure.

In some implementations, a method of performing a cryotherapy procedure can include introducing a cryotherapy balloon catheter at a treatment site inside a patient's body; regulating, during a first phase of a cryotherapy procedure, flow of cryogenic fluid to and exhaust from a distal balloon portion of the cryotherapy balloon catheter to cause a) a first pressure to be reached inside the distal balloon portion that is sufficiently high to cause an outer wall of the distal balloon portion to be pressed against body tissue at the treatment site, and b) a first temperature to be reached inside the distal balloon portion that is sufficiently low to cause the body tissue to freeze to the outer wall; and regulating, during a second phase of the cryotherapy procedure, flow of cryogenic fluid to and exhaust from the distal balloon portion to reduce pressure inside the distal balloon portion to a second pressure that is less than the first pressure, causing a temperature inside the distal portion to reach a second temperature that is below the first temperature.

The cryotherapy balloon catheter can be configured to enable Joule-Thomson cooling inside the distal balloon portion when cryogenic fluid is delivered to the distal balloon portion and resulting gas is exhausted from the distal balloon portion. In some implementations, the first temperature can be less than 0° C. In some implementations, the second temperature can be between −89° C. and −91° C. Regulating the flow of cryogenic fluid to and exhaust from the distal balloon portion can include regulating the flows such that heat is extracted from the body tissue at a greater rate during the second phase than a rate at which heat is extracted from the body tissue during the first phase.

In some implementations, the first pressure is approximately five pounds per square inch (PSI) above ambient pressure. In some implementations, the first pressure is approximately 5-25 PSI above ambient pressure. Ambient pressure may be characterized by atmospheric air pressure adjacent to the patient's body. The second pressure can be approximately equal to ambient pressure. The second pressure can be negative relative to ambient pressure. The second pressure can be maintained at a value that is sufficient to prevent the outer wall from being peeled away from the body tissue by vacuum forces inside the distal balloon portion or by elastic forces of material that makes up the distal balloon portion. The method can further include inflating the distal balloon portion.

The method can further include regulating, after the second phase, the flow of cryogenic fluid to and exhaust from the distal balloon portion such that minimal heat is extracted from the body tissue, allowing the body tissue to warm up. The method can further include deflating the distal balloon portion, introducing the cryotherapy balloon catheter to a second treatment site, and regulating the flow of cryogenic fluid to and exhaust from the distal balloon portion to repeat the first and second phases of the cryotherapy procedure at the second treatment site. Regulating flow of cryogenic fluid to and exhaust from the distal balloon portion can include regulating flow of liquid nitrous oxide to the distal balloon portion and flow of gaseous nitrous oxide from the distal balloon portion.

In some implementations, a cryotherapy catheter includes an elongate member and an inflatable balloon at a distal end of the elongate member, the elongate member having lumens formed therein to supply cryogenic fluid to a chamber of the balloon and to channel exhaust from the balloon chamber; and a controller programmed to control a first rate at which the cryogenic fluid is supplied to the balloon chamber and a second rate at which exhaust is channeled from the balloon chamber, wherein the controller is programmed to a) develop, during a first phase of a cryotherapy procedure, a first pressure inside the balloon chamber at a value that is greater than a second pressure outside and adjacent to a proximal end of the elongate member, and b) develop, during a second phase of the cryotherapy procedure, the first pressure at a value that is less than the second pressure. The second pressure can be an ambient pressure, wherein the ambient pressure can be characterized as atmospheric air pressure adjacent to the patient's body.

In some implementations, the controller is programmed to supply cryogenic fluid to the balloon chamber such that the cryogenic fluid boils at a first temperature in an environment of the first pressure, and boils at a second temperature, which is lower than the first temperature, at pressures that are less than the second pressure.

In some implementations, a cryotherapy catheter includes an elongate member and an inflatable balloon at a distal end of the elongate member, the elongate member having lumens formed therein to supply cryogenic fluid to a chamber of the balloon and to channel exhaust from the balloon chamber; and a controller programmed to control a first rate at which the cryogenic fluid is supplied to the balloon chamber and a second rate at which exhaust is channeled from the balloon chamber, wherein the controller is programmed to a) develop, during a first phase of a cryotherapy procedure, a first pressure inside the balloon chamber at a value that is greater than an ambient pressure outside and adjacent to a proximal end of the elongate member, and b) develop, during a second phase of the cryotherapy procedure, a second pressure inside the balloon chamber at a value that is less than the first pressure. The inflatable balloon can be configured to be disposed inside a lumen or body cavity of a human patient to deliver cryotherapy to tissue of the lumen or body cavity.

DETAILED DESCRIPTION

In a cryotherapy balloon catheter in which cryogenic fluid is delivered to and released in a balloon portion, where it undergoes a phase change that cools the balloon portion by the Joule-Thomson effect, pressure inside the balloon can affect the boiling point of the cryogenic fluid, and thus the temperature to which the balloon portion can be cooled. In some implementations, lowering the pressure inside the balloon portion results in a lower temperature, which can accelerate a cryotherapy procedure. Some cryotherapy procedures include two phases: an initial treatment phase during which the cryotherapy balloon is inflated against body tissue that is to be treated (e.g., the ostium of a pulmonary vein) and cooled enough to cause its surface to be frozen to the body tissue; and a second treatment phase during which the pressure can be lowered inside the balloon, resulting in a lower surface temperature of the balloon, which may accelerate the cryotherapy procedure.

