Patent ID: 12226602

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention are directed to devices for delivering implantable devices to the atrial septum of the heart, and thus may be useful in treating subjects suffering from heart failure or other disorders associated with elevated left atrial pressure. For example, the inventive device may be designed to deliver an hourglass or “diabolo” shaped stent, preferably formed of a shape memory metal as described in U.S. Pat. No. 9,629,715 to Nitzan, assigned to the assignee of the present invention, the entire contents of which are incorporated herein by reference. The delivery device is configured to lodge the stent securely in the atrial septum, preferably the fossa ovalis, to function as an interatrial shunt, allowing blood flow from the left atrium to the right atrium.

Referring toFIGS.1A and1B, apparatus100is provided for delivering interatrial shunt devices, e.g., devices described in U.S. Pat. No. 9,629,715 to Nitzan and U.S. Pat. No. 9,713,696 to Yacoby, assigned to the assignee of the present invention, the entire contents of each of which are incorporated herein by reference. Apparatus100may include distal end102, catheter104, and proximal end106having handle108. Distal end102comprises components suitable for coupling apparatus100to devices of the present invention, as described in detail below. Catheter104comprises a biocompatible tube shaft of suitable size, e.g., approximately 14 Fr., and suitable length, e.g., approximately 75-100 cm and preferably 85 cm. Proximal end106comprises handle108that is configured to be manipulated, e.g., by a human hand, to transition components in distal end102from an engaged position shown inFIG.1Ato a disengaged position shown inFIG.1B. Handle108may be manipulated, for example, by moving finger grips110proximally from a locked position shown inFIG.1Ato an unlocked position shown inFIG.1B. In addition, handle108may be manipulated by moving finger grips110distally from the locked position to the unlocked position so as to transition components in distal end102from the disengaged position to the engaged position to load devices of the present invention.

FIGS.2A and2Billustrate distal end102in the engaged position ofFIG.1Aand the disengaged position ofFIG.1B, respectively. At distal end102, apparatus100may include latching legs112,114, and116having hook portions118,120, and122, respectively. Latching legs112,114, and116comprise a biocompatible material such as a biocompatible metal or polymer, and are positioned longitudinally and radially so as to firmly secure devices of the present invention for delivery. Hook portions118,120, and122extend outwardly from the distal end of latching legs112,114, and116, respectively, and are configured to fit securely between struts and rings of the devices of the present invention. Preferably, hook portions118,120, and122hook outwardly away from center axis123of catheter104in both the engaged and disengaged positions as shown inFIGS.1A and1B. Center axis123is centered relative to catheter104on both a longitudinal and cross-sectional basis. By facing outwardly from center axis123, hook portions118,120, and122may engage the inner surface of the device, e.g., within a lumen of a shunt. In one embodiment, hook portions118,120, and122hook generally perpendicularly away from center axis123from a radial perspective. As will be readily understood by one of ordinary skill in the art, while three latching legs are illustrated, more or fewer latching legs may be used without departing from the scope of the present invention. For example, one, two, four, five, six, or more latching legs may be used. Catheter104may include cover tube124which may have a larger diameter than the remaining shaft of catheter104. Cover tube124comprises a biocompatible material such as a biocompatible metal or polymer, and may be the same or different material than the remaining shaft of catheter104. Components at distal end102, such as latching legs112,114, and116, may be at least partially disposed within cover tube124. For example, the proximal ends of latching legs112,114, and116may be coupled to annular member148and cover tube124by laser welding.

Referring now toFIGS.3A to3D, the inner components at distal end102of apparatus100are illustrated.FIGS.3A and3Brespectively illustrate distal end102in the engaged position ofFIGS.1A and2Aand the disengaged position ofFIGS.1B and2B. As shown inFIG.3A, catheter104and cover tube124comprise lumens126and128, respectively, for housing the inner components. Latching legs112and114share common ramp portion130having inner section132and outer section134while latching leg116has separate ramp portion136having inner section138and outer section140. Inner sections132and138are angled so as to be positioned closer to the central axis of catheter104and cover tube124relative to the positions of outer sections134and140. Latching legs may also include jogs and protrusions. For example, latching leg116illustratively includes protrusion142proximal to ramp portion136, and jog144between hook portion122and ramp portion136. Protrusion142is configured to contact the distal surface of annular member148to maintain suitable positioning of latching leg116. Jog144is shaped to prevent release ring146from moving too distally.

Release ring146is coupled to latching legs112,114, and116. For example, latching legs112,114, and116may be partially disposed within release ring146as illustrated inFIGS.3A to3D. Release ring146is moveable within cover tube124. Release ring146may be located in a first position, e.g., an engaged position, where release ring146contacts inner sections132and138of ramp portions130and136such that latching legs112,114, and116extend radially outward as shown inFIGS.3A and3C. Release ring146may be moved to a second position, e.g., a disengaged position, where release ring146contacts outer sections134and140of ramp portions130and136such that latching legs112,114, and116move radially inward as shown inFIGS.3B and3D. In one embodiment, release ring146is configured to move from the second position to the first position to load a device of the present invention and to move from the first position to the second position to release the device.

Annular member148may be partially disposed in the proximal end of cover tube124and configured to couple cover tube124to catheter104via a suitable coupling mechanism, e.g., teeth150, ribs. Annular member148includes lumen152sized to accept pull-cord154therethrough.

Pull-cord154is coupled to release ring146and actuation of pull-cord154moves release ring146from the first position shown inFIG.3Ato the second position shown inFIG.3B, and vice versa. In a preferred embodiment, pull-cord154is coupled to handle108such that pull-cord154is actuated by moving finger grips110from a locked position shown inFIG.1Ato an unlocked position shown inFIG.1B, and vice versa.

Pull-cord154may be coupled to release ring146via release ring base156. In this embodiment, release ring base156is directly coupled to release ring146and pull-cord154such that actuation of pull-cord154moves release ring base156to move release ring146from the first position the second position, and vice versa.

Spring158may be coupled to the proximal surface of release ring base156and the distal surface of annular member148such that release ring base156and annular member148maintain spring158therebetween. Spring158is configured to bias release ring146towards a particular position such as towards the first position as shown inFIG.3A.

FIGS.3A and3Cillustrate the components at distal end102in an engaged position, whereFIG.3Comits cover tube124for clarity. As pull-cord154is actuated, e.g., via handle108, release ring146is moved, e.g., via release ring base156, from the engaged position to the disengaged position shown inFIGS.3B and3D, whereFIG.3Domits cover tube124for clarity. Release ring146slides along ramp portions130and136from inner sections132and138to outer sections134and140such that latching legs112,114, and116move from being extended radially outward to being positioned radially inward. As release ring146moves from the engaged position to the disengaged position, spring158is compressed and as release ring146moves from the disengaged position to the engaged position, spring158is decompressed.

FIG.4Aillustrates the components at distal end102of apparatus100engaged to an exemplary device of the present invention andFIG.4Billustrates the components disengaged from the exemplary device. Device400includes rings402and struts404and may be constructed similar to devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler, assigned to the assignee of the present invention, the entire contents of each of which are incorporated herein by reference. As shown inFIG.4A, latching legs112,114, and116are sized, shaped, angled, and spaced apart from one another so as to engage device400in openings between rings402and struts404when device400is in a contracted, delivery state. Hook portions118,120, and122are sized, shaped, and angled to fit between rings402and struts404. Hook portions118,120,122also hook outwardly away from the center axis at the distal end of the delivery apparatus. Accordingly, hook portions118,120,122may be disposed in the lumen of device400in the engaged position ofFIG.4Aand engage device400from within the inner surface of device400such that hook portions118,120,122extend radially beyond the inner surface of device400. For example, hook portions118,120,122may extend radially to the outer surface of device400or beyond the outer surface of device400. As shown inFIG.4B, latching legs112,114, and116are configured to move radially inward a sufficient distance to decouple hook portions118,120, and122from device400in the disengaged position, thereby releasing device400for implantation.

FIG.5is a flowchart of exemplary method500of delivering device400illustrated inFIGS.4A and4Bto reduce left atrial pressure in a subject, for example, a human having CHF, using apparatus100illustrated inFIGS.1A-1B. Some of the steps of method500may be further elaborated by referring toFIGS.6A-6Q.

Referring toFIG.5, first, a device and apparatus for delivering the device are provided (step501). The device may be an hourglass-shaped device having a plurality of sinusoidal rings connected by longitudinally extending struts that define first and second flared end regions and a neck disposed therebetween, as well as an optional tissue valve coupled to the second flared end region.

Then, the device is collapsed radially to a contracted, delivery state and coupled to the delivery apparatus (step502). For example, as illustrated inFIGS.6A-6C, device400may be loaded into tapered loading tube600by first placing device400within wide diameter end602of loading tube600as shown inFIG.6A. Then, using loading tool604, device400is crimped down within loading tube600. Loading tool604includes thin leg end606having two thin legs and wide leg end608having two wide legs. Device400may be pushed into loading tube600first by thin leg end606as illustrated inFIG.6Band then pushed further into loading tube600by wide leg end608as illustrated inFIG.6C. As will be understood by a person ordinarily skilled in the art, thin leg end606may have more than two thin legs, e.g., three, four, or more thin legs, and accordingly, wide leg end608may have more than two wide legs, e.g., three, four, or more wide legs.

InFIG.6D, device400is disposed within thin diameter end610of loading tube600. Thin diameter end610has a suitable internal diameter for contracting the device, e.g., approximately 14 Fr. Loading tube600includes tapered section612between wide diameter end602and thin diameter end610. Tapered section612facilitates radial compression of device400into thin diameter end610. Loading tube600is coupled to loading cartridge614via coupling section616having a suitable coupling mechanism, e.g., threads, ribs. Loading cartridge614may be transparent and has a suitable internal diameter, e.g., approximately 14 Fr.

