Abstract: This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) having core structure (I), pharmaceutical compositions containing at least one such modulator, methods of treatment of CFTR mediated diseases, including cystic fibrosis, using such modulators and pharmaceutical compositions, combination pharmaceutical compositions and combination therapies employing those modulators, and processes and intermediates for making such modulators.

Abstract: An implant includes a frame, and a textile mounted on the frame. The textile includes fibers formed from a mixture of a polymer and an additive molecule. The additive molecule includes a polyurethane backbone and one or more fluorinated end-groups at at least one end of the backbone. Other embodiments are also described.

Abstract: A prosthetic spacer assembly includes a spacer body, a first anchor, and a second anchor. The first anchor and the second anchor are each connected to the spacer body. The first anchor is configured to capture a first native valve leaflet between the first anchor and the spacer body. The second anchor is configured to capture a second native valve leaflet between the second anchor and the spacer body. When inside a delivery sheath, the first anchor and the second anchor can extend distally from the spacer body.

Abstract: In one example, an implantable prosthetic device comprises a spacer body portion configured to be disposed between native leaflets of a heart, and an anchor portion configured to secure the native leaflets against the spacer body portion. The prosthetic device can be movable between multiple configurations. A size of the spacer body is configured to be adjusted after the spacer body is placed between the native valve leaflets and the pair of anchors are placed against the ventricular surfaces of the native heart valve leaflets. A delivery apparatus can have a first shaft and a second shaft, wherein movement of the first shaft relative to the second shaft moves the anchor portion relative to the spacer body.

Abstract: In one representative embodiment, an implantable prosthetic device comprises a spacer body portion configured to be disposed between native leaflets of a heart, and an anchor portion configured to secure the native leaflets against the spacer body portion. The prosthetic device can be movable between multiple configurations. The spacer body can be made from braided, self-expandable metallic thread. A delivery apparatus can have a first shaft and a second shaft, wherein movement of the first shaft relative to the second shaft moves the anchor portion relative to the spacer body.

Abstract: A prosthetic heart valve assembly includes a self-expandable stent having a flared upper portion, a lower portion, and an intermediate portion extending from the upper portion to the lower portion. The stent includes upwardly bent hooks extending from an outer surface of the stent, which are adapted to engage native leaflet tissue. The stent further includes an elongate anchoring member extending from the lower portion of the stent, which is adapted to be secured to a ventricle wall via a prong portion. When deployed within the native heart valve, the flared upper portion contacts a supra-annular surface of the native heart valve for preventing downward migration of the prosthetic heart valve assembly toward the ventricle and the upwardly bent hooks and the elongate anchoring member prevent upward migration of the prosthetic heart valve assembly toward an atrium.

Abstract: A system for replacing a native valve of the heart includes a delivery apparatus having a sheath and a prosthetic valve. The prosthetic valve includes a frame having an annular main body, a plurality of ventricular anchors attached to the main body, an atrial anchor attached to an atrial end portion of the main body, and a valve structure disposed within the main body of the frame. The prosthetic valve is disposed within a distal end portion of the sheath in a compressed, delivery state. When the prosthetic valve is deployed from the sheath, the main body of the frame radially expands to a radially expanded state, the ventricular anchors expand to a deployed state alongside the main body of the frame for capturing native leaflets of the native valve, and the atrial anchor expands to a deployed state extending radially outwardly from the main body.

Abstract: A prosthetic spacer assembly includes a spacer, a first anchor, and a second anchor. The first anchor and the second anchor are each connected to the spacer. The first anchor curves around the spacer when viewed from an upstream end. The second anchor curves around the spacer when viewed from the upstream end.

Abstract: A prosthetic heart valve assembly includes a self-expandable stent having an inlet end and an outlet end and a passageway extending therethrough. The stent includes a plurality of rows of prongs on the outer surface of the stent. A valve portion comprising a plurality of leaflets is positioned within the passageway for permitting blood to flow through the passageway from the inlet end to the outlet end while blocking flow in the opposite direction. The stent further includes a flared upper portion shaped for placement along a supra-annular surface of an annulus for preventing downward migration of the prosthetic valve assembly into a ventricle. Each of the prongs has a tip pointing toward the inlet end for penetrating surrounding tissue and preventing upward migration of the prosthetic heart valve assembly toward an atrium.

Abstract: A prosthetic heart valve for implantation at a native heart valve includes a multi-part frame. The multi-part frame includes a cylindrical main body and a ventricular anchor component surrounding the main body. The main body includes a plurality of struts arranged in a lattice pattern. The ventricular anchor component is attached to the main body only at an outflow end of the main body and extends toward an inflow end of the main body. The prosthetic valve further includes a valve structure having three leaflets made from pericardium. The multi-part frame is radially compressible for delivery within a sheath of a delivery catheter and is self-expandable for deployment within an annulus of the native valve. The main body and the ventricular anchor component are formed separately and are attached by a locking mechanism for reducing strain between the main body and the ventricular anchor component.

Abstract: A prosthetic spacer assembly includes a spacer body, a first anchor, and a second anchor. The first anchor and the second anchor are each connected to the spacer body. The first anchor is configured to capture a first native valve leaflet between the first anchor and the spacer body. The second anchor is configured to capture a second native valve leaflet between the second anchor and the spacer body.