FIGS. 1A and 1Billustrate example details of a cryotherapy balloon catheter100that can be used to deliver cryotherapy, andFIGS. 1A and 1Bfurther depict an example first treatment phase (FIG. 1A) and second treatment phase (FIG. 1B) during which cryotherapy can be provided to body tissue. Additional details of an example cryotherapy balloon catheter are described below with reference to FIGS.7and8A-8C.

The cryotherapy balloon catheter100ofFIGS. 1A and 1Bhas a distal cryotherapy balloon103that can be inserted into a body lumen of a patient, such as, for example, a blood vessel or other internal body structure. More particularly, for example, the distal cryotherapy balloon103can be inserted (in a deflated state), through appropriate blood vessels, into a patient's heart, and specifically into the patient's left atrium. Once in the patient's left atrium, the cryotherapy balloon can be employed to ablate tissue of the pulmonary veins (e.g., tissue at the ostium of one or more pulmonary veins) in order to eliminate aberrant electrical signals that may be causing atrial fibrillation in the patient. Similarly, the cryotherapy balloon catheter100can be routed to other treatment sites inside a patient and employed to treat other conditions. During whatever treatment is performed, a proximal end106of the cryotherapy balloon catheter remains outside the patient.

Between the proximal end106and the distal cryotherapy balloon103is an elongate member109(e.g., a catheter shaft) having various internal lumens, including a supply lumen112for delivering a cryogenic fluid to the distal cryotherapy balloon103. The cryogenic fluid can be released into a chamber115of the balloon103, where it undergoes a phase change to a gas. As a result of the phase change, heat is extracted from the surroundings of the chamber115, thereby cooling the surface118of the balloon103and body tissue121that is in contact with the surface118(e.g., via the Joule-Thomson effect). The elongate member109also includes an exhaust lumen124for exhausting the resulting gas from the chamber115.

Pressure inside the chamber115, PINTERNAL—A, can affect the temperature at which the cryogenic fluid changes state from a liquid to a gas (e.g., the boiling point). That is, with brief reference toFIG. 2, the cryogenic fluid may have one boiling temperature at atmospheric pressure, TB—ATMOS; another, higher boiling temperature, TB—POS, at a higher pressure; and another, lower boiling temperature, TB—NEG, at a lower pressure. By raising the pressure inside the chamber115, the boiling temperature of the cryogenic fluid (and thus the temperature that can be achieved at the surface118) can be increased; by lowering the pressure inside the chamber115, the boiling temperature can be decreased.

In some implementations, as will now be described in greater detail, a cryotherapy procedure can include a first treatment phase in which pressure inside the chamber115is higher than pressure inside the chamber115during the second treatment phase. In such implementations, pressure during the first treatment phase may be sufficient to inflate the balloon103and establish firm contact between the balloon103and body tissue121to be treated. A layer of ice can form between the body tissue121and the balloon103during the first treatment phase, freezing the body tissue121to the balloon surface118. In the second treatment phase, pressure can be reduced to lower the temperature (e.g., to accelerate the cryotherapy procedure), and the layer of ice can cause the tissue121to remain adhered to the balloon surface118.

During the first treatment phase (Phase A), as depicted inFIG. 1A, an internal balloon pressure, PINTERNAL—A, can be developed to a value that is greater than ambient pressure at the proximal end106of the cryotherapy catheter100. As used herein, ambient pressure can refer to atmospheric pressure at the location of the patient being treated with the cryotherapy catheter (that is, atmospheric pressure given the altitude of the patient and other pressure-determining characteristics of the air immediately surrounding the patient). Thus, when the balloon103is outside of a patient (and not subject to compressive forces other than atmospheric pressure and elastic forces of the balloon itself), the balloon103will generally inflate when the pressure inside the chamber115is greater than the ambient pressure. Conversely, the balloon103will generally not inflate when the pressure inside the chamber115is less than ambient pressure. Additional pressure (above ambient pressure) may be required to inflate the balloon103inside the patient. For example, additional pressure may be needed to overcome pressure exerted by tissue against which the balloon103is expanding (e.g., tissue of the patient's pulmonary vein), pressure exerted by blood flow against the balloon103, or other pressures exerted by the patient's body or the balloon material itself.

Maintaining PINTERNAL—Agreater than PEXTERNALduring the first treatment phase can enable the balloon103to be inflated, such that its outer surface118maintains contact with adjacent body tissue121. To ensure good contact, PINTERNAL—Amay be greater than PEXTERNALby some margin, Δ1. For example, in some implementations, PINTERNAL—Ais maintained at approximately (e.g., within 5%, 10%, or 25%) 5 PSI above PEXTERNALso that the balloon103exerts sufficient force against the adjacent tissue121. In other implementations, a greater margin is maintained, such as approximately (e.g., within 5%, 10%, or 25%) 10, 15, 20, or 25 PSI. As shown inFIG. 1A, the relationship between pressures inside and outside the chamber115may be expressed as PINTERNAL—A+Δ1>=PEXTERNAL.