Referring toFIG.6E, device400is pushed into loading cartridge614using pusher618. Pusher618has a suitable diameter, e.g., approximately 14 Fr., and may have a “star”-shaped end (not shown). In accordance with one aspect of the invention, the thin leg end of loading tool604is long enough to serve as pusher618. Loading cartridge614is disconnected from loading tube600and connected to hemostasis valve section620, which may be a Tuohy-Borst valve, as shown inFIG.6F. Valve section620includes knob622and Y-connector624. Distal end102of apparatus100is inserted through knob622of valve section620. Knob622and Y-connector624are adjusted to permit movement of apparatus100while maintaining a seal to prevent fluid leakage, e.g., air leakage, blood leakage. The steps shown inFIGS.6A-6Fmay be performed while device400is immersed in an anticoagulant such as heparinized saline.

FIGS.6G and6Hillustrate coupling device400to apparatus100at distal end102. Distal end102is advanced within loading cartridge614toward device400. The components of distal end102may be in the disengaged position as illustrated inFIG.6G. For example, the release ring at distal end102may contact an outer section of the ramp portions of the latching legs such that the latching legs are disposed radially inward. Next, distal end102is moved longitudinally toward device400and rotated to align the latching legs with suitable portions of device400, e.g., at openings between struts and rings of device400. Once suitable position is achieved, the components of distal end102may move to the engaged position as illustrated inFIG.6H. For example, the release ring may be moved via a pull-cord and handle such that the release ring contacts an inner section of the ramp portions of the latching legs so the latching legs extend radially outward. In accordance with another aspect of the invention, the release ring may be moved via a PEEK tube as described in further detail below. A medical professional, e.g., a clinician, may verify that device400is engaged to apparatus100by slowing advancing and retracting apparatus100a distance, e.g., approximately 5 mm, while device400remains in loading cartridge614. In addition, a clinician may verify that apparatus100is capable of disengaging from device400within loading cartridge614by pressing handle to cause the components at distal end102to disengage and then moving distal end102away from device400. After such verification, the clinician may reengage apparatus100to device400. Preferably, device400is loaded into loading cartridge614shortly before implantation, so as to avoid unnecessarily compressing device400or re-setting of the optional closed shape of leaflets, which may interfere with later deployment or operation of the device.

Referring back toFIG.5, the device then is implanted, first by identifying the fossa ovalis of the heart septum, across which device400is to be deployed (step503). Specifically, a trans-septal puncture device, e.g., a mechanical needle such as a BROCKENBROUGH needle or a radiofrequency trans-septal puncture device, may be percutaneously introduced into the right atrium via the subject's venous vasculature, for example, via the femoral artery. Then, under fluoroscopic and/or echocardiographic visualization, the needle is pressed against the fossa ovalis, at a pressure insufficient to puncture the fossa ovalis. The pressure from the needle causes “tenting” of the fossa ovalis, i.e., causes the fossa ovalis to stretch into the left atrium. Other portions of the atrial septum are thick and muscular, and so do not stretch to the same extent as the fossa ovalis. Thus, by visualizing the extent to which different portions of the atrial septum tents under pressure from the needle, the fossa ovalis may be identified, and in particular, the central portion of the fossa ovalis may be located.

The fossa ovalis (particularly its central region) may be punctured with the trans-septal puncture device, and a guidewire may be inserted through the puncture by threading the guidewire through the needle into the left atrium, and then removing the needle (step504). The puncture through the fossa ovalis then may be expanded by advancing a dilator over the guidewire through the puncture (step505). Alternatively, a dilator may be advanced over the trans-septal puncture device, without the need for a guidewire. The dilator is used to further dilate the puncture and a sheath then is advanced over the dilator and through the fossa ovalis; the dilator and guidewire or needle then are removed. The sheath, which may be 14 Fr., is then flushed.

Distal end102of apparatus100, with device400coupled thereto in a contracted, delivery state, then is advanced into the sheath (step506). For example, the delivery system may be flushed, e.g., via fluid connected to fluid tube630, and then loading cartridge614may be coupled to sheath626, e.g., via port627, as illustrated inFIG.6I. The clinician should verify that loading cartridge contains no air therein. In accordance with another aspect of the invention, a Tuohy Borst adapter having a Luer fitting may be used which allows for continuous flushing of the loading cartridge during connection of the loading cartridge to the hemostasis valve of the delivery sheath. Next, while holding sheath626in place, loading cartridge614is advanced distally within port627as illustrated inFIG.6J. The device and delivery apparatus are advanced distally in sheath626until proximal end106of apparatus100is a predetermined distance X, e.g., approximately 1 cm, from knob622as illustrated inFIG.6K. The delivery system again may be flushed, e.g., via fluid connected to fluid tube630. The engagement of the latching legs of apparatus100with device400permit movement of device400longitudinally forward and longitudinally backward through sheath626.

Then, under fluoroscopic and/or echocardiographic visualization, sheath626may be repositioned such that the distal tip of sheath626is disposed a predetermined distance, e.g., approximately 1-2 cm, distal to the fossa ovalis within the left atrium. Next, device400and apparatus100are advanced distally such that the device is partially advanced out of the sheath so the first flared end of the device protrudes out of the sheath and into the left atrium, and expands to its deployed state (step507). For example, device400and apparatus100may be advanced distally until the handle at proximal end106contacts knob622as shown inFIG.6L. In a preferred embodiment, the distance between proximal end106and distal end102of delivery device100is adjustable such that only the first flared end of shunt device400protrudes out of the sheath when the handle at proximal end106contacts knob622. Such advancement causes device400to partially protrude out of sheath626and into left atrium LA, which causes the first flared end region to expand in the left atrium LA, as shown inFIG.6M. The first flared end region of device400may protrude beyond the atrial septum AS into left atrium LA such that the angle θ between center axis628of device400, sheath626, apparatus100, and/or catheter104and the outer surface of the atrial septum at the left atrial side below device400is generally perpendicular, e.g., between about 80 and about 100 degrees, between about 85 and about 95 degrees, or about 90 degrees, as shown inFIG.6M. Alternatively, device400may be positioned across the atrial septum AS, e.g., across a puncture through the fossa ovalis, at a non-perpendicular angle between center axis628and the outer wall of the atrial septum at the left atrial side below device400. For example, the angle θ′ may be substantially greater than 90 degrees as shown inFIG.6N. Such an angle may be appropriate when device400, sheath626, apparatus100, and/or catheter104are advanced toward the atrial septum transapically or through the inferior vena cava. Exemplary angles θ′ between center axis628and the outer surface of the atrial septum below device400include between about 110 and about 170 degrees, between about 120 and about 50 degrees, between about 130 and about 150 degrees about 120 degrees, about 125 degrees, about 130 degrees, about 135 degrees, about 140 degrees, about 145 degrees, about 150 degrees, about 155 degrees, about 160 degrees, about 165 degrees, and about 170 degrees.

As another example, the angle θ″ may be substantially less than 90 degrees as shown inFIG.6O. Such an angle may be appropriate when device400, sheath626, apparatus100, and/or catheter104are advanced toward the atrial septum through the superior vena cava. Exemplary angles θ″ between center axis628and the outer surface of the atrial septum at the left atrial side below device400include between about 10 and about 70 degrees, between about 20 and about 60 degrees, between about 30 and about 50 degrees, about 10 degrees, about 15 degrees, about 20 degrees, about 25 degrees, about 30 degrees, about 35 degrees, about 40 degrees, about 45 degrees, about 50 degrees, about 55 degrees, about 60 degrees, about 65 degrees, and about 70 degrees.

An hourglass shape may aid in non-perpendicular deployment because the flared ends of the device engage the atrial septum, even when positioned at an angle relative to the central axis of the puncture through the atrial septum.

Next, under fluoroscopic and/or echocardiographic visualization, it is verified that the first flared end of the device protrudes from sheath626and then knob622of Tuohy-Borst connector620is used to lock the delivery system in place within the sheath626. Sheath626, along with the delivery system100are pulled proximally causing the first flared end region of device400to engage the left side of the atrial septum AS as shown inFIG.6M. For example, as the latching legs of apparatus100are engaged with device400within sheath626, device400is prevented from accidental deployment wholly within the left atrium LA, which may also assist in positioning the device when advanced at non-perpendicular angles as described inFIGS.6N and6O.

Using fluoroscopic and/or echocardiographic visualization, the clinician next verifies that the device is positioned across the fossa ovalis. The clinician then reduces the pulling force of the sheath and allows the fossa ovalis to straighten. Then, while holding sheath626in place, knob622is released and the components at distal end102of apparatus100are moved from an engaged position to a disengaged position, e.g., by actuating handle108as shown inFIG.6P. Then, apparatus100is pulled proximally with the sheath626a predetermined distance, e.g., approximately 5-6 cm.

The shunt device then may be fully deployed by pulling the sheath proximally causing the first flared end region to engage the left side of the atrial septum and the neck of the device to lodge in the puncture through the fossa ovalis, and allowing expansion of the second flared end of the device into the right atrium as shown inFIG.6Q(step508). Any remaining components of the delivery system then may be removed, e.g., sheath and distal end of delivery apparatus (step509). Once positioned in the fossa ovalis, the device shunts blood from the left atrium to the right atrium when the left atrial pressure exceeds the right atrial pressure (step510), thus facilitating treatment and/or the amelioration of symptoms associated with CHF.

Referring toFIGS.7A and7B, an alternative exemplary apparatus is provided for delivering interatrial shunt devices, e.g., device400ofFIGS.4A and4B, and/or devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler. Apparatus700includes distal end702, catheter704, proximal end706, and knob system703. Distal end702comprises components suitable for coupling apparatus700to devices of the present invention, as described in detail below. Catheter704comprises a biocompatible tube shaft of suitable size, e.g., approximately 14 Fr., and suitable length, e.g., approximately 75-100 cm and preferably 85 cm. Proximal end706includes handle708that is designed to be manipulated, e.g., by a human hand, to transition components in distal end702from an engaged position to a disengaged position. In addition, apparatus700includes Luer connector705in communication with control tube707extending from proximal end706to distal end702of apparatus100. For example, control tube707may extend through catheter704and through handle708for over-the-wire flushing, e.g., via a Tuohy Borst adapter connected to apparatus700. Control tube707has a lumen extending therethrough sized to receive a guidewire.

