Patent Description:
Various types and configurations of prosthetic heart valves are used to replace diseased natural human heart valves. The actual shape and configuration of any particularly prosthetic heart valve is dependent to some extent upon the valve being replaced (i.e., mitral valve, tricuspid valve, aortic valve, or pulmonary valve). In general, the prosthetic heart valve designs attempt to replicate the function of the valve being replaced and thus will include valve leaflet-like structures used with either bioprosthesis or mechanical heart valves prosthesis. As used throughout the specification, a "prosthetic heart valve" is intended to encompass bioprosthetic heart valves having leaflets made of a biological material (e.g., harvested porcine valve leaflets, or bovine, equine, ovine or porcine pericardial leaflets, small intestinal submucosa), along with synthetic leaflet materials or other materials.

Stented bioprosthetic heart valves have a frame (or stent) to which the biological valve material is attached. The biological valve members are sutured to the stent that provides support for the valve member in the patient's body. The stent prevents the biological valve members from collapsing and simplifies the insertion of the valve into the annulus of the patient after excision of the diseased valve. The stented bioprosthetic valve imitates the natural action of heart valves and provides a structure that is relatively compatible with the cardiovascular system. Stented prosthetic heart valves are believed to have important clinical advantages over mechanical or non-tissue prosthetic valves.

For many percutaneous delivery and implantation systems, the stent frame of the valved stent is made of a self-expanding material and construction. The stent frame is made of nitinol (a nickel and titanium alloy). With these systems, the valved stent is crimped down to a desired size and held in that compressed arrangement within an outer sheath, for example. Retracting the sheath from the valved stent allows the stent to self-expand to a larger diameter, such as when the valved stent is in a desired position within a patient.

Typically a stented transcatheter valve having a self-expanding frame, such as a nitinol based frame, is cooled prior to loading into the delivery system. The cooling process brings the valve out of the austenitic and into the martensitic phase. While in the martensitic phase, nitinol is more malleable. Often an ice bath based solution of approximately <NUM> is employed in order that the nitinol frame enters the martensitic state and becomes malleable and can be compressed for loading to a delivery system. In some stented transcatheter valves, the tissue used in the valve is in a "dry" state and is processed using glycerine, alcohols, other chemicals, and combinations thereof rather than a "wet" state and processed with excess glutaraldehyde. In valves including "dry" tissue, it is desirable to maintain the tissue in a dry state and avoid processes that use aqueous or liquid solutions. For dry tissue loaded onto a nitinol based frame or other self-expanding frame, it is desirable to cool the frame to a malleable, collapsible, state without exposing the tissue to an aqueous solution.

One aspect of the present disclosure includes a method of compressing a stented prosthetic heart valve. The method including inserting a stented prosthetic heart valve having a self-expandable stent frame into a container. A cooling element is initiated in the container. Heat is transferred through a thermal conductor to cool an interior of the container. A temperature of the self-expandable stent frame is reduced while located within the container to a critical temperature. An outer diameter of the stented prosthetic heart valve is compressed while the stented prosthetic heart valve is at the critical temperature.

Another aspect of the present disclosure includes a method of loading a stented prosthetic heart valve to a transcatheter delivery system. The method includes inserting a stented prosthetic heart valve in an expanded state into a first chamber of a cooling vessel. Cooling is initiated in a second chamber of the cooling vessel. Heat is transferred from the first chamber to the second chamber through a thermally conductive wall to cool an interior of the first chamber. A temperature of the stented prosthetic heart valve is reduced to the critical temperature while located within the first chamber. The stented prosthetic heart valve is removed from the first chamber. The stented prosthetic heart valve is compressed while at the critical temperature. The compressed stented prosthetic heart valve is inserted into a delivery system.

<CIT> relates to a device for collapsing and loading a heart valve into a minimally invasive delivery system. <CIT> relates to protective loading stents. The claimed subject-matter is defined in independent claim <NUM>. Aspects, embodiments and examples of the present disclosure which are not encompassed by the appended claims are not part of the claimed subject-matter and are provided for illustrative purposes.