In some implementations, PINTERNAL—Ais regulated by controlling either or both of the rates at which cryogenic fluid is introduced into the chamber115(or correspondingly, the rate at which the cryogenic fluid is introduced into the supply lumen112, RATE1A) and the rate at which exhaust is channeled from the chamber115, RATE2A. The control may be accomplished, for example, by a controller, one or more valves, and one or more pumps, as described below with reference toFIG. 7. In some implementations, PINTERNAL—Acan be primarily controlled by regulating RATE2A. That is, RATE2Amay have a much greater affect on PINTERNAL—Athan RATE1A, and accordingly, RATE2Amay be precisely controlled with a closed loop control system. RATE1A, on the other hand, may be less precisely controlled with an open-loop control system.

In some implementations, the first phase of cryotherapy that is depicted inFIG. 1Amay be relatively short in duration relative to a second phase, and may serve primarily to freeze the adjacent tissue121to the surface118of the balloon103. Once the adjacent tissue121is frozen to the surface118, contact between the tissue121and surface118can be maintained by a layer of ice (element127inFIG. 1B) between the tissue121and surface118, even if the pressure inside the chamber115is reduced. An example second treatment phase is now described in more detail with reference toFIG. 1B.

FIG. 1Bdepicts a second phase of cryotherapy during which the pressure inside the chamber115, PINTERNAL—B, may be reduced relative to PEXTERNAL(e.g., in order to lower the boiling temperature of the cryogenic fluid and the corresponding temperature, TB, on the surface118of the balloon103). In particular, as depicted, PINTERNAL—Bmay be less than PINTERNAL—Aby some threshold, Δ2. That is, in some implementations, PINTERNAL—B+Δ2<=PINTERNAL—A.

In some implementations, PINTERNAL—Bis close to, but still greater than, ambient pressure (e.g., positive relative to PEXTERNAL). In other implementations, PINTERNAL—Bis negative relative to PEXTERNAL. That is, in the latter implementations, a partial vacuum may be maintained in the chamber115. In any case, the lower pressure inside the chamber115during the second treatment phase, relative to the first treatment phase, results in a lower temperature, TB, at the surface118, than the temperature TAat the surface118in the first treatment phase. The lower pressure in the second treatment phase is graphically depicted by the partially deflated appearance of the balloon103inFIG. 1B.

Even though the balloon103may be partially deflated in the second treatment phase, contact between the surface118of the balloon103and adjacent tissue121can be maintained by the layer of ice127formed during the first treatment phase. This contact can be maintained as long as the attractive force of the ice127is greater than any elastic force of the balloon103and any vacuum force created by the pressure inside the chamber115, both of which may tend to draw the surface118of the balloon103away from the tissue121. That is, although PINTERNAL—Bmay be lower than PINTERNAL—A, PINTERNAL—Bmay still need to be maintained above a level at which the balloon surface is peeled away from the tissue121by a force that exceeds the attractive force of the ice127.

FIG. 3illustrates another view of the cryotherapy balloon103, positioned to deliver cryotherapy to the body tissue121. For purposes of example, the tissue121will be described and depicted as corresponding to the ostium302of a pulmonary vein306in the heart of a patient, but the reader will appreciate that the cryotherapy balloon103can be employed to deliver cryotherapy to other body structures (e.g., arteries or veins; lymph nodes; other body lumens, cavities, or glands, etc.).

During an example cryotherapy treatment, the above-described process of allowing cryogenic fluid to undergo a phase change inside the balloon103causes Joule-Thomson cooling of the surface118of the balloon103and corresponding ablation of the adjacent tissue in regions121A and121B. As depicted inFIG. 3and described above with reference toFIGS. 1A and 1B, a layer of ice127may form between the balloon103and the tissue121A and121B. Ice may also form within the tissue itself, in regions121A and121B.

In some implementations, ablation (e.g., permanent and therapeutic alteration or remodeling of the tissue in regions121A and121B) occurs when the tissue reaches a certain temperature. For example, tissue of human pulmonary veins may begin to be ablated around −10° C. In some procedures, it may be desirable to cool the tissue by some margin beyond the temperature at which it begins to be ablated. More particularly, for example, it may be desirable to cool the tissue to −20° C. Moreover, it may be desirable to cool the entire region of tissue to the desired temperature—that is, the entire thickness of the pulmonary vein306in this example. In order to cool the entire thickness of the pulmonary vein at regions121A and121B, the surface of the balloon should generally be much cooler than the desired therapeutic temperature. Thus, for example, to cool the outer wall308of the pulmonary vein to −20° C., the temperature of the surface118of the balloon may be maintained at −60° C. or lower, for some period of time.

Generally, the greater the temperature difference between the surface118of the balloon103and the body tissue121A and121B being treated, the faster heat is extracted from the body tissue121A and121B. Thus, to facilitate as short a cryotherapy procedure as possible, it may be desirable maintain the surface118at very low temperatures. This may be particularly true in light of dynamics in play as the tissue121A and121B is cooled. In particular, the tissue in regions121A and121B may cool at a non-uniform rate. For example, the tissue121A and121B may cool at one rate until portions freeze, at which point, heat may be conducted within the frozen portions differently (e.g., some tissue may act as an insulator against further heat flow once it is frozen; other tissue may conduct heat better once frozen). Other dynamics may also affect how the tissue121A and121B cools, such as, for example, heat released by metabolic processes inside the tissue121A and121B, or heat flow resulting from blood perfusion within the tissue121A and121B. Heat flow within the body tissue121A and121B is now described in more detail with reference toFIGS. 4A-4I.