Like handle108, handle708may be manipulated, for example, by moving finger grips710proximally from a locked position shown to an unlocked position. In addition, handle708may be manipulated by moving finger grips710distally from the locked position to the unlocked position so as to transition components in distal end702from the disengaged position to the engaged position to load devices of the present invention. Handle708also may include securement mechanism709coupled to handle safety lock711such that finger grips710cannot be moved until handle safety lock711is released. Upon activation, handle708is retained in position, enabling a single user to perform the procedure.

FIGS.8A and8Billustrate distal end702in the engaged position and the disengaged position, respectively. At distal end702, apparatus700may include latching legs712,714, and716having hook portions718,720, and722, respectively. Latching legs712,714, and716comprise a biocompatible material such as a biocompatible metal or polymer, and are positioned longitudinally and radially so as to firmly secure devices of the present invention for delivery. Hook portions718,720, and722extend outwardly from the distal end of latching legs712,714, and716, respectively, and are configured to fit securely between struts and rings of the devices of the present invention. Preferably, hook portions718,720, and722hook outwardly away from center axis723of catheter704in both the engaged and disengaged positions as shown inFIGS.8A and8B. Center axis723is centered relative to catheter704on both a longitudinal and cross-sectional basis. By facing outwardly from center axis723, hook portions718,720, and722may engage the inner surface of the device, e.g., within a lumen of a shunt.

In one embodiment, hook portions718,720, and722move generally radially away from center axis723. The angle between the lower surface of the hook portion and the longitudinal axis of the latching leg is preferably less than 90 degrees and greater than 75 degrees, e.g., 87 degrees, as shown inFIG.8Cto enable a more secure engagement with the shunt. For example, an angle less than 75 degrees could result in failure to disengage the shunt from the delivery device after deployment, whereas an angle greater than 90 degrees could result in failure to achieve half-way retrieval of the shunt by the delivery device. Such improved engagement allows the delivery device to pull the distal flange of a half-deployed shunt back into the sheath (“halfway-retrieval”) in the event the shunt's distal flange is deployed in an undesired location. As will be readily understood by one of ordinary skill in the art, while three latching legs are illustrated, more or fewer latching legs may be used without departing from the scope of the present invention. For example, one, two, four, five, six, or more latching legs may be used.

Catheter704may include cover tube724which may have a larger diameter than the remaining shaft of catheter704. Cover tube724comprises a biocompatible material such as a biocompatible metal or polymer, and may be the same or different material than the remaining shaft of catheter704. Components at distal end702, such as latching legs712,714, and716, may be at least partially disposed within cover tube724. Referring back toFIGS.8A and8B, distal end702includes control tube707, e.g., a polyether ether ketone (PEEK) tube, having a lumen extending therethrough sized to receive a guidewire, as described in more detail below. Control tube707is moveable between an engaged position, where the distal end of control tube707extends past the distal end of cover tube724as shown inFIG.8A, and a disengaged position, where the distal end of control tube707is moved proximally, but still extends past the distal end of cover tube724as shown inFIG.8B.

Referring now toFIGS.9A to9D, the inner components at distal end702of apparatus700are described.FIGS.9A and9Brespectively illustrate distal end702in the engaged position ofFIG.8Aand the disengaged position ofFIG.8B, respectively. As shown inFIG.9A, catheter704and cover tube724comprise lumens726and728, respectively, for housing the inner components. Latching legs712and714share common ramp portion730having inner section732and outer section734while latching leg716has separate ramp portion736having inner section738and outer section740. Inner sections732and738are angled so as to be positioned closer to central axis723of catheter704and cover tube724relative to the positions of outer sections734and740. Latching legs may also include jogs and protrusions. For example, latching leg716illustratively includes protrusion742proximal to ramp portion736, and jog744between hook portion722and ramp portion736. Protrusion742is configured to contact the distal surface of annular member748to maintain suitable positioning of latching leg716. Jog744is shaped to prevent release ring746from moving too far distally.

Release ring746is coupled to latching legs712,714, and716. For example, latching legs712,714, and716may be partially disposed within release ring746as illustrated inFIGS.9A to9D. Release ring746is moveable within cover tube724. Release ring746may be located in a first position, e.g., an engaged position, where release ring746contacts inner sections732and738of ramp portions730and736such that latching legs712,714, and716extend radially outward as shown inFIGS.9A and9C. Release ring746may be moved to a second position, e.g., a disengaged position, where release ring746contacts outer sections734and740of ramp portions730and736such that latching legs712,714, and716move radially inward as shown inFIGS.9B and9D. In one embodiment, release ring746is configured to move from the second position to the first position to load a device of the present invention and to move from the first position to the second position to release the device.

Annular member748may be partially disposed in the proximal end of cover tube724and configured to couple cover tube724to catheter704via a suitable coupling mechanism, e.g., teeth750, ribs. Annular member748includes lumen752sized to accept control tube707therethrough.

Control tube707is coupled to release ring746and actuation of control tube707moves release ring746from the first position shown inFIG.9Ato the second position shown inFIG.9B, and vice versa. In a preferred embodiment, control tube707is coupled to handle708such that control tube707is actuated by moving finger grips710from a locked position to an unlocked position, and vice versa. In addition, control tube707includes lumen755extending therethrough sized to receive a guidewire such that distal end702of apparatus700may be advanced over a guidewire to the desired device deployment location. The over-the-wire capability enables safe retrieval of a fully embolized device.

Control tube707may be coupled to release ring746via release ring base756. In this embodiment, release ring base756is directly coupled to release ring746and control tube707such that actuation of control tube707moves release ring base756to move release ring746from the first position the second position, and vice versa.

Spring758may be coupled to the proximal surface of release ring base756and the distal surface of annular member748such that release ring base756and annular member748maintain spring758therebetween. Spring758is configured to bias release ring746towards a particular position such as towards the first position as shown inFIG.9A.

FIGS.9A and9Cillustrate the components at distal end702in an engaged position, whereFIG.9Comits cover tube724for clarity. As control tube707is actuated, e.g., via handle708, release ring746is moved, e.g., via release ring base756, from the engaged position to the disengaged position shown inFIGS.9B and9D, whereFIG.9Domits cover tube724for clarity. Release ring746slides along ramp portions730and736from inner sections732and738to outer sections734and740such that latching legs712,714, and716move from being extended radially outward to being positioned radially inward. As release ring746moves from the engaged position to the disengaged position, spring758is compressed and as release ring746moves from the disengaged position to the engaged position, spring758is decompressed.

FIG.10Aillustrates the components at distal end702of apparatus700engaged to an exemplary interatrial shunt device andFIG.10Billustrates the components disengaged from the exemplary device. Device400includes rings402and struts404and may be constructed similar to devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler. As shown inFIG.10A, latching legs712,714, and716are sized, shaped, angled, and spaced apart from one another so as to engage device400in openings between rings402and struts404when device400is in a contracted, delivery state. Hook portions718,720, and722also are sized, shaped, and angled to fit between rings402and struts404and hook portions718,720,722hook outwardly away from the center axis at the distal end of the delivery apparatus such that hook portions718,720,722are disposed in the lumen of device400in the engaged position ofFIG.10Aand engage at the inner surface of device400. Preferably, hook portions718,720, and722move radially away from center axis723at an angle less than 90 degrees, e.g., 87 degrees, toward proximal end706of apparatus700as shown inFIG.8Cto enable halfway retrieval of a partially deployed device. As shown inFIG.10B, latching legs712,714, and716are configured to move radially inward a sufficient distance to decouple hook portions718,720, and722from device400in the disengaged position, thereby releasing device400for implantation.

FIG.11is a flowchart of exemplary method1100of delivering device400to reduce left atrial pressure in a subject, for example, a human having a heart condition, using apparatus700illustrated inFIGS.7A and7B. Steps1101-1104are similar to steps501-504described inFIG.5, except that apparatus700is used instead of apparatus100, and for brevity are not discussed again here. At step1105, a dilator having a guidewire lumen sized and shaped to receive the guidewire therethrough is advanced over the guidewire across the atrial septum through the fossa ovalis into the left atrium. A sheath is then advanced over the dilator across the atrial septum through the fossa ovalis into the left atrium. The dilator is then removed. In accordance with another aspect of the present invention, a sheath having a dilator disposed therein may be advanced together over the guidewire across the atrial septum through the fossa ovalis into the left atrium.

At step1106, distal end702of apparatus700, with device400coupled thereto, is advanced through the sheath over the guidewire until proximal end706of apparatus700is a predetermined distance from the proximal end of the sheath such that distal end702of apparatus700is a predetermined distance from the distal end of the sheath. The guidewire is received from the Luer connector705via lumen755of control tube707. Steps1107-1110are similar to steps507-510described inFIG.5, except that apparatus700is used instead of apparatus100and the guidewire may be removed through Luer connector705at step1109, and for brevity are not described again herein. Thus, for example, the components at distal end702of apparatus700, e.g., latching legs712,714, and716, are moved from an engaged position to a disengaged position, e.g., by actuating the handle at proximal end706to decouple hook portions718,720, and722from device400in the disengaged position, before the sheath is retracted to deploy device400within the atrial septum.

In accordance with another aspect of the present invention, knob system703may be used for length adjustment of apparatus700relative to the sheath during deployment of device400at the atrial septum, e.g., to assist in halfway retrieval of device400. For example, referring now toFIGS.12A-12C, knob system703includes proximal knob1202, distal knob1204, and optional lock nut1206. Referring toFIG.12A, proximal knob1202may be pulled proximally to enable rotating distal knob1204clockwise to assist in “halfway retrieval” of device400as described here. Distal knob1204is rotatable to shorten the distance between the knob1204and the distal end702of apparatus700, thus pulling distal end702proximally within the sheath. For example, in the event that the first flared end region of device400is deployed and the second flared end region is still in a collapsed state within the sheath and coupled to distal end702of apparatus700, distal knob1204may be rotated clockwise to retract distal end702, and thus device400, within the sheath. As distal end702is retracted within the sheath, device400is also retracted, thus causing the first flared end region to collapse into the sheath.

