Patent Publication Number: US-2016220357-A1

Title: Novel concept to reduce left atrial pressure in systolic and diastolic hf patients to treat pulmonary edema and reduce hospitalization rates

Description:
CLAIM OF PRIORITY 
     This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/111,970, filed on Feb. 4, 2015, the entire contents of which are hereby incorporated by reference. 
    
    
     BACKGROUND 
     Heart failure is a growing epidemic worldwide. In the United States, the incidence of heart failure has remained stable over the past several decades, with more than 650,000 new heart failure cases diagnosed annually. Heart failure incidence increases with age, rising from approximately 20 per 1,000 individuals aged 65 to 69 years to more than 80 per 1,000 individuals aged at least 85 years. Approximately 5,100,000 persons in the United States have clinically manifested heart failure, and the prevalence continues to rise. Patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) have a poor prognosis; each of these broad types of heart failure account for about half of heart failure patients in the United States. 
     Shortness of breath, or dyspnea, is the symptom hallmark of heart failure due to either HFrEF or HFpEF. Dyspnea is due to pulmonary congestion, which is a consequence of elevated left atrial pressure. A subset of patients with pulmonary congestion will have pulmonary edema. Pulmonary edema is the condition where lung fluid accumulates in the air spaces and parenchyma of the lungs causing impaired ventilation, decreased gas exchange and an increased respiratory drive. The traditional treatment of pulmonary edema due to heart failure requires hospitalization and administration of intravenous diuretic therapy. 
     SUMMARY 
     Devices, methods, and systems provided herein can reduce the left atrial pressure. In some cases, a reduction of left atrial pressure can prevent patients from going into pulmonary edema and therefore potentially improve patient outcomes, patient comfort, and reduce or eliminate hospital stays. 
     In some aspects, devices provided herein can include implantable transseptal flow control components. Implantable transseptal flow control components provided herein can be adapted to be implanted in an opening in a septal wall between a left atrium and a right atrium. In a closed configuration, the implantable transseptal flow control components provided herein prevent blood from flowing through the opening. In an open configuration, the implantable transseptal flow control components provided herein allows blood to flow from the left atrium to the right atrium. Implantable transseptal flow control components provided herein can remain in a closed configuration when a pressure differential between the left atrium and the right atrium is less than a first non-zero predetermined threshold pressure value. Implantable transseptal flow control components provided herein can transition into an open configuration when the pressure differential exceeds the first non-zero predetermined threshold pressure value. When in a closed configuration, implantable transseptal flow control components provided herein can be configured such that blood does not stagnate at a location proximate to a left atrium flow control component side when the pressure differential is below a second predetermined threshold pressure value. In some cases, implantable transseptal flow control components provided herein provide zero dead space when in a closed configuration below a second predetermined threshold pressure value. In some cases, implantable transseptal flow control components provided herein can be configured such that blood does not stagnate at a location proximate to either the left or right atrium flow control component sides when the pressure differential is below the second predetermined threshold pressure value. As defined herein, a pressure differential between the left atrium and the right atrium is the pressure of the left atrium in excess of the pressure of the right atrium, thus the pressure differential can be both positive (i.e, the left atrium pressure greater than the right atrium pressure) and negative (i.e., the right atrium pressure greater than the left atrium pressure. In some cases, implantable transseptal flow control components provided here will remain in a closed configuration when the pressure differential is negative. 
     Stagnating blood within chambers of the heart can result in thrombosis and/or blood clots around a flow control component. Normally, a flow control component is adapted to open repeatedly with each heartbeat, thus blood found in dead spaces in the flow control components&#39; closed configurations is repeatedly flushed away. Implantable transseptal flow control components provided herein, however, are adapted to only open upon a pressure differential between the left atrium and the right atrium exceeding a predetermined threshold value, thus implantable transseptal flow control components provided herein may not open for hours, days, weeks, or even months at a time. Accordingly, implantable transseptal flow control components provided here allow for the reduction of or limiting of a pressure difference between the left and right atrium that also mitigates issues associated with stagnating blood. 
     In some aspects, an implantable transseptal flow control component provided herein is adapted to be implanted in an opening in a septal wall between a left atrium and a right atrium and adapted to prevent blood from flowing through the opening when in a closed configuration. The flow control component can be adapted to remain in a closed configuration when a pressure differential between the left atrium and the right atrium is less than a first non-zero predetermined threshold pressure value and transition into an open configuration when the pressure differential exceeds the first non-zero predetermined threshold pressure value. The flow control component can be configured such that blood does not stagnate at a location proximate to a left atrium flow control component side when the pressure differential is below a second predetermined threshold pressure value. In some cases, the flow control component can be configured such that a periodic opening of the flow control component during each cardiac cycle is less than 100 ml/minute to prevent stagnation. The implantable flow control component provided herein can include at least a first member. In some cases, the second predetermined threshold pressure value is less than or equal to the first non-zero predetermined threshold pressure value. In some cases, the first predetermined threshold pressure value is between 10 mmHg and 15 mmHg. 