FIGS. 4A-4Iillustrate various thermal profiles over time corresponding to different temperatures on the surface118of the balloon103. In particular,FIGS. 4A-4Cillustrate simulated isotherms for human body tissue 5 mm in thickness at 50, 100, and 150 seconds after a −60° C. object (e.g., the cryotherapy balloon103) is brought into contact with the tissue. As depicted in these figures, a cold front moves deeper into the tissue as time progresses. Thus, as shown inFIGS. 4A-4C, after 50 seconds of being in contact with a −60° C. object, tissue 3 mm deep is likely to be at −10° C., and a −20° C. front is likely to have penetrated about 2.4 mm; after 100 seconds, the −10° C. front is likely to have penetrated about 4.1 mm, and the −20° C. front is likely to have penetrated 3 mm; after 150 seconds, almost all of the 5 mm thick tissue (about 4.8 mm) is likely to be at −10° C., and the 20° C. front is likely to have penetrated 3.6 mm. Isotherms for other temperatures are also shown for reference to depict the progressive cooling of the body tissue121over time.

Turning briefly to the physiology of cryotherapy, different therapeutic results may be achieved by different levels of cooling. For example, with respect to treating atrial fibrillation by remodeling tissue of the pulmonary veins (e.g., permanently altering the electrical structure or characteristics), it may be desirable to bring tissue over the full thickness of the portion of the pulmonary vein being treated to about −20° C. or colder. A typical human pulmonary vein may have a thickness in the range of 1-5 mm, so a physician may deliver cryotherapy to the pulmonary vein until it is expected that the entire thickness has reached the desired temperature (e.g., −20° C.). The temperature of −20° C. is merely provided as an example. Some tissue may be remodeled, or partially remodeled, at a higher temperature, such as −10° C., but the physician may treat beyond the temperature at which remodeling begins in order to increase the efficacy of the treatment. Other kinds of tissue may be remodeled or otherwise treated at different temperatures.

At higher temperatures (e.g., −5° C., 0° C., 5° C., or some other hypothermic value), a temporary, reversible change in the body tissue may occur. For example, with respect to the aberrant electrical pathways that can give rise to atrial fibrillation, tissue through which the electrical pathways form can be chilled to a temperature that does not permanently remodel the tissue but that temporarily disrupts the electrical pathways. This chilling, which may be referred to as cryomapping, can be used to confirm that remodeling of the intended treatment site will be efficacious, without causing other adverse side effects (e.g., a conduction block in an undesirable location). Following confirmation (e.g., through the use of electrical probes and/or stimuli), the tissue can be permanently remodeled by being cooled to lower temperatures (e.g., −10° C., −20° C., or lower temperatures).

FIGS. 4D-4Fillustrate simulated isotherms for human body tissue 5 mm in thickness at 50, 100, and 150 seconds after a −80° C. object (e.g., a cryotherapy balloon) is brought into contact with the tissue. In these figures, the cold front moves through the tissue121at a faster rate than the cold front moves in the implementation depicted inFIGS. 4A-4C. In particular, after 50 seconds of being in contact with a −80° C. object, tissue 3.7 mm deep is likely to be at −10° C., and a −20° C. front is likely to have penetrated about 3.1 mm; after 100 seconds, the −10° C. front is likely to have penetrated about 4.1 mm, and the −20° C. front is likely to have penetrated 4.2 mm; after 150 seconds, almost all of the 5 mm thick tissue (about 4.8 mm) is likely to be at −20° C.FIGS. 4G-4Idepict an even faster cooling rate that may result when the surface118of the balloon103is at about −90° C. In particular, a −20° C. cold front may penetrate the tissue121to a depth of 3.5 mm, 4.5 mm and more than 5 mm after 50, 100, and 150 seconds respectively.

As can be seen fromFIGS. 4A-4I, a cryotherapy procedure can be accelerated by lowering the temperature at the surface118of the balloon103. For a procedure in which it is desirable to cool tissue 5 mm thick to a temperature of −20° C., comparison ofFIGS. 4B and 4Hreveal differences in treatment time—inFIG. 4H, almost the entire thickness of the tissue is treated after 100 seconds, while inFIG. 4B, the tissue is treated only to about 60% of the desired depth. Additional data related to treatment times is presented in a slightly different format inFIG. 5.

FIG. 5is a bar graph depicting time (in seconds) that may be necessary for certain body tissue to be ablated to a depth of 5 mm, by a cryotherapy device having a particular surface temperature. As depicted, a cryotherapy device having a surface temperature of −70° C. may require more than 250 seconds to ablate tissue to a depth of 5 mm. In comparison, tissue may be ablated to a depth of 5 mm within 150-175 seconds by a cryotherapy device having a surface temperature of −80° C., and this time may be reduced to about 125 seconds when the cryotherapy device has a temperature of about −90° C. Thus, as depicted inFIG. 5, time needed to ablate tissue to a particular therapeutic depth (e.g., 5 mm) can be reduced by reducing the temperature of the device that is in contact with the tissue.

One way to reduce the temperature of the device that delivers the cryotherapy is to reduce the pressure inside the device, as is described above with reference toFIGS. 1A,1B,2, and3. When the device is an inflatable cryotherapy balloon, the pressure can be reduced in a second treatment phase, after the tissue to be treated is frozen to the outside of the balloon during a first treatment phase, as described above.