Referring now toFIGS.12B and12C, lock nut1206is moveable between an open and closed position to permit retraction of proximal knob1202, and thereby rotation of distal knob1204. Referring toFIG.12B, lock nut1206is in an open position such that proximal knob1202may be pulled proximally and distal knob1204may be rotated to the adjust the length of catheter704relative to the length of the sheath. When the length of catheter704relative to the length of the sheath is at the desired amount, lock nut1206may be moved to the closed position as shown inFIG.12Cto fix the set length.

Referring toFIG.13A, an alternative distal end of an apparatus for delivering devices of the present invention is provided. Distal end1302is constructed similar to distal end102described inFIGS.2A to3D, or distal end702described inFIGS.8A to9D, except that distal end1302includes tube1304extending distally from cover tube1306. Thus, distal end1302includes hook portions1308and1310that move away from a center axis of the catheter as described above, and tube1304includes windows1312and1314sized for hook portions1308and1310to protrude through in the engaged position as described inFIGS.2A,3A,3C,8A,9A, and9C to engage device400in a collapsed state within sheath1316. As shown inFIG.13A, when hook portions1308and1310are in the disengaged position as described inFIGS.2B,3B,3D,8B,9B, and9D, hook portions1308and1310do not extend beyond the diameter of tube1304which prevents the risk of entanglement. As will be readily understood by one of ordinary skill in the art, while two latching legs are illustrated, more or fewer latching legs may be used without departing from the scope of the present invention. For example, one, three, four, five, six, or more latching legs may be used, and accordingly, tube1304may include a corresponding number of windows.

Referring toFIGS.13B-13D, an alternative distal end of an apparatus for delivering devices of the present invention is provided. Distal end1301is constructed similar to distal end1302described inFIG.13A, and accordingly, distal end102described inFIGS.2A to3Dand/or distal end702described inFIGS.8A to9D, except that instead of tube1304, distal end1301includes cap1303extending distally from cover tube1305. Thus, distal end1301includes one or more hook portions1307that move away from a center axis of the catheter as described above, and cap1303includes one or more windows1309sized for hook portions1307to protrude through in the engaged position as described above to engage device400in a collapsed state within the sheath. Cap1303has a rounded surface and is sized and shaped such that when hooks portions1307are retracted, cap1303prevents the shunt from being dragged inward along with hooks portions1307, insuring that the shunt is released. As will be understood by a person having ordinary skill in the art, tube1304and cap1303may be two separate components coupled together or may be formed as a single unitary component.

As described above with regard to, e.g., distal end102ofFIGS.2A to3D, hook portions1307is coupled to ramp portion1311that interacts with release ring1313to cause hook portions1307to move radially inward/outward responsive to the longitudinal position of release ring1313relative to ramp portion1311. For example, as shown inFIGS.13C and13D, release ring1313is positioned along ramp portion1311such that hook portions1307protrudes out through windows1309of cap1303. As shown inFIG.13D, the inner surface of cover tube1305may include ridge1317sized and shaped to prevent release ring1313from moving too far distally within cover tube1305. Moreover, spring1317may cause release ring1313to be pushed against ridge1317, thereby biasing hook portions1307in the engaged positioned, unless actuated by the user.

For example, to engage hook portions1307from the shunt device, release ring1313may be moved proximally via pull-chord1315. As release ring1313slides proximally along ramp portion1311, hook portions1317move radially inward toward the central axis of the catheter within window1309, to thereby disengage with the shunt device without dragging the shunt device inward and insure that the shunt device is released.

Referring toFIG.14, an alternative exemplary apparatus is provided for delivering interatrial shunt devices, e.g., device400ofFIG.4A,4B or6Q, and/or devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler. Apparatus1400includes distal end1402, catheter1404, and proximal end1406having handle1408for actuating distal end1402. Distal end1402is sized and shaped to be advanced through sheath1410, which is sized to extend between distal end1402and proximal end1406over catheter1404. Apparatus1400may include inner catheter1411extending from distal end1402through catheter1404and through proximal end1406, e.g., past the proximal most part as shown. Inner catheter1411has a lumen sized to receive a guidewire therethrough.

Exemplary method1500of delivering device400to reduce left atrial pressure in a subject, for example, a human having a heart pathology, using apparatus1400illustrated inFIG.14will now be described with reference toFIG.15. Some of the steps of method1500may be further elaborated by referring toFIGS.16A-16T. Steps1501-1507are similar to steps1101-1107described inFIG.11, except that apparatus1400is used instead of apparatus700, and thus for brevity these steps are not discussed again here.FIG.16Ais a perspective view of proximal end1406of apparatus1400andFIG.16Bis a partial cross-sectional view illustrating internal components.FIGS.16A and16Billustrate handle1408at proximal end1406of apparatus1400when distal end1402having device400coupled thereto, and catheter1404are advanced over the guidewire and through sheath1410across the fossa ovalis (step1506). Handle1408includes first actuator1422, second actuator1423, and third actuator1424for actuating the components within the distal region of sheath1410such that the shunt transitions between a contracted delivery state, to a partially expanded state, and then to a fully expanded deployed state. First, second, and third actuators1422,1423, and1424may be buttons, switches, levers, touchscreens, or the like. First, second, and third actuators1422,1423, and1424may be combined into a single component, two components, or may be more than three components.

In addition, handle1408includes knob1401. The inner components of knob1401includes a threaded portion that corresponds with a threaded portion coupled to sheath1410. Accordingly, as knob1401is rotated about the longitudinal axis of handle1408, rotational movement of knob1401is converted to translational movement of the threaded portion coupled to sheath1410along the longitudinal axis of handle1408, thereby causing movement of sheath1410relative to catheter1404. This permits gradual adjustment of the length of sheath1410relative to catheter1404, and accordingly halfway-retrieval of device400when device is halfway deployed as will be described in further detail below. Knob1401may not be rotated until third actuator1424is moved from a locked position to an unlocked position.

As illustrated inFIG.16B, third actuator1424may be coupled to third actuator component1413rotatable about the longitudinal axis of handle1408, parallel to inner catheter1411, between a first, second, and third position. For example,FIGS.16A and16Billustrate third actuator1424in the first position, such that third actuator1424is centered within opening1433of the housing of handle1408. Third actuator component1413may include a toothed pattern along its proximal end for engaging with a corresponding indent along the distal end of actuator ring1415, wherein actuator ring1415is freely rotatable about the longitudinal axis of handle1408. As shown inFIG.16B, there is a defined space between an edge of the tooth of third actuator component1413and an edge of the indent of actuator ring1415when third actuator1424is in the first position. When third actuator1424is moved to the third position, such that third actuator component1413is rotated, e.g., clockwise, about the longitudinal axis of handle1408, the edge of the tooth of third actuator component1413engages with the edge of the indent of actuator ring1415. This prevents actuator ring1415from rotating in an opposite direction, e.g., counter-clockwise, about the longitudinal axis of handle1408. Thus, second actuator1423and second actuator component1417are also prevented from moving distally within opening1435along the longitudinal axis of handle1408.

When third actuator1424is moved to the second position, such that third actuator component1413is rotated, e.g., counter-clockwise, about the longitudinal axis of handle1408, the space between the edge of the tooth of third actuator component1413and the edge of the indent of actuator ring1415increases such that actuator ring1415is free to rotate in the same direction, e.g., counter-clockwise until the edge of the indent of actuator ring1415engages with the edge of the tooth of third actuator component1413. In addition, third actuator component1413is operatively coupled to a locking mechanism between inner catheter1411and a hub disposed within the distal region of sheath1410as described in further detail below.

Actuator ring1415also may include a grooved pattern along its proximal end for engaging with a corresponding indent along the distal end of second actuator component1417coupled to second actuator1423. Accordingly, the edge of the tooth of third actuator component1413may further engage with the indent of actuator ring1415, to thereby rotate actuator ring1415until the groove of actuator ring1415engages with the indent of second actuator component1417. Second actuator1423may be moveable between a first and second position. For example,FIGS.16A and16Billustrate second actuator1423in the first position, such that first actuator1422is positioned proximally relative to opening1435of the housing of handle1408. Third actuator component1413, actuator ring1415, and second actuator component1423include a lumen sized and shaped to receive first actuator component1419coupled to first actuator1422. In addition, the lumens of third actuator component1413and actuator ring1415are sized and shaped to permit rotation about first actuator component1419, whereas the lumen of second actuator component1417may be sized and shaped such that second actuator component1417is only permitted to move longitudinally along first actuator component1419.

First actuator component1419is moveable along the longitudinal axis of handle1408, parallel to inner catheter1411, between a first and second position. For example,FIGS.16A and16Billustrate first actuator1422in the first position, such that first actuator1422is positioned distally relative to opening1437of the housing of handle1408. As illustrated inFIG.16B, first actuator component1419may include one or more lumens1421sized and shaped to receive one or more guiderails1431, such that first actuator component1419is moveable between the first and second positions along guiderails1431. One or more guiderails1431are coupled at one end to second actuator component1417, and coupled at an opposite end to pusher plate1440disposed at the proximal end of handle1408, wherein pusher plate1440is fixedly coupled to a proximal portion of inner catheter1411. Accordingly, movement of second actuator component1417from the first position to the second position causes pusher plate to move distally within the housing of handle1408via guiderails1431, thereby causing inner catheter1411to move distally within the distal region of sheath1410.

First actuator component1419includes a lumen sized and shaped to receive centering element1429, wherein centering element1429is fixed relative to handle1408. First actuator1422is further coupled to proximal portion1427sized and shaped to move within a lumen of centering element1429. Proximal portion1427includes a lumen sized and shaped to receive inner catheter1411, such that proximal portion1427is moveable between the first and second positions along inner catheter1411. First actuator1422may be moveably coupled to inner catheter1411via proximal portion1427, and may include port1439for coupling to a fluid source to introduce fluid into the guidewire lumen of inner catheter1411for flushing. In addition, first actuator component1419is coupled to sheath1410for extending and retracting the distal end of sheath1410as described in further detail below.