     In some cases, the open configuration defines a passage through the flow control component that increases with an increasing pressure differential after the pressure differential exceeds the first non-zero predetermined threshold pressure value. In some cases, the size of the opening can increase in diameter in a step-like function relative to the pressure differential. In some cases, the size of the opening can increase in diameter exponentially over a desired pressure range. In some cases, the opening can increase in diameter linearly over a desired pressure range. 
     In some cases, the first member is compliant. In some cases, the first member can be adapted to flex in response to pressure differential. In some cases, the first member defines a collapsed passage there through when the pressure differential is less than the second predetermined threshold pressure value. 
     In some cases, the flow control component can include a second member. In some cases, the second member configured to form a shape-stable support structure when the flow control component is implanted. The term “shape-stable” as used herein means that it is less compliant than the first member. In some cases, the shape-stable second member can be adapted to expand from a retracted configuration to an expanded configuration that is less compliant than the first member. In some cases, the shape-stable member can include compliant materials that interlock when in an expanded configuration to be less compliant than the first member. In some cases, the shape-stable member comprises inelastic materials. 
     In some cases, the second member defines passage there through and the first member overlies and seals the passage when the pressure differential is below the second predetermined threshold pressure value. In some cases, the first member has a semi-circular shape. In some cases, the first member defines at least one passage there through. In some cases, the first and second members are both disk shaped and connected along a periphery of the disks or at a central location of each disk. In some cases, the first member comprises a shape memory metal. In some cases, the first member forms at least one lobe structure. 
     In some cases, the flow control component comprises a spring, a magnet, or a combination thereof. 
     In some cases, the flow control component can include a controller adapted to detect the pressure differential and control the opening and closing of the flow control component based on the detected pressure differential. 
     In some aspects, an implantable transseptal flow control component provided herein can include a shape-stable member and a compliant member. The flow control component can be adapted to be implanted in an opening in a septal wall between a left atrium and a right atrium. The shape-stable member and the compliant member can define a passage there through. The shape-stable member and the compliant member can be attached at at least one location and overlying each other to seal off any passages through the flow control component when the flow control component is in a closed configuration to prevent blood from flowing through the opening. The flow control component can be adapted to remain in a closed configuration when a pressure differential between the left atrium and the right atrium is less than a first non-zero predetermined threshold pressure value and transition into an open configuration when the pressure differential exceeds the first non-zero predetermined threshold pressure value. In some cases, the shape-stable member can be adapted to be collapsed for insertion and expanded for placement within the opening, the shape-stable member being compliant in the expanded configuration. In some cases, the shape-stable member and the compliant member are each disk shaped and attached and sealed together at a central location or along a periphery of at least one disk. In some cases, the compliant member can include a shape memory wire therein. 
     In some aspects, an implantable transseptal flow control component provided herein can include compliant member defining a collapsed passage there through. The compliant member can be adapted to be implanted in an opening in a septal wall between a left atrium and a right atrium. The collapsed passage can be adapted to remain in a closed configuration when a pressure differential between the left atrium and the right atrium is less than a first non-zero predetermined threshold pressure value and transition into an open configuration when the pressure differential exceeds the first non-zero predetermined threshold pressure value. 
     The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. 
    
    
     
       DESCRIPTION OF DRAWINGS 
         FIGS. 1A-1D  depict views of a heart showing the placement of a first embodiment of an implantable transseptal flow control component provided herein.  FIGS. 1A and 1B  depict the placement of the implantable transseptal flow control component from the right atrium.  FIGS. 1C and 1D  depict the placement of the implantable transseptal flow control component from the left atrium. 
         FIGS. 2A-2F  depict how the first embodiment shown in  FIGS. 1A-1D  can alternate between stages of open and closed configurations when implanted. 
         FIGS. 3A-3G  depict how an implantable transseptal flow control component according to a second embodiment can alternate between stages of open and closed configurations when implanted. 
         FIGS. 4A and 4B  depict an implantable transseptal flow control component according to a third embodiment. 
         FIGS. 5A and 5B  depict an implantable transseptal flow control component according to a fourth embodiment. 
         FIGS. 6A and 6B  depict an implantable transseptal flow control component according to a fifth embodiment. 
         FIGS. 7A-7F  depict an implantable transseptal flow control component according to a sixth embodiment.  FIGS. 7A-7C  depict the component in a closed configuration.  FIGS. 7D-7F  depict the component in an open configuration. 
         FIGS. 8A-8C  depict an implantable transseptal flow control component according to a seventh embodiment. 
         FIGS. 9A-9E  depict an implantable transseptal flow control component according to an eighth embodiment.  FIGS. 9A-9D  depict the flow control component in a closed configuration.  FIG. 9E  depicts the flow control component in an open configuration. 