Various advantages may result from accelerating a cryotherapy procedure by reducing the temperature of the cryotherapy device, such as a balloon, used to deliver the cryotherapy. In general, for example, it is advantageous to minimize procedure time for reasons of safety. The longer a procedure lasts, the greater risk there may be for complications, such as internal clotting, structural damage to tissue or organs that are not directly treated but that may be affected by the treatment device (e.g., vessels and heart structures through which a cryotherapy catheter may pass in order to reach specific treatment sites), physician fatigue, etc.

In the case of cryotherapy delivered by a balloon catheter and for the purpose of treating atrial fibrillation, even small reductions in treatment time of a region of tissue may significantly reduce overall treatment time for a procedure. For example, a cryotherapy procedure to treat atrial fibrillation may involve treatment of multiple pulmonary veins (e.g., all four pulmonary veins that are typically present in a human patient), and each pulmonary vein may be treated multiple times (e.g., two times) to increase efficacy of the treatment. Accordingly, even a small improvement of treatment time of a single region of tissue, when multiplied by eight separate treatment cycles, may appreciably reduce the overall treatment time required for the cryotherapy procedure.

Cryotherapy procedures involving inflatable cryotherapy balloons may be particularly advantageous relative to other methods of ablating tissue. For example, some cryotherapy devices enable physicians to first perform cryomapping on target tissue to confirm that permanently ablating the tissue will bring about therapeutic results (e.g., reduce or eliminate aberrant electrical pathways) without causing undesirable collateral damage (e.g., a conduction block). Other techniques may not permit such confirmation testing that is possible with cryotherapy techniques. Delivery of cryotherapy with an inflatable balloon can also be advantageous, since a balloon may conform to multiple differently shaped or sized regions or vessels, and may deliver cryotherapy to an entire circumferential region at one time.

FIG. 6is a flow diagram illustrating an example method600of treating body tissue with the cryotherapy balloon catheter100. As shown in one implementation, and with reference to the preceding figures, the method600can include positioning (601) the cryotherapy balloon103at a treatment site inside a patient's body. For example, with reference to a procedure to treat atrial fibrillation, a cryotherapy catheter can be introduced to a patient's left atrium—and more particularly to the ostium of one of the patient's pulmonary veins—by being introduced into the patient's femoral artery, routed through the inferior vena cava, into the right atrium, through the transseptal wall, and into the left atrium (above-referenced anatomic features not shown in the figures).

Once the balloon103is positioned (601), a first treatment phase of a cryotherapy procedure can be performed (604). In particular, flow of cryogenic fluid to and flow of exhaust from the chamber115of the balloon103(see, e.g.,FIG. 1A) can be regulated (e.g., by a controller, valves, and/or pumps, as described below with reference toFIG. 7) such that a first pressure inside the chamber115is reached that causes the balloon103to inflate and firmly impinge on tissue121to be treated. Within the chamber115, cryogenic fluid can be released and changed into a gas, resulting in Joule-Thomson cooling of the chamber115, the surface118of the balloon, and the body tissue121that is in contact with the surface. During the first treatment phase, the body tissue121can freeze to the surface118of the balloon.

Once the tissue121freezes to the surface118of the balloon103, a second phase of the cryotherapy procedure can be performed (607). In particular, flow of cryogenic fluid to and flow of exhaust from the chamber115of the balloon103(see, e.g.,FIG. 1B) can be regulated such that a second pressure inside the chamber115is reached, which is lower than the first pressure. This second, lower pressure is possible because of a layer of ice127between the tissue121and the surface118of the balloon103that forms during the first treatment phase and adheres the tissue121to the surface118of the balloon103. The lower pressure can reduce the boiling point of the cryogenic fluid, resulting in a lower temperature at the surface118of the balloon103during the second treatment phase.

The second phase of the cryotherapy procedure can be maintained until it is determined (610) that the ablation is complete. In some implementations, the time needed to ablate the tissue121is determined (610) based on average thickness of the tissue being treated, heat flow within the tissue121(e.g., as modeled and depicted inFIGS. 4A-4I), and temperature of the surface118of the balloon103. For example, the second treatment phase may be maintained for about 125 seconds to treat a pulmonary vein that is likely to be about 5 mm thick (e.g., the pulmonary vein of a large adult), when a pressure is reached inside the chamber115that is low enough to allow the temperature at the surface118to reach −90° C.

Once an ablation cycle is determined (610) to be complete for a particular region of tissue121, the tissue121can be allowed to warm up (613). In particular, for example, flow of cryogenic fluid to an exhaust from the chamber115can be regulated (e.g., decreased) such that only a small amount of heat (if any) is extracted from the surface118of the balloon, during which time, natural processes can warm the tissue121back up (e.g., blood perfusion, heat conducted from adjacent tissue that has not been cooled, heat released from metabolic processes in the cooled or adjacent tissue, etc.).

When the tissue is sufficiently warm, it may no longer adhere to the surface118of the balloon103. That is, the process of warming can result in the layer of ice127melting. Once the ice127melts, the balloon103can be repositioned (601) at another site, and the process can be repeated, if desired. In particular, for example, the balloon103can be deflated (e.g., by stopping the flow of cryogenic fluid to the chamber115and briefly continuing the flow of exhaust from the chamber115) and steered (601) to another pulmonary vein, where the first and second phases of cryotherapy treatment can be repeated (604,607).