FIG.16Cillustrates distal end1402having device400coupled thereto in a collapsed state and catheter1404disposed within the distal portion of sheath1410(shown in cross-section for clarity), e.g., in a position suitable for percutaneous delivery to the left atrium of the patient. Distal end1402includes hub1412disposed distal to the distal end of catheter1404. Hub1412may have engagement portion1428disposed distal to ring portion1426, and a proximal portion that is moveably disposed within a cavity of catheter1404as described in further detail below. Ring portion1426has a diameter that is equal to or slightly less than the diameter of the inner wall of sheath1410such that hub1412may move backwards and forwards within sheath1410. Engagement portion1428of hub1412has a diameter less than that of ring portion1426, such that device400may fit between the outer surface of engagement portion1428and sheath1410when device400is in a collapsed, delivery state. Engagement portion1428may have a cylindrical shape and a curved distal end as shown. Hub1412is moveable relative to catheter1404within sheath1410along an inner catheter disposed within a lumen extending through hub1412and catheter1404as described in further detail below. Hub1412is releaseably coupled to the distal end of catheter1404via a locking mechanism operatively coupled to third actuator1424, such that actuation of third actuator1424from the first position to the second position causes the locking mechanism to unlock, thereby decoupling hub1412from catheter1404.

In addition, hub1412includes one or more engagers, e.g., protrusions1414,1416and1418, extending radially outward from a central axis of catheter1404, such that the one or more engagers are disposed circumferentially about the outer surface of hub1412, e.g., at engagement portion1428, and are configured to fit securely between struts and rings of the interatrial devices for delivery. Thus, each of the one or more engagers may be sized to engage device400in openings between rings402and struts404when device400is in a contracted, delivery state. For example, the distance from the central axis of hub1412to the outermost surface of each of the one or more engagers is equal to or slightly less than the inner radius of sheath1410so that hub1412may be moveable within sheath1410. The distance from the central axis of hub1412to the outermost surface of each of the one or more engagers may be equal to the distance from the central axis of hub1412to the outer surface of ring portion1426. Accordingly, device400may be constrained between the one or more engagers and ring portion1426, and between engagement portion1428and sheath1410in order to prevent dislodgement or early deployment of device400within sheath1410. As shown inFIG.16C, protrusions1414and1416engage device400in openings between rings402and struts404such that device400is constrained between hub1412and the inner wall of sheath1410in a contracted, delivery state. As will be readily understood by one of ordinary skill in the art, while two engagers are illustrated, more or fewer engagers may be used without departing from the scope of the present invention. For example, one, three, four, five, six, seven, eight, or more engagers may be used.

FIG.16Dis a partial cross-sectional schematic of the delivery apparatus within the sheath during step1506, wherein the delivery apparatus is coupled to device400, andFIG.16Eillustrates the delivery apparatus ofFIG.16Dwith device400omitted for clarity. As shown inFIG.16D, the distal end of sheath1410, with the delivery apparatus disposed therein, is advanced across the atrial septum AS. Protrusions1414and1416fit securely between struts and rings of device400such that device400is constrained between protrusions1414and1416and ring portion1426, and between engagement portion1428and sheath1410. As shown inFIG.16E, hub1412is adjacent to catheter1404such that proximal portion1432of hub1412is disposed within cavity1436of catheter1404. Cavity1436is sized and shaped to receive proximal portion1432of hub1412a predetermined distance. Cavity1436has a larger outer diameter than the outer diameter for the lumen in catheter1404that receives inner catheter1411. Proximal portion1432is coupled to ring portion1426via connector1434. Hub1412may be releaseably coupled to catheter1404via a locking mechanism for engaging catheter1404to at least one of ring portion1426or proximal portion1432.

In addition, inner catheter1411is disposed within a central lumen extending through hub1412and catheter1404. Inner catheter1411may include a stop, e.g., lock ring1438, fixed at a distal end of inner catheter1411, wherein lock ring1438is sized and shaped to be disposed within cavity1430of hub1412. Cavity1430may extend through at least a portion of engagement portion1428of hub1412, or completely through engagement portion1428of hub1412and at least a portion of ring portion1426of hub1412. Lock ring1438ensures that hub1412does not extend beyond a predetermined distance distally along inner catheter1411, and that inner catheter1411does not retract beyond the predetermined distance proximally relative to hub1412. Inner catheter1411also may include guidewire lumen1425sized and shaped to receive a guidewire therethrough. For example, delivery apparatus1400may be advanced over a guidewire such that the distal end of sheath1410having distal end1402coupled to device400disposed therein, is positioned across the fossa ovalis.

Referring now toFIGS.16F and16G, first actuator1422is then moved from a first initial position to a second position within opening1437of the housing of handle1408, which causes distal end1402including inner catheter1411and hub1412having device400coupled thereto, and catheter1404to move relative to sheath1410. As illustrated inFIG.16G, movement of first actuator1422causes first actuator component1419to move from the first initial position to the second position through the lumens of second actuator component1417, actuator ring1415, and third actuator component1413along guiderail1431, and proximal portion1427to move from the first initial position to the second position along inner catheter1411within centering element1429. Specifically, movement of first actuator1424from the first initial position to the second position causes first actuator component1419operatively coupled to sheath1410to move sheath1410relative to catheter1404, hub1412, and inner catheter1411, thereby exposing first flared end region401of device400beyond the distal end of sheath1410such that first flared end region401expands to its deployed state in the left atrium as shown inFIG.16H(step1507). According to one aspect of the invention, actuation of first actuator1422may cause catheter1404, hub1412, and inner catheter1411to be advanced distally while sheath1410remains stationary with respect to atrial septum AS.

FIG.16Iis a cross-sectional schematic of the delivery apparatus within the sheath during step1507, wherein device400is partially deployed, andFIG.16Jillustrates the delivery apparatus ofFIG.16Iwith device400omitted for clarity. As shown inFIG.16I, first flared end region401of device400is deployed in the left atrium of the patient a predetermined distance from the atrial septum AS. Referring toFIG.16J, the delivery apparatus, e.g., hub1412and catheter1404moves distally within sheath1410relative to sheath1410, such that first flared end region401extends beyond the distal end of sheath1410and transitions from a collapsed, delivery state to an expanded, deployed state within the left atrium, while the second flared end of device400remains in a collapsed, delivery state within the distal end of sheath1410.

Referring now toFIGS.16K and16L, second actuator1423may then be moved from the first initial position to the second position which causes second actuator component1417to move distally along first actuator component1419within the housing of handle1408. As second actuator component1417moves distally along first actuator component1419, the distal edge of second actuator component1417interacts with the groove of actuator ring1415, thereby causing actuator ring1415to rotate until the indent of actuator ring1415engages with the edge of the tooth of third actuator component1413. In addition, movement of second actuator component1417from the first initial position to the second position causes inner catheter1411to move distally relative to hub1412, catheter1404, and sheath1410via guiderails1431and pusher plate1440as illustrated inFIG.16M. Accordingly, the delivery apparatus, e.g., sheath1410, inner catheter1411, catheter1404, and hub1412coupled to device400, may be pulled proximally until first flared end region401engages the atrial septum from within the left atrium (step1508).

FIG.16Nis a cross-sectional schematic of the delivery apparatus within the sheath during step1508, wherein inner catheter1411has been moved distally relative to sheath1410, hub1412, and catheter1404such that lock ring1438is no longer disposed within cavity1430of engagement portion1428of hub1412, and the delivery apparatus is pulled proximally until first flared end region401engages the left side of atrial septum AS.FIG.16Oillustrates the delivery apparatus ofFIG.16Nwith device400omitted for clarity. Specifically,FIG.16Oillustrates sheath1410, hub1412, inner catheter1411, and catheter1404pulled proximally with respect to atrial septum AS. Using fluoroscopic or echocardiographic visualization, the clinician next verifies that the device is positioned across the fossa ovalis. The clinician then reduces the pulling force of sheath1410, catheter1404, and hub1412, and allows the fossa ovalis to straighten. In accordance with one aspect of the present invention, the physician may reduce and/or stop the pulling force of the delivery apparatus upon force feedback provided by the atrial septum against the delivery apparatus, which indicates that device400is properly positioned within the opening of the atrial septum. This may prevent accidentally deploying the entire device in the left atrium and may assist in positioning the device when advanced at non-perpendicular angles.

Referring back toFIG.16L, third actuator1424may then be moved from the first initial position to the second position, which causes third actuator component1413to rotate about first actuator component1419. The engagement between the tooth of third actuator component1413and the indent of actuator ring1415allows rotation of third actuator component1413to rotate actuator ring1415in the same direction, e.g., counter-clockwise, until the groove of actuator ring1415engages with the indent of second actuator component1417. This causes the locking mechanism to decouple hub1412and catheter1404to permit full deployment of device400.

If for any reason device400is not in the proper position for deployment within the atrial septum, sheath1410may be advanced over device400while catheter1404is stationary, thereby collapsing first flared end region401within sheath1410. Specifically, knob1401of handle1408may be rotated to cause sheath1410to move translationally relative to catheter1404and device400, to thereby collapse device400within sheath1410. For example, sheath1410may be moved over collapsed device400until device400is completely collapsed within sheath1410. Distal end1402, with device400disposed therein, may then be retrieved. Alternatively, distal end1402may be repositioned relative to the fossa ovalis of the atrial septum prior to partially advancing first flared end region401out of sheath1410within the left atrium.

When third actuator1424is in the second position and hub1412and catheter1404are decoupled, the delivery apparatus may be pulled proximally by the physician such that the atrial septum maintains device400in position against the left side of the atrial septum until second flared end region403of device400is no longer constrained between hub1412and sheath1410as shown inFIG.16P. As sheath1410, catheter1404, and inner catheter1411are retracted proximally, hub1412remains stationary with respect to the atrial septum as the one or more engagers of hub1412are engaged with the struts of second flared end region403of device400within sheath1410. Hub1412is permitted to move distally along inner catheter1411until cavity1430of hub1412prevents lock ring1438of inner catheter1411from further proximal movement. When second flared end region403of device400is exposed beyond the distal end of sheath1410, second flared end region403then transitions from a collapsed, delivery state to an expanded, deployed state within the right atrium, and neck region405is lodged in the puncture of the atrial septum (step1509).