         FIG. 10  depict an implantable transseptal flow control component according to a ninth embodiment. 
         FIGS. 11A-11I  depict an implantable transseptal flow control component according to a tenth embodiment. 
         FIGS. 12A and 12B  depict an implantable transseptal flow control component according to an eleventh embodiment. 
         FIGS. 13A-13D  depict an implantable transseptal flow control component according to a twelfth embodiment. 
         FIG. 14  depict an implantable transseptal flow control component according to a thirteenth embodiment. 
         FIG. 15  depict an implantable transseptal flow control component according to a fourteenth embodiment. 
         FIG. 16  depict an implantable transseptal flow control component according to a fifteenth embodiment. 
         FIG. 17  depicts possible iris configurations of an implantable transseptal flow control component. 
         FIGS. 18A-18C  depict a support frame for a collapsible compliant member, which can be used with implantable transseptal flow control components provided herein. 
         FIGS. 19A-19C  depicts an example of a delivery catheter, which can be used with implantable transseptal flow control components provided herein.  FIGS. 19B and 19C  depict how the flow control component provided herein can be loaded into a delivery catheter. 
     
    
    
     Like reference symbols in the various drawings indicate like elements. 
     DETAILED DESCRIPTION 
     Implantable transseptal flow control components provided herein are designed to be placed in an opening in the septum between the left atrium and the right atrium, to open once a non-zero predetermined pressure difference between the left atrium and the right atrium is reached, and to include a structure within the left atrium such that blood does not stagnate around the flow control component in at least the left atrium. Method provided herein include methods of making implantable transseptal flow control components and methods of implanting implantable transseptal flow control components in an opening in the septum between the left atrium and the right atrium. Systems provided herein can include an implantable transseptal flow control component and a delivery catheter. 
     Although a variety of different embodiments of implantable transseptal flow control components are provided herein, each can limit the stagnation of blood in and around the flow control component, particularly in the left atrium. In some cases, flow control components provided herein provide zero dead space when in a closed configuration below a second predetermined threshold pressure value. In some cases, implantable transseptal flow control components provided herein can be configured such that blood does not stagnate at a location proximate to either the left or right atrium flow control component sides when the pressure differential is below the second predetermined threshold pressure value. Stagnating blood within chambers of the heart can result in thrombosis and/or blood clots around a flow control component. Normally, a flow control component is adapted to open repeatedly with each heartbeat, thus blood found in dead spaces in the flow control components&#39; closed configurations is repeatedly flushed away. Implantable transseptal flow control components provided herein, however, are adapted to only open upon a pressure differential between the left atrium and the right atrium exceeding a predetermined threshold value, thus implantable transseptal flow control components provided herein may not open for hours, days, weeks, or even months at a time. Accordingly, implantable transseptal flow control components provided here allow for the easing of a pressure difference between the left and right atrium without disallowing for any pressure differential and limiting issues associated with stagnating blood. In some cases, implantable transseptal flow control components provided herein can be adapted to fluctuate between a closed configuration and a partially open configuration for normal healthy pressure conditions within the left and right atriums. 
       FIGS. 1A-1D  depict views of a heart  100  showing the placement of a particular embodiment of an implantable transseptal flow control component  201  provided herein. As shown in  FIGS. 1A and 1B , implantable transseptal flow control component  201  has a duckbill (also described as a bill) that extends into the right atrium (RA). As shown in  FIGS. 1C and 1D , implantable transseptal flow control component  201  can be approximately flush with the septum in the left atrium (LA) to limit the stagnation of blood around flow control component  201  in the left atrium. In some cases, flow control component  201  can be inserted into an opening formed at the location of the Fossa Ovalis. In some cases, methods provided herein can include cutting an opening in the septum between the left atrium and the right atrium. In some cases, the hole can be cut by a delivery catheter. In some cases, systems provided herein can include a delivery device adapted to first cut an opening in the septum and then deliver a flow control component (e.g., flow control component  201 ) into the opening. In some cases, a delivery device provided herein is adapted to be positioned in the left atrium or the right atrium transvascularly. Although  FIGS. 1A-1D  depict the placement of flow control component  201 , which is shown in greater detail in  FIGS. 2A-2E  and discussed below in greater detail below, other embodiments of implantable transseptal flow control components provided herein, such as those shown in  FIGS. 3A-16 , can be placed in an opening in the same location. 
     Flow control components, such as flow control component  201  of  FIGS. 1A-1D , can include a circular cross-sectional body portion suitably shaped for insertion into the opening formed at the Fossa Ovalis. In some cases, the circular cross-sectional body portion has a diameter of about 0.5 inches (about 12 millimeters (mm)). In some cases, the diameter of the circular cross-sectional body portion is between 0.4 inches and 0.6 inches (between 10 mm and 15 mm). Other embodiments of the flow control component discussed herein can have the same or substantially the same diameter. 