The methods and devices of the present disclosure are useful in cooling a stented prosthetic heart valve having a self-expandable stent frame without exposing the stented prosthetic heart valve to liquid during cooling. The stented prosthetic heart valve or other device can be in a wet state or a dry state. The stented prosthetic heart valve or other device can desirably be processed and maintained in a dry state in accordance with aspects of the present disclosure. Regardless, in accordance with aspects of the present disclosure, the stented prosthetic heart valve is fluidly separated from the cooling element while positioned within the cooling device, and is thus, indirectly exposed to the cooling element. In other words, the stented prosthetic heart valve is not directly exposed to the cooling element during cooling. In accordance with the present disclosure, heat is removed from the stented prosthetic heart valve disposed in the cooling vessel via the cooling element disposed within the cooling vessel in isolation from the stented prosthetic heart valve.

<FIG> and <FIG> illustrate perspective and cross-sectional views of a cooling device <NUM> useful in cooling a medical device such as a stented prosthetic heart valve in accordance with aspects of the present disclosure. The cooling device <NUM> is suitable to accommodate housing a cooling element and a stented prosthetic heart valve (not shown) separately. The cooling device <NUM> includes a cooling vessel <NUM> having a first chamber <NUM> suitable for containing the stented prosthetic heart valve separate from the second chamber <NUM> suitable for accommodating the cooling element. The first chamber <NUM> is sized and shaped to accommodate a single valve in both expanded and compressed states. A first, or inner, sidewall <NUM> defines a perimeter of the first chamber <NUM>. The first sidewall <NUM> can be formed of a rigid, thermally conductive material such as stainless steel or ceramic, for example. The second chamber <NUM> is defined between the first sidewall <NUM> and a second, exterior, sidewall <NUM>. In some embodiments, the cooling device <NUM> is cylindrical and the second chamber <NUM> has a larger diameter than the first chamber <NUM>. In other words, in some examples, the second chamber <NUM> encircles the first chamber <NUM>. The first sidewall <NUM> separates the first chamber <NUM> from the second chamber <NUM>.

A bottom cap <NUM> extends across both the first and second chambers <NUM>, <NUM> along lower wall edges of the first and second sidewalls <NUM>, <NUM> to seal the chambers <NUM>, <NUM> at a first end <NUM>. The bottom cap <NUM> can be planar, stepped, or other surface shapes. The bottom cap <NUM> is suitable to provide a resting surface for placement of the cooling vessel <NUM> on a table or countertop, for example. The first and second chambers <NUM>, <NUM> are fluidly separated from one another along the first sidewall <NUM> and the bottom cap <NUM>. A second end <NUM>, opposite the first end <NUM>, provides access to the first and second chambers <NUM>, <NUM>.

In one embodiment, the first chamber <NUM> has a diameter that is at least slightly greater than the size of a single stented prosthetic heart valve (not shown) in a fully expanded state. The first chamber <NUM> is sized such that an air gap, or space, can be formed between the expanded heart valve and the first sidewall <NUM> when the heart valve is housed in the first chamber <NUM>. The air gap can allow for a generally even conductance of cooling through the first sidewall <NUM>, from the cooling element housed in the second chamber <NUM>, to the valve in the first chamber <NUM>. The second chamber <NUM> is sized to accommodate a cooling element and surround at least a side perimeter of the first chamber <NUM>.