FIG.16Qis a cross-sectional schematic of the delivery apparatus within the sheath during step1509, wherein the delivery apparatus is pulled proximally such that second flared end region403of device400is no longer constrained between hub1412and sheath1410.FIG.16Rillustrates the delivery apparatus ofFIG.16Qwith device400omitted for clarity. As shown inFIG.16Q, sheath1410is no longer disposed over protrusions1414and1416such that second flared end region403is no longer constrained in the collapsed, delivery state, thereby causing first flared end region401to engage the left side of the atrial septum and neck region405of the device to lodge in the puncture through the fossa ovalis, and allowing expansion of second flared end region403of the device into the right atrium as shown inFIG.16S.

Referring back toFIG.16R, inner catheter1411, catheter1404, and sheath1410are pulled proximally while hub1412of the delivery apparatus, e.g., engagement portion1428, ring portion1426, and proximal portion1432, remains stationary with respect to atrial septum AS until at least a portion of proximal portion1432of hub1412is no longer disposed within cavity1436of catheter1404. In addition, at least a partial portion of ring lock1438of inner catheter1411may be disposed within cavity1430of engagement portion1428of the hub. As described above, ring lock1438and cavity1430prevent inner catheter1411from being pulled proximally relative to the hub beyond a predetermined distance.

Any remaining components of the delivery system then may be removed, e.g., sheath, distal end of delivery apparatus, the catheter, and the guidewire (step1510). Once positioned in the fossa ovalis as shown inFIG.16T, device400shunts blood from the left atrium to the right atrium when the left atrial pressure exceeds the right atrial pressure (step1511), thus facilitating treatment and/or the amelioration of symptoms associated with CHF.

It should be noted that the inventive devices also may be used with patients having disorders other than heart failure. For example, in one embodiment the device may be implanted in a subject suffering from myocardial infarction, for example in the period immediately following myocardial infarction (e.g., within a few days of the event, or within two weeks of the event, or even within six months of the event). During such a period, the heart remodels to compensate for reduced myocardial function. For some subjects suffering from severe myocardial infarction, such remodeling may cause the function of the left ventricle to significantly deteriorate, which may lead to development of heart failure Implanting an inventive device during the period immediately following myocardial infarction may inhibit such deterioration in the left ventricle by reducing LAP and LVEDP during the remodeling period. The device optionally then may be removed as described in further detail below.

Exemplary method1700of retrieving device400from a subject, for example, from a puncture through the fossa ovalis, will now be described with reference toFIG.17. The steps of method1700may be further elaborated by referring toFIGS.18A-18F.

FIG.17is a flow chart of steps in an exemplary method of retrieving an hourglass-shaped device implanted in a puncture through the fossa ovalis in accordance with the present invention. At step1701, a retrieval system for retrieving an implanted shunt device, e.g., hourglass-shaped device400ofFIG.4, is provided. For example, the retrieval system includes a retrieval catheter, e.g., grappling hook, having one or more hook portions at the distal end thereof which preferably are formed of a shape memory metal and are biased toward a position radially outward from a central axis of the retrieval catheter, a restraint member coupled to a control tube and positioned over at least a portion of the retrieval catheter, and a sheath having a lumen sized and shaped to receive the retrieval catheter and the restraint member. The hook portions are sized and shaped to align with the openings between the struts and rings of the shunt device. Accordingly, the number of hook portions may correspond with the number of openings between the struts and rings of the shunt device.

At step1702, a guidewire is inserted through the neck of the implanted shunt device through the fossa ovalis of the atrial septum into the left atrium. The guidewire may be inserted using techniques readily known in the art. At step1703, the sheath is inserted over the guidewire and positioned in proximity to the flared end region of the shunt device disposed in right atrium. The guidewire may then be removed. At step1704, the retrieval catheter and the restraint member are delivered through the sheath in proximity to the flared end region of the shunt device disposed in right atrium.FIG.18Ais a partial cross-sectional schematic of retrieval system1800during step1704. As illustrated inFIG.18A, sheath1802having retrieval catheter1804and restraint member1808disposed therein is positioned in proximity to second flared end region403of device400within the right atrium. Restraint member1808is positioned over a portion of retrieval catheter1804such that hook portions1806are maintained in a compressed configuration within sheath1802. Although only two hook portions1806are illustrated inFIG.18A, as will be understood by a person ordinarily skilled in the art, retrieval catheter1804may include less or more than two hook portions, e.g., one, three, four, five, or six hook portions. Restraint member1808may be moved proximally and distally over retrieval catheter1804within sheath1802via control tube1810. Alternatively, a control wire having sufficient stiffness may be used to move restraint member1808within sheath1802.

At step1705, retrieval catheter1804along with restraint member1808are advanced distally and exposed beyond the distal end of sheath1802within the right atrium such that hook portions1806are within at least a portion of second flared end region403of device400, as illustrated inFIG.18B. At step1706, restraint member1808is retracted proximally along retrieval catheter1804within sheath1802via control tube1810. Accordingly, hook portions1806expand radially outward from the central axis of retrieval catheter1804as they are no longer restrained by restraint member1808, as illustrated inFIG.18C. At step1707, retrieval catheter1804may be adjusted to align hook portions1806with the openings between the struts and rings of second flared end region403of device400.

At step1708, while hook portions1806are maintained in placed and engaged with second flared end region403of device400, restraint member1808is advanced distally toward hook portions1806via control tube1810, thereby causing hook portions1806, and accordingly second flared end region403, to transition to a compressed configuration, as illustrated inFIG.18D. Next, at step1709, sheath1802is advanced distally over retrieval catheter1804and device400, through the atrial septum AS and into the left atrium, thereby causing first flared end region401of device400to transition to a compressed configuration within sheath1802, as illustrated inFIG.18E. Finally, at step1710, system1800is pulled proximally to remove retrieval system1800and device400from the patient, as illustrated inFIG.18F.

In accordance with another aspect of the present invention, exemplary method1900of retrieving device400from a subject, for example, from a puncture through the fossa ovalis, will now be described with reference toFIG.19. The steps of method1900may be further elaborated by referring toFIGS.20A-20G.

FIG.19is a flow chart of steps in an exemplary method of retrieving an hourglass-shaped device implanted in a puncture through the fossa ovalis in accordance with the present invention. At step1901, a retrieval system for retrieving an implanted shunt device, e.g., hourglass-shaped device400ofFIG.4, is provided. For example, the retrieval system includes grappling hook having one or more hook portions at the distal region thereof which preferably are formed of a shape memory metal and are biased radially inward toward a central axis of the retrieval system, an inflatable balloon catheter, and a sheath having a lumen sized and shaped to receive the grappling hook and the inflatable balloon catheter. The one or more curved hooked portions of the grappling hook are sized and shaped to align with the openings between the struts and rings of the shunt device in an expanded state. Accordingly, the number of hook portions may correspond with the number of openings between the struts and rings of the shunt device. As will be understood by a person ordinarily skilled in the art, the inflatable balloon catheter may be delivered within a separate balloon channel moveable within the sheath.

At step1902, a guidewire is inserted through the neck of the implanted shunt device through the fossa ovalis of the atrial septum into the left atrium. The guidewire may be inserted using techniques readily known in the art. At step1903, the sheath is inserted over the guidewire and positioned in proximity to the flared end region of the shunt device disposed in right atrium. At step1904, the grappling hook and the inflatable balloon catheter are delivered through the sheath over the guidewire in proximity to the flared end region of the shunt device disposed in right atrium.FIG.20Ais a partial cross-sectional schematic of retrieval system2000during step1904. As illustrated inFIG.20A, sheath2002having grappling hook2004and inflatable balloon catheter2008in a deflated state disposed therein is positioned in proximity to second flared end region403of device400within the right atrium. Although only two hook portions2006are illustrated inFIG.20A, as will be understood by a person ordinarily skilled in the art, grappling hook2004may include less or more than two hook portions2006, e.g., one, three, four, five, or six hook portions. Hook portions2006of grappling hook2004may be joined together at a proximal region of grappling hook2004, e.g., via a ring having a lumen sized and shaped to receive inflatable balloon catheter2008such that grappling hook2004may move proximally or distally over inflatable balloon catheter2008within sheath2002.

At step1905, inflatable balloon catheter2008is advanced distally, e.g., over the guidewire (not shown), and exposed beyond the distal end of sheath2002within the right atrium in a deflated condition such that inflatable balloon catheter2008is positioned within at least a portion of second flared end region403of device400, as illustrated inFIG.20B. At step1906, inflatable balloon catheter2008is inflated to an inflated state within at least a portion of second flared end region403and neck region405of device400, as illustrated inFIG.20C. For example, inflatable balloon catheter2008may be coupled to a source of fluid at its proximal end outside the patient's body for inflation of inflatable balloon catheter2008, and may expand to have a diameter equal to the diameter of neck region405of device400. Inflation of inflatable balloon catheter2008aligns retrieval system2000with device400.

At step1907, grappling hook2004is advanced distally and exposed beyond the distal end of sheath2002within the right atrium. As illustrated inFIG.20D, hook portions2006of grappling hook2004bend radially outwardly in an expanded state as they move across the surface of inflatable balloon catheter2008in the inflated state. At step1908, grappling hook2004may be adjusted to align hook portions2006with the openings between the struts and rings of second flared end region403of device400.

At step1909, while hook portions2006are maintained in placed and engaged with second flared end region403of device400, inflatable balloon catheter2008is deflated and advanced distally into the left atrium. Alternatively, inflatable balloon catheter2008may be deflated and removed from the patient's body or deflated and retracted into a balloon channel within sheath2002. Deflation of inflatable balloon catheter2008causes hook portions2006of grappling hook2004, and accordingly second flared end region403, to transition to a compressed configuration, as illustrated inFIG.20E.