       FIGS. 2A-2E  better depict the embodiment shown in  FIGS. 1A-1D  and shows how it can alternate between stages of open and closed configurations when implanted. Each of  FIGS. 2A-2E  depicts a frontal view (e.g., from the right atrium) and a cross-sectional view.  FIG. 2F  depicts how the stages of  FIGS. 2A-2E  correspond to heart chamber pressures. 
     As shown in  FIGS. 2A-2E , the structure of flow control component  201  can be contoured to close with increasing RA pressure. In some cases, such as that shown, flow control component  201  includes a bill adapted to extend into a right atrium (RA) space. Flow control component  201  can include an open lip-like geometry presented to the LA space. Flow control component  201  can have a smooth LA face, which can limit sites for turbulent eddy generation. The LA face can be geometrically biased to open with increasing LA pressure relative to the right atrium. 
     Flow control component  201  defines a passage  207  therethrough. In some cases, passage  207  can be defined as an opening having a cross-sectional dimension, e.g., a diameter, of between 5 to 10 millimeters. Passage  207  is collapsed when there is no pressure differential between opposite sides of flow control component  201 , as shown in  FIG. 2A . Alternatively, as shown in  FIGS. 2B-2E , flow control component  201 , can open when the pressure differential between the pressure in the left atrium and the pressure in the right atrium exceeds a predetermined threshold pressure value, e.g., the first predetermined threshold pressure. In some cases, the predetermined threshold pressure value is about 10 kilopascals (kPa) (about 7.5 millimeters of mercury (mmHg)). Accordingly, in some cases, passage  207  can open when the pressure differential between the pressure in the left atrium and the pressure in the right atrium exceeds about 10 kPa (about 7.5 mmHg). In some cases, the predetermined threshold pressure value is a pressure value between 0.7 kPa and 1.3 kPa (between 7.5 mmHg and 10 mmHg), or between 1.3 kPa and 2 kPa (between 10 mmHg and 15 mmHg). 
     Flow control component  201  can include an elastic material. In some cases, flow control component  201  have a double walled tubular structure. In some cases, a space between walls can be filled with an elastic material. Suitable materials for the walls can include elastomeric polymers such as silicones, styrene-isobutylene-styrenes (SIBS), poly-isobutylene polyurethanes (PIB-PUR), biocompatible fluoropolymers, para-methoxy-N-methylamphetamines (PMMA), silicones, polyethylene terephthalates (PET), polytetrafluoroethylenes (PTFE), and combinations thereof. Suitable materials for material included in a space between the walls include polymer foams, braided mesh made of one or a combination of metal and synthetic polymer materials such as nitinol (NiTi), polyurethanes, silicones, biocompatible fluoropolymers, poly(styrene-block-isobutylene-block-styrene) (SIBS), para-methoxy-N-methylamphetamines (PMMA), silicones, polyethylene terephthalates (PET), polytetrafluoroethylenes (PTFE), and combinations thereof. 
       FIG. 2F  depicts the pressures of different heart chambers for both an exemplary healthy/nondiseased patient and for an exemplary diseased patient. As shown, the health/nondiseased patient shows a slightly higher pressure in the left atrium than in the right atrium. A diseased patient during periods of no exercise and no stress having a flow control component  201  would have the flow control component  201  mostly remain in state  1  ( FIG. 2A ), where it is closed, but periodically have a pressure differentially increase sufficiently to partially open valve  201  in state  2  ( FIG. 2B ). In state  1 , flow control component  201  is fully closed, and occurs at points in cardiac cycle when the RA pressure is equal to or greater than the LA pressure or when the pressure differential between the left atrium and the right atrium is less than a predetermined threshold value, which can be less than the maximum pressure differential experienced in a healthy/nondiseased heart. State  1  can prevent regurgitation, but a periodic state  2  can provide a clearing function for removing residual blood from a coaptation zone in passage  207  to prevent adhesion between opposite sides of a collapsed passage  207 . As shown, state  2  has passage  207  only partially open. In some cases, state  2  can be configured to prevent more than about 2% of the cardiac output from passing through flow control component  201  during a cardiac cycle (e.g., about 50 ml/minute of blood). 
     In some cases, flow control component  201  can be configured such that blood does not stagnate at a location proximate to a left atrium flow control component side when the pressure differential is below a second predetermined threshold pressure value. In some cases, the flow control component  201  can be configured such a periodic opening of the flow control component during each cardiac cycle is less than 100 ml/minute to prevent stagnation. 
     For a patient in a diseased state with or without exercise, LA pressure can be significantly elevated above normal. As shown in  FIGS. 2C-2E , larger pressure differences between left atrium and right atrium can force open the flow control component orifice to an increasingly larger diameter. Flow control component  201  changes states  1 - 5  depending on pressure difference in cardiac cycle. As will be discussed below, other embodiments of flow control components provided herein can also provide for increasing passage sizes with increasing pressure differentials. 