Once cryotherapy treatment has been delivered to all desired sites (e.g., all four pulmonary veins, multiple times at each vein), the cryotherapy catheter100can be removed from the patient. That is, the balloon103can be deflated, and the cryotherapy catheter100can be withdrawn back through the septal wall, right atrium, inferior vena cava, and out the femoral artery. This path is merely exemplary, and the reader will appreciate that the cryotherapy catheter can be positioned at any desired treatment site, via any appropriate path.

Additional details of the example cryotherapy catheter100are now described with reference toFIG. 7. As described above, the cryotherapy catheter100includes an elongate member109that has an inflatable balloon103at a distal end706. The balloon103has an internal chamber (not shown inFIG. 7, but shown inFIGS. 1A and 1Band referred to in this description as chamber115) to which cryogenic fluid is delivered to cool the internal chamber, the external surface118of the balloon103, and adjacent body tissue. A port device702is attached to the proximal end106of the elongate member109. The port device702provides connections to various external equipment, including a cryogenic fluid source730and an exhaust pump727.

The catheter's elongate member109has multiple internal lumens (not shown inFIG. 7). The lumens allow cryogenic fluid to be delivered distally from the external cryogenic fluid source730to the internal chamber of the balloon103. In addition, the internal lumens of the elongate member109allow exhaust resulting from delivery of cryogenic fluid to the internal chamber115of the balloon103to be delivered proximally from the internal chamber115to the external exhaust pump727. During operation, there may be continuous circulation within the elongate member109of cryogenic fluid distally and exhaust proximally.

A controller728can regulate flow of cryogenic fluid to the internal chamber of the balloon103and flow of exhaust from the balloon. In particular, for example, the controller728can, in one implementation as shown, regulate a valve729that controls flow of the cryogenic fluid from the cryogenic fluid source730. The cryogenic fluid source730may be, for example, a pressured flask of cryogenic fluid. In other implementations (not shown), the controller controls a pump and/or pump valve combination to deliver cryogenic fluid to the internal chamber of the balloon. Similarly, the controller728can regulate a valve731and/or vacuum pump727to regulate flow of exhaust from the internal chamber of the balloon.

By controlling both the rate at which cryogenic fluid is delivered to the balloon103and the rate at which exhaust is extracted from the balloon103, the controller728can develop and maintain a pressure inside the balloon103at a number of different values. For example, when cryogenic fluid is delivered at a very low rate to the balloon103, and exhaust is similarly extracted at a very low rate, the balloon103may be inflated, but very little heat (if any) may be extracted from the balloon103or from body tissue that is in contact with the balloon. As another example, when cryogenic fluid is delivered at a higher rate, a greater amount of heat can be extracted from the balloon103and from body tissue that is in contact with the balloon. Varying the rate at which exhaust is extracted from the balloon103relative to the rate at which the cryogenic fluid is supplied to the balloon can control the pressure. In particular, for example, for a given rate at which the cryogenic fluid is supplied to the balloon, a greater rate at which exhaust is extracted from the balloon103will generally result in lower pressure inside the balloon, and a lower rate at which exhaust is extracted from the balloon103will generally result in greater pressure inside the balloon.

To precisely control pressures or flow rates, the controller103may employ either or both of open- or closed-loop control systems. For example, in some implementations, a rate at which cryogenic fluid (e.g., the position of the valve729) may be controlled with an open-loop control system, and a rate at which exhaust is extracted from the balloon103(e.g., the position of the valve731or force exerted by the pump727) may be controlled with a closed-loop control system. In other implementations, both rates may be controlled by closed-loop control systems. In a closed-loop control system, some feedback mechanism is provided. For example, to control the rate at which exhaust is extracted from the balloon103, the controller728may employ an exhaust flow device (not shown), a pressure sensor (not shown) inside the balloon103or elsewhere in the system, or another feedback sensor. In addition, the controller728may employ an ambient pressure gauge732in one of its control loops (e.g., to measure atmospheric pressure at the proximal end106of the cryotherapy catheter (that is, the end that remains outside the patient)).

In some implementations, as mentioned above, pressure inside the balloon103may be primarily controlled by controlling the rate at which exhaust is extracted from the balloon103(given the significant difference between the large volume of gas resulting from a corresponding smaller volume of cryogenic fluid being released into the balloon103). Temperature inside the balloon103, on the other hand, may depend on control of both the flow of cryogenic fluid and the flow of exhaust.

The controller728itself can take many different forms. In some implementations, the controller728is a dedicated electrical circuit employing various sensors, logic elements, and actuators. In other implementations, the controller728is a computer-based system that includes a programmable element, such as a microcontroller or microprocessor, which can execute program instructions stored in a corresponding memory or memories. Such a computer-based system can take many forms, may include many input and output devices, and may be integrated with other system functions, such as the monitoring equipment742, a computer network, other devices that are typically employed during a cryotherapy procedure, etc. For example, a single computer-based system may include a processor that executes instructions to provide the controller function, display imaging information associated with a cryotherapy procedure (e.g., from an imaging device); display pressure, temperature, and time information (e.g., elapsed time since a given phase of treatment was started); and serve as an overall interface to the cryotherapy catheter. In general, various types of controllers are possible and contemplated, and any suitable controller728can be employed.