Next, at step1910, sheath2002is advanced distally over grappling hook2004, device400, and inflatable balloon catheter2008, through the atrial septum AS and into the left atrium, thereby causing first flared end region401of device400to transition to a compressed configuration within sheath2002, as illustrated inFIG.20F. Finally, at step1911, system2000is pulled proximally to remove retrieval system2000and device400from the patient, as illustrated inFIG.18G.

Referring toFIG.21A, an alternative exemplary apparatus is provided for delivering interatrial shunt devices, e.g., device400ofFIG.4A,4B or6Q, and/or devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler. Apparatus2100includes distal end2102, catheter2104, and proximal end2106having handle2108for actuating distal end2102. Distal end2102is removeably coupled to distal tip2110having flexible pigtail-shaped portion2112extending therefrom as illustrated inFIG.21B. Apparatus2100may include an engagement apparatus disposed within catheter2104extending from proximal end2106to distal end2102for delivery and/or retrieval of the interatrial shunt device. The components of apparatus2100may include a guidewire lumen sized to receive a guidewire therethrough as described in further detail below.

Referring now toFIG.22, an exemplary loading tool is provided for loading an exemplary hourglass-shaped interatrial shunt constructed in accordance with the principles of the present invention into distal end2102of apparatus2100. Loading tool2200includes proximal loader2202and distal loader2204. Proximal loader2202and distal loader2204may be constructed from, e.g., injection molding, and made of a transparent plastic material such that loading of device400therein may be visible by the user. Proximal loader2202has lumen2208extending from proximal end2201to distal end2203of proximal loader2202, wherein lumen2208is sized and shaped to receive device400in a collapsed delivery state as well as distal tip2110and catheter2104of apparatus2100. As illustrated inFIG.22, lumen2208has conical shaped cavity2206at its distal open end which corresponds to the shape of one of the flared end regions of device400, e.g., the flared end region configured to be disposed within the left atrium when device400is implanted. Further, cavity2206is sized such that device400must be inserted into proximal loader2202in a specific orientation as will be described in further detail below, thereby ensuring proper loading of device400into apparatus2100. In addition, distal loader2204has cavity2210sized and shaped to receive distal end2203of proximal loader2202.

Exemplary method2300of using loading tool2200to load device400into apparatus2100will now be described with reference toFIG.23. Some of the steps of method2300may be further elaborated be referring toFIGS.24A-24F.FIG.24Aillustrates proximal loader2202, distal loader2204, the distal components of apparatus2100, and device400. As illustrated inFIG.24A, apparatus2100is positioned within proximal loader2202such that the distal portion of catheter2104and engagement apparatus2120are disposed within lumen2208, and distal tip2110extends beyond distal end2203of proximal loader2202(step2301). As shown inFIG.24A, distal tip2110is moveably coupled to catheter2104via pull-cord2114. Engagement apparatus2120may be constructed similar to delivery apparatus100ofFIG.1Aand delivery apparatus700ofFIG.7A. For example, engagement apparatus2120includes latching legs having hook portions which may be controllably transitioned between a disengaged and engaged position for engaging with device400in a collapsed delivery state. Engagement apparatus2120is moveably disposed within the lumen of catheter2104and may be coupled to the distal end of an inner catheter disposed within catheter2104.

FIG.24Billustrates device400coupled to distal tip2110of apparatus2100while apparatus2100is disposed within lumen2208of proximal loader2202(step2302). Specifically, device400is inserted over pigtail-shaped portion2112to be disposed over distal tip2110, such that the outlet end of second flared end region403of device400is adjacent to cavity2206of proximal loader2202. Cavity2206has a size and shape that corresponds to first flared end region401in an expanded state, and which may receive the outlet end of second flared end region403of device400in the expanded state. This ensures that device400is properly loaded into apparatus2100as the inlet end of first flared end region401could not be inserted into cavity2206of proximal loader2202.

FIG.24Cillustrates proximal loader2202having apparatus2100coupled to device400therein, advanced within cavity2210of distal loader2204(step2303). Specifically, proximal loader2202is advanced within cavity2210of distal loader2204until first flared end region401of device400contacts the inner wall of cavity2210. As proximal loader2202, and accordingly apparatus2201, are further advanced into cavity2210of distal loader2204(step2304), second flared end region403transitions from an expanded stated to a collapsed delivery state within lumen2208of proximal loader2202as illustrated inFIG.24D. Specifically, the conical shape of cavity2206of proximal loader2202causes second flared end region403to crimp into the collapsed state as force is applied to second flared end region403by proximal loader2202. In addition, pigtail-shaped portion2212and at least a portion of distal tip2110extend beyond an opening of distal loader2204. Steps2303and2304may be completed in a single motion.

In accordance with the principles of the present invention, the latching legs and hook portions of engagement apparatus2120may be actuated to be in a disengaged position, e.g., contracted inward, before proximal loader2202is completely advanced within distal loader2204so that the engagement hooks of engagement apparatus2120may be appropriately aligned with the struts of second flared end region403of device400, and so that second flared end region403can smoothly enter lumen2208of proximal loader2202. Once aligned, the latching legs and hook portions of engagement apparatus2120may be actuated to be in a engaged position to engage with second flared end region403of device400within lumen2208of proximal loader2202(step2305).

FIG.24Eillustrates catheter2104advanced further through lumen2208of proximal loader2202over engagement apparatus2120, device400, and pull-cord2114until the distal end of catheter2104engages with distal tip2110(step2306). Specifically, as the distal tip of catheter2104comes into contact with first flared end region401, further advancement of catheter2104against the outer surface of first flared end region401cause first flared end region401to crimp into a collapsed state within the lumen of catheter2104. The distal end of catheter2104may then be coupled to distal tip2110(step2307). Finally, apparatus2100having device400in a collapsed delivery state therein and engaged with engagement apparatus2120within catheter2104of apparatus2100, is removed from proximal loader2202and distal loader2204(step2308).

FIG.25Aillustrates catheter2104coupled to distal tip2110of apparatus2100. As shown inFIG.25A, apparatus2100may include radiopaque marker2122disposed at the distal end of catheter2104for assisting in accurate deployment of device400within the interatrial septum. Specifically, as described in further detail below, radiopaque marker2122may be visualized by the physician during the delivery procedure to ensure that it is aligned with the atrial septum for proper delivery.FIG.25Billustrates the components within catheter2104with device400loaded therein. As illustrated inFIG.25B, collapsed device400is positioned within catheter2104such that one end is engaged with engagement apparatus2120, and the other end is aligned with radiopaque marker2122so that the neck region of device400is a predetermined distance from radiopaque marker2122. As described in further detail below, knowing where the neck region of device400is within catheter2104, by knowing its distance from radiopaque marker2122will assist in proper and accurate deployment of device400within the fossa ovalis.

FIG.25Cis a cross-sectional view of the distal end of apparatus2100. As shown inFIG.25C, apparatus2100may include guidewire lumen2116extending therethrough, e.g., from an opening at the end of pigtail-shaped portion2116through distal tip2110and pull-cord2114to the proximal end of apparatus2100. Guidewire lumen2116is sized and shaped to receive a guidewire so that apparatus2100may be advanced over the guidewire across the atrial septum for implantation of device400. In addition, as illustrated inFIG.25C, engagement apparatus2120includes hook portions2118which may be constructed similar to the hook portions of delivery apparatus100ofFIG.1Aand delivery apparatus700ofFIG.7A, for engaging and disengaging device400with engagement apparatus2120.

FIGS.26A and26Billustrates handle2108coupled to distal end2106of apparatus2100. As shown inFIG.26A, handle2108includes safety trigger2126and knob2124. As illustrated inFIG.26B, knob2124includes a threaded portion that corresponds with threaded portion of catheter component2127coupled to catheter2104. Accordingly, as knob2124is rotated about the longitudinal axis of handle2108, rotational movement of knob2124is converted to translational movement of catheter component2127along the longitudinal axis of handle2108, thereby causing movement of catheter2104relative to engagement apparatus2120. This permits gradual adjustment of the length of catheter2104relative to engagement apparatus2120, and accordingly halfway-retrieval of device400when device is halfway deployed as will be described in further detail below. Knob2124may not be rotated until safety trigger2126is moved from a locked position to an unlocked position.

Exemplary method2700of delivering device400to reduce left atrial pressure in a subject, for example, a human having a heart pathology, using apparatus2100illustrated inFIG.21Awill now be described with reference toFIG.27. Some of the steps of method2700may be further elaborated by referring toFIGS.28A-28I.

At step2701, an interatrial shunt, e.g., device400, and apparatus2100ofFIG.21Afor delivering device400are provided. Then, at step2702, device400is collapsed radially to a contracted delivery state and coupled to apparatus2100, e.g., using method2300ofFIG.23. Steps2703and2704are similar to steps503and504described inFIG.5, and thus for brevity these steps are not discussed again here.FIG.28Aillustrates guidewire2801disposed across the atrial septum in left atrium LA (step2704).

Pigtail-shaped portion2112of distal tip2110of delivery apparatus2100with device400collapsed therein and coupled to engagement apparatus2120of apparatus2100is then advanced over guidewire2801through the puncture in the fossa ovalis and into left atrium LA (step2705) as illustrated inFIG.28B. Next, catheter2104is retracted proximally relative to distal tip2110and engagement apparatus2120coupled to collapsed device400such that device400is partially advanced out of catheter2104(step2706). Such advancement causes device400to partially protrude out of catheter2104and into left atrium LA, which causes the first flared end region to expand to its deployed expanded state in the left atrium LA, as shown inFIG.28C.

Then, under fluoroscopic and/or echocardiographic visualization, apparatus2100may be repositioned such that radiopaque marker2801is aligned with the fossa ovalis (step2707) as illustrated inFIGS.28D and28E. As shown inFIG.28E, when apparatus2100is in the proper position, the neck region of device400will be aligned with the fossa ovalis for accurate deployment of device400within the atrial septum. Thus, device400will be loaded to a specific position within catheter2104of apparatus2100relative to radiopaque marker2122during method2300described above.