The cooling device <NUM> can include a top cap <NUM> operably removable from the cooling vessel <NUM>. The top cap <NUM> can be coupled to the second end <NUM> of the cooling vessel <NUM>. The top cap <NUM> is removable, or operable, to provide access to at least the first chamber <NUM>. In some embodiments, the top cap <NUM> can provide access to both the first and second chambers <NUM>, <NUM>. The top cap <NUM> can include a funneling portion <NUM> extending above and away from the first chamber <NUM>. In one embodiment, the funneling portion <NUM> is centrally positioned on the top cap <NUM>. The funneling portion <NUM> is centrally aligned with the first chamber <NUM> when the top cap <NUM> is coupled to the cooling vessel <NUM>. An interior <NUM> of the funneling portion <NUM> is fluidly open to the first chamber <NUM>. The funneling portion <NUM> can be a truncated conical shape, for example, with a base <NUM> and a delivery port <NUM> opposite the base <NUM>. The funneling portion <NUM> tapers inwardly from the base <NUM> to the delivery port <NUM>. The base <NUM> has a diameter that is greater than a diameter of the delivery port <NUM>. A diameter of the base <NUM> of the funneling portion <NUM> is approximately equal to the diameter of the first chamber <NUM>. In one embodiment, the diameter of the base <NUM> of the funneling portion <NUM> is slightly smaller than the diameter of first sidewall <NUM>. A rim <NUM> radially extends outward from the base of the funneling portion <NUM>. A lower surface <NUM> of the rim <NUM> provides a coupling surface with the second end <NUM> of the cooling vessel <NUM>. The funneling portion <NUM> can provide compression of the stented prosthetic heart valve during extraction of the cooled malleable valve from the first channel <NUM>, passing through the funneling portion <NUM> and exiting through the delivery port <NUM> of the cooling device <NUM>.

In some embodiments, the top cap <NUM> can be mated and aligned to the cooling vessel <NUM> when coupled. For example, the top cap <NUM> can include alignment slots <NUM> that can be matingly engaged with alignment tabs <NUM> of the cooling vessel <NUM>. In some embodiments, the top cap <NUM> releasably, lockingly engages with the cooling vessel <NUM>. A collar <NUM> can be included at the delivery port <NUM> of the funneling portion <NUM>. The collar <NUM> is a circular segment of a diameter smaller than the base <NUM> diameter. In some embodiment, a lid or plug (not shown) may be included at the delivery port <NUM> to temporarily seal the interior of the funneling portion <NUM> and the first chamber <NUM> from ambient air and retain the cooled air in the first chamber <NUM> when the cooling element is initiated. A height of the top cap <NUM> can be substantially equivalent to a height of the cooling vessel <NUM>, with both the top cap <NUM> and the cooling vessel <NUM> being at least slightly greater than a height of the stented prosthetic heart valve. The top cap <NUM> minimizes heat entering the first chamber <NUM> from the ambient air and cooling escaping from the first and second chambers <NUM>, <NUM> into the ambient air during cooling.

With further reference to the cross-section of the cooling device <NUM> illustrated in <FIG>, an interior surface of the first sidewall <NUM> and bottom cap <NUM> within the first chamber <NUM> can include projections <NUM>. The projections <NUM> are formed of a non-conductive material such as polymer, for example, or other non-conductive material. The projections <NUM> can assist in maintaining a valve a desired distance from the thermally conductive first sidewall <NUM>. The projections <NUM> can assist in maintaining a valve centered within the first chamber <NUM>. In <FIG>, a single ring-shaped projection <NUM> is illustrated as an example. The projections <NUM> can be ring-shaped, rounded bumps, or any other suitable shape.

The cooling device <NUM> is portable and can be handheld. The cooling device <NUM> is easily transportable into a surgical theater, for example, and is sterilizable. In one embodiment, the stented prosthetic heart valve is loaded into the cooling device <NUM>, cooled, and compressed for loading onto a delivery system during the manufacturing process. In one embodiment, the stented prosthetic heart valve is inserted into the first chamber <NUM> of the cooling device <NUM> for cooling. One of the cooling systems described below is initiated causing the self-expandable frame of the stented prosthetic heart valve to cool to a critical malleable temperature. The critical temperature can vary based on the valve design and heat treatment process; however, a typical value can be <NUM>-<NUM>° C. In one embodiment, the critical temperature is less than or equal to <NUM>° C (Celsius). The stented prosthetic heart valve remains fluidly separated from the cooling element during the entirety of cooling. The cooling devices in accordance with the present disclosure can be employed to remove heat from the first chamber <NUM> and the stented prosthetic heart valve removably contained within the first chamber <NUM>. The first sidewall <NUM> is a thermal conductor. Heat is transferred from the first chamber <NUM> through the thermally conductive first sidewall <NUM> to cool the first chamber via the cooling element in the second chamber <NUM>. The self-expandable stent frame of the stented prosthetic heart valve can be comprised of nitinol, for example. Nitinol is malleable at cool temperatures. The temperature of the self-expanding stent frame can be reduced to the critical temperature and the outer diameter of the stented prosthetic heart valve can be compressed while at the critical temperature. The stented prosthetic heart valve is extracted through the delivery port <NUM>, and can be compressed during extraction through the funneling portion <NUM>, for loading onto the delivery system. The stented prosthetic heart valve can then be packaged on the delivery system for use in the surgical theater. The stented prosthetic heart valve is fluidly separated from and indirectly exposed to the cooling element as described further below.