       FIGS. 3A-3G  depict how an implantable transseptal flow control component  301  according to a second embodiment can alternate between stages of open and closed configurations when implanted. Flow control component  301  includes a shape-stable disk  307  and a compliant disk  304  connected centrally  302 . Shape-stable disk  307  can be flexible so that it can be collapsed and expanded between a non-deployed state (for delivery) and an expanded deployed state. When in the deployed state, shape-stable disk  307  is strong enough to resist deformation due to the blood flow through and/or around shape-stable disk  307 . Shape-stable disk  307  defines passages  308  therethrough. As will be discussed below, shape-stable disk  307  can be collapsible (e.g., for intravascular delivery). In some cases, for example, shape-stable disk  307  can include a collapsible frame and a non-elastic but flexible sheet. 
     In some cases, flow control components can be fully or partially contained within the inter-atrial septum. In some cases, flow control components can be fully or partially project outwardly from one or both sides of the septum. In some cases, at least a portion of the flow control component, e.g. shape-stable disk  307  of  FIGS. 3A-3G  or a central portion of flow control component, can have a thickness of about 1 mm to about 5 mm. In some cases, portions of the flow control components have a thickness of about 1 to about 2 mm, or about 2 mm to about 5 mm, or about 5 mm to about 10 mm. 
     Compliant disk  304  can include a shape memory wire  306  embedded in the compliant member to urge the compliant disk  304  towards shape-stable disk  307 . As shown in  FIG. 3A , state  1  depicts a closed configuration where compliant disk  304  overlies and seals passages  308  due to a lack of a pressure differential exceeding a predetermined threshold value. Shape memory wires  306  can be designed to control a pressure differential required to overcome the shape memory properties of the shape memory wires  306 . In some cases, shape memory materials discussed herein can be a nickel-titanium alloy (e.g., nitinol). As shown in  FIG. 3B , state  2  results in a flexing of compliant disk  304  to allow flow of blood through passages  308 . Similar to that discussed above with regards to  FIGS. 2A-2F , a diseased patient during a period of no exercise and no stress can have heart pressures that cause flow control component  301  to alternate between state  1  and state  2 , optionally with each cardiac cycle, to periodically flush residual blood from coaptation zone between compliant disk  304  and shape-stable disk  307 . As shown in  FIGS. 3C-3E , a diseased heart can experience higher pressure differentials and thus reach state  3  and state  4 .  FIGS. 3F and 3G  depict perspective views of flow control component  301  in state  2  and state  4 , respectively. 
     In some cases, flow control component  301  can be configured such that blood does not stagnate at a location proximate to a left atrium flow control component side when the pressure differential is below a second predetermined threshold pressure value. In some cases, the flow control component  301  can be configured such a periodic opening of the flow control component during each cardiac cycle is less than 100 ml/minute to prevent stagnation. 
       FIGS. 4A and 4B  depict an implantable transseptal flow control component  401  according to a third embodiment.  FIGS. 5A and 5B  depict an implantable transseptal flow control component according to a fourth embodiment.  FIGS. 6A and 6B  depict an implantable transseptal flow control component according to a fifth embodiment. Each of  FIGS. 4A-6B  depict embodiments that are similar to that depicted in  FIGS. 3A-3G , but differ with regard to the compliant disk. As shown in  FIGS. 4A and 4B , flow control component  401  includes a compliant disk  404  secured to a shape-stable disk  407  at a central axis  402 . Flow control component  401  is shown in a state when a pressure differential is greater than a predetermined threshold value such that blood can flow through passages  408  in shape-stable disk  407 . As shown,  FIGS. 4A and 4B  do not include a shape memory (e.g., nitinol) wire. As shown in  FIGS. 5A and 5B , flow control component  501  includes a compliant disk  504  secured to a shape-stable disk  507  at a central axis  502 . Flow control component  501  is shown in a state when a pressure differential is less than a predetermined threshold value such that the flow control component is closed and blood cannot flow through passages  508  in shape-stable disk  507 . As shown,  FIGS. 5A and 5B  have a compliant disk including a shape memory (e.g., nitinol) wire. As shown in  FIGS. 6A and 6B , flow control component  601  includes a compliant disk  604  secured to a shape-stable disk  607  at a central axis  602 . Flow control component  601  is shown in a state when a pressure differential is less than a predetermined threshold value such that the flow control component is closed and blood cannot flow through passages  608  in shape-stable disk  607 . As shown,  FIGS. 6A and 6B  have a compliant disk including a shape memory (e.g., nitinol) wire. 