If for any reason device400is not in the proper position for deployment within the atrial septum, catheter2104may be advanced over device400while distal tip2110is stationary, thereby collapsing the first flared end region within catheter2104(step2708) as illustrated inFIG.28F. Specifically, knob2124of handle2108may be rotated to cause catheter2104to move translationally relative to engagement apparatus2120and distal tip2110of apparatus2100, to thereby collapse device400within catheter2104. For example, catheter2104may be moved over collapsed device400until catheter2104engages with distal tip2110as shown inFIG.28F. Apparatus2100, with device400disposed therein, may then be retrieved, e.g., over guidewire2801(step2709). Alternatively, apparatus2100may be repositioned relative to the fossa ovalis of the atrial septum prior to returning to step2706and partially advancing the first flared end region out of catheter2104within left atrium LA.

After step2707described above, when device400is properly positioned relative to the atrial septum, engagement apparatus2120may be disengaged from device400, e.g., hook portions2118may be moved from an engaged positioned radially inward to a disengaged position. Then, catheter2104may be retracted proximally relative to distal tip2110, causing the second flared end region of device400to be exposed within right atrium RA beyond the distal end of catheter2104such that the second flared end region transitions from the collapsed delivery state to an expanded state within right atrium RA (step2710) as illustrated inFIG.28G. Specifically, knob2124of handle2108may be rotated in the opposite direction to cause catheter2104to move translationally relative to engagement apparatus2120and distal tip2110of apparatus2100, to thereby expose the second flared end region of device400within right atrium RA. Accordingly, the flared end region of device400will be disposed within left atrium LA, the neck region of device400will be lodged within the puncture through the fossa ovalis, and the second flared end region of device400will be disposed within right atrium RA. In addition, pull-cord2114will be positioned within a central lumen of device400.

As illustrated inFIG.28H, which shows device400from within right atrium RA, distal tip2110is sized and shaped to fit through the central lumen of device400in the full expanded state. When device400is fully expanded within the atrial septum, apparatus2100may be retrieved (step2711) by pulling distal2100proximally, e.g., until catheter2104engages with distal tip2110as shown inFIG.28I. Guidewire2801may then be removed. Blood may then be shunted from left atrium LA to right atrium RA through device400, e.g., when left atrial pressure exceeds right atrial pressure (step2712).

Referring now toFIGS.29A-29D, an exemplary guidewire loading tool constructed in accordance with the principles of the present invention is described. Guidewire loading tool2900is designed for use with loading cartridge614ofFIGS.6D-6I. Specifically, as illustrated inFIGS.29A-29D, guidewire loading tool2900has proximal portion2903and distal portion2901, and two flexible wings, e.g., first flexible wing2902and second flexible wing2904, coupled to and extending radially away from distal portion2901. First flexible wing2902and second flexible wing2904each have lateral end portions having an edge that runs parallel to the longitudinal axis of proximal portion2903and distal portion2901, which permit guidewire loading tool2900to be placed on a flat horizontal surface while a guidewire is loaded therein as described in further detail below.

In addition, guidewire loading tool2900has central lumen2905extending through proximal portion2903and distal portion2901, sized and shaped to receive loading cartridge614therein, e.g., when device400is collapsed in a delivery state within loading cartridge614as described above with reference toFIG.6F. Referring again toFIG.29A, first and second flexible wings2902and2904are designed such that when a force is applied against first and second flexible wings2902and2904toward each other, the diameter of central lumen2905is increased to permit insertion and removal of loading cartridge614therein. Accordingly, first and second flexible wings2902and2904are biased toward an open position whereby central lumen2905has a smaller diameter than when first and second flexible wings2902and2904are pressed toward each other.

Referring now toFIGS.30A-30E, an exemplary method of using guidewire loading tool2900to load a guidewire is provided. As shown inFIG.30A, guidewire loading tool2900is inserted over loading cartridge614having device400collapsed therein. Specifically, first and second flexible wings2902and2904are pressed toward each other to increase the diameter of central lumen2905, and loading cartridge614is positioned within central lumen2905. First and second flexible wings may then be released such that loading cartridge614is securely disposed within central lumen2905of guidewire loading tool2900as illustrated inFIG.30B.

Next, as illustrated inFIG.30C, a guidewire is inserted through a lumen of device400collapsed within loading cartridge614disposed within central lumen2905of guidewire loading tool2900. The guidewire may be fed therethrough and extend beyond a proximal end of loading cartridge614. As shown inFIG.30D, when the guidewire is sufficiently inserted within loading cartridge614and guidewire loading tool2900, first and second flexible wings2902and2904may be pressed toward each other to enlarge central lumen2905. Accordingly, guidewire loading tool2900may be removed from loading cartridge614as shown inFIG.30E.

Exemplary method3100of delivering device400to reduce left atrial pressure in a subject, for example, a human having a heart pathology will now be described with reference toFIG.27. Some of the steps of method3100may be further elaborated by referring toFIGS.32A-32K. Steps3101-3104may be identical to steps2701-2704ofFIG.27, and therefore will not be discussed for brevity. Thus, at step3104, guidewire3201will be positioned across atrial septum AS such that the distal end of guidewire3201is positioned in left atrium LA as shown inFIG.32A.

At step3105, the distal end of sheath3202having cap3204disposed thereon is advanced over guidewire3201to a position within right atrium RA adjacent atrial septum AS, as shown inFIG.32B. Sheath3202includes balloon3206disposed thereon, proximal to the distal end of sheath3202by a predetermined distance as described in further detail below. Accordingly, balloon3206may be coupled to a source of fluid external to the patient via an inflation lumen disposed either within or along the exterior of sheath3202. Cap3204may form a seal with the distal end of sheath3202such that fluid cannot leak into or out of the lumen of sheath3202during delivery of sheath3202to the target location.

At step3106, balloon3206may be inflated via the external fluid source and the inflation lumen until balloon3206reaches a desired inflated size, as shown inFIG.32C. For example, balloon3206may be inflate with any biocompatible fluid, e.g., saline, water, or air. At step3107, when balloon3206is in its inflated state, the distal end of sheath3202, along with cap3204, are advanced through the puncture in the fossa ovalis of atrial septum AS until inflated balloon3206engages the right side of atrial septum AS from within right atrium RA, as shown inFIG.32D. The force feedback provided by atrial septum AS against balloon3206informs the physician that the distal end of sheath3202is in the desired position within left atrium LA for the next phase of implantation of the shunt device. Accordingly, balloon3206will be disposed at a predetermined position along sheath3202from the distal end of sheath3202. Thus, unlike the retention devices described in U.S. Pat. No. 5,312,341 to Turi, inflatable balloon3206of the present invention is inflated in the right atrium of the patient, proximal to the atrial septum to prevent sheath3202from advancing more than a predetermined distance into the left atrium, allowing for safe deployment of device400.

At step3108, cap3204may be decoupled from the distal end of sheath3202, and retracted through the lumen of sheath3202and removed over guidewire3201, as shown inFIG.32E. Referring now toFIG.31B, at step3109, the distal end of the delivery apparatus having device400coupled thereto in a collapsed configured within sheath3202may be advanced through the lumen of sheath3202over guidewire3201such that device400is position within left atrium LA within sheath3202.

Solely for exemplary purposes,FIGS.32F-32Iillustrate delivery apparatus1301ofFIGS.13B-13Das used to delivery device400; however, as will be understood by a person having ordinary skill in the art, any of the delivery apparatuses discussed herein may be used to delivery device400in accordance with the exemplary steps of method3100. Accordingly, at step3110, delivery device1301is advanced through the lumen of sheath3202until device400is partially advanced out of the distal end of sheath3202such that the first flared end region of device400is exposed beyond the distal end of sheath3202and transitions from a collapsed delivery state to an expanded deployed state within left atrium LA, as shown inFIG.32F. While delivery apparatus1301is being advanced through sheath3202, the physician may continuously or periodically apply a slight forward force on sheath3202to ensure that force feedback is being observed by the physician due to atrial septum AS and balloon3206to ensure that the distal end of sheath3202is appropriately positioned during deployment of device400.

At step3111, delivery apparatus1301may be disengaged from the second flared end region of device400while the second flared end region is in a collapsed delivery state within sheath3202as discussed above. For example, the release ring of delivery apparatus1301may be retracted, thereby causing the hook portions to move radially inward to disengage with device400within sheath3202. Once disengaged, delivery apparatus1301may be retracted and/or completely removed from sheath3202, as shown inFIG.32G. At step3112, sheath3202is retracted along with device400partially disposed therein until the first flared end region of device400engages with the left side of atrial septum AS within left atrium LA, the neck of device400is lodged within the puncture of the fossa ovalis. As sheath3202is further retracted, the force of atrial septum AS against the first flared end region of device400causes device400to be fully exposed from the distal end of sheath3202such that the second flared end region transitions from the collapsed delivery state within sheath3202to the expanded deployed state within right atrium RA, as shown inFIG.32H.

At step3113, balloon3206is deflated via the inflation lumen, as shown inFIG.32I. At step3114, sheath3202and delivery apparatus1301may be retrieved as shown inFIG.32J, followed by removal of guidewire3201as shown inFIG.32K. At step3115, as described above, blood may be shunted from left atrium LA to right atrium RA through device400implanted at atrial septum AS, e.g., when left atrial pressure exceeds right atrial pressure.

While various illustrative embodiments of the invention are described above, it will be apparent to one skilled in the art that various changes and modifications may be made herein without departing from the invention. It will further be appreciated that the devices described herein may be implanted in other positions in the heart. For example, device400may be implanted in an orientation so as to shunt blood from the right atrium to the left atrium, thus decreasing right atrial pressure; such a feature may be useful for treating a high right atrial pressure that occurs in pulmonary hypertension. Similarly, device400may be implanted across the ventricular septum, in an orientation suitable to shunt blood from the left ventricle to the right ventricle, or in an orientation suitable to shunt blood from the right ventricle to the left ventricle. The appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the invention.