<FIG> is a cross-sectional illustration of a cooling device <NUM> including a cooling element <NUM> in accordance with principles of the present disclosure. Similar to the cooling device <NUM> of <FIG> and described above, the cooling device <NUM> includes the first chamber <NUM> suitable for removably containing the stented prosthetic heart valve and the second chamber <NUM> suitable for accommodating the cooling element <NUM>. The first chamber <NUM> is sized and shaped to accommodate the valve in expanded and compressed states. The first sidewall <NUM> defines a perimeter of the first chamber <NUM> and is formed of a rigid, thermally conductive material. The second chamber <NUM> is defined between the first sidewall <NUM> and a second sidewall <NUM>. In one embodiment, the cooling element <NUM> housed in the second chamber <NUM> is divided into two portions 14a, 14b with a thin barrier <NUM> fluidly separating the two portions 14a, 14b. The barrier <NUM> can be positioned and extend between the first sidewall <NUM> and the second sidewall <NUM>. The barrier <NUM> can be positioned in any suitable manner to fluidly separate the two portions 14a, 14b within the second chamber <NUM>. In one embodiment, the second sidewall <NUM> is flexible and can be manipulated with applied pressure. The barrier <NUM> can be pierced, broken, or otherwise ruptured by an application of pressure. For example, rupture or failure of the barrier <NUM> can be caused by squeezing of the second sidewall <NUM> and the barrier <NUM> inward as indicated by arrows "A" toward the first sidewall <NUM> until failure of the barrier <NUM> occurs. In one embodiment, water contained in the first portion 14a of the second chamber <NUM> is initially separated from chemicals (e.g., ammonium nitrate) contained in a second portion 14b. Upon failure of the barrier <NUM>, an endothermic reaction occurs in response to a reaction of the chemicals from the second portion 14b contacting and mixing with water in the first portion 14a.

<FIG> is a cross-sectional illustration of a cooling device <NUM> including a cooling element <NUM> in accordance with principles of the present disclosure. The cooling device <NUM> includes a first chamber <NUM> suitable for removably containing the stented prosthetic heart valve and a second chamber <NUM> suitable for accommodating the cooling element <NUM>. The first chamber <NUM> is sized and shaped to accommodate the valve in expanded and compressed states. The first sidewall <NUM> defines a perimeter of the first chamber <NUM> and is formed of a rigid, thermally conductive material. The second chamber <NUM> is defined between the first sidewall <NUM> and a second sidewall <NUM>. In one embodiment, the second sidewall <NUM> is a rigid wall. An inlet port <NUM> is included providing at the second wall <NUM>. The inlet port <NUM> can include a luer coupling or other appropriate coupling means suitable to connect for delivery of cooling fluid into an interior of the second chamber <NUM>. The interior of the second chamber <NUM> can include coils <NUM> for circulating the coolant, or refrigerant such as Freon, for example, within the second chamber <NUM>. In one embodiment, the coils <NUM> wrap around and contact the outer surface of the first sidewall <NUM>. Heat is transferred from the first chamber <NUM> and the valve housed within the first chamber <NUM> upon initiating cooling of the cooling element <NUM>.