The catheter100shown inFIG. 7is an over-the-wire type catheter. Such a catheter100uses a guidewire712, extending from the distal end706of the catheter100. In some implementations, the guidewire712may be pre-positioned inside a patient's body. Once the guidewire712is properly positioned, the balloon103(in a deflated state) and the elongate member109can be routed over the guidewire712to a treatment site. In some implementations, the guidewire712and balloon portion103of the catheter103may be advanced together to a treatment site inside a patient's body, with the guidewire portion712leading the balloon103by some distance (e.g., several inches). When the guidewire portion712reaches the treatment site, the balloon103may then be advanced over the guidewire712until it also reaches the treatment site. Other implementations are contemplated, such as steerable catheters that do not employ a guidewire.

The catheter100includes a manipulator736, by which a medical practitioner may navigate the guidewire712and balloon103through a patient's body to a treatment site. In some implementations, release of cryogenic fluid into the cooling chamber may inflate the balloon103to a shape similar to that shown inFIG. 7. In other implementations, a pressure source724may be used to inflate the balloon103independently of the release of cryogenic fluid into the internal chamber115of the balloon103. The pressure source724may also be used to inflate an anchor member on the end of the guidewire712(not shown).

The catheter100includes a connector739for connecting monitoring equipment742. The monitoring equipment may be used, for example, to monitor temperature or pressure at the distal end of the catheter100. To aid in positioning the treatment member103of the catheter100inside a patient's body, various marker bands733are also disposed at the distal end706of the catheter100. The marker bands733may be opaque when the catheter is viewed by x-ray or other imaging techniques.

In some implementations, the balloon103, and a corresponding separate internal cooling chamber, if present (e.g., balloon821, shown inFIG. 8A), may be formed from a polymer including, but not limited to, polyolefin copolymer, polyester, polyethylene teraphthalate, polyethylene, polyether-block-amide, polyamide (e.g., nylon), polyimide, latex, or urethane. For example, certain implementations of the balloon103comprise PEBAX® 7033 material (70D poly ether amide block). The balloon103may be made by blow-molding a polymer extrusion into the desired shape. In some implementations, the balloon103may be constructed to expand to a desired shape when pressurized without elastically deforming substantially beyond the desired shape.

A number of ancillary processes may be used to affect the material properties of the balloon103. For example, the polymer extrusion may be exposed to gamma radiation which can alter the polymer infrastructure to provide uniform expansion during blow molding and additional burst strength when in use. In addition, the molded balloon103may be exposed to a low temperature plasma field which can alter the surface properties to provide enhanced adhesion characteristics. Those skilled in the art will recognize that other materials and manufacturing processes may be used to provide balloon103(and any internal balloon(s)) suitable for use with the catheter.

FIG. 8Ashows a longitudinal cross-section of the example cryotherapy balloon103and an example elongate member109through which cryogenic fluid and exhaust may be cycled to and from the internal chamber115of the cryotherapy balloon103. As shown inFIG. 8A, cryogenic fluid may be delivered from an external source (e.g.,730inFIG. 7) to a cooling chamber115internal to the balloon103, via a coolant delivery lumen112. The coolant may be released into the cooling chamber115from an opening at the end of the delivery lumen112, or the coolant may be released through a cryotherapy device819(seeFIG. 8C) disposed at the end of the delivery lumen112. In some implementations, the cooling device819includes a coiled extension835having a number of apertures837from which pressurized liquid coolant can escape and change state to a gas. In some implementations, the exhaust lumen124may be defined generally by the outer layer of the elongate shaft109, as shown. In other implementations, the catheter may include one or more dedicated exhaust lumen structures (not shown) that are defined independently of the elongate member109.

In some implementations, as described above, the coolant undergoes a phase change within the cooling chamber115, cooling the chamber115via the Joule-Thomson effect, as well as cooling the external surface118of the outermost balloon103and a patient's body tissue that is adjacent to the external surface118of the outer balloon. In other implementations, cryogenic fluid is applied to (e.g., sprayed against) the walls of the cooling chamber, where it vaporizes, directly cooling the chamber wall and the external surface118. The cryogenic fluid, or gas if the fluid has undergone a phase change, is then exhausted through an exhaust lumen124to a reservoir, pump, or vacuum source external to the catheter (e.g.,727inFIG. 7). In some implementations, there is a continuous cycle of cryogenic fluid to the cooling chamber115via the delivery lumen112and exhaust from the cooling chamber115via the exhaust lumen124.

The coolant that is cycled into the balloon115is one that will provide the appropriate heat transfer characteristics consistent with the goals of treatment. In some implementations, liquid N2O may be used as a cryo coolant. When liquid N2O is used, it may be transported to the cooling chamber115in the liquid phase where it changes to a gas at the end of the coolant delivery lumen112, or from the apertures837of a cooling device819. Other implementations may use Freon, Argon gas, and CO2gas, or other agents, as coolants. Still other implementations may use liquid coolant, and the temperature or pressure of the liquid coolant may be controlled in a manner appropriate to achieve the desired therapeutic effect.