       FIGS. 7A-7F  depict an implantable transseptal flow control component  701  according to a sixth embodiment.  FIGS. 7A-7C  depict it in a closed configuration, e.g., state  1 .  FIGS. 7D-7F  depict it in an open configuration, e.g., state  3 .  FIGS. 7A and 7D  depict views from the right atrium.  FIGS. 7C and 7F  depict views from the left atrium.  FIGS. 7B and 7E  depict side views. As shown in  FIGS. 7A-7F , compliant disk  704  is sealed to shape-stable disk  707  along a periphery of each disk. Shape-stable disk  707  defines at least one passage  708  there through and compliant disk  704  defines at least one passage  705  there through, but passages  705  and  708  are non-aligned such that compliant disk  704  overlies the holes in shape-stable disk  707  when the pressure differential is below a predetermined threshold. As shown in  FIG. 7E , a pressure differential above a predetermined threshold can cause compliant disk  704  to balloon out to form a path for fluid to flow between passage  705  and passage  708 . 
       FIGS. 8A-8C  depict an implantable transseptal flow control component  801  according to a seventh embodiment. As shown a compliant disk  804  defines a central passage  805  there through and shape-stable disk  807  includes peripheral cutouts  809 . Compliant disk  804  and shape-stable disk  807  can be secured together intermittently along a periphery of the disk to allow for a space to open between the compliant disk  804  and the shape-stable disk  807  along the periphery (e.g., at the peripheral cutouts  809 ).  FIGS. 8A-8C  depict flow control component  801  in a closed configuration (state  1 ), but open configurations (states  2 - 4 ) can also exist with increasing pressure differences. 
       FIGS. 9A-9E  depict an implantable transseptal flow control component  901  according to an eighth embodiment. As shown, flow control component  901  includes a shape-stable ring  902 , a shape-stable semicircle member  907  secured to a portion of shape-stable ring  902 , and a compliant flap  904  secured to the shape-stable ring  902  such that flap  904  and shape-stable semicircle member  907  can provide a closed configuration, such as shown in  FIGS. 9A-9C .  FIG. 9A  depicts a view from the RA side.  FIG. 9B  depicts a view from the LA side.  FIG. 9C  depicts a side view, showing a closed position.  FIG. 9D  depicts a side view showing a partial ballooning of flexible flap  904  while flow control component  901  remains closed. In some cases, this ballooning can pulsate during unstressed cardiac cycles to provide a clearing function to clear residual blood from areas along the interface between flap  904  and shape-stable semicircle member  907 .  FIG. 9E  depicts flow control component  901  in an open configuration after a pressure differential between left atrium and right atrium exceeds a predetermined threshold value. 
       FIG. 10  depicts an implantable transseptal flow control component  1001  according to a ninth embodiment, which includes a shape-stable ring  1007  and a flexible flap  1004  adapted remain in a closed configuration for pressure differentials below a threshold pressure value and to change to an open configuration when a pressure differential exceeds the threshold pressure value. 
       FIGS. 11A-11I  depict an implantable transseptal flow control component  1101  according to a tenth embodiment. As shown, flow control component  1101  includes a compliant disk  1104  having three coapting leaflets  1105  and a shape-stable frame  1107  including multiple passages  1108  there through. In some cases, shape-stable frame  1107  can be a porous structure. An outer ring of shape-stable frame  1107  can include a recess  1109  for receiving compliant disk  1104  to form a secure connection between frame  1107  and disk  1104 . When in use, a negative pressure gradient in the direction of compliant disk  1104  can cause leaflets  1105  to deflect allowing fluid flow. Negative pressure gradient in the direction of compliant frame  1107  can force leaflets  1105  to coapt while compliant frame  1107  can prevent leaflets  1105  from inverting. Leaflets  1105  can have shape memory adapted to require a predetermined pressure differential before the leaflets  1105  transition to an open configuration. In some cases, leaflets  1105  can include a shape memory wire (e.g., a nitinol wire) in order to impart shape memory to the leaflets  1105 . 
       FIGS. 12-12A  depict an implantable transseptal flow control component  1201  according to an eleventh embodiment. Flow control component  1201  can include a plurality of lobes  1204 . In some cases, flow control component  1204  includes at least  4  lobes. In some cases, flow control component  1204  includes at least  5  lobes, at least  6  lobes, at least  8  lobes, or at least  10  lobes. In some cases, lobes  1204  can be filled with blood via a parachute flow control component. Lobes  1204  are attached to a central location of a frame member  1207  adapted to fit within an opening in a septum between the left atrium and the right atrium. Frame member  1207  can define one or more passages  1208  along its periphery. When the pressure in the right atrium exceeds that of the left atrium, the lobes can deflect towards passages  1208  to close flow control component  1201 . When the pressure in the left atrium exceeds that of the right atrium by a predetermined threshold value, lobes  1204  can deflect inward to allow for blood to flow through passages  1208  and around lobes  1205 . In some cases, lobes  1204  can include shape memory materials (e.g., nickel-titanium alloy such as nitinol) in order to have flow control component  1201  in a closed configuration when the pressure difference is below a predetermined threshold value. 