A cooling device <NUM> illustrated in <FIG> is similar to the cooling devices <NUM>, <NUM> described above. The cooling device <NUM> includes a first chamber <NUM> suitable for removably containing the stented prosthetic heart valve and a second chamber <NUM> suitable for accommodating a cooling element <NUM>. Cooling element <NUM> is a thermoelectric cooler (TEC). The first chamber <NUM> is sized and shaped to accommodate the valve in expanded and compressed states. A first sidewall <NUM> defines a perimeter of the first chamber <NUM>. The first sidewall <NUM> can be formed of a rigid, thermally conductive material, for example, stainless steel or ceramic. The second chamber <NUM> is defined between the first sidewall <NUM> and a second sidewall <NUM>. The second sidewall <NUM> is a rigid wall. A power source is coupled to the cooling device at a connection <NUM> positioned at the second wall <NUM> to power, or apply a voltage across, the TEC <NUM> to apply cooling to the first chamber <NUM> and valve housed therein. The TEC transfers heat from the first chamber <NUM>, on the interior side of the TEC, to the exterior side of the TEC and second chamber <NUM> housing the TEC.

<FIG> is a flow chart of a method of compressing a stented prosthetic heart valve. The method includes a step <NUM> of inserting a stented prosthetic heart valve having a self-expandable stent frame into a cooling vessel. At step <NUM>, a cooling element is initiated. At step <NUM>, heat is transferred through a thermally conductive wall to cool an interior of the container. At step <NUM>, the temperature of the self-expandable stent frame is reduced while located within the container to a critical temperature of not greater than <NUM>° C. At step <NUM>, an outer diameter of the stented prosthetic heart valve is compressed while the stented prosthetic heart valve is at the critical temperature.

<FIG> is a flow chart of a method of loading a stented prosthetic heart valve to a transcatheter delivery system. The method includes a step <NUM> of inserting a stented prosthetic heart valve in an expanded state into a first chamber of a cooling vessel. The top cap <NUM> of the cooling device can be coupled to the cooling vessel after inserting the stented prosthetic heart vessel, isolating the valve from directly contacting a cooling element. At step <NUM>, cooling is then initiated in a second chamber of the cooling vessel. In one embodiment, cooling is initiated by manually compressing the exterior of the cooling vessel to cause mixing of reagents for an endothermic reaction. In another embodiment, cooling is initiated with thermoelectric cooling. In another embodiment, cooling is initiated with circulating coolant in the second chamber of the cooling vessel. The circulating coolant, or other cooling element, is fluidly separated from the stented prosthetic heart valve within the cooling vessel during cooling. Regardless, of the manner of cooling, the valve is maintained in a dry state. At step <NUM>, heat is transferred from the first chamber to the second chamber through a thermally conductive wall to cool an interior of the first chamber. At step <NUM>, a temperature of the stented prosthetic heart valve is reduced while located within the first chamber to a critical temperature of not greater than <NUM>° C. The step of reducing the temperature of the stented prosthetic heart valve includes the first chamber being free of liquid. At step <NUM>, the stented prosthetic heart valve is removed from the first chamber. At step <NUM>, the stented prosthetic heart valve is compressed while at the critical temperature. At step <NUM>, the compressed stented prosthetic heart valve is inserted into, or mounted onto, a delivery system. Notably, steps <NUM>-<NUM> can be completed while maintaining the stented prosthetic heart valve in a dry state.

Claim 1:
A method of loading a stented prosthetic heart valve to a transcatheter delivery system, comprising:
inserting a stented prosthetic heart valve in an expanded state into a first chamber (<NUM>) of a cooling vessel (<NUM>);
initiating cooling in a second chamber (<NUM>) of the cooling vessel (<NUM>);
transferring heat from the first chamber (<NUM>) to the second chamber (<NUM>) through a thermally conductive wall (<NUM>) to cool an interior of the first chamber (<NUM>);
reducing a temperature of the stented prosthetic heart valve while located within the first chamber (<NUM>) to a critical temperature of not greater than <NUM>° C;
removing the stented prosthetic heart valve from the first chamber (<NUM>);
compressing the stented prosthetic heart valve while at the critical temperature; and
inserting the compressed stented prosthetic heart valve into a delivery system.