In some implementations, as shown, a second balloon821is provided within the outer balloon103to isolate the cryogenic fluid within the cooling chamber115. In these implementations, the outer balloon103forms a safety chamber that prevents coolant from escaping if the cooling chamber115balloon821bursts. A separate vacuum lumen (not shown) may be provided to evacuate any gas or liquid that escapes from the internal cooling chamber115. In operation, the outer and inner balloons103and821may expand and deflate together. In some implementations, release of coolant inflates the balloons103and821. In some implementations, the balloons103and821are first inflated by the injection of an inflation fluid or gas (e.g., a saline solution or an inert gas), after which the coolant may be introduced to the cooling chamber115.

FIG. 8Bshows a radial cross-section along the line A-A that is shown inFIG. 8A. As shown inFIG. 8B, the coolant delivery lumen112is adjacent to the guidewire lumen813, and the guidewire lumen813is shown to be substantially coaxial with the exhaust lumen124, which corresponds to the overall shaft (e.g., elongate member109) of the catheter. In some implementations, lumens may have other arrangements, and more or fewer lumens may be included in the catheter. For example, the coolant delivery lumen112may be disposed coaxially around the guidewire lumen813; the guidewire lumen813may be omitted in a steerable catheter design; lumens for steering members may be provided; one or more vacuum lumens may be included; one or more exhaust lumens may be included that are independent of the outer layer of the catheter shaft109; additional lumens may be provided for inflating or deflating the balloons103or831or for inflating or deflating other balloons not shown inFIG. 8A; and additional lumens may be provided to control an anchor member that may be disposed on a guidewire near the distal portion of the balloon103.

FIG. 9is a flow diagram illustrating an example method900of controlling pressure and temperature in the balloon103. In some implementations, the method900is implemented by the controller728shown inFIG. 7. As shown in one implementation, the method900can include various decision elements that determine whether the balloon103is to be inflated (901) or deflated (910), whether a first treatment phase is to be performed (904) or whether a second treatment phase is to be performed (907). The decision elements can, in some implementations, be evaluated based on user input received by the controller728. For example, during a cryotherapy procedure, a physician may provide input to the controller728(e.g., through a command entered through a user interface of a computer device, through manual actuation of a switch, etc.) to inflate the balloon or initiate a particular phase of treatment.

When it is determined (901) that the balloon is to be inflated, the controller728can actuate (913) appropriate valves (e.g., valves729and731) to deliver a small amount cryogenic fluid to the balloon103in order to develop a positive first pressure. In some implementations, a burst of cryogenic fluid is delivered to the balloon103to develop the positive first pressure. In other implementations, a low rate of continuous flow of cryogenic fluid is established and an appropriate corresponding low rate of exhaust extraction is also established through control of the valves729and731, or the valve729and the pump727. To establish an appropriate flow rate and pressure, the controller728may employ the ambient pressure gauge732, a pressure sensor (not shown in the figures) inside or fluidly coupled to the balloon103, a balloon position sensor (e.g., imaging tools that detect the outer surface of the balloon103), etc.

When it is determined (904) that a first phase of treatment is to be initiated, the controller728can actuate (916) the valves729and731to deliver a relatively large flow rate of cryogenic fluid to the balloon (e.g., relative to flow necessary to merely keep the balloon103inflated), and to extract a correspondingly large amount of exhaust from the balloon103. The rates of delivery and extraction can be controlled such that a positive second pressure is developed and maintained inside the balloon. That is, relative to ambient pressure and other compressive forces that may exist at the balloon (e.g., from elastic forces of the balloon itself or from compressive forces exerted by tissue of the body lumen or cavity being treated), a positive pressure inside the balloon103may be developed, such that the balloon103is inflated and firmly in contact with adjacent body tissue. With such firm contact, high flow rate of cryogenic fluid to the balloon, and the resulting low temperature caused by the Joule-Thomson expansion of the cryogenic fluid to a gas inside the balloon, tissue that is adjacent to the balloon103can freeze to the surface of the balloon103.

When it is determined (907) that a second phase of treatment is to be initiated, the controller728can actuate (919) the valves729and731to deliver a similar rate of cryogenic fluid to the balloon that was delivered in the first phase (916), but the rate at which exhaust is extracted can be slightly increased, to develop a third pressure that is lower than the second pressure. That is, the valve731can be opened slightly, or the force exerted by the vacuum pump727can be increased slightly, resulting in a lower pressure inside the balloon. As described above, this lower pressure can result in a lower boiling temperature of the cryogenic fluid inside the balloon103and a corresponding lower temperature on the surface of the balloon103.

When it is determined (910) that the balloon is to be deflated, the controller728can actuate (922) the valves such that flow of cryogenic fluid to the balloon103is stopped, and flow of exhaust from the balloon103is briefly continued. Continuation of the flow of exhaust (e.g., by closing the valve731after the valve729), can create a vacuum inside the balloon103that can draw the material of the balloon103radially inward, toward a central axis of the balloon103. After the balloon is deflated, it can be removed from the patient in any appropriate manner.

The above description makes reference to controlling valves729and731by way of example, but the reader will appreciate that various other methods of controlling flow to and from the balloon103can be employed, including, for example, controlling the pump727, or controlling other pumps or valves that are not shown in the figures but that may be included in cryotherapy catheter systems.

A number of implementations have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of this document. Accordingly, other implementations are within the scope of the following claims.