       FIG. 13  depicts an implantable transseptal flow control component  1301  according to a twelfth embodiment.  FIG. 14  depicts an implantable transseptal flow control component  1401  according to a thirteenth embodiment. Flow control components  1301  and  1401  include a spring-based mechanism. For example, a shape memory material (e.g., stainless steel or a nickel-titanium alloy such as nitinol) can form a frame that opens based on a pressure gradient. 
       FIGS. 13A-D  depicts a flow control component  1301  in four stages based on four different pressures: P 0 , P 1 , P 2 , and P 3 . P 0  is less than P 1 , which is less than P 2 , which is less than P 3 . Flow control component  1301  includes three springs  1303 ,  1305 , and  1307 . Spring  1303  can be a 0.08 inch (2 mm) spring, spring  1305  can be a 0.2 inch (5 mm) spring, and spring  1307  can be a 0.4 inch (10 mm) spring when the flow control component  1301  is at a pressure of P 0 . As shown in  FIG. 13 , with increasing pressures, springs  1303 ,  1305 , and  1307  can progressively release to allow for the passage to expand to provide an increase in flow. In panel A, for a pressure gradient of P 0 , none of the spring mechanisms have actuated. In panel B, the weakest spring  1303  which was maintaining the opening at a 0.08 inch (2 mm) diameter is actuated by pressure P 1 , resulting in an opening that is limited by the stronger spring  1305  at the 0.2 inch (5 mm) diameter. In panel C, the pressure P 2  releases the 0.2 inch (5 mm) diameter spring  1305  resulting in a diameter of 0.4 inch (10 mm) limited spring  1307 . Finally, as shown in panel D, pressure P 3  will release the final spring  1307  allowing for full flow of diameter &gt;0.4 inch (10 mm). In some cases, flow control component  1301  can be arranged such that pressure differential of less than 0.7 kPa (5 mmHg), 1.3 kPa (10 mmHg), or 2 kPa (15 mmHg) will close flow control component  1301 . 
       FIG. 14  depicts a similar arrangement to  FIG. 13 , but in  FIG. 14  springs are compressed with increasing pressures. Flow control component  1401  include one or more springs, such as springs  1403 , which is shown in two states, state A  1403   a  and state B  1403   b.  At lower pressures, spring  1403  is in state A  1403   a,  which allows for a reduced width opening or a closure of the opening in flow control component  1401  between channel walls  1409   a.  When pressure is increased, one or more of the springs will compress to be in state  1403   b  to allow for an increased opening between channel walls  1409   b.  Although only one pair of springs (in two states) is shown in  FIG. 14 , it is contemplated that each side could include multiple springs each having different strengths so as to have the channel expand to different preset diameters with increasing pressures, similar to that described above in reference to  FIG. 13 . In some cases, flow control component  1401  can be arranged such that pressure differential of less than 1.33 kPa (10 mmHg) will close flow control component  1401 . In some cases, springs  1403  can be circumferential for a round flow lumen. In some cases, springs can be linear springs. In some cases, linear springs can be included in the bill design previously disclosed herein. 
       FIG. 15  depicts an implantable transseptal flow control component  1501  according to a fourteenth embodiment. As shown, flow control component  1501  includes a frame  1502  and a hinged-door  1504  connected via hinge  1503 , a limiting cord  1505 , and a set of magnets  1506  and  1507  positioned on hinged door  1504  and frame  1502  opposite hinge  1503 . For flow control component  1501 , the strength of the magnetic pull can balance the pressure force from the blood such that the hinged door  1504  only moves to an open configuration upon a pressure difference between the left atrium and right atrium exceeding a predetermined threshold value. In some cases, a spring can be provided to bias the hinged door towards a closed configuration. 
       FIG. 16  depicts an implantable transseptal flow control component  1601  according to a fifteenth embodiment. Flow control component  1601  also includes a frame  1602  and a spring loaded hinged door  1604  connected via a spring loaded hinge  1603  and a set of magnets  1606  and  1607 . Spring loaded hinge can bias the hinged door towards a closed configuration and have the opening grow large with greater pressure differentials. 
     Magnets, springs, and/or limiting cords such as shown in  FIGS. 15 and 16  can be applied to each of the other embodiments discussed herein. 
     In some cases, a flow control component provided herein can be a metallic iris, such as the iris designs shown in  FIG. 17 . A metallic iris can be can be activated by electrical energy from a supply source. An electrical energy supply source can be internal or external to the body. An external source—for example, a doctor or nurse can use an RF transmitter externally to activate the flow control component which has an RF receiver. An internal source—in some cases, a pacemaker or ICD battery can be implanted and used to activate a flow control component or using the existing battery of a pacemaker or ICD already implanted in the diseased patient. The opening of the iris can be modulated in some cases using imaging modalities, such as fluoro or TEE/ICE, can be used to determine an appropriate opening of a hole in the septum between the left atrium and the right atrium. Alternatively, the iris could have a pressure sensor on the LA side or both on the LA and RA side and then based on a feedback loop system be opened using the internal energy source once a pre-determined and calibrated threshold has been achieved. 