Abstract: An implant includes an interface and a wing that is coupled to the interface. A catheter is transluminally advanceable to a heart chamber upstream of a heart valve of a subject and houses the implant. A delivery tool comprises a shaft and a driver. Via engagement with the interface, the shaft is configured to (i) deploy the implant out of the catheter such that, within the chamber, the wing extends away from the interface; and (ii) position the implant in a position in which the interface is at a site in the heart and the wing extends over a first leaflet of the valve toward an opposing leaflet of the valve. The driver is configured to secure the implant in the position by driving an anchor through the interface and into tissue at the site. Other embodiments are also described.

Abstract: An anchor for a prosthetic heart valve includes a core, a first cover layer, and a second cover layer. The core includes a plurality of helical turns. One or more outflow turns of the plurality of helical turns has a diameter configured to be disposed on an outflow side of a native valve, and one or more inflow turns of the plurality of helical turns has a diameter configured to be disposed on an inflow side of a native valve. The first cover layer is disposed over and contacts the helical core, and the first cover layer includes a first material. The second cover layer is disposed over and contacts the first cover layer, and the second cover layer includes a second material, which is different than the first material.

Abstract: A heart valve prosthesis that can be quickly and easily implanted during a surgical procedure is provided. The prosthetic valve has a base stent that is deployed at a treatment site, and a valve component configured to quickly connect to the base stent. The base stent may take the form of a self- or balloon-expandable stent that expands outward against the native valve with or without leaflet excision. The valve component has a non-expandable prosthetic valve and a self- or balloon-expandable coupling stent for attachment to the base stent, thereby fixing the position of the valve component relative to the base stent. The prosthetic valve may be a commercially available to valve with a sewing ring and the coupling stent attaches to the sewing ring. The system is particularly suited for rapid deployment of heart valves in a conventional open-heart surgical environment. A catheter-based system and method for deployment is provided.

Abstract: A prosthetic apparatus for implantation in a native heart valve includes a main body for placement within the native annulus. The main body is compressible to a radially compressed state for delivery into the heart and is self-expandable from the compressed state to a radially expanded state for implantation. A valve structure is mounted within a lumen of the main body and preferably forms three leaflets made of pericardium. Ventricular anchors are coupled to a ventricular end portion of the main body. The ventricular anchors are adapted to be straightened for delivery to the native heart valve and are biased to spring back to a pre-formed bent shape for capturing the native heart valve leaflets between the main body and the ventricular anchors. An atrial sealing member may be provided along an atrial portion of the main body for impeding the flow of blood between the main body and the native annulus.

Abstract: A coiled anchor is positioned at a mitral valve by extending and deflecting a catheter such that a distal end portion of the catheter has a curved shape that is disposed in a left atrium and a distal end of the catheter is positioned near a commissure of the mitral valve. A ventricular portion of the coiled anchor is advanced from the catheter under the mitral valve at the commissure and into a left ventricle. An atrial portion of the coiled anchor is deployed in the left atrium by retracting the catheter off the atrial portion of the coiled anchor while maintaining the position of the ventricular portion of the coiled anchor in the left ventricle.

Abstract: A heart valve prosthesis that can be quickly and easily implanted during a surgical procedure is provided. The prosthetic valve has a base stent that is deployed at a treatment site, and a valve component configured to quickly connect to the base stent. The base stent may take the form of a self- or balloon-expandable stent that expands outward against the native valve with or without leaflet excision. The valve component has a non-expandable prosthetic valve and a self- or balloon-expandable coupling stent for attachment to the base stent, thereby fixing the position of the valve component relative to the base stent. The prosthetic valve may be a commercially available to valve with a sewing ring and the coupling stent attaches to the sewing ring. The system is particularly suited for rapid deployment of heart valves in a conventional open-heart surgical environment. A catheter-based system and method for deployment is provided.

Abstract: Apparatuses and methods for loading and deploying implants from delivery apparatuses. The apparatuses in certain embodiments may comprise crimping devices for compressing an implant for insertion into a portion of a delivery apparatus. The apparatuses in certain embodiments may comprise features of delivery apparatuses allowing for improved loading and deployment of an implant from the delivery apparatuses.

Abstract: Methods for replacing a native heart valve. An anchor comprises coils adapted to support a heart valve prosthesis. The anchor is positioned at a native heart valve. An expansible heart valve prosthesis is delivered into the anchor and expanded inside the coils. This moves at least one coil from a first diameter to a second, larger diameter while securing the anchor and the heart valve prosthesis relative to each other. The heart valve prosthesis comprises a seal on the expansible heart valve prosthesis. Additional apparatus and methods are disclosed.

Abstract: Methods and systems for replacing a native heart valve are disclosed. A system comprises a delivery catheter having a deflectable distal tip configured to bend in one or more directions relative to a native annulus of a native heart valve when the distal tip is positioned within an atrium of a heart and a helical anchor configured to be carried within the delivery catheter in a delivery configuration and to be axially movable relative to the deflectable distal tip. The helical anchor has a coiled configuration comprising a plurality of turns after being delivered from the deflectable distal tip into the heart, where the coiled configuration is configured to support a heart valve prosthesis.