     The iris can be mounted on a shape-stable ring such as in  FIG. 9A  i.e.  902 . The default state of the iris can be in a closed position. 
     In some cases, systems provided herein can include controllers adapted to control the opening of a flow control component provided herein. A controller can be implanted or external. In some cases, the controller can activate control based on an algorithm within electronics such as a pacemakers or ICD type device to open a specific amount at specific times of the day (such as during sleep) or during specific activities (such as during exercise). Alternatively, the opening of the device can be based on internal feedback from one or more pressure sensors placed just in the left atrium or in both the left and right atriums. In some cases, pressure sensors can be incorporated into flow control components provided herein or mounted separately in the body, such as on the left atrial appendage closure frame placed in the left atrial appendage. 
     In some cases, methods and systems provided herein can monitor the number of times or rate of activation of a flow control component provided herein and transmit that value through RF signals to an external display unit. In some cases, a doctor or nurse could find a rate, time, and/or change in activation useful for evaluating the progression of heart failure. In some cases, flow control components provided herein can be monitored for appropriate operation by detecting a sound of the flow control component opening and closing similar to standard heart sounds. For example, flow control components provided herein can be designed to create a sound undetectable to a human ear, but detectable by an electronic sensor. In some cases, flow control components provided herein can include piezoresistive or piezoelectric elements that are activated by the open-close cycle and transmit this information to an external device through RF or to an internal device such as the pacemaker or ICD or standalone implantable controller. In some cases, an internal implantable device can be included in systems provided herein or used in methods provided herein to monitor flow control components provided herein. For example, an internal implantable device for monitoring flow control components provided herein can be similar to a low voltage pacing system. In some cases, a monitoring system can be incorporated into another implanted device, such as a pacemaker, which may be able to allow for continuous monitoring and the upload of data via telemetry. 
       FIGS. 18A-18  C depict a support frame  1811  for a collapsible shape-stable member, which can be used with implantable transseptal flow control components provided herein.  FIGS. 18A-18C  depict flow control component  1801 . Frame  1811  includes wire segments that form a ring  1812 , which can be used to stretch a non-elastic material to form a shape-stable member in the embodiments discussed above in regards to  FIGS. 3A-16 . Frame  1811  can collapse when sheared in directions parallel with the axis of ring  1812 . The wire segments making up ring  1812  includes a series of loops  1813  and V-shaped elements  1814 , which are capable of transformation into a generally tubular, constrainable shape. In some cases, frame  1811  can include a shape memory material (e.g., a nickel-titanium alloy such as Nitinol). In some cases, a phase transition of a shape memory material can be used to control the expansion and retraction of the frame from a collapsed configuration to a shape-stable expanded configuration. 
     For example, with Nitinol, cooling the structure to its Martensitic state, the structure can be significantly manipulated without damage to the structure. As long as the low martensitic temperature is maintained the structure will remain very ductile and retain its manipulated shape until warmed. The first step to the transition to a constrainable tubular form is to chill the structure to its martensitic state and maintain the cool environment. Referring to  FIGS. 18B and 18C , the structure can be manually manipulated to generally orientate the loops  1813  into an advantageous position for final constrainment. All of the loops  1813  can be reoriented, e.g., partially tipped or bent, into the desired direction from the depicted plane a to somewhere beyond the depicted plane b, towards the plane c. Loops can be reoriented using cool metal tools while maintaining a cool environment (e.g., cold air or submerged in very cold solution). Once the loops have achieved a general constrainable orientation (sufficient bias to guide all loops in the desired direction when force constrained in an iris) as shown in a similar sample structure, the device can be placed into a pre-cooled constrainment iris tool. The structure can be constrained into a loadable tubular state and is ready to be loaded onto the delivery catheter. As long as the device is kept below its austenitic start temperature, it will remain in the constrained tubular state. Once loaded into the delivery catheter, such as shown in  FIGS. 19A-19C , in a similar manner as the like device that is depicted, the device will remain in that orientation until deployed into its final physiological deployment location. When the outer sheath is retracted in the body, the device will warm from the heat of the blood. This will phase transition the metal through its austenitic range to its finish temperature. The device will return to its stress relieved original shape. The catheter is withdrawn and the device will function as designed. 
     In some cases, embodiments of the flow control components discussed herein can be configured such that blood does not stagnate at a location proximate to a left atrium flow control component side when the pressure differential is below a second predetermined threshold pressure value. In some cases, embodiments of the flow control component discussed herein can be configured such a periodic opening of the flow control component during each cardiac cycle is less than 100 ml/minute to prevent stagnation. 
